Waleed Ghanima

• Cooper, Nichola; Bussel, James; Ghanima, Waleed; Provan, Drew; Tomiyama, Yoshiaki & Hou, Ming [Vis alle 18 forfattere av denne artikkelen] (2026). Exploring the Burden on Patients Living With and Receiving Treatment for Immune Thrombocytopenia (ITP): Patient and Physician Perceptions From the ITP World Impact Survey (I-WISh) 2.0. American Journal of Hematology. ISSN 0361-8609. doi: 10.1002/ajh.70379. Fulltekst i vitenarkiv
• Bhangu, Gurjeet; Greutert, Sophie; Robert-Ebadi, Helia; Kline, Jeffrey; Righini, Marc & Penaloza, Andrea [Vis alle 15 forfattere av denne artikkelen] (2026). Diagnostic management of suspected acute pulmonary embolism in the postpartum period. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. doi: 10.1016/j.jtha.2026.05.010. Fulltekst i vitenarkiv
• Garabet, Lamya Samir Noori & Ghanima, Waleed (2026). Thrombosis in immune thrombocytopenia. British Journal of Haematology. ISSN 0007-1048. 208(6), s. 1924–1927. doi: 10.1111/bjh.70474. Fulltekst i vitenarkiv
• Jørgensen, Camilla Tøvik; Riva, Nicoletta; Pettersen, Heidi Hassel; Frønæs, Synne Grønvold; Ghanima, Waleed & Tavoly, Mazdak (2026). Treatment strategies, bleeding, long-term recurrence and mortality in abdominal vein thrombosis: Findings from the TROLL registry. Thrombosis Research. ISSN 0049-3848. 262. doi: 10.1016/j.thromres.2026.109724. Fulltekst i vitenarkiv
• Tavoly, Mazdak; Jørgensen, Camilla Tøvik; Sandblad, Katarina Glise; Ghanima, Waleed & Garabet, Lamya Samir Noori (2026). The impact of symptom duration on D-dimer: results from the Venous Thrombosis Registry in Østfold Hospital. Research and Practice in Thrombosis and Haemostasis (RPTH). 10(3). doi: 10.1016/j.rpth.2026.103457. Fulltekst i vitenarkiv
• Cooper, Nichola; Broome, Catherine M.; Miyakawa, Yoshitaka; McDonald, Vickie; Al-Samkari, Hanny & Khelif, Abderrahim [Vis alle 546 forfattere av denne artikkelen] (2026). Efficacy and Safety of Subcutaneous Efgartigimod PH20 in Adults With Primary Immune Thrombocytopenia (ADVANCE SC): A Multicenter, Randomized, Double-Blinded, Placebo-Controlled, Phase 3 Trial. American Journal of Hematology. ISSN 0361-8609. doi: 10.1002/ajh.70303. Fulltekst i vitenarkiv
• Asady, Elia; Jelsness-Jørgensen, Lars-Petter; Ghanima, Waleed; Klok, F. A.; Kahn, Susan R. & Boon, Gudula J.A.M. [Vis alle 9 forfattere av denne artikkelen] (2026). Item generation for a new disease-specific health-related quality of life questionnaire in patients with deep vein thrombosis: an international multicenter study. Research and Practice in Thrombosis and Haemostasis (RPTH). 10(3). doi: 10.1016/j.rpth.2026.103443. Fulltekst i vitenarkiv
• Tsykunova, Galina; Kristiansen, Eskild Bendix; Tvedt, Tor Henrik Andersson; Frederiksen, Henrik; Christiansen, Christian Fynbo & Linder, Marie [Vis alle 8 forfattere av denne artikkelen] (2026). Factors associated with response to rituximab in patients with immune thrombocytopenia. HemaSphere. 10(5). doi: 10.1002/hem3.70373. Fulltekst i vitenarkiv
• Ghanima, Waleed & Hou, Yu (2026). Anti-CD38 therapy in immune thrombocytopenia (ITP). British Journal of Haematology. ISSN 0007-1048. doi: 10.1111/bjh.70493. Fulltekst i vitenarkiv
• Liu, Zhenyu; Rebetz, Johan; Garabet, Lamya Samir Noori; Ghanima, Waleed; Xu, Peipei & Wadenvik, Hans [Vis alle 9 forfattere av denne artikkelen] (2026). MicroRNAs as potential architects of immune dysregulation and megakaryocytic failure in immune thrombocytopenia. British Journal of Haematology. ISSN 0007-1048. doi: 10.1111/bjh.70485. Fulltekst i vitenarkiv
• Dhayyat, Adam; Stavem, Knut; Jervan, Øyvind; Hilde, Janne Mykland; Rashid, Diyar Nori Mohamad & Gleditsch, Jostein [Vis alle 8 forfattere av denne artikkelen] (2026). Stress Echocardiography to Detect Exercise Pulmonary Hypertension in Patients With Chronic Thromboembolic Pulmonary Disease. Pulmonary Medicine. ISSN 2090-1836. 2026(1). doi: 10.1155/pm/4127338. Fulltekst i vitenarkiv
• Mjali, Ahmed; Matti, Bassam Francis; Ghanima, Waleed; Provan, Drew; Abbas, Nareen Tawfeeq & Naji, Alaadin Sahham [Vis alle 16 forfattere av denne artikkelen] (2025). Iraqi consensus recommendations for the diagnosis and management of immune thrombocytopenia. Hematology. ISSN 1024-5332. 30(1). doi: 10.1080/16078454.2025.2555045. Fulltekst i vitenarkiv Vis sammendrag

  Background and Objectives The management of ITP has evolved with evidence-based international guidelines. However, Iraq’s unique challenges, including variations in clinical practice and treatment disparities, necessitate localized guidance to bridge global recommendations and real-world practice. This expert consensus aims to provide a comprehensive and practical framework for diagnosing and managing ITP within the Iraqi healthcare setting. Methods A 16-member multidisciplinary ITP specialist panel (Iraq, Norway, UK), including hematologists, laboratory experts, and related specialists, conducted a systematic PubMed / PubMed Central / Embase review (January 2003–December 2024) using key terms ‘primary immune thrombocytopenia’ and ‘idiopathic thrombocytopenic purpura’ (English human studies, excluding conference abstracts). Using a modified Delphi method, consensus was reached on 43 ITP diagnosis/treatment/management statements. After a single voting round, the panel refined the recommendations to ensure their applicability to Iraq’s healthcare system. Final recommendations were categorized using evidence grading system. Results Corticosteroids were the preferred first-line therapy, with intravenous immunoglobulin (IVIG) reserved for urgent platelet elevation. The panel discouraged prolonged corticosteroid use due to adverse effects and defined clear criteria for second-line therapies. Thrombopoietin receptor agonists (TPO-RAs) and rituximab were recommended second-line, while splenectomy was considered a last resort, only after the failure of multiple medical therapies. Special populations received tailored recommendations, including pregnant patients, pediatric cases, and high-thrombosis-risk individuals. Recommendations incorporated quality of life, emphasizing patient-centered care and minimizing unnecessary medication exposure. Conclusion This expert consensus provides a structured, evidence-informed approach to ITP diagnosis and management in Iraq, balancing best practices with local healthcare realities.

• Kuter, David J. & Ghanima, Waleed (2025). Evaluating rilzabrutinib in the treatment of immune thrombocytopenia. Immunotherapy. ISSN 1750-743X. 17(11), s. 767–782. doi: 10.1080/1750743X.2025.2545170. Fulltekst i vitenarkiv Vis sammendrag

  There is an unmet need for newer treatment options in immune thrombocytopenia (ITP) that address its underlying complex immune dysregulation, induce durable platelet responses, are well tolerated, and improve fatigue and overall quality of life. Rilzabrutinib, an oral, reversible covalent Bruton tyrosine kinase (BTK) inhibitor, is effective through its multi-immune modulation mechanisms by inhibiting B-cell activation, possibly decreasing autoantibody production, preventing FcγR-mediated phagocytosis in the spleen and liver, and reducing chronic inflammation. Preclinical studies of rilzabrutinib in immune-mediated disease settings demonstrated high selectivity, full reversibility, and durable BTK occupancy. Oral rilzabrutinib 400 mg BID demonstrated rapid, durable platelet count increases in patients with persistent/chronic ITP in the phase 2 LUNA2 study and significantly improved durable platelet response vs placebo in the pivotal phase 3 LUNA3 trial. Additionally, rilzabrutinib improved multiple disease aspects including fatigue and bleeding with a well-tolerated safety profile. Through multi-immune modulation, rilzabrutinib achieves rapid and durable platelet response, improves fatigue, and decreases bleeding in ITP patients. It is well tolerated with an acceptable safety profile. Efficacy may be increased if administered earlier in the course of disease. Longer-term studies, and investigations in pediatric patients and other immune-mediated diseases are underway.

• Moulis, Guillaume; Chen, Frederick; Carli, Giuseppe; Ghanima, Waleed; Trautmann-Grill, Karolin & Stauch, Thomas [Vis alle 22 forfattere av denne artikkelen] (2025). Use of second-line and beyond maintenance therapies in adult patients with primary immune thrombocytopenia in Europe: a parallel study of six prospective multicenter national registries. Haematologica. ISSN 0390-6078. 110(12), s. 3094–3098. doi: 10.3324/haematol.2025.287408. Fulltekst i vitenarkiv Vis sammendrag

  Not available.

• Mai, Vicky; Takada, Toshihiko; Kraaijpoel, Noemie; Es, Nick van; Mallick, Ranjeeta & Stals, Milou A.M. [Vis alle 26 forfattere av denne artikkelen] (2025). Safety and efficiency of diagnostic strategies for ruling out pulmonary embolism in patients with chronic lung disease: an individual-patient data meta-analysis. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. doi: 10.1016/j.jtha.2025.10.004. Fulltekst i vitenarkiv
• Vrotniakaite-Bajerciene, Kristina; Mallick, Ranjeeta; Takada, Toshihiko; Kraaijpoel, Noemie; Smeden, Maarten van & Moons, Karel G.M. [Vis alle 22 forfattere av denne artikkelen] (2025). Safety and efficiency of D-dimer testing in combination with clinical decision rules to exclude pulmonary embolism in patients with cancer: individual patient data meta-analysis. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. s. 1–14. doi: 10.1016/j.jtha.2025.10.035. Fulltekst i vitenarkiv
• Kuter, David J.; Ghanima, Waleed; Cooper, Nichola; Liebman, Howard A.; Zhang, Lei & Hu, Yu [Vis alle 32 forfattere av denne artikkelen] (2025). Safety and efficacy of rilzabrutinib vs placebo in adults with immune thrombocytopenia: the phase 3 LUNA3 study. Blood. ISSN 0006-4971. 145(24), s. 2926–2926. doi: 10.1182/blood.2024027336. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Rilzabrutinib is a covalent, reversible Bruton tyrosine kinase inhibitor targeting multiple immune thrombocytopenia (ITP)-related mechanisms. The phase 3 LUNA3 study in previously treated adults with persistent/chronic ITP evaluated oral rilzabrutinib 400 mg twice daily (n = 133) vs placebo (n = 69) for 24 weeks. At baseline overall, median age was 47 years, 63% female, 7.7 year median ITP duration, and 28% prior splenectomy. Overall (N = 202), 85 (64%) rilzabrutinib and 22 (32%) placebo patients achieved platelet response (≥50 × 109/L or 30 × 109/L to <50 × 109/L and doubled from baseline) during the first 12 weeks and were eligible to continue. The primary end point, durable platelet response (platelet count ≥50 × 109/L for ≥two-thirds of ≥8 of the last 12 of 24 weeks without rescue therapy), was observed in 31 (23%) rilzabrutinib vs 0 placebo patients (P < .0001). All secondary efficacy end points were significantly superior for rilzabrutinib (P < .05). Median time to first platelet response was 15 days in rilzabrutinib responders. Rilzabrutinib significantly reduced rescue therapy use by 52% (P = .0007) and improved week 25 bleeding scores (P = .0006). Improved physical fatigue was sustained from week 13 (P = .01) through 25 (P = .0003). Treatment-related adverse events were mainly grade 1/2. One rilzabrutinib patient with multiple risk factors had serious treatment-related grade 3 peripheral embolism (lower left leg), and another died from unrelated pneumonia. Rilzabrutinib in patients who failed multiple previous ITP therapies showed rapid and durable platelet response, reduced rescue medication and bleeding, improved physical fatigue, and favorable safety. Trial registration: www.clinicaltrials.gov (#NCT04562766) and www.clinicaltrialsregister.eu (#2020-002063-60).

• Cuker, Adam; Stauch, Thomas; Cooper, Nichola; Al-Samkari, Hanny; Michel, Marc & Ghanima, Waleed [Vis alle 26 forfattere av denne artikkelen] (2025). Ianalumab plus Eltrombopag in Immune Thrombocytopenia. New England Journal of Medicine. ISSN 0028-4793. 394(15), s. 1503–1513. doi: 10.1056/nejmoa2515168. Fulltekst i vitenarkiv
• Mohamad, Hodo; Jørgensen, Camilla Tøvik; Ghanima, Waleed; Tavoly, Mazdak & Frønæs, Synne Grønvold (2025). Clinical use and safety of empiric anticoagulation during diagnostic work-up for deep vein thrombosis. Hematology. ISSN 1024-5332. 30(1). doi: 10.1080/16078454.2025.2573586. Fulltekst i vitenarkiv Vis sammendrag

  Background: Previous studies suggest the safety of empiric anticoagulation administered to patients with suspected deep vein thrombosis (DVT) before the work-up is completed. However, the safety of such practice has not been thoroughly studied in the primary care setting. Objectives: To describe the clinical use and safety of empiric low molecular-weight heparin (LMWH) in patients evaluated for suspected DVT in the prehospital, primary care setting. Methods: Patients evaluated for suspected DVT between February 2015 and November 2018 in the Emergency Department at Østfold Hospital, Norway, were eligible for inclusion. Pattern of use of empiric LMWH was evaluated regarding the type of anticoagulant agent and dosage (therapeutic vs sub-therapeutic). Safety, defined as major and clinically relevant non-major bleeding (CRNMB) events, and development of pulmonary embolism (PE) after the initiation of empiric therapy, was assessed in all patients receiving empiric anticoagulation 48 h post-enrolment. Results: Of the 1653 patients referred to Østfold Hospital with suspected DVT, 328 patients (19.8%) received LMWH. Of these, 54 (16.5%) received therapeutic doses, 232 (70.7%) sub-therapeutic doses, whereas 42 (12.8%) received unknown doses. Enoxaparin was prescribed to 303 patients (94.2%), while 25 patients (7.6%) received dalteparin. DVT was confirmed in 69 patients (21.0%). No major bleeding events or deaths occurred. Two patients (0.6%) experienced CRNMB events. None of the patients developed PE after the initiation of empiric therapy. Conclusions: Most patients received sub-therapeutic doses of empiric LMWH. Bleeding complications were low, indicating that empiric anticoagulation was safe. Empiric anticoagulation was often prescribed irrespective of the pre-test probability score and the bleeding risk.Trial registration: ClinicalTrials.gov identifier: NCT02486445.

• Jørgensen, Camilla Tøvik; Tavoly, Mazdak; Pettersen, Heidi Hassel; Frønæs, Synne Grønvold; Ghanima, Waleed & Gleditsch, Jostein (2025). Long-term recurrence, bleeding, and mortality after first-time subsegmental pulmonary embolism compared to more proximal pulmonary embolism: Findings from the TROLL registry. Thrombosis Research. ISSN 0049-3848. 252, s. 109386–109386. doi: 10.1016/j.thromres.2025.109386. Fulltekst i vitenarkiv Vis sammendrag

  Background: Subsegmental pulmonary embolism (SSPE) refers to clots that exclusively obstruct the subsegmental arteries. Data on long-term recurrence and bleeding risks following SSPE remain limited. Objectives: To determine the long-term incidence of venous thromboembolism (VTE) recurrence after cessation of anticoagulation in patients with SSPE compared to those with more proximal PE (non-SSPE), to assess major and clinically relevant non-major bleeding (CRNMB), and to evaluate 30-day and 31-365-day all-cause mortality. Methods: Between January 2005 and May 2020, 1135 cancer-free patients with a first-time computed tomography-verified PE were identified from The Venous Thrombosis Registry in ØstfOLd HospitaL (TROLL), Norway. Results: Among the 1135 patients, 72 (6.3 %) were diagnosed with SSPE, while 1063 (93.7 %) had more proximal PE. Median age was 70 years (IQR: 58-80), and 51.4 % were women. The 10-year cumulative incidence of VTE recurrence after discontinuation of anticoagulation was 16.5 % (95 % CI: 4.5-35.1) in the SSPE group compared to 28.4 % (95 % CI: 24.5-32.4) in the non-SSPE group (p = 0.08). The 6-month cumulative incidence of major bleeding was 1.4 % (95 % CI, 0.1-6.6) in SSPE cases and 4.6 % (95 % CI: 3.4-5.9) in non-SSPE cases (p = 0.23). The 30-day all-cause mortality rate was 9.7 % (95 % CI: 4.8-19.3) for SSPE and 4.4 % (95 % CI: 3.3-5.8) for non-SSPE (p = 0.04). Conclusion: While the VTE recurrence rate following SSPE was lower than in non-SSPE cases, it remained high, with 16.5 % recurrence within 10 years. Major bleeding rate was lower for SSPE than non-SSPE (1.4 % vs. 4.6 %, p = 0.23). Unexpectedly, the 30-days mortality rate following SSPE was significantly higher compared to non-SSPE cases.

• Ghanima, Waleed; Vágó, Emese; Acquavella, John & Horváth-Puhó, Erzsébet (2025). The Epidemiology of Alpha-1 Antitrypsin Deficiency in Norway. Clinical Epidemiology. 17, s. 891–901. doi: 10.2147/clep.s551265. Fulltekst i vitenarkiv Vis sammendrag

  Background: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition characterized by insufficient levels of alpha-1 antitrypsin and elevated risk of lung and liver disease. We aimed to estimate the prevalence and incidence of diagnosed AATD (dAATD) in Norway, and mortality after dAATD. Methods: A nationwide cohort of individuals diagnosed with AATD between 2008 and 2019 was identified from the Norwegian Patient Registry. Prevalence and incidence rates were standardized to the Norwegian population as of December 31, 2019. Mortality rate ratios (MRRs) were calculated to compare mortality between patients with dAATD and a randomly sampled, 10:1 matched general population comparison cohort. Results: A total of 827 patients with dAATD were identified during the study period. The prevalence of dAATD in Norway at the end of 2019 was 10.7 per 100,000 people (95% confidence interval [CI]: 9.8– 11.5), and the incidence rate was 1.4 per 100,000 person-years (95% CI: 1.3– 1.5). Mortality among patients with dAATD was markedly elevated, with an MRR of 6.2 (95% CI: 5.3– 7.2) with respect to the general population comparison cohort. Among patients with AATD, 26.8% had an emphysema diagnosis, 12.5% had an asthma diagnosis, and 6.4% had a liver disease diagnosis. Conclusion: This study provides the first national estimates of dAATD frequency and mortality in Norway. The mortality for patients with dAATD was found to be markedly elevated compared with their age and sex matched peers, indicating a substantial disease burden and suggesting the need for improved diagnosis and earlier therapeutic interventions.

• Ghanima, Waleed; Pohjantähti, Hanna; Lambrelli, Dimitra; Nordstrom, Beth; Booth, Alison & Graham, Sophie [Vis alle 12 forfattere av denne artikkelen] (2025). Comparative safety and effectiveness of direct oral anticoagulants and warfarin in patients with venous thromboembolism in Finland, Norway and Sweden. Journal of Comparative Effectiveness Research. ISSN 2042-6305. 14(11). doi: 10.57264/cer-2024-0207. Fulltekst i vitenarkiv Vis sammendrag

  Aim: Clinical trial data have demonstrated that direct oral anticoagulants (DOACs) are both noninferior to and safer than conventional therapy for the treatment of venous thromboembolism (VTE). This study aimed to compare the effectiveness and safety of DOACs versus warfarin using Nordic population-based registries. Materials & methods: This observational cohort study used Swedish, Norwegian and Finnish national administrative data from 2012 to 2018. We identified treatment-naive adult patients with noncancer-related VTE treated with either a DOAC (apixaban or rivaroxaban) or warfarin. We employed inverse probability of treatment weighting for each DOAC-warfarin comparison and assessed the risks of bleeding (overall and by site: gastrointestinal bleeding [GI], intracranial bleeding [ICH], or other bleeding) and recurrent VTE within 6 months after treatment initiation. Cox proportional hazards models estimated the adjusted hazard ratios of each end point. Country estimates were combined using meta-analyses. Results: After inverse probability of treatment weighting, 22,450 warfarin, 14,542 apixaban and 23,002 rivaroxaban patients were included. At 6 months, for apixaban versus warfarin, the risk of bleeding was lower overall (hazard ratio: 0.51 [95% CI: 0.43, 0.61]) and by site (GI: 0.65 [0.45, 0.93]; ICH: 0.58 [0.34, 0.97]; other: 0.45 [0.34, 0.58]). For recurrent VTE the risk was similar for apixaban versus warfarin (0.85 [0.71, 1.02]). For rivaroxaban versus warfarin the risk of bleeding was lower for overall and other bleeding (0.86 [0.75, 0.99]; 0.81 [0.69, 0.95], respectively), but similar for GI and ICH bleeding (1.06 [0.84, 1.34]; 0.68 [0.47, 1.00], respectively). For recurrent VTE the risk was lower for rivaroxaban versus warfarin (0.74 [0.63, 0.87]). Conclusion: DOACs showed improved safety and at least similar effectiveness compared with warfarin, which is in line with clinical trial estimates.

• Ghanima, Waleed; Cooper, Nichola; Bozzi, Sylvie; Daak, Ahmed; Gouia, Imene & Cordoba, Matias [Vis alle 10 forfattere av denne artikkelen] (2025). A Qualitative Study on Patient Experience with Signs, Symptoms, and Daily Impacts of Immune Thrombocytopenia. Patient. ISSN 1178-1653. 19(The Patient), s. 69–82. doi: 10.1007/s40271-025-00762-6. Fulltekst i vitenarkiv Vis sammendrag

  Background Primary immune thrombocytopenia (ITP) adversely impacts a patient’s health-related quality of life (HRQoL). Objective This study explored patients’ experiences with signs, symptoms, and impacts of ITP and updated the conceptual disease model for HRQoL in patients with ITP. Methods Adult patients with ITP were included in the study. Patients with any comorbidity where fatigue was a key symptom (e.g., anemia) were excluded. A concept elicitation interview assessed signs, symptoms, and impacts from the patients’ perspective, and cognitive debriefing assessed the validity of the selected patient-reported outcome instruments (ITP-Patient Assessment Questionnaire, Patient Global Impression of Severity of Fatigue, Patient Global Impression on Severity, and Patient Global Impression on Change scales). Symptoms/impacts mentioned by ≥ 50% of patients and a “bothersomeness” rating of ≥ 5 were considered salient. The preliminary conceptual model was updated based on the concepts reported by more than one patient. Results A total of 18 patients (mean age 42.7 ± standard deviation 14.7 years; female 78%) were interviewed. Six salient symptoms included fatigue (94%; n = 17), bruising (83%; n = 15), petechiae (72%; n = 13), difficulty staying awake during the day, difficulty falling asleep, and difficulty staying asleep (all symptoms related to sleep: 50%, n = 9). Six key impacts that emerged included those on work (72%; n = 13), worry and fear (67%; n = 12), limited physical or sporting activities, the perceived need to be cautious to avoid getting hurt, and family, friends, and social life (all 56%; n = 10). Conclusion This study highlighted six key symptoms of ITP and its impacts on patients with ITP. The concept elicitation findings were used to update the conceptual model, and—during cognitive debriefing—patients found the patient-reported outcome instruments easy to understand and relevant to their experience.

• Tsykunova, Galina; Holme, Pål Andre; Tran, Hoa Thi Tuyet; Frederiksen, Henrik; Tjønnfjord, Eirik & Munthe, Ludvig Andre [Vis alle 16 forfattere av denne artikkelen] (2025). Safety and Efficacy of Daratumumab in Immune Thrombocytopenia. Blood Advances. ISSN 2473-9529. 10(1), s. 143–154. doi: 10.1182/bloodadvances.2025017279. Fulltekst i vitenarkiv Vis sammendrag

  Resistance to B-cell targeted therapies in immune thrombocytopenia (ITP) has been linked to persistence of autoantibody-producing CD38-positive long-lived plasma cells. CD38 antibody daratumumab has been proposed as a potential therapy for ITP. This multicenter, open-label, phase II study evaluated safety and efficacy of daratumumab in 21 previously treated ITP patients. Following a safety run-in, two dosing cohorts were included, receiving eight and ten subcutaneous injections of 1800 mg daratumumab weekly, respectively. Primary endpoints were safety and response (two consecutive platelet counts ≥50x109/L at week 12 for the safety run-in/Cohort 1, and at week 16 for Cohort 2). At baseline, median platelet count was 17x109/L, median number of prior therapies was four. Most treatment-emergent adverse events were transient grade 1-2, most commonly infections (38%).Two patients (4.7%) experienced grade 3 adverse events, one infusion-related reaction, and one SARS-CoV-2 infection with acute renal failure. Ten patients (48%) met the primary efficacy endpoint. Sustained response (two consecutive platelet counts ≥50x109/L at week 24) was achieved in eight patients (38%). Two patients relapsed after week 24. There was no difference in response or relapse rates between cohorts. Patient-reported quality of life measured by SF-36 improved in responding patients. Daratumumab decreased immunoglobulin levels in all patients, and substantially reduced CD38+ cells in peripheral blood and bone marrow. There was no significant difference in anti-platelet antibodies between responders and non-responders. This study confirms CD38 as an important target in ITP. NCT04703621; EudraCT 2019-004683-22.

• Ghanima, Waleed; Garabet, Lamya Samir Noori; Kapur, Rick & Provan, Drew (2025). Immune thrombocytopenia: Modern management, knowledge gaps, and future perspectives. Iraqi Journal of Hematology. ISSN 2072-8069. doi: 10.4103/ijh.ijh_9_25. Fulltekst i vitenarkiv
• Garabet, Lamya Samir Noori; Rangberg, Anbjørg; Eriksson, Anna Maria; Jonassen, Christine M; Teruel-Montoya, Raul & Lozano, Maria Luisa [Vis alle 16 forfattere av denne artikkelen] (2025). MicroRNA-199a-5p may be a diagnostic biomarker of primary ITP. British Journal of Haematology. ISSN 0007-1048. 206(5), s. 1443–1449. doi: 10.1111/bjh.19987. Fulltekst i vitenarkiv
• Haukeland-Parker, Stacey Marie; Jervan, Øyvind; Ghanima, Waleed; Spruit, Martijn A.; Holst, Rene & Gleditsch, Jostein [Vis alle 13 forfattere av denne artikkelen] (2025). Exercise capacity, dyspnea, and quality of life 6 months after exercise-based rehabilitation in patients with persistent dyspnea following pulmonary embolism. Research and Practice in Thrombosis and Haemostasis (RPTH). 9(2). doi: 10.1016/j.rpth.2025.102736. Fulltekst i vitenarkiv Vis sammendrag

  Background Exercise is safe and effective in the short-term following pulmonary embolism. To date, little is known about the long-term effects. Objectives The aim of the study was to investigate whether the effects of exercise-based rehabilitation are maintained 6 months after completion in patients with persistent dyspnea following pulmonary embolism when compared with usual care. Methods A 2-center, randomized controlled trial compared 8 weeks of exercise-based rehabilitation with usual care. Patients were reassessed postintervention and 6 months later. Exercise capacity was measured with the incremental shuttle walk test (ISWT). Dyspnea was assessed with the Shortness of Breath Questionnaire, and health-related quality of life was assessed with disease-specific (Pulmonary Embolism Quality of Life Questionnaire) and generic questionnaires. Results In total, 159 of 211 randomized patients attended follow-up 6 months postintervention. The significant improvement on the ISWT in the rehabilitation group was maintained at the 6-month follow-up (96 m; SE: 15 m; 95% CI: 66, 127). There were no changes on the ISWT in the control group at either time point. From postintervention to 6×-month follow-up, the rehabilitation group had further improvements in dyspnea compared with the control group (−3 points; SE: 1.4; 95% CI: −6, −1; P = .02). Health-related quality of life improved in both groups although superior improvements were seen in the rehabilitation group. Conclusion The improvement in exercise capacity after 8 weeks of exercise-based rehabilitation in patients with pulmonary embolism and persistent dyspnea was maintained at the 6-month follow-up, while no improvement was observed in the control group, highlighting the relevance of offering rehabilitation to these patients.

• Haukeland-Parker, Stacey Marie; Jervan, Øyvind; Ghanima, Waleed; Spruit, Martijn A.; Hubin, Aliaksandr & Tavoly, Mazdak [Vis alle 10 forfattere av denne artikkelen] (2025). The effect of exercise-based rehabilitation on objective physical activity levels in patients with persistent dyspnoea following pulmonary embolism. Thrombosis Research. ISSN 0049-3848. 252. doi: 10.1016/j.thromres.2025.109362. Fulltekst i vitenarkiv Vis sammendrag

  Background Rehabilitation improves exercise capacity following pulmonary embolism (PE), but it is unclear whether this improvement is transferred into increased physical activity. Objectives. To explore the effect of exercise-based rehabilitation on objective measures of physical activity in patients with persistent dyspnoea following PE compared to standard care. Methods This pre-planned substudy compared an eight-week exercise-based rehabilitation program to usual care. Number of steps per day and time spent in sedentary, low, moderate and vigorous physical activity (in number of metabolic equivalent of tasks) were measured for seven consecutive days at baseline prior to intervention start and at post-intervention using accelerometery. Data were analysed with a mixed-effect generalised linear model. Results Complete data was provided by 48 patients at both timepoints (mean age 58 years, 54 % men) with 54 % randomised to rehabilitation. There were no significant differences between groups at baseline. The majority of time (717 min per day) was spent in sedentary activity and mean number of steps per day was 6701. At post-intervention, there were no significant differences between groups in any of the objectively measured physical activity parameters (p > 0.05). Conclusion In this cohort, exercise-based rehabilitation following PE did not change daily physical activity levels compared to usual care control group.

• Ghanima, Waleed; Boronat, Francisco Javier Lucas; Carrai, Valentina & Rackwitz, Stefan (2025). Sustained response off treatment after fostamatinib in refractory immune thrombocytopenia: A series of four case reports. Hematology. ISSN 1024-5332. 30(1). doi: 10.1080/16078454.2025.2456687. Fulltekst i vitenarkiv
• Svalastoga, Marte; Larsen, Trine-Lise; Brekke, Jorunn; Enden, Tone Rønnaug; Frøen, Hege & Garresori, Herish [Vis alle 15 forfattere av denne artikkelen] (2025). Effect of drug interactions with apixaban on clinical outcomes in cancer patients with venous thromboembolism. Frontiers in Oncology. 15. doi: 10.3389/fonc.2025.1520725. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: It is unclear how drug-interaction with apixaban influences recurrent venous thromboembolism (VTE) and bleedings in cancer patients. Methods: A post-hoc analysis of a single-arm interventional clinical trial on apixaban treatment of cancer patients with VTE to investigate whether the occurrence of any of the endpoints could be associated with the concurrent use of an interacting drug. Drugs taken by the patients during the trial period were categorized as either increasing bleeding risk, increasing thrombosis risk, both or neither. Results: 298 patients were divided into groups based on whether they used no interacting drugs (controls, n=74), drugs increasing bleeding risk (n=55), drugs increasing thrombosis risk (n=8), or both (n=161). Odds ratios (OR) were calculated for recurrent VTE, clinically relevant non-major bleeding (CRNMB), and major bleeding during the 36-month follow-up period. Each patient took a median of 13 different drugs over the study period. 67% of the patients used drugs expected to both increase bleeding and thrombosis. The use of fluconazole appeared associated with CRNMB (OR 3.6, 95% confidence interval (CI) 0.99-13), but not with major bleeding (OR 0.56, 95% CI 0.06 - 4.8). Non-steroid anti-inflammatory drugs were not associated with CRNMB (OR 1.0, 95% CI 0.25-4.1) or major bleedings (OR 0.72, 95% CI 0.14 - 3.6). Use of antiplatelet therapy was not associated with CRNMB (OR 0.75, 95% CI, 0.22 - 2.58) or major bleeding (OR 0.2, 95% CI, 0.02-1.6). There were no major bleedings in 23 patients using aprepitant nor in the 10 patients taking macrolides. We found no association between drugs and recurrent VTE, except that there were no recurrent VTE in 19 patients using bevacizumab. Conclusions: Despite the high number of drugs taken that could potentially interact with apixaban, none were found to clearly influence clinical outcomes, except that fluconazole may increase the risk of CRNMB.

• Halstensen, Thor-David; Hardeland, Camilla; Ghanima, Waleed; Grøndahl, Vigdis Abrahamsen; Hubin, Aliaksandr & Jørgensen, Camilla Tøvik [Vis alle 8 forfattere av denne artikkelen] (2025). External validation of the DAYS score for suspected deep vein thrombosis. Research and Practice in Thrombosis and Haemostasis (RPTH). 9(4). doi: 10.1016/j.rpth.2025.102885. Fulltekst i vitenarkiv
• Viermyr, Hans-Kittil; Halvorsen, Bente; Sagen, Ellen Lund; Michelsen, Annika Elisabet; Barratt-Due, Andreas & Kåsine, Trine [Vis alle 73 forfattere av denne artikkelen] (2024). High viral loads combined with inflammatory markers predict disease severity in hospitalized COVID-19 patients: Results from the NOR-Solidarity trial. Journal of Internal Medicine. ISSN 0954-6820. 296(3), s. 249–259. doi: 10.1111/joim.13820. Fulltekst i vitenarkiv Vis sammendrag

  Objectives To investigate temporal changes in the association between SARS-CoV2 viral load (VL) and markers of inflammation during hospitalization, as well as the ability of these markers alone or in combination to predict severe outcomes. Methods Serial oropharyngeal and blood samples were obtained from hospitalized COVID-19 patients (n = 160). Levels of inflammatory markers and oropharyngeal VL were measured during hospitalization (admission, days 3–5, and days 7–10) and related to severe outcomes (respiratory failure/intensive care unit admission). Results Elevated admission levels of IL (interleukin)-6, IL-33, IL-8, monocyte chemoattractant protein-1 (MCP-1), interferon-γ-induced protein 10 (IP-10), IL-1β, and IL-1Ra were associated with severe outcomes during hospitalization. Although no inflammatory markers correlated with VL at baseline, there was a significant correlation between VL and levels of IP-10 and MCP-1 at days 3–5, accompanied by IL-8 and IL-6 at days 7–10. Finally, there was a seemingly additive effect of IP-10, MCP-1, and IL-6 in predicting severe outcomes when combined with high VL at baseline. Conclusions An increasing number of inflammatory markers were associated with VL during the first 10 days of hospitalization, and several of these markers were associated with severe outcomes, in particular when combined with elevated VL. Future studies should assess the potential for combining antiviral and immunomodulatory treatment, preferably guided by viral and inflammatory biomarkers, for the selection of high-risk patients.

• Mannering, Nikolaj; Hansen, Dennis Lund; Moulis, Guillaume; Ghanima, Waleed; Pottegård, Anton & Frederiksen, Henrik (2024). Risk of fractures and use of bisphosphonates in adult patients with immune thrombocytopenia—A nationwide population-based study. British Journal of Haematology. ISSN 0007-1048. doi: 10.1111/bjh.19301. Fulltekst i vitenarkiv Vis sammendrag

  Corticosteroids remain the first-line treatment of immune thrombocytopenia (ITP), but increase the risk of osteoporosis and fractures. Bisphosphonates are used for the treatment of osteoporosis, but their usage among patients with ITP has not been systemically described. We investigated the risk of fractures and the use of bisphosphonates in adult patients with primary (pITP) and secondary ITP (sITP) compared with matched comparators in a nationwide registry-based cohort study. We identified 4030 patients with pITP (median age 60 years [IQR, 40–74]), 550 with sITP (median age 59 years [IQR, 43–74]) and 182 939 age–sex-matched general population comparators. All individuals were followed for incident fractures. Bisphosphonate use was estimated for calendar-years and in temporal relation to the ITP diagnosis. Adjusted cause-specific hazard ratio (csHR) for any fracture was 1.37 (95% confidence interval [CI] 1.23; 1.54) for pITP and 1.54 (1.17; 2.03) for sITP. The first-year csHR was 1.82 (1.39; 2.40) for pITP and 2.78 (1.58; 4.91) for sITP. Bisphosphonate use over calendar-years and in the early years following ITP diagnosis was higher among patients with ITP diagnosis compared with the general population. In conclusion, the risk of fractures and the use of bisphosphonates are higher in patients with ITP compared with the general population.

• Dhayyat, Adam; Hilde, Janne Mykland; Jervan, Øyvind; Rashid, Diyar Nori Mohamad; Gleditsch, Jostein & Stavem, Knut [Vis alle 8 forfattere av denne artikkelen] (2024). Exercise pulmonary hypertension in chronic thromboembolic pulmonary disease: A right heart catheterization study. Pulmonary Circulation (PC). ISSN 2045-8932. 14(4). doi: 10.1002/pul2.70018. Fulltekst i vitenarkiv Vis sammendrag

  Many patients with chronic thromboembolic pulmonary disease (CTEPD) suffer from exertional dyspnea. It is unclear if CTEPD is associated with exercise pulmonary hypertension (ePH). This cross-sectional study aimed to determine the occurrence of ePH in patients with CTEPD and to identify the haemodynamic changes during exercise. We recruited 36 patients with persistent dyspnoea and residual perfusion defects by ventilation/perfusion scintigraphy from a large cohort of patients with previous pulmonary embolism. All patients underwent exercise right heart catheterization before being classified into the following groups: (1) CTEPD without ePH; comprising patients with normal mean pulmonary artery pressure (mPAP) of ≤20 mmHg, but with mPAP/cardiac output (CO) slope of ≤3 mmHg/L/min, (2) CTEPD with ePH (CTEPD-ePH); those with CTEPD with an mPAP/CO slope of >3 mmHg/L/min, (3) chronic thromboembolic pulmonary hypertension (CTEPH); those with mPAP >20 mmHg, pulmonary arterial wedge pressure (PAWP) ≤ 15 mmHg and pulmonary vascular resistance >2 WU. The postcapillary contribution during exercise was considered present if the PAWP/CO slope of >2 mmHg/L/min. CTEPD without resting pulmonary hypertension (PH) was present in 29 (81%) of the 36 patients, of whom six (21%) had ePH, while five (14%) had CTEPH. Two patients had unclassified PH. Two (33%) of the six patients with CTEPD-ePH had a PAWP/CO slope of >2 mmHg/L/min, compared with two (40%) of the five of those with CTEPH. In conclusion, about 20% of patients with CTEPD and exertional dyspnoea had ePH. Exercise right heart catheterization revealed a notable proportion of patients with postcapillary contribution.

• Galovic, Aleksandra Grdinic; Radovanovic, Sandro; Gleditsch, Jostein; Jørgensen, Camilla Tøvik; Asady, Elia & Pettersen, Heidi Hassel [Vis alle 8 forfattere av denne artikkelen] (2024). Developing a machine learning model for bleeding prediction in patients with cancer-associated thrombosis receiving anticoagulation therapy. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. doi: 10.1016/j.jtha.2023.12.034. Fulltekst i vitenarkiv
• Rahhal, Alaa; Provan, Drew; Ghanima, Waleed; González-López, Tomás José; Shunnar, Khaled & Najim, Mostafa [Vis alle 10 forfattere av denne artikkelen] (2024). A practical guide to the management of immune thrombocytopenia co-existing with acute coronary syndrome. Frontiers in Medicine. 11. doi: 10.3389/fmed.2024.1348941. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: Immune thrombocytopenia (ITP) management with co-existing acute coronary syndrome (ACS) remains challenging as it requires a clinically relevant balance between the risk and outcomes of thrombosis and the risk of bleeding. However, the literature evaluating the treatment approaches in this high-risk population is scarce. Methods and Results: In this review, we aimed to summarize the available literature on the safety of ITP first- and second-line therapies to provide a practical guide on the management of ITP co-existing with ACS. We recommend holding antithrombotic therapy, including antiplatelet agents and anticoagulation, in severe thrombocytopenia with a platelet count < 30 × 109/L and using a single antiplatelet agent when the platelet count falls between 30 and 50 × 109/L. We provide a stepwise approach according to platelet count and response to initial therapy, starting with corticosteroids, with or without intravenous immunoglobulin (IVIG) with a dose limit of 35 g, followed by thrombopoietin receptor agonists (TPO-RAs) to a target platelet count of 200 × 109/L and then rituximab. Conclusion: Our review may serve as a practical guide for clinicians in the management of ITP co-existing with ACS.

• Mingot-Castellano, Maria Eva; Bastida, Jose Maria; Ghanima, Waleed; Ruiz Sainz, Elena; Nuñez Vazquez, Ramiro & Pedrote Amador, Begoña [Vis alle 9 forfattere av denne artikkelen] (2024). Avatrombopag plus fostamatinib combination as treatment in patients with multirefractory immune thrombocytopenia. British Journal of Haematology. ISSN 0007-1048. doi: 10.1111/bjh.19602. Fulltekst i vitenarkiv
• Kuter, David J.; Mayer, Jiri; Efraim, Merlin; Bogdanov, Lachezar H.; Baker, Ross & Kaplan, Zane [Vis alle 18 forfattere av denne artikkelen] (2024). Long-term treatment with rilzabrutinib in patients with immune thrombocytopenia. Blood Advances. ISSN 2473-9529. 8(7), s. 1715–1724. doi: 10.1182/bloodadvances.2023012044. Fulltekst i vitenarkiv Vis sammendrag

  Immune thrombocytopenia (ITP) is an autoimmune disease associated with autoantibody-mediated platelet destruction and impaired platelet production, resulting in thrombocytopenia and a predisposition to bleeding. The ongoing, global phase 1/2 study showed that rilzabrutinib, a Bruton tyrosine kinase inhibitor specifically developed to treat autoimmune disorders, could be an efficacious and well-tolerated treatment for ITP. Clinical activity, durability of response, and safety were evaluated in 16 responding patients who continued rilzabrutinib 400 mg twice daily in the long-term extension (LTE) study. At LTE entry, the median platelet count was 87 × 109/L in all patients, 68 × 109/L in those who had rilzabrutinib monotherapy (n = 5), and 156 × 109/L in patients who received concomitant ITP medication (thrombopoietin-receptor agonists and/or corticosteroids, n = 11). At a median duration of treatment of 478 days (range, 303-764), 11 of 16 patients (69%) continued to receive rilzabrutinib. A platelet count of ≥50 × 109/L was reported in 93% of patients for more than half of their monthly visits. The median percentage of LTE weeks with platelet counts ≥30 × 109/L and ≥50 × 109/L was 100% and 88%, respectively. Five patients discontinued concomitant ITP therapy and maintained median platelet counts of 106 × 109/L at 3 to 6 months after stopping concomitant ITP therapy. Adverse events related to treatment were grade 1 or 2 and transient, with no bleeding, thrombotic, or serious adverse events. With continued rilzabrutinib treatment in the LTE, platelet responses were durable and stable over time with no new safety signals. This trial is registered at www.clinicaltrials.gov as #NCT03395210 and www.clinicaltrialsregister.eu as EudraCT 2017-004012-19.

• Sorano, Ruslan; Ripon, Kazi Shah Nawaz; Magnusson, Lars Vidar; Halstensen, Thor-David & Ghanima, Waleed (2024). Enhancing Deep Vein Thrombosis Diagnosis with Multi-Objective Evolutionary Algorithm and Machine Learning. I Ogul, Hasan; Aamodt, Jonas Moræus; Misra, Sanjay & Kjølerbakken, Kai Morgan (Red.), 2024 4th International Conference on Applied Artificial Intelligence (ICAPAI). IEEE (Institute of Electrical and Electronics Engineers). ISSN 9798350349764. s. 1–1. doi: 10.1109/ICAPAI61893.2024.10541216. Fulltekst i vitenarkiv
• Zaboras, Zygimantas; Jørgensen, Camilla Tøvik; Stensvold, Andreas; Pettersen, Heidi Hassel; Galovic, Aleksandra Grdinic & Brækkan, Sigrid Kufaas [Vis alle 8 forfattere av denne artikkelen] (2024). Real-world Data on Treatment Patterns and Bleeding in Cancer-associated Thrombosis: Data from the TROLL Registry. TH Open. 8(1), s. e132–e140. doi: 10.1055/s-0044-1782219. Fulltekst i vitenarkiv Vis sammendrag

  Background International guidelines are increasingly recommending direct oral anticoagulants (DOACs) as the first-line treatment for cancer-associated thrombosis (CAT). However, data regarding treatment patterns and adherence to guidelines in patients with CAT are scarce. Objectives This study aimed to explore anticoagulant treatment patterns in patients with CAT and to calculate the incidence rates of bleeding events. Methods Patients ≥18 years with active cancer and a first-time venous thromboembolism between 2005 and 2020 were identified through the Venous T hrombosis R egistry in Østf OL d Hospita L . Outcome measures were patterns of anticoagulant treatment during the study period and bleeding events. We calculated overall incidence rates per 100 person-years and 6- and 12-month cumulative incidence of major and clinically relevant nonmajor bleeding (CRNMB) during anticoagulant treatment. Results Median age of 842 CAT patients at the time of thrombosis was 69 years (interquartile range 61-77), and 443 (5

• Ghanima, Waleed; Cuker, Adam & Michel, Marc (2024). Insights on treatment of adult ITP: algorithm for management and role of multimodal therapy. Hematology ASH Education Program. ISSN 1520-4391. 2024(1), s. 678–684. doi: 10.1182/hematology.2024000594. Fulltekst i vitenarkiv Vis sammendrag

  The management of immune thrombocytopenia (ITP) is continuously evolving with the development and introduction of newer therapies and a better understanding of the disease. Corticosteroids still represent the cornerstone of first-line treatment. Patients who fail to achieve remission with a short course of corticosteroids require subsequent therapy. Most guidelines recommend starting with either a thrombopoietin receptor agonist (TPO-RA), rituximab, or fostamatinib since these agents have been investigated in randomized trials and have well-characterized efficacy and safety profiles. Patients' involvement to reach a shared decision regarding choice of therapy is essential as these treatments have different modes of administration and mechanisms of action. Less than 10% will fail to respond to and/or be intolerant of multiple second-line therapeutic options and thus be considered to have refractory ITP and require a third-line therapeutic option. Such patients may require drugs with different targets or a combination of drugs with different mechanisms of action. Combining a TPO-RA and an immunomodulatory agent may be an appropriate approach at this stage. Many studies have been conducted during the last 2 decades investigating the efficacy and safety of combinations strategies for first and later lines of therapies. Yet none of these are recommended by current guidelines or have gained wide acceptance and consensus.

• Christiansen, Christian Fynbo; Risbo, Nickolaj; Ghanima, Waleed; Linder, Marie; Bahmanyar, Shahram & Seesaghur, Anouchka [Vis alle 9 forfattere av denne artikkelen] (2024). Platelet response to romiplostim amongst patients with newly diagnosed, persistent, and chronic immune thrombocytopenia in routine clinical practice in Denmark, Sweden, and Norway. British Journal of Haematology. ISSN 0007-1048. doi: 10.1111/bjh.19688. Fulltekst i vitenarkiv
• Maitland, Hillary; Lambert, Catherine & Ghanima, Waleed (2024). Patient-centric care in primary immune thrombocytopenia (ITP): shared decision-making and assessment of health-related quality of life. Hematology. ISSN 1024-5332. 29(1). doi: 10.1080/16078454.2024.2375177. Fulltekst i vitenarkiv Vis sammendrag

  Immune thrombocytopenia (ITP), an autoimmune disease characterized by low platelet counts and increased bleeding risk, can impair health-related quality of life (HRQoL), impacting patients’ daily lives and mental health. A number of patient-reported outcome (PRO) measures (both generic and specific to ITP) can be used to understand the impact of ITP on HRQoL and generate evidence to guide disease management. As well-developed PRO tools could help in HRQoL assessment, their optimization could help to solidify a patient-centric approach to ITP management. Shared decision-making is a collaborative process between a patient and their healthcare professional in making decisions about care. Treatment decisions based on this shared process between physician and patient are recommended by clinical guidelines. The goal of this narrative review is to discuss treatment decisions with regards to patient-centric ITP management, with a focus on the impact of PRO measures and the process of shared decision-making in practice.

• Cimini, Ludovica Anna; Luijten, Dieuwke; Barco, Stefano; Ghanima, Waleed; Jervan, Øyvind & Kahn, Susan R. [Vis alle 15 forfattere av denne artikkelen] (2024). Pulmonary perfusion defects or residual vascular obstruction and persistent symptoms after pulmonary embolism: a systematic review and meta-analysis. European Respiratory Journal Open Research (ERJ Open Research). 10(4). doi: 10.1183/23120541.01010-2023. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: Up to 50% of pulmonary embolism (PE) patients have perfusion defects or residual vascular obstruction during follow-up despite adequate anticoagulant treatment, and a similar percentage experience chronic functional limitations and/or dyspnoea post-PE. We aimed to evaluate the association between pulmonary perfusion defects or residual vascular obstruction and functional recovery after PE. Methods: We performed a systematic review and meta-analysis including studies assessing both the presence of perfusion defects or residual vascular obstruction and functional recovery (i.e. persistent symptoms, quality of life, exercise endurance). An odds ratio was pooled for perfusion defects or residual vascular obstruction and persistent symptoms using a random-effect model. Results: 12 studies were included totalling 1888 PE patients; at a median of 6 months after PE (range 2–72 months), 34% had perfusion defects or residual vascular obstruction and 37% reported persistent symptoms. Among patients with perfusion defects or residual vascular obstruction, 48% (95% CI 37–60%, I2=82%) remained symptomatic during follow-up, compared to 34% (95% CI 20–51%, I2=96%) of patients without such defects. Presence of perfusion defects or residual vascular obstruction was associated with persistent symptoms (OR 2.15, 95% CI 1.66–2.78; I2=0%, τ=0). Notably, there was no association between these defects and quality of life or cardiopulmonary exercise test parameters. Conclusion: While the odds of having persistent symptoms was higher in patients with perfusion defects or residual vascular obstruction after acute PE, a significant proportion of these patients reported no limitations. A possible causality between perfusion defects or residual vascular obstruction and residual functional limitation therefore remains to be proven.

• Halstensen, Thor-David; Hardeland, Camilla; Ghanima, Waleed; Grøndahl, Vigdis Abrahamsen; Hubin, Aliaksandr & Tavoly, Mazdak (2024). Development and internal validation of a simple clinical score for the estimation of the probability of deep vein thrombosis in outpatient emergency department patients. Research and Practice in Thrombosis and Haemostasis (RPTH). 8(8). doi: 10.1016/j.rpth.2024.102608. Fulltekst i vitenarkiv Vis sammendrag

  Background: Wells score comprises subjective elements, making physicians reluctant to use Wells score or cause them to use it incorrectly. Objectives: To develop and internally validate a prediction score that is objective and simple for evaluating suspected deep vein thrombosis (DVT), with a safety comparable with that of Wells score. Methods: We performed a post hoc analysis using data from the Ri-Schedule study (NCT02486445) involving suspected DVT patients at Østfold Hospital’s Emergency Department, Norway (2015-2018). Candidate variables were identified through bootstrapping technique, with a confirmed DVT diagnosis as the outcome variable. Sensitivity, specificity, negative predictive value (NPV), and positive predictive values (PPV) were estimated and compared with the 2-tier Wells score. Results: Among 1312 patients (median age, 64 years [IQR, 52-73]; 55% women), 19.9% were diagnosed with DVT. Exploration of 30 variables identified tenderness along deep veins and previous venous thromboembolism as significant predictors (selection frequency >60% in 1000 bootstrapping samples). The derived score categorized 450 patients with 0 items as unlikely to have DVT, of whom 8.0% were diagnosed with DVT, compared with 8.2% in DVT unlikely category according to Wells score. Compared with Wells score, the derived score demonstrated sensitivity of 86.2 (95% CI, 81.4-90.2) vs 80.1 (95% CI, 74.7-84.8), specificity of 39.4 (95% CI, 36.4-42.4) vs 55.3 (95% CI, 52.2-58.3), NPV of 92.0 (95% CI, 89.4-94.0) vs 91.8 (95% CI, 89.7-93.5), and PPV of 26.1 (95% CI, 24.8-27.5) vs 30.8 (95% CI, 28.9-32.8). When incorporating D-dimer cutoff of <0.5 mg/mL, the derived score had sensitivity of 99.6 (95% CI, 97.9-99.9), specificity of 16.1 (95% CI, 13.1-18.4), NPV of 99.4 (95% CI, 96.0-99.9), and PPV of 22.8 (95% CI, 22.3-23.3). Conclusion: The derived DVT score, with 2 objective variables, had a comparable safety with that of the Wells score. However, an external validation is mandated prior to clinical use.

• Øvrebotten, Tarjei; Mecinaj, Albulena; Stavem, Knut; Ghanima, Waleed; Brønstad, Eivind & Durheim, Michael Thomas [Vis alle 14 forfattere av denne artikkelen] (2024). Trajectory of cardiac troponin T following moderate-to-severe COVID-19 and the association with cardiac abnormalities. BMC Cardiovascular Disorders. 24(1). doi: 10.1186/s12872-024-03854-7. Fulltekst i vitenarkiv Vis sammendrag

  Background COVID-19 has been associated with cardiac troponin T (cTnT) elevations and changes in cardiac structure and function, but the link between cardiac dysfunction and high-sensitive cardiac troponin T (hs-cTnT) in the acute and convalescent phase is unclear. Objective To assess whether hs-cTnT concentrations are associated with cardiac dysfunction and structural abnormalities after hospitalization for COVID-19, and to evaluate the performance of hs-cTnT to rule out cardiac pathology. Methods Patients hospitalized with COVID-19 had hs-cTnT measured during the index hospitalization and after 3-and 12 months, when they also underwent an echocardiographic study. A subset also underwent cardiovascular magnetic resonance imaging (CMR) after 6 months. Cardiac abnormalities were defined as left ventricular hypertrophy or dysfunction, right ventricular dysfunction, or CMR late gadolinium. Results We included 189 patients with hs-cTnT concentrations measured during hospitalization for COVID-19, and after 3-and 12 months: Geometric mean (95%CI) 13 (11–15) ng/L, 7 (6–8) ng/L and 7 (6–8) ng/L, respectively. Cardiac abnormalities after 3 months were present in 45 (30%) and 3 (8%) of patients with hs-cTnT ≥ and < 5 ng/L at 3 months, respectively (negative predictive value 92.3% [95%CI 88.5–96.1%]). The performance was similar in patients with and without dyspnea. Hs-cTnT decreased from hospitalization to 3 months (more pronounced in intensive care unit-treated patients) and remained unchanged from 3 to 12 months, regardless of the presence of cardiac abnormalities. Conclusion Higher hs-cTnT concentrations in the convalescent phase of COVID-19 are associated with the presence of cardiac pathology and low concentrations (< 5 ng/L) may support in ruling out cardiac pathology following the infection.

• Haukeland-Parker, Stacey Marie; Jervan, Øyvind; Ghanima, Waleed; Spruit, Martijn A.; Holst, Rene & Tavoly, Mazdak [Vis alle 8 forfattere av denne artikkelen] (2024). Physical activity following pulmonary embolism and clinical correlates in selected patients: a cross-sectional study. Research and Practice in Thrombosis and Haemostasis (RPTH). 8(2). doi: 10.1016/j.rpth.2024.102366. Fulltekst i vitenarkiv Vis sammendrag

  Background: There is limited knowledge regarding physical activity and clinical correlates among people who have suffered a pulmonary embolism (PE). Objectives: To assess physical activity levels after PE and potential clinical correlates. Methods: One hundred forty-five individuals free of major comorbidities were recruited at a mean of 23 months (range, 6-72) after PE diagnosis. Physical activity was assessed by steps/day on the Sensewear monitor for 7 consecutive days, exercise capacity with the incremental shuttle walk test, and cardiac function with left ventricular ejection fraction (LVEF). The association between physical activity and other variables was analyzed by a mixed-effects model. Results: Participants achieved a mean of 6494 (SD, 3294; range, 1147-18.486) steps/day. The mixed-effects model showed that physical activity was significantly associated with exercise capacity (β-coefficient, 0.04; 95% CI, 0.03-0.05) and LVEF (β-coefficient, −0.81; 95% CI, −1.42 to −0.21). The analysis further showed that men became less physically active with increasing age (β-coefficient, −0.14; 95% CI, −0.24 to −0.04), whereas no change with age could be detected for women. Conclusion: In selected post-PE patients, physical activity seems to be associated with exercise capacity and LVEF but not with quality of life, dyspnea, or characteristics of the initial PE. Men appear to become less physically active with increasing age.

• Jervan, Øyvind; Haukeland-Parker, Stacey Marie; Gleditsch, Jostein; Tavoly, Mazdak; Klok, Frederikus A. & Steine, Kjetil [Vis alle 14 forfattere av denne artikkelen] (2023). The Effects of Exercise Training in Patients With Persistent Dyspnea Following Pulmonary Embolism: A Randomized Controlled Trial. Chest. ISSN 0012-3692. 164(4), s. 981–991. doi: 10.1016/j.chest.2023.04.042. Fulltekst i vitenarkiv Vis sammendrag

  Bakgrunn Vedvarende dyspné, funksjonelle begrensninger og redusert livskvalitet (QoL) er vanlig etter lungeemboli (PE). Rehabilitering er et potensielt behandlingsalternativ , men den vitenskapelige dokumentasjonen er begrenset. Forskningsspørsmål Forbedrer et treningsbasert rehabiliteringsprogram treningskapasiteten hos PE-overlevere med vedvarende dyspné? Studiedesign og metoder Denne randomiserte kontrollerte studien ble utført ved to sykehus. Pasienter med vedvarende dyspné etter PE diagnostisert 6 til 72 måneder tidligere, uten kardiopulmonale komorbiditeter, ble randomisert 1:1 til enten rehabiliterings- eller kontrollgruppen. Rehabiliteringsprogrammet besto av to ukentlige økter med fysisk trening i 8 uker og en pedagogisk økt. Kontrollgruppen fikk vanlig pleie. Det primære endepunktet var forskjellen i Incremental Shuttle Walk Test mellom grupper ved oppfølging. Sekundære endepunkter inkluderte forskjeller i Endurance Shuttle Walk Test (ESWT), QoL (EQ-5D og lungeemboli-QoL spørreskjemaer) og dyspné (Shortness of Breath spørreskjema). Resultater Totalt 211 forsøkspersoner ble inkludert: 108 (51 %) ble randomisert til rehabiliteringsgruppen og 103 (49 %) til kontrollgruppen. Ved oppfølging presterte deltakerne fordelt på rehabiliteringsgruppen bedre på ISWT sammenlignet med kontrollgruppen (gjennomsnittlig forskjell, 53,0 m; 95 % KI, 17,7-88,3; P = 0,0035). Rehabiliteringsgruppen rapporterte bedre skårer på spørreskjemaet lungeemboli-kvalitet (gjennomsnittlig forskjell, –4 %; 95 % KI, –0,09 til 0,00; P = 0,041) ved oppfølging, men det var ingen forskjeller i generisk livskvalitet, dyspné. score, eller ESWT. Ingen uønskede hendelser oppsto under intervensjonen. Tolkning Hos pasienter med vedvarende dyspné etter PE hadde de som gjennomgikk rehabilitering bedre treningskapasitet ved oppfølging enn de som fikk vanlig behandling. Rehabilitering bør vurderes hos pasienter med vedvarende dyspné etter PE. Ytterligere forskning er imidlertid nødvendig for å vurdere optimal pasientvalg, tidspunkt, modus og varighet av rehabilitering.

• Es, Nick Van; Takada, Toshihiko; Kraaijpoel, Noemie; Klok, Frederikus A.; Stals, Milou A. M. & Büller, Harry R. [Vis alle 23 forfattere av denne artikkelen] (2023). Diagnostic management of acute pulmonary embolism: a prediction model based on a patient data meta-analysis. European Heart Journal. ISSN 0195-668X. 44(32), s. 3073–3081. doi: 10.1093/eurheartj/ehad417. Fulltekst i vitenarkiv
• Tønne, Brita; Pedersen, Marit Holmefjord; Frønæs, Synne Grønvold; Jørgensen, Camilla Tøvik; Amundsen, Erik Koldberg & Mæhlum, Julie Berge [Vis alle 10 forfattere av denne artikkelen] (2023). Evaluation of the diagnostic performance of three D-dimer assays in patients with suspected deep vein thrombosis: STA-Liatest D-Di plus, Tina-quant D-dimer Gen. 2, and INNOVANCE D-dimer. Thrombosis Update. 13. doi: 10.1016/j.tru.2023.100147. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: D-dimer is a crucial test to exclude deep vein thrombosis (DVT). We aimed to evaluate the per- formance of three D-dimer assays: STA-Liatest D-Di Plus (Diagnostica Stago), Tina-quant D-Dimer Gen. 2 (Roche Diagnostics), and INNOVANCE D-Dimer (Siemens Healthineers Diagnostics) in the exclusion of DVT. Methods: Samples (n = 1032) and clinical data were acquired from a prospective outcome study (Rivaroxaban for Scheduled Work-up of Deep Vein Thrombosis – the Ri-Schedule study), which included patients referred to the emergency department with suspected lower-limb DVT. D-dimer was determined with STA-Liatest, and only patients with positive D-dimer values (≥0.5 μg/mL) as stand-alone, were referred for compression ultrasonog- raphy to confirm or exclude DVT. Patients were followed up 90 days after inclusion. Samples were also analyzed with Tina-quant Gen. 2, and INNOVANCE assays. The diagnostic performances of the three assays were investigated. Results: Positive D-dimer (≥0.5 μg/mL) was found in 733 patients (71%) with STA-Liatest, 691 patients (67%) with Tina-quant Gen. 2, and 766 (74%) with INNOVANCE. DVT was confirmed by compression ultrasonography in 196 patients (27%) with positive D-dimer with STA-Liatest. Of those, six (3%) had negative D-dimer (<0.5 μg/ mL) with at least one of the three assays yielding a failure rate of 0.7% with STA-Liatest, 2% with Tina-quant Gen. 2, and 2% with INNOVANCE. The sensitivity and negative predictive value (NPV) for STA-Liatest were 99.0% (95% CI 96.4–99.9) and 99.3% (95% CI 97.4–99.8), for Tina-quant Gen. 2 97.5% (95% CI 94.1–99.2) and 98.5% (95% CI 96.6–99.4), and for INNOVANCE 98.0% (95% CI 94.9–99.0) and 98.5% (95% CI 96.1–99.4) respectively. The efficiency to exclude DVT based on D-dimer as a stand-alone test was 29% (95% CI 26–33) for STA-Liatest, 33% (95% CI 30–37) for Tina-quant Gen. 2, and 26% (95% CI 23–29) for INNOVANCE. Conclusion: STA-Liatest, Tina-quant Gen. 2, and INNOVANCE showed good performances with sensitivity ≥97% and NPV ≥98%. The efficiency to exclude DVT varied and was highest for Tina-quant Gen. 2, whereas the failure rate was lowest for STA-Liatest.

• Jervan, Øyvind; Dhayyat, Adam; Gleditsch, Jostein; Haukeland-Parker, Stacey Marie; Tavoly, Mazdak & Klok, Frederikus A. [Vis alle 10 forfattere av denne artikkelen] (2023). Demographic, clinical, and echocardiographic factors associated with residual perfusion defects beyond six months after pulmonary embolism. Thrombosis Research. ISSN 0049-3848. 229, s. 7–14. doi: 10.1016/j.thromres.2023.06.004. Fulltekst i vitenarkiv Vis sammendrag

  Background Residual perfusion defects (RPD) after pulmonary embolism (PE) are common. Primary aim This study aimed to determine the prevalence of RPD in a cohort diagnosed with PE 6–72 months earlier, and to determine demographic, clinical, and echocardiographic variables associated with RPD. Methods Patients aged 18–75 years with prior PE, confirmed by computed tomography pulmonary angiography 6–72 months earlier, were included. Participants (N = 286) completed a diagnostic work-up consisting of transthoracic echocardiography and ventilation/perfusion scintigraphy. Demographic, clinical, and echocardiographic characteristics between participants with RPD and those without RPD were explored in univariate analyses using t-test or Mann-Whitney U test. Multiple logistic regression analysis was used to assess the association between selected variables and RPD. Results RPD were detected in 72/286 patients (25.2 %, 95 % CI:20.5 %–30.5 %). Greater tricuspid annular plane systolic excursion (TAPSE) (adjusted odds ratio (aOR) 1.10, 95 % CI:1.00–1.21, p = 0.048) at echocardiographic follow-up, greater thrombotic burden at diagnosis, as assessed by mean bilateral proximal extension of the clot (MBPEC) score 3–4 (aOR 2.08, 95 % CI:1.06–4.06, p = 0.032), and unprovoked PE (aOR 2.25, 95 % CI:1.13–4.48, p = 0.021) were independently associated with increased risk of RPD, whereas increased pulmonary artery acceleration time was associated with a lower risk of RPD (aOR 0.72, 95 % CI:0.62–0.83, p < 0.001, per 10 ms). Dyspnoea was not associated with RPD. Conclusion RPD were common after PE. Reduced pulmonary artery acceleration time and greater TAPSE on echocardiography at follow-up, greater thrombotic burden at diagnosis, and unprovoked PE were associated with RPD.

• Gleditsch, Jostein; Jervan, Øyvind; Klok, Frederikus A; Holst, Rene; Hopp, Einar & Tavoly, Mazdak [Vis alle 7 forfattere av denne artikkelen] (2023). Does the clot burden as assessed by the Mean Bilateral Proximal Extension of the Clot score reflect mortality and adverse outcome after pulmonary embolism? Acta Radiologica Open. 12(6). doi: 10.1177/20584601231187094. Fulltekst i vitenarkiv Vis sammendrag

  Background Rapid diagnosis and risk stratification are important to reduce the risk of adverse clinical events and mortality in acute pulmonary embolism (PE). Although clot burden has not been consistently shown to correlate with disease outcomes, proximally located PE is generally perceived as more severe. Purpose To explore the ability of the Mean Bilateral Proximal Extension of the Clot (MBPEC) score to predict mortality and adverse outcome. Methods This was a single center retrospective cohort study. 1743 patients with computed tomography pulmonary arteriography (CTPA) verified PE diagnosed between 2005 and 2020 were included. Patients with active malignancy were excluded. The PE clot burden was assessed with MBPEC score: The most proximal extension of PE was scored in each lung from 1 = sub-segmental to 4 = central. The MBPEC score is the score from each lung divided by two and rounded up to nearest integer. Results We found inconsistent associations between higher and lower MBPEC scores versus mortality. The all-cause 30-day mortality of 3.9% (95% CI: 3.0–4.9). The PE-related mortality was 2.4% (95% CI: 1.7–3.3). Patients with MBPEC score 1 had higher all-cause mortality compared to patients with MBPEC score 4: Crude Hazard Ratio (cHR) was 2.02 (95% CI: 1.09–3.72). PE-related mortality was lower in patients with MBPEC score 3 compared to score 4: cHR 0.22 (95% CI: 0.05–0.93). Patients with MBPEC score 4 did more often receive systemic thrombolysis compared to patients with MBPEC score 1–3: 3.2% vs. 0.6% ( p &lt; .001). Patients with MBPEC score 4 where more often admitted to the intensive care unit: 13% vs. 4.7% ( p &lt; .001). Conclusion We found no consistent association between the MBPEC score and mortality. Our results therefore indicate that peripheral PE does not necessarily entail a lower morality risk than proximal PE.

• Myklebust-Hansen, Hans Joakim; Hasvik, Eivind Olay; Solyga, Volker & Ghanima, Waleed (2023). The feasibility of self-performing measurements of peripheral oxygen saturation and respiratory exercises in home-isolated COVID-19 patients—a single-arm prospective trial. Pilot and Feasibility Studies. 9(1). doi: 10.1186/s40814-023-01415-x. Fulltekst i vitenarkiv Vis sammendrag

  Background COVID-19 is a highly contagious disease where isolation of infected individuals is deemed warranted. If possible, home isolation is preferred over hospitalization. This implies a need for methods of observation that can ensure the safety of these patients. Preventive treatment methods that can both decrease the probability for development of critical disease and hopefully decrease the need for hospitalization would be an added benefit. This was a single-arm prospective pilot study performed to assess the feasibility of performing self-measurements of SpO2 and respiratory exercises in at-home isolated COVID-19 patients. Method A total of 40 ambulant SARS-CoV-2-positive individuals in home isolation were followed up for a period of 14 days. At baseline, they were equipped with a pulse oximeter, PEF meter, a project diary to note all measurements, and simple instructions on how to perform respiratory exercises. No other contact was made, but participants were instructed to contact the hospital based on given criteria for blood oxygenation levels and dyspnea severity and to return study equipment and the project diary at the end of study. Results During the follow-up period, 35 participants (87.5%) recorded daily SpO2 measurements, and 12 (30%) adhered to daily respiratory exercises as instructed. Four participants (10%) were admitted to hospital during the follow-up period. Five participants terminated follow-up prematurely. Conclusions Performing self-measurements of SpO2 during home isolation due to COVID-19 infection is feasible. The feasibility of performing respiratory exercises in ambulant patients is questionable and may require more motivational interventions to increase adherence. Trial registration ClinicalTrials.gov identifier: NCT04647747.

• Kanagaratnam, Prapa; Francis, Darrel P.; Chamie, Daniel; Coyle, Clare; Marynina, Alena & Katritsis, George [Vis alle 40 forfattere av denne artikkelen] (2023). A randomized controlled trial to investigate the use of acute coronary syndrome therapy in patients hospitalized with COVID-19: the COVID-19 Acute Coronary Syndrome trial. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. 21(8), s. 2213–2222. doi: 10.1016/j.jtha.2023.04.045. Fulltekst i vitenarkiv Vis sammendrag

  Background Patients hospitalized with COVID-19 suffer thrombotic complications. Risk factors for poor outcomes are shared with coronary artery disease. Objectives To investigate the efficacy of an acute coronary syndrome regimen in patients hospitalized with COVID-19 and coronary disease risk factors. Methods A randomized controlled, open-label trial across acute hospitals (United Kingdom and Brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28 days. Primary efficacy and safety outcomes were 30-day mortality and bleeding. The key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, or death). Results Three hundred twenty patients from 9 centers were randomized. The trial terminated early due to low recruitment. At 30 days, there was no significant difference in mortality (intervention vs control, 11.5% vs 15%; unadjusted odds ratio [OR], 0.73; 95% CI, 0.38-1.41; p = .355). Significant bleeds were infrequent and were not significantly different between the arms (intervention vs control, 1.9% vs 1.9%; p > .999). Using a Bayesian Markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (OR, 1.46; 95% credible interval [CrI], 0.88-2.37; Pr [beta > 0], 93%; adjusted OR, 1.50; 95% CrI, 0.91-2.45; Pr [beta > 0], 95%) and median time to discharge to home was 2 days shorter (95% CrI, −4 to 0; 2% probability that it was worse). Conclusion Acute coronary syndrome treatment regimen was associated with a reduction in the length of hospital stay without an excess in major bleeding. A larger trial is needed to evaluate mortality.

• Rinde, Fridtjof Balteskard; Jørgensen, Camilla Tøvik; Pettersen, Heidi Hassel; Hansen, John Bjarne; Ghanima, Waleed & Brækkan, Sigrid Kufaas (2023). Low D-dimer levels at diagnosis of venous thromboembolism are associated with reduced risk of recurrence: data from the TROLL registry. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. doi: 10.1016/j.jtha.2023.03.026. Fulltekst i vitenarkiv Vis sammendrag

  Background: Venous thromboembolism (VTE) is a frequent disease with a high risk of recurrence. It has been suggested that the D-dimer level at the time of VTE diagnosis can be used to identify patients at a low risk of recurrence. Objectives: We aimed to investigate the impact of D-dimer levels measured at the time of VTE diagnosis on the risk of recurrence in a large cohort of patients with a first-time VTE.<p> <p>Methods: The study included 2585 patients with first symptomatic non-cancer–associated VTE from the Venous Thrombosis Registry in Østfold Hospital (TROLL) (2005- 2020). All recurrent events during the follow-up were recorded, and cumulative incidences of recurrence were estimated according to D-dimer levels of ≤1900 ng/mL (≤25th percentile) and >1900 ng/mL. <p>Results: During a median follow-up of 3.3 years, 395 patients experienced a recurrent VTE. The 1- and 5-year cumulative incidences of recurrence were 2.9% (95% CI: 1.8- 4.6) and 11.4% (95% CI: 8.7-14.8), respectively, in those with a D-dimer concentration of ≤1900 ng/mL and 5.0% (95% CI, 4.0-6.1) and 18.3% (95% CI: 16.2-20.6), respectively, in those with a D-dimer concentration of >1900 ng/mL, respectively. In patients with unprovoked VTE, the 5-year cumulative incidence was 14.3% (95% CI: 10.3-19.7) in the ≤1900-ng/mL category, and 20.2% (95% CI: 17.3-23.5) in the >1900-ng/mL category. <p>Conclusions: D-dimer levels within the lowest quartile, measured at the time of VTE diagnosis, were associated with lower recurrence risk. Our findings imply that D-dimer levels measured at the time of diagnosis may be used to identify patients with VTE at a low risk of recurrent VTE.

• Larsen, Trine-Lise; Svalastoga, Marte; Brekke, Jorunn; Enden, Tone Rønnaug; Frøen, Hege & Garresori, Herish [Vis alle 16 forfattere av denne artikkelen] (2023). Arterial events in cancer patients treated with apixaban for venous thrombosis. Thrombosis Research. ISSN 0049-3848. 228, s. 128–133. doi: 10.1016/j.thromres.2023.05.017. Fulltekst i vitenarkiv
• Kuter, David J.; Bussel, James B.; Ghanima, Waleed; Cooper, Nichola; Gernsheimer, Terry & Lambert, Michele P. [Vis alle 11 forfattere av denne artikkelen] (2023). Rilzabrutinib versus placebo in adults and adolescents with persistent or chronic immune thrombocytopenia: LUNA 3 phase III study. Therapeutic Advances in Hematology (TAH). ISSN 2040-6207. 14. doi: 10.1177/20406207231205431. Fulltekst i vitenarkiv Vis sammendrag

  Background: Immune thrombocytopenia (ITP) is characterized by primarily autoantibody-mediated platelet destruction and impaired platelet production resulting in thrombocytopenia and an increased risk of bleeding. Other manifestations include increased risk of thrombosis and diminished quality of life. Current treatment approaches are directed toward lowering the rate of platelet destruction or stimulating platelet production to prevent bleeding. Rilzabrutinib is an oral, reversible, potent Bruton tyrosine kinase inhibitor that was specifically designed to treat immune-mediated diseases and mediates its therapeutic effect through a dual mechanism of action: (1) inhibiting B-cell activation and (2) interrupting antibody-coated cell phagocytosis by Fc gamma receptor in spleen and liver. A 24-week dose-finding phase I/II study of rilzabrutinib in patients with ITP showed a 40% platelet response (⩾2 consecutive platelet counts of ⩾50 × 10 9 /L and increase from baseline ⩾20 × 10 9 /L without rescue medication use) and a well-tolerated safety profile with only grade 1/2 transient adverse events across dose levels. Objectives: Assess the efficacy and safety of oral rilzabrutinib in adult and adolescent patients with persistent or chronic ITP. Design: Rilzabrutinib 400 mg BID is being evaluated in the ongoing LUNA 3 multicenter, double-blind, placebo-controlled phase III study. Methods and analysis: The primary endpoint is durable platelet response, defined as achieving platelet counts of ⩾50 × 10 9 /L for at least two-thirds of ⩾8 available weekly scheduled platelet measurements during the last 12 weeks (including ⩾2 available measurements within the last 6 weeks) of the 24-week blinded treatment period in the absence of rescue therapy. Ethics: Ethical guidelines and informed consent are followed. Discussion: The LUNA 3 trial will further investigate rilzabrutinib’s safety and efficacy in adult and adolescent patients, with the primary goal of addressing a major objective in treating patients with ITP: durability of platelet response. Trail Registration: ClinicalTrials.gov NCT04562766: https://clinicaltrials.gov/ct2/show/NCT04562766 ; EU Clinical Trials Register EudraCT 2020-002063-60: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2020-002063-60 .

• Lambert, Catherine; Maitland, Hillary & Ghanima, Waleed (2023). Risk-based and individualised management of bleeding and thrombotic events in adults with primary immune thrombocytopenia (ITP). European Journal of Haematology. ISSN 0902-4441. doi: 10.1111/ejh.14154. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Although bleeding is one of the main symptoms of primary immune thrombocytopenia (ITP), risk factors for bleeding have yet to be fully established. Low platelet count (PC; &lt;20–30 × 10 9 /L) is generally indicative of increased risk of bleeding. However, PC and bleeding events cannot be fully correlated; many other patient‐ and disease‐related factors are thought to contribute to increased bleeding risk. Furthermore, even though ITP patients have thrombocytopenia and are at increased risk of bleeding, ITP also carries higher risk of thrombotic events. Factors like older age and certain ITP treatments are associated with increased thrombotic risk. Women's health in ITP requires particular attention concerning haemorrhagic and thrombotic complications. Management of bleeding/thrombotic risk, and eventually antithrombotic therapies in ITP patients, should be based on individual risk profiles, using a tailored, patient‐centric approach. Currently, evidence‐based recommendations and validated tools are lacking to support decision‐making and help clinicians weigh risk of bleeding against thrombosis. Moreover, evidence is lacking about optimal PC for achieving haemostasis in invasive procedures settings. Further research is needed to fully define risk factors for each event, enabling development of comprehensive risk stratification approaches. This review discusses risk‐based and individualised management of bleeding and thrombosis risk in adults with primary ITP.

• Hussaini, Parwana; Larsen, Trine-Lise; Ghanima, Waleed & Dahm, Anders Erik A (2023). Risk factors for bleeding in cancer patients treated with conventional dose followed by low-dose apixaban for venous thromboembolism. Thrombosis and Haemostasis. ISSN 0340-6245. doi: 10.1055/a-2188-8773. Fulltekst i vitenarkiv
• Arnold, Donald M.; Clerici, Bianca; Ilicheva, Ekaterina & Ghanima, Waleed (2023). Refractory immune thrombocytopenia in adults: Towards a new definition. British Journal of Haematology. ISSN 0007-1048. 203(1), s. 23–27. doi: 10.1111/bjh.19075. Fulltekst i vitenarkiv
• Jørgensen, Camilla Tøvik; Brækkan, Sigrid Kufaas; Førsund, Eli; Pettersen, Heidi Hassel; Tjønnfjord, Eirik & Ghanima, Waleed [Vis alle 7 forfattere av denne artikkelen] (2023). Incidence of venous thromboembolism, recurrence, and bleeding after isolated superficial vein thrombosis: findings from the Venous Thrombosis Registry in Østfold Hospital. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. doi: 10.1016/j.jtha.2023.10.017. Fulltekst i vitenarkiv Vis sammendrag

  Background - There are limited data on the long-term risk of venous thromboembolism (VTE) after high-risk isolated superficial vein thrombosis (iSVT) treated with anticoagulants.<p> <p>Objectives - To determine the short- and long-term risk of VTE and iSVT recurrence after cessation of anticoagulant treatment and to calculate 45-day cumulative bleeding incidence in patients with iSVT.<p> <p>Methods - Between January 2014 and December 2021, 229 patients with high-risk iSVT (ie, thrombus length ≥5cm), without active cancer, with no history of VTE or iSVT, and who had received anticoagulant treatment for the iSVT were identified through the Venous Thrombosis Registry in Østfold Hospital (TROLL registry), Norway. Cumulative incidences of VTE and iSVT recurrence, as well as cumulative incidences of major and clinically relevant nonmajor bleeding events, were assessed.<p> <p>Results - Median age was 60 years (IQR, 48-71), and 125 (55%) were women. Most patients were treated with direct oral anticoagulants (74%), and of these, 79% received a dose of rivaroxaban 10 mg daily. Low-molecular-weight heparin was given to 26% of the patients. The 1- and 5-year cumulative incidences of VTE after iSVT were 4.6% (95% CI, 2.5-8.3) and 15.9% (95% CI, 10.8-22.9), respectively. Further, the 1- and 5-year cumulative incidences of iSVT recurrence were 6.5% (95% CI, 3.9-10.7) and 15.9% (95% CI, 10.8-23.1), respectively. The overall 45-day cumulative incidence of major and clinically relevant nonmajor bleeding events was 0.4% (95% CI, 0.06-3.06) and 1.8% (95% CI, 0.7-4.6), respectively. No major bleeding events were observed in patients treated with direct oral anticoagulants.<p> <p>Conclusion - Despite anticoagulant treatment, the risk of VTE after high-risk iSVT was substantial, while bleeding complications were low.

• Jørgensen, Camilla Tøvik; Tavoly, Mazdak; Førsund, Elise; Pettersen, Heidi Hassel; Tjønnfjord, Eirik & Ghanima, Waleed [Vis alle 7 forfattere av denne artikkelen] (2023). Incidence of bleeding and recurrence in isolated distal deep vein thrombosis: findings from the Venous Thrombosis Registry in Østfold Hospital. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. 21(10), s. 2824–2832. doi: 10.1016/j.jtha.2023.06.028. Fulltekst i vitenarkiv Vis sammendrag

  Background - Isolated distal deep vein thrombosis (IDDVT) is a common presentation of deep vein thrombosis. There are limited data on the long-term risk of recurrence after IDDVT.<p> <p>Objectives - We aimed to determine the short- and long-term incidence of venous thrombosis (VTE) recurrence after cessation of anticoagulation and the 3-month incidence of bleeding during anticoagulant treatment in patients with IDDVT.<p> <p>Methods - Between January 2005 and May 2020, 475 patients with IDDVT and without active cancer were identified from the Venous Thrombosis Registry in Østfold Hospital, which is an ongoing registry of consecutive patients with VTE at Østfold Hospital, Norway. Major and clinically relevant, nonmajor bleeding as well as recurrent VTE were registered, and the cumulative incidences of these events were assessed.<p> <p>Results - The median age of the patients was 59 years (IQR, 48-72 years), 243 (51%) patients were women, and 175 events (36.8%) were classified as unprovoked. The 1-, 5-, and 10-year cumulative incidences of recurrent VTE were 5.6% (95% CI, 3.7-8.4), 14.7% (95% CI, 11.1-19.4), and 27.2% (95% CI, 21.1-34.5), respectively. The recurrence rates were higher for unprovoked IDDVT than for provoked IDDVT. Among the recurrent events, 18 (29%) were pulmonary embolisms and 21 (33%) were proximal deep vein thromboses. The 3-month cumulative incidence of major bleeding was 1.5% (95% CI, 0.7-3.1) overall and 0.8% (95% CI, 0.2-3.1) when restricted to patients treated with direct oral anticoagulants.<p> <p>Conclusion - Despite initial treatment, the long-term risk of VTE recurrence after first-time IDDVT is high. The bleeding rates during anticoagulation, particularly with direct oral anticoagulants, were acceptably low.

• Jong, Cindy Michelle Maria De; Hout, Wilbert Van Den; Dijk, Christel E Van; Heim, Noor; Dam, Lisette F Van & Dronkers, Charlotte [Vis alle 24 forfattere av denne artikkelen] (2023). Cost-effectiveness of performing reference ultrasonography in patients with deep vein thrombosis. Thrombosis and Haemostasis. ISSN 0340-6245. doi: 10.1055/a-2213-9230. Fulltekst i vitenarkiv
• Åkesson, Alexander; Bussel, James B.; Martin, Myriam; Blom, Anna M.; Klintman, Jenny & Ghanima, Waleed [Vis alle 8 forfattere av denne artikkelen] (2023). Complement activation negatively affects the platelet response to thrombopoietin receptor agonists in patients with immune thrombocytopenia: a prospective cohort study. Platelets. ISSN 0953-7104. 34(1). doi: 10.1080/09537104.2022.2159019. Fulltekst i vitenarkiv
• Cooper, Nichola; Ghanima, Waleed; Vianelli, Nicola; Valcárcel, David; Yavaşoğlu, İrfan & Melikyan, Anait [Vis alle 13 forfattere av denne artikkelen] (2023). Sustained response off-treatment in eltrombopag-treated adult patients with ITP who are refractory or relapsed after first-line steroids: Primary, final, and ad-hoc analyses of the Phase II TAPER trial. American Journal of Hematology. ISSN 0361-8609. doi: 10.1002/ajh.27131. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Immune thrombocytopenia (ITP) is characterized by reduced platelet count due to increased destruction and is categorized according to the time following diagnosis (newly diagnosed, persistent, chronic). First‐line corticosteroid therapy is associated with transient response, high relapse rates, and considerable toxicity. TAPER (NCT03524612) is a Phase II, prospective, single‐arm trial investigating whether eltrombopag can induce a sustained response off‐treatment (SRoT) in adult patients with ITP after first‐line corticosteroid failure. This study defines SRoT as an off‐treatment period wherein platelet count remains above 30 × 10 9 /L in the absence of bleeding or rescue therapy. The primary endpoint was the proportion of patients who achieved SRoT until Month 12, which was 30.5% ( n  = 32/105; p  &lt; .0001 testing hypothesis H1: proportion &gt;15%) following eltrombopag tapering and discontinuation, and median SRoT duration was ~8 months until Month 12. Median platelet count increased within 1 month of treatment and remained elevated until Month 12. Quality of life improved within 3 months and was maintained. Headache (21%) was the most common adverse event. None of the 4 deaths reported were considered treatment‐related. In summary, ~one‐third of patients achieved SRoT until Month 12 following eltrombopag tapering and discontinuation. An ad‐hoc early‐use analysis, stratified by ITP duration at baseline, assessed initial hematologic responses and safety. Results suggest that eltrombopag has similar efficacy in newly diagnosed and later stages of ITP. In follow‐up until Month 24, a median SRoT duration of ~22 months was observed ( n  = 20). The safety profile was comparable across analyses and ITP duration groups and aligned with its well‐established safety profile.

• Tholin, Birgitte; Ghanima, Waleed; Selle, Maria & Stavem, Knut (2023). Incidence and determinants of venous thromboembolism over 90 days in hospitalized and nonhospitalized patients with COVID-19. Journal of Internal Medicine. ISSN 0954-6820. 294(6), s. 721–729. doi: 10.1111/joim.13706. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Introduction COVID‐19 is associated with an increased risk of venous thromboembolism (VTE), but there is great variation among reported incidence rates. Most previous studies have focused on hospitalized patients with COVID‐19, and only a few reports are from population‐based registries. Methods We studied the 90‐day incidence of VTE, associated risk factors and all‐cause mortality in hospitalized and nonhospitalized patients with COVID‐19 in a nationwide cohort. Data on hospitalizations and outpatient visits were extracted from two national registries with mandatory reporting linked by a unique national identification number carried by all Norwegian residents. We performed Cox proportional hazards regression to determine risk factors for VTE after infection with SARS‐CoV‐2. Results Our study included 30,495 patients with positive SARS‐CoV‐2 polymerase chain reaction with a mean (SD) age of 41.9 (17.3) years, and 53% were males. Only 2081 (6.8%) were hospitalized. The 90‐day incidence of VTE was 0.3% (95% CI: 0.21–0.33) overall and 2.9% (95% CI: 2.3–3.7) in hospitalized patients. Age (hazard ratio [HR] 1.28 per decade, 95% CI: 1.11–1.48, p  &lt; 0.05), history of previous VTE (HR 4.69, 95% CI: 2.34–9.40, p  &lt; 0.05), and hospitalization for COVID‐19 (HR 23.83, 95% CI: 13.48–42.13, p &lt;  0.05) were associated with risk of VTE. Conclusions The 90‐day incidence of VTE in hospitalized and nonhospitalized patients with COVID‐19 was in the lower end compared with previous reports, with considerably higher rates in hospitalized than nonhospitalized patients. Risk factors for VTE were consistent with previously reported studies.

• Pradier, Michelle; Rodger, Marc A.; Ghanima, Waleed; Kovacs, Michael J.; Shivakumar, Sudeep & Kahn, Susan R. [Vis alle 10 forfattere av denne artikkelen] (2023). Performance and Head-to-Head Comparison of Three Clinical Models to Predict Occurrence of Postthrombotic Syndrome: A Validation Study. Thrombosis and Haemostasis. ISSN 0340-6245. 123(7), s. 692–699. doi: 10.1055/a-2039-3388. Fulltekst i vitenarkiv
• Kuter, David J.; Efraim, Merlin; Mayer, Jiri; Trněný, Marek; McDonald, Vickie & Bird, Robert [Vis alle 29 forfattere av denne artikkelen] (2022). Rilzabrutinib, an oral BTK inhibitor, in immune thrombocytopenia. New England Journal of Medicine. ISSN 0028-4793. 386(15), s. 1421–1431. doi: 10.1056/NEJMoa2110297. Fulltekst i vitenarkiv
• Ng, Sara; Rodger, Marc A.; Ghanima, Waleed; Kovacs, Michael J.; Shivakumar, Sudeep & Kahn, Susan R. [Vis alle 10 forfattere av denne artikkelen] (2022). External Validation of the Patient-Reported Villalta Scale for the Diagnosis of Postthrombotic Syndrome. Thrombosis and Haemostasis. ISSN 0340-6245. 122(8), s. 1379–1383. doi: 10.1055/a-1738-1313. Fulltekst i vitenarkiv
• Tholin, Birgitte; Fiskvik, Hilde; Tveita, Anders Aune; Tsykunova, Galina; Opperud, Helene & Busterud, Kari [Vis alle 11 forfattere av denne artikkelen] (2022). Thromboembolic complications during and after hospitalization for COVID-19: Incidence, risk factors and thromboprophylaxis. Thrombosis Update. 6, s. 1–6. doi: 10.1016/j.tru.2021.100096. Fulltekst i vitenarkiv Vis sammendrag

  Introduction The incidence of thromboembolism during COVID-19 and the use of thromboprophylaxis vary greatly between studies. Only a few studies have investigated the rate of thromboembolism post-discharge. This study determined the 90-day incidence of venous and arterial thromboembolic complications, risk factors for venous thromboembolic events and characterized the use of thromboprophylaxis during and after hospitalization. Materials and methods We retrospectively reviewed medical records for adult patients hospitalized for >24 h for COVID-19 before May 15, 2020, in ten Norwegian hospitals. We extracted data on demographics, thromboembolic complications, thromboembolic risk factors, and the use of thromboprophylaxis. Cox proportional hazards regression was used to determine risk factors for VTE. Results 550 patients were included. The 90-day incidence of arterial and venous thromboembolism in hospitalized patients was 6.9% (95% CI: 5.1–9.3) overall and 13.8% in the ICU. Male sex (hazard ratio (HR) 7.44, 95% CI 1.73–32.02, p = 0.007) and previous VTE (HR 6.11, 95% CI: 1.74–21.39, p = 0.005) were associated with risk of VTE in multivariable analysis. Thromboprophylaxis was started in 334 patients (61%) with a median duration of 7 days (25th–75th percentile 3–13); in the VTE population 10/23 (43%) started thromboprophylaxis prior to diagnosis. After discharge 20/223 patients received extended thromboprophylaxis and 2/223 (0.7%, 95% CI: 0.3–1.9) had a thromboembolism. Conclusions The 90-day incidence of thromboembolism in COVID-19 patients was 7%, but <1% after discharge. Risk factors were male sex and previous VTE. Most patients received thromboprophylaxis during hospitalization, but only <10% after discharge.

• Delluc, Aurélien; Ghanima, Waleed; Kovacs, Michael J.; Shivakumar, Sudeep; Kahn, Susan R. & Sandset, Per Morten [Vis alle 9 forfattere av denne artikkelen] (2022). Prevention of post-thrombotic syndrome with rosuvastatin: A multicenter randomized controlled pilot trial (SAVER). Thrombosis Research. ISSN 0049-3848. 213, s. 119–124. doi: 10.1016/j.thromres.2022.03.014. Fulltekst i vitenarkiv
• Stavem, Knut; Einvik, Gunnar; Tholin, Birgitte; Ghanima, Waleed; Hessen, Erik & Lundqvist, Christofer (2022). Cognitive function in non-hospitalized patients 8–13 months after acute COVID-19 infection: A cohort study in Norway. PLOS ONE. 17(8). doi: 10.1371/journal.pone.0273352. Fulltekst i vitenarkiv Vis sammendrag

  Studies have reported reduced cognitive function following COVID-19 illness, mostly from hospital settings with short follow-up times. This study recruited non-hospitalized COVID-19 patients from a general population to study prevalence of late cognitive impairment and associations with initial symptoms. We invited patients with PCR-confirmed COVID-19. A postal questionnaire addressed basic demographics, initial COVID-19 symptoms and co-morbidity about 4 months after diagnosis. About 7 months later, we conducted cognitive tests using the Cambridge Neuropsychological Test Automated Battery, comprising four tests for short-term memory, attention and executive function. We present descriptive statistics using z-scores relative to UK population norms and defined impairment as z-score &lt;-1.5. We used multivariable logistic regression with impairment as outcome. Continuous domain scores were analysed by multiple linear regression. Of the initial 458 participants; 305 were invited, and 234 (77%) completed cognitive testing. At median 11 (range 8–13) months after PCR positivity, cognitive scores for short term memory, visuospatial processing, learning and attention were lower than norms (p≤0.001). In each domain, 4–14% were cognitively impaired; 68/232 (29%) were impaired in ≥ 1 of 4 tests. There was no association between initial symptom severity and impairment. Multivariable linear regression showed association between spatial working memory and initial symptom load (6–9 symptoms vs. 0–5, coef. 4.26, 95% CI: 0.65; 7.86). No other dimension scores were associated with symptom load. At median 11 months after out-of-hospital SARS-Cov-2 infection, minor cognitive impairment was seen with little association between COVID-19 symptom severity and outcome.

• Chakrabarti, Prantar; George, Biju; Shanmukhaiah, Chandrakala; Sharma, Lalit Mohan; Udupi, Shashank & Ghanima, Waleed (2022). How do patients and physicians perceive immune thrombocytopenia (ITP) as a disease? Results from Indian analysis of ITP World Impact Survey (I-WISh). Journal of Patient-Reported Outcomes. 6. doi: 10.1186/s41687-022-00429-y. Fulltekst i vitenarkiv
• Larsen, Trine-Lise; Garresori, Herish; Brekke, Jorunn; Enden, Tone Rønnaug; Frøen, Hege & Jacobsen, Eva-Marie [Vis alle 15 forfattere av denne artikkelen] (2022). Low dose apixaban as secondary prophylaxis of venous thromboembolism in cancer patients – 30 months follow-up. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. 20(5), s. 1166–1181. doi: 10.1111/jth.15666. Fulltekst i vitenarkiv Vis sammendrag

  Background There are no data on the effect of low-dose anticoagulation as secondary prophylaxis for venous thromboembolism (VTE) in cancer patients. We assessed the efficacy and safety of low-dose apixaban for 30 months, after initial 6 months of full-dose treatment. Methods We included 298 patients with cancer and any type of VTE in a single arm interventional clinical trial. All patients were treated with full-dose apixaban (5 mg twice daily) for 6 months. Total 196 patients with active cancer after 6 months treatment continued with apixaban 2.5 mg twice daily for another 30 months. The main endpoints were recurrent VTE, major bleeding and clinically relevant non-major bleeding. Results During the 30 months of treatment with low-dose apixaban 14 (7.6%; 95% confidence interval (CI) 4.0%–11.7%) patients experienced recurrent VTE, six (3.1%; 95% CI 1.1%–6.5%) experienced major bleeding and 16 (8.1%, 95% CI: 4.7%–12.8%) experienced clinically relevant non-major bleeding. The incidence rate per person month of recurrent VTE was 0.8% (95% CI 0.41–1.6) at 2–6 months with full-dose apixaban, and 1.0% (95% CI 0.5–1.9) at 7–12 months with low-dose apixaban. The incidence rate of major bleeding was 1.1% (95% CI 0.6–2.0) at 2–6 months, and 0.3% (95% CI 0.1–1.0) at 7–12 months. Between 12 and 36 months the incidence rate of recurrent VTE and major bleedings remained low. Conclusion Dose reduction of apixaban to 2.5 mg twice daily seems safe after 6 months of full-dose treatment. After 12 months the incidence rate of recurrent VTE and major bleeding remained low.

• Tsykunova, Galina & Ghanima, Waleed (2022). Avatrombopag for the Treatment of Adult Patients with Chronic Immune Thrombocytopenia (cITP): Focus on Patient Selection and Perspectives. Therapeutics and Clinical Risk Management. ISSN 1176-6336. 18, s. 273–286. doi: 10.2147/TCRM.S251672. Fulltekst i vitenarkiv Vis sammendrag

  Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by a reduced number of circulating platelets due to immune-mediated destruction and decreased platelet production in the bone marrow. Thrombopoietin receptor agonists (TPO-RAs) are highly effective and widely used in the treatment of patients with steroid treatment failure or dependency. Avatrombopag represents a new supplement to the TPO-RAs family. It was originally approved for the treatment of thrombocytopenia in patients with chronic liver disease who are scheduled to undergo an invasive procedure. However, labeled indications for avatrombopag have been relatively recently expanded to include treatment of chronic ITP in adults with insufficient response to the previous treatments. In this article, we provide an overview of pharmacodynamics and pharmacokinetics of avatrombopag as well as results of the clinical trials related to safety and efficacy of avatrombopag with a perspective on current clinical use. Available data so far suggests that avatrombopag can be effectively used in ITP patients and has a favorable safety profile. Though further studies are needed to affirm the efficacy and safety, avatrombopag has the potential to become a TPO agonist of choice for many patients with ITP.

• Bistervels, Ingrid M.; Bavalia, Roisin; Beyer-Westendorf, Jan; Cate-Hoek, Arina J. ten; Schellong, Sebastian M. & Kovacs, Michael J. [Vis alle 34 forfattere av denne artikkelen] (2022). Postthrombotic syndrome and quality of life after deep vein thrombosis in patients treated with edoxaban versus warfarin. Research and Practice in Thrombosis and Haemostasis (RPTH). 6(5). doi: 10.1002/rth2.12748. Fulltekst i vitenarkiv Vis sammendrag

  Background Postthrombotic syndrome (PTS) is a long‐term complication after deep vein thrombosis (DVT) and can affect quality of life (QoL). Pathogenesis is not fully understood but inadequate anticoagulant therapy with vitamin K antagonists is a known risk factor for the development of PTS. Objectives To compare the prevalence of PTS after acute DVT and the long‐term QoL following DVT between patients treated with edoxaban or warfarin. Methods We performed a long‐term follow‐up study in a subset of patients with DVT who participated in the Hokusai‐VTE trial between 2010 and 2012 (NCT00986154). Primary outcome was the prevalence of PTS, defined by the Villalta score. The secondary outcome was QoL, assessed by validated disease‐specific (VEINES‐QOL) and generic health‐related (SF‐36) questionnaires. Results Between 2017 and 2020, 316 patients were enrolled in 26 centers in eight countries, of which 168 (53%) patients had been assigned to edoxaban and 148 (47%) to warfarin during the Hokusai‐VTE trial. Clinical, demographic, and thrombus‐specific characteristics were comparable for both groups. Mean (SD) time since randomization in the Hokusai‐VTE trial was 7.0 (1.0) years. PTS was diagnosed in 85 (51%) patients treated with edoxaban and 62 (42%) patients treated with warfarin (adjusted odds ratio 1.6, 95% CI 1.0–2.6). Mean differences in QoL scores between treatment groups were not clinically relevant. Conclusion Contrary to our hypothesis, the prevalence of PTS tended to be higher in patients treated with edoxaban compared with warfarin. No differences in QoL were observed. Further research is warranted to unravel the role of anticoagulant therapy on development of PTS.

• Cooper, Nichola; Ghanima, Waleed; Hill, Quentin A.; Nicolson, Phillip LR.; Markovtsov, Vadmin & Kessler, Craig (2022). Recent advances in understanding spleen tyrosine kinase (SYK) in human biology and disease, with a focus on fostamatinib. Platelets. ISSN 0953-7104. 34(1). doi: 10.1080/09537104.2022.2131751. Fulltekst i vitenarkiv Vis sammendrag

  Spleen tyrosine kinase (SYK) is an important regulatory molecule of signal transduction pathways involved in the pathogenesis of autoimmune diseases such as immune thrombocytopenia (ITP), and the SYK-signaling pathway has emerged as a potential target for the treatment of numerous diseases. The aim of this narrative review is to summarize the biological properties of SYK and its involvement in disease pathways, provide an update on SYK inhibitors in the treatment of ITP, and consider other potential applications. Fostamatinib, the only licensed SYK inhibitor to date, produces clinical response in ITP patients, including those who are refractory to other treatments. It appears to reduce the risk of thrombotic events and may therefore be a drug to consider for patients with an increased thrombotic risk. Encouraging results have also been obtained in the treatment of warm autoimmune hemolytic anemia. Several other SYK inhibitors have entered clinical trials for a range of indications, reflecting the ability of these drugs to affect multiple signaling pathways. SYK inhibitors have the potential to target several aspects of COVID-19 pathogenesis including thrombosis, without affecting normal hemostasis, and data from the first study of fostamatinib in COVID-19 are encouraging. It is hoped that ongoing trials in autoimmune indications other than ITP, as well as in hematological malignancies and other disorders, confirm the promise of SYK inhibitors.

• Garabet, Lamya Samir Noori; Eriksson, Anna Maria; Tjønnfjord, Eirik; Cui, Xueyan; Olsen, Magnus Kringstad & Jacobsen, Hege [Vis alle 18 forfattere av denne artikkelen] (2022). SARS-CoV-2 vaccines are not associated with hypercoagulability in apparently healthy people. Research and Practice in Thrombosis and Haemostasis (RPTH). 7(1). doi: 10.1016/j.rpth.2022.100002. Fulltekst i vitenarkiv Vis sammendrag

  Background: SARS-CoV-2 adenoviral vector DNA vaccines have been linked to the rare but serious thrombotic postvaccine complication vaccine-induced immune thrombotic thrombocytopenia. This has raised concerns regarding the possibility of increased thrombotic risk after any SARS-CoV-2 vaccines. <p><p>Objectives: To investigate whether SARS-CoV-2 vaccines cause coagulation activation leading to a hypercoagulable state. Methods: This observational study included 567 health care personnel; 521 were recruited after the first dose of adenoviral vector ChAdOx1-S (Vaxzevria, AstraZeneca) vaccine and 46 were recruited prospectively before vaccination with a messenger RNA (mRNA) vaccine, either Spikevax (Moderna, n = 38) or Comirnaty (Pfizer-BioNTech, n = 8). In the mRNA group, samples were acquired before and 1 to 2 weeks after vaccination. In addition to the prevaccination samples, 56 unvaccinated blood donors were recruited as controls (total n = 102). Thrombin generation, D-dimer levels, and free tissue factor pathway inhibitor (TFPI) levels were analyzed. <p>Results: No participant experienced thrombosis, vaccine-induced immune thrombotic thrombocytopenia, or thrombocytopenia (platelet count <100 × 10⁹ /L) 1 week to 1 month postvaccination. There was no increase in thrombin generation, D-dimer level, or TFPI level in the ChAdOx1-S vaccine group compared with controls or after the mRNA vaccines compared with baseline values. Eleven of 513 (2.1%) participants vaccinated with ChAdOx1-S had anti-PF4/polyanion antibodies without a concomitant increase in thrombin generation. <p>Conclusion: In this study, SARS-CoV-2 vaccines were not associated with thrombosis, thrombocytopenia, increased thrombin generation, D-dimer levels, or TFPI levels compared with baseline or unvaccinated controls. These findings argue against the subclinical activation of coagulation post-COVID-19 vaccination.

• Jørgensen, Camilla Tøvik; Tavoly, Mazdak; Pettersen, Heidi Hassel; Førsund, Eli; Roaldsnes, Christina & Olsen, Magnus Kringstad [Vis alle 12 forfattere av denne artikkelen] (2022). The venous thrombosis registry in Østfold Hospital (TROLL registry) - design and cohort description. Research and Practice in Thrombosis and Haemostasis (RPTH). 6(5), s. 1–10. doi: 10.1002/rth2.12770. Fulltekst i vitenarkiv Vis sammendrag

  Purpose The incidence of venous thromboembolism (VTE) is expected to increase over the next decades, further increasing its substantial impact on patients and health care resources. Registries have the benefit of reporting real-world data without excluding clinically important subgroups. Our aim was to describe a Norwegian VTE registry and to provide descriptive data on the population and management. Registry Population The Venous Thrombosis Registry in Østfold Hospital (TROLL) is an ongoing registry of consecutive patients diagnosed with, treated, and/or followed up for VTE at Østfold Hospital, Norway, since 2005. Baseline and follow-up data, including demographics, clinical features, risk factors, diagnostic procedures, classification of VTE, and treatment were collected during hospitalization, and at scheduled outpatient visits. Findings to Date From January 2005 to June 2021, 5037 patients were eligible for research in TROLL. Median age was 67 years (interquartile range, 55–77), and 2622 (52.1%) were male. Of these, 2736 (54.3%) had pulmonary embolism (PE), 2034 (40.4%) had deep vein thrombosis (DVT), and 265 (5.3%) had upper-extremity DVT or splanchnic or cerebral sinus vein thrombosis. In total, 2330 (46.3%) were classified as unprovoked VTE, and 1131 (22.5%) had cancer. Direct oral anticoagulants were the most frequent therapeutic agents (39.3%) followed by low-molecular-weight heparins (30.4%) and vitamin K antagonists (30.3%). Outpatient treatment for PE increased from 4% in 2005 to 23% in 2019. Future Plans TROLL is a population-based ongoing registry that represents a valuable source of real-world data that will be used for future research on the management and outcomes of VTE.

• Tavoly, Mazdak; Asady, Elia; Wik, Hilde Skuterud & Ghanima, Waleed (2022). Measuring Quality of Life after Venous Thromboembolism: Who, When, and How? Seminars in Thrombosis and Hemostasis. ISSN 0094-6176. doi: 10.1055/s-0042-1754390. Fulltekst i vitenarkiv
• Geersing, Geert-Jan; Takada, Toshihiko; Klok, Frederikus A.; Büller, Harry R.; Courtney, D. Mark & Freund, Yonathan [Vis alle 23 forfattere av denne artikkelen] (2022). Ruling out pulmonary embolism across different healthcare settings: A systematic review and individual patient data meta-analysis. PLoS Medicine. ISSN 1549-1277. 19(1). doi: 10.1371/journal.pmed.1003905. Fulltekst i vitenarkiv Vis sammendrag

  Background The challenging clinical dilemma of detecting pulmonary embolism (PE) in suspected patients is encountered in a variety of healthcare settings. We hypothesized that the optimal diagnostic approach to detect these patients in terms of safety and efficiency depends on underlying PE prevalence, case mix, and physician experience, overall reflected by the type of setting where patients are initially assessed. The objective of this study was to assess the capability of ruling out PE by available diagnostic strategies across all possible settings. Methods and findings We performed a literature search (MEDLINE) followed by an individual patient data (IPD) meta-analysis (MA; 23 studies), including patients from self-referral emergency care (n = 12,612), primary healthcare clinics (n = 3,174), referred secondary care (n = 17,052), and hospitalized or nursing home patients (n = 2,410). Multilevel logistic regression was performed to evaluate diagnostic performance of the Wells and revised Geneva rules, both using fixed and adapted D-dimer thresholds to age or pretest probability (PTP), for the YEARS algorithm and for the Pulmonary Embolism Rule-out Criteria (PERC). All strategies were tested separately in each healthcare setting. Following studies done in this field, the primary diagnostic metrices estimated from the models were the “failure rate” of each strategy—i.e., the proportion of missed PE among patients categorized as “PE excluded” and “efficiency”—defined as the proportion of patients categorized as “PE excluded” among all patients. In self-referral emergency care, the PERC algorithm excludes PE in 21% of suspected patients at a failure rate of 1.12% (95% confidence interval [CI] 0.74 to 1.70), whereas this increases to 6.01% (4.09 to 8.75) in referred patients to secondary care at an efficiency of 10%. In patients from primary healthcare and those referred to secondary care, strategies adjusting D-dimer to PTP are the most efficient (range: 43% to 62%) at a failure rate ranging between 0.25% and 3.06%, with higher failure rates observed in patients referred to secondary care. For this latter setting, strategies adjusting D-dimer to age are associated with a lower failure rate ranging between 0.65% and 0.81%, yet are also less efficient (range: 33% and 35%). For all strategies, failure rates are highest in hospitalized or nursing home patients, ranging between 1.68% and 5.13%, at an efficiency ranging between 15% and 30%. The main limitation of the primary analyses was that the diagnostic performance of each strategy was compared in different sets of studies since the availability of items used in each diagnostic strategy differed across included studies; however, sensitivity analyses suggested that the findings were robust. Conclusions The capability of safely and efficiently ruling out PE of available diagnostic strategies differs for different healthcare settings. The findings of this IPD MA help in determining the optimum diagnostic strategies for ruling out PE per healthcare setting, balancing the trade-off between failure rate and efficiency of each strategy.

Se alle arbeider i NVA

• Drivet, Elsa Maria Caroline; Tsykunova, Galina; Egner, Ingrid Marie; Lund, Katrine Persgård; Goll, Guro Løvik & Tran, Hoa Thi Thyuet [Vis alle 11 forfattere av denne artikkelen] (2026). Interleukin-17-associated inflammation in non-responders and B-cell remodeling after daratumumab in refractory immune thrombocytopenia. Haematologica. ISSN 0390-6078. doi: 10.3324/haematol.2026.301032. Fulltekst i vitenarkiv Vis sammendrag

  Not available.

• Haukeland-Parker, Stacey; Jervan, Øyvind; Ghanima, Waleed; Spruit, Martijn A.; Hubin, Aliaksandr & Gleditsch, Jostein [Vis alle 10 forfattere av denne artikkelen] (2026). The effect of exercise-based rehabilitation on objectively measured daily physical activity levels in patients with persistent dyspnoea after pulmonary embolism. Fulltekst i vitenarkiv
• Haukeland-Parker, Stacey; Jervan, Øyvind; Ghanima, Waleed; Spruit, Martijn A.; Holst, Rene & Gleditsch, Jostein [Vis alle 13 forfattere av denne artikkelen] (2026). Exercise capacity, dyspnoea and health-related quality of life six months after exercise- based rehabilitation in patients with persistent dyspnea following pulmonary embolism. Fulltekst i vitenarkiv
• Kazaryan, Airazat M.; Hagve, Martin Iversen; Augestad, Knut Magne; Nordby, Tom; Edwin, Bjørn von Gohren & Ghanima, Waleed (2025). Academic writing in medicine and healthcare. Frontiers in Medicine. 12. doi: 10.3389/fmed.2025.1617752. Fulltekst i vitenarkiv Vis sammendrag

  The article highlights factors that can motivate doctors to do medical research. Various types of medical publications are presented. In addition, prerequisites that can contribute to successful publication are described. An overview of trends in research publication is given as well as an explanation of the terms discovery and innovation. The role and importance of research and scientific writing for progress in medicine and healthcare are discussed here. The connection between medical practice and research is also highlighted. Not least, the need for support from supervisors and management in the research and publication process is highlighted.

• Jørgensen, Camilla Tøvik & Ghanima, Waleed (2025). Hvor god effekt har kompresjonsstrømper mot posttrombotisk syndrom? Sykepleien Forskning. ISSN 1890-2936. s. 103176–103176. doi: 10.4220/sykepleiens.2025.103176. Fulltekst i vitenarkiv
• Garabet, Lamya Samir Noori; Ghanima, Waleed; Bussel, James; Tran, Hoa Thi Tuyet; Brodin, Ellen Elisabeth & Mathisen, Åse-Berit [Vis alle 10 forfattere av denne artikkelen] (2025). Increased ultra-large von Willebrand factor multimers in immune thrombocytopenia. British Journal of Haematology. ISSN 0007-1048. 207(2), s. 657–661. doi: 10.1111/bjh.20205. Fulltekst i vitenarkiv
• Kazaryan, Airazat M.; Hagve, Martin Iversen; Mala, Tom; Augestad, Knut Magne; Nordby, Tom & Edwin, Bjørn von Gohren [Vis alle 7 forfattere av denne artikkelen] (2024). Forskning og vitenskaplig skriving 3. Formidling av forskningen i moderne tid – bedre tilgang, nye medier og fagfellerollen. Kirurgen. ISSN 1504-8888. 4, s. 238–240. Fulltekst i vitenarkiv Vis sammendrag

  Denne artikkelserien som består av tre kronikker belyser faktorer som kan motivere til medisinsk forskning. Ulike typer av medisinske publikasjoner framstilles. I tillegg beskrives forutsetninger som kan bidra til vellykket publisering. Det gis en oversikt over trender i forskningspublisering, samt forklaring av betegnelsene oppdagelse og innovasjon. Her drøftes også forskningen og den vitenskapelige skrivningens rolle og betydning for framgangen innen medisin og helsevesen, og videre belyses sammenhengen mellom medisinsk praksis og forskning. Ikke minst poengteres behov om støtte fra veileder og ledelse i forsknings- og publiseringsprosessen. Kronikk 3 omhandler tema «Formidling av forskningen»

• Kazaryan, Airazat M.; Mala, Tom; Hagve, Martin Iversen; Augestad, Knut Magne; Nordby, Tom & Ghanima, Waleed [Vis alle 7 forfattere av denne artikkelen] (2024). Forskning og vitenskaplig skriving 2. Fra ide til ferdig artikkel. Kirurgen. ISSN 1504-8888. 4, s. 234–237. Fulltekst i vitenarkiv Vis sammendrag

  Denne artikkelserien, som består av tre kronikker, belyser faktorer som kan motivere til medisinsk forskning. Ulike typer av medisinske publikasjoner framstilles. I tillegg beskrives forutsetninger som kan bidra til vellykket publisering. Det gis en oversikt over trender i forskningspublisering samt forklaring av betegnelsene oppdagelse og innovasjon. Her drøftes også forskningen og den vitenskapelige skrivningens rolle og betydning for framgangen innen medisin og helsevesen, og videre belyses sammenhengen mellom medisinsk praksis og forskning. Ikke minst poengteres behov om støtte fra veileder og ledelse i forsknings- og publiseringsprosessen. Kronikk 2 inkluderer tema «Fra idé til ferdig artikkel»

• Tønne, Brita; Pedersen, Marit Holmefjord; Fronas, Synne G.; Jørgensen, Camilla Tøvik; Amundsen, Erik Koldberg & Mæhlum, Julie Berge [Vis alle 10 forfattere av denne artikkelen] (2024). Corrigendum to “Evaluation of the diagnostic performance of three D-dimer assays in patients with suspected deep vein thrombosis: STA-Liatest D-Di Plus, Tina-quant D-Dimer Gen. 2, and INNOVANCE D-Dimer” [Thrombosis Update, 13(2023) 100147](S2666572723000184)(10.1016/j.tru.2023.100147). Thrombosis Update. 15. doi: 10.1016/j.tru.2024.100178. Fulltekst i vitenarkiv
• Kazarian, Airazat; Mala, Tom; Hagve, Martin Iversen; Augestad, Knut Magne; Nordby, Tom & Edwin, Bjørn von Gohren [Vis alle 7 forfattere av denne artikkelen] (2024). Forskning og vitenskaplig skriving 1. Hvordan komme igang ? Kirurgen. ISSN 1504-8888. Fulltekst i vitenarkiv
• Haukeland-Parker, Stacey Marie; Jervan, Øyvind; Ghanima, Waleed; Spruit, Martijn A.; Holst, Rene & Gleditsch, Jostein [Vis alle 8 forfattere av denne artikkelen] (2024). The effect of exercise-based rehabilitation on daily physical activity following pulmonary embolism. Fulltekst i vitenarkiv
• Larsen, Trine-Lise; Ghanima, Waleed; Sandset, Per Morten; Frøen, Hege; Jacobsen, Eva-Marie & Torfoss, Dag [Vis alle 7 forfattere av denne artikkelen] (2023). Faktor Xa-hemmere til forebygging og behandling av venøs tromboembolisme ved kreft. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(1). doi: 10.4045/tidsskr.22.0228. Fulltekst i vitenarkiv Vis sammendrag

  Venøs tromboembolisme er en hyppig komplikasjon ved kreftsykdom. Prevalensen varierer med krefttype og øker proporsjonalt med kreftstadium. De siste 15–20 årene har lavmolekylært heparin vært anbefalt som førstevalg ved behandling. Nye internasjonale retningslinjer åpner nå for å bruke direkte faktor Xa-hemmere både som profylakse mot og behandling av venøs tromboembolisme. Profylakse bør som hovedregel kun startes hos dem med moderat til høy risiko. Før man starter med antikoagulasjonsbehandling må man vurdere blødningsrisikoen. Både tromboseutvikling og blødningsrisiko kan endre seg og bør derfor vurderes fortløpende. I denne kliniske oversikten diskuteres bruk av antikoagulasjonsbehandling hos kreftpasienter, med særlig vekt på bruk av direkte faktor Xa-hemmere.

• Ghanima, Waleed; Hill, Quentin A. & Kuter, David J. (2023). ITP definitions: Time for an update. British Journal of Haematology. ISSN 0007-1048. 201(5), s. 1005–1006. doi: 10.1111/bjh.18791. Fulltekst i vitenarkiv
• Jervan, Øyvind; Haukeland-Parker, Stacey Marie; Gleditsch, Jostein; Tavoly, Mazdak; Klok, Frederikus A. & Steine, Kjetil [Vis alle 14 forfattere av denne artikkelen] (2023). Rehabilitation to improve exercise capacity and quality of life after pulmonary embolism. Fulltekst i vitenarkiv
• Haukeland-Parker, Stacey Marie; Jervan, Øyvind; Ghanima, Waleed; Spruit, Martijn A.; Tavoly, Mazdak & Gleditsch, Jostein [Vis alle 7 forfattere av denne artikkelen] (2023). Objectively measured physical activity in patients after pulmonary embolism and its clinical correlates. Fulltekst i vitenarkiv
• Mohamad, Hodo; Frønæs, Synne Grønvold; Jørgensen, Camilla Tøvik; Tavoly, Mazdak; Garabet, Lamya Samir Noori & Ghanima, Waleed (2022). The effect of rivaroxaban on the diagnostic value of D-dimer in patients with suspected deep vein thrombosis. Thrombosis Research. ISSN 0049-3848. 216, s. 22–24. doi: 10.1016/j.thromres.2022.05.017. Fulltekst i vitenarkiv
• Larsen, Trine-Lise; Garresori, Herish; Brekke, Jorunn; Enden, Tone Rønnaug; Frøen, Hege & Jacobsen, Eva-Marie [Vis alle 15 forfattere av denne artikkelen] (2022). “Low dose apixaban as secondary prophylaxis of venous thromboembolism in cancer patients - 30 months follow-up”: Reply. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. 20(8), s. 1937–1939. doi: 10.1111/jth.15774. Fulltekst i vitenarkiv
• Moulis, Guillaume; Cooper, Nichola; Ghanima, Waleed; Gonzalez-Lopez, Tomas Jose; Kühne, Thomas & Lozano, Maria Luisa [Vis alle 17 forfattere av denne artikkelen] (2022). Registries in immune thrombocytopenia (ITP) in Europe: the European Research Consortium on ITP (ERCI) network. British Journal of Haematology. ISSN 0007-1048. doi: 10.1111/bjh.18111. Fulltekst i vitenarkiv
• Holme, Pål Andre; Ghanima, Waleed; Wik, Hilde Skuterud; Jacobsen, Eva-Marie & Fløisand, Yngvar (2022). Koagulasjonsforstyrrelser. I Birkeland, Kåre Inge; Gullestad, Lars & Aabakken, Lars (Red.), Indremedisin I. Fagbokforlaget. ISSN 9788245043365. s. 447–458. Fulltekst i vitenarkiv

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