Publications
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Dybedal, Ingunn; Iversen, Nina; Jacobsen, Anne Flem; Bjørge, Line; Chaireti, Roza & Henriksson, Carola Elisabeth
[Show all 12 contributors for this article]
(2025).
Hereditary antithrombin deficiency and venous thrombosis in pregnancy–results of a retrospective multicenter study.
Journal of Thrombosis and Haemostasis.
ISSN 1538-7933.
23(9),
p. 2807–2818.
doi:
10.1016/j.jtha.2025.03.001.
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Background
The optimal anticoagulant regimen to prevent pregnancy-related venous thrombosis (VT) in women with antithrombin (AT) deficiency is unknown.
Objectives
This study aims to identify optimal doses of low-molecular-weight heparin (LMWH) to prevent pregnancy-related VT and to investigate if AT concentrate peripartum could reduce postpartum VT in women with AT deficiency.
Methods
This retrospective study includes 115 pregnancies in 57 women with subclassified AT deficiency treated with LMWH in Denmark, Norway, and Sweden (1991-2017).
Results
In pregnancies with high-risk AT deficiency, LMWH doses of <5000 IU/24 h, 5000 to 12 500 IU/24 h, and >12 500 IU/24 h revealed different VT risks (P = .02). The hazard ratios for VT were 1.0 (reference), 0.5 (95% CI [0.1, 2.3]), and 0 (95% CI [0, ∞]), correspondingly. Of the additional risk factors, only previous VT reached statistical significance. In 100 pregnancies with high-risk AT deficiency, 15 VTs occurred in contrast to none in the 15 pregnancies with low-/intermediate-risk AT deficiency. Six of the 12 antepartum VTs occurred before week 9. All had a prior VT, and 5 were hormone-associated. Of these 5, 1 had received a LMWH dose of 7500 IU/24 h and 3 had received a LMWH dose of 10 000 IU/24 h, respectively. AT concentrate, given peripartum in 66 of the 74 term pregnancies, resulted in 1 VT (1.5%). Without AT concentrate (8 pregnancies), 2 VTs occurred (25%; 95% CI [2, 61]). Peripartum hemorrhage (>1000 mL) occurred in 8 (11%) term pregnancies. Six had received therapeutic LMWH doses.
Conclusion
In high-risk AT deficiency pregnancies with previous VT, our results support prophylaxis with high prophylactic doses of LMWH from confirmed pregnancy. Hence, AT concentrate should be given peri-/postpartum
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Røed-Undlien, Henriette; Schultz, Nina Haagenrud; Amundsen, Erik Koldberg; Wollmann, Birgit Malene Tovik; Molden, Espen & Akerkar, Rupali Rajendra
[Show all 7 contributors for this article]
(2024).
Does in vitro hemolysis affect measurements of plasma apixaban concentration by UPLC-MS and anti-Xa assay?
International Journal of Laboratory Hematology (IJLH).
ISSN 1751-5521.
46(5),
p. 946–952.
doi:
10.1111/ijlh.14311.
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Introduction: Hemolytic interference may impact various laboratory tests, including coagulation analyses. Apixaban is the most commonly used direct oral anticoagulant in Norway, and there is lacking knowledge on how apixaban concentration measure- ments might be influenced by hemolysis. Moreover, hemolysis-induced alterations in apixaban levels could potentially impact the risk of bleeding in specific clinical scenar- ios. We wanted to study whether hemolysis would increase apixaban concentration and investigate the impact of hemolytic interference on apixaban concentration measurements. Methods: Blood samples from 20 apixaban-treated patients and 8 healthy controls were hemolyzed in vitro by a freeze method. The degree of hemolysis was measured with plasma free hemoglobin (PfHb) at baseline and two levels of hemolysis. Apixa- ban concentration was measured in plasma using both the chromogenic anti-Xa method and the ultraperformance liquid chromatography mass spectrometry (UPLC-MS). Thrombin generation assay was performed to assess coagulability. Results: UPLC-MS measurements showed a mean concentration change of 1.66% (±3.2%, p = 0.005) and anti-Xa assay showed a mean concentration change of 3.37% (±6.5%, p = 0.09) with increasing hemolysis. Thrombin generation lagtime decreased, and endogenous thrombin potential and peak thrombin increased with increasing hemolysis in both the control group and the apixaban group. Conclusion: Apixaban concentration measurements by anti-Xa assay and UPLC-MS were not affected by hemolysis to a clinically relevant extent. Furthermore, hemolysis did not lead to hypocoagulability when assessed by thrombin generation.
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Røed-Undlien, Henriette; Schultz, Nina Haagenrud; Husebråten, Inger; Wollmann, Birgit Malene Tovik; Akerkar, Rupali Rajendra & Molden, Espen
[Show all 8 contributors for this article]
(2024).
Apixaban removal during emergency surgery for type A acute aortic dissection: a prospective cohort study.
International Journal of Surgery (IJS).
ISSN 1743-9191.
110(12),
p. 7782–7790.
doi:
10.1097/JS9.0000000000002137.
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Background: Acute type A aortic dissection (ATAAD) has a high mortality, and acute aortic repair is the only curative treatment. In patients treated with factor Xa (FXa) inhibitors, the risk of severe disease-related complications such as cardiac tamponade and hemodynamic shock must be balanced against the potential for severe perioperative bleeding. The aim was to study intraoperative changes in plasma levels of the FXa inhibitor apixaban when using hemoadsorption during acute thoracic aortic repair. Materials and methods: This is a single-center prospective cohort study. Eight apixaban-treated patients presenting with ATAAD underwent acute thoracic aortic repair with intraoperative hemoadsorption with CytoSorb. Apixaban concentrations were measured at the start of cardiopulmonary bypass (CPB) and after 5, 15, 30, 60, and 90 min of CPB, at CPB weaning, 30 min after CPB weaning and 24 h postoperatively, using ultraperformance liquid chromatography–mass spectrometry (UPLC-MS). Results: After 30 min of CPB with hemoadsorption, mean apixaban concentration ( ± SD) was reduced by 59% from 108 ( ± 69) μg/l to 44 ( ± 20) μg/l (P = 0.009). There was a further reduction to 37 ( ± 17) μg/l at CPB weaning (P = 0.008). Apixaban concentration displayed an increase to 56 ( ± 29) μg/l 24 h postoperatively (P = 0.01). In-hospital mortality was 25%. The mean 24H chest tube drainage volume was 621 ( ± 136) ml. Conclusion: Intraoperative hemoadsorption lowers apixaban levels in patients undergoing emergency surgery for ATAAD. Further research is needed to determine its impact on perioperative bleeding complications and mortality.
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Fagerhol, Magne Kristoffer; Schultz, Nina Haagenrud; Mirlashari, Mohammad Reza; Wiedmann, Markus; Nissen-Meyer, Lise Sofie Haug & Søraas, Arne Vasli Lund
[Show all 7 contributors for this article]
(2023).
DNase analysed by a novel competitive assay in patients with complications after ChAdOx1 nCoV-19 vaccination and in normal unvaccinated blood donors.
Scandinavian Journal of Immunology.
ISSN 0300-9475.
98(1).
doi:
10.1111/sji.13274.
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Abstract Increased levels of neutrophil extracellular traps (NETs) have been detected in individuals with vaccine complications after the ChAdOx1 nCov vaccine with a correlation between the severity of vaccine side effects and the level of NETosis. DNases may disrupt NETs by degrading their content of DNA, and a balance has been reported between NETs and DNases. Because of this and since the inflammatory marker NETs may be used as a confirmatory test in diagnosing VITT, it is of interest to monitor levels of DNase in patients with increased NETs levels. The current novel rapid DNase ELISA was tested in blood samples of patients with known increased levels of NETs with or without VITT after ChAdOx1 nCoV‐19 vaccination. DNase levels in VITT patients were significantly increased compared with normal unvaccinated blood donors and compared with patients with post‐vaccination symptoms but not VITT. However, since EDTA was found to inhibit DNase, serum and not EDTA‐plasma samples should be applied for DNase testing. The novel DNase assay may serve as a supplementary test to the NETs test when analysing samples from patients with suspected increased NETs levels.
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Tarasco, Erika; Krogh, Anne Sophie von; Hrdlickova, Radomira; Braschler, Thomas R.; Iwaniec, Teresa & Knöbl, Paul N.
[Show all 21 contributors for this article]
(2022).
Hereditary thrombotic thrombocytopenic purpura and COVID-19: Impacts of vaccination and infection in this rare disease.
Research and Practice in Thrombosis and Haemostasis (RPTH).
6(7).
doi:
10.1002/rth2.12814.
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1 Introduction Severe COVID‐19 is associated with an important increase of von Willebrand factor and mild lowering of ADAMTS13 activity that may, in the presence of a strong inflammatory reaction, increase the risk of acute thrombotic thrombocytopenic purpura (TTP). Although acute episodes of immune‐mediated TTP associated with COVID‐19 or SARS‐CoV‐2 vaccination have been reported, data about clinical evolution of hereditary TTP (hTTP) during the pandemic are scarce. 2 Method We conducted a survey among adult patients of the International Hereditary TTP Registry about SARS‐CoV‐2 vaccination, COVID‐19, and occurrence of acute hTTP episodes. 3 Results Of 122 adult hTTP patients invited to participate, 86 (70.5%) responded. Sixty‐five had been vaccinated (75.6%), of which 14 had received in addition a booster, resulting in 139 individual vaccine shots. Although vaccinations in patients on plasma prophylaxis were done within 1 week of the last plasma infusion, all 23 patients treated with plasma on demand were vaccinated without prior plasma infusions. One patient on uninterrupted weekly plasma infusions presented within 3 days from his second vaccination with neurological symptoms and computed tomography scan 9 days later showed subacute ischemic/hemorrhagic frontal lobe infarction. A second male patient developed acute myocarditis after his second dose of mRNA‐1273 vaccine. Twelve (14%) patients had COVID‐19, associated with an acute hTTP episode in three of them: one patient had a transient ischemic attack, one a stroke, and a pregnant woman was hospitalized to intensify plasma treatment. 4 Discussion The risk of an acute episode triggered by COVID‐19 seems higher than following vaccination in hTTP patients, who can be safely vaccinated against SARS‐CoV‐2.
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Schultz, Nina Haagenrud; Søraas, Arne Vasli; Sørvoll, Ingvild Hausberg; Akkøk, Cigdem Ahaein; Vetlesen, Annette & Jagjit, Bhamra Singh
[Show all 13 contributors for this article]
(2022).
Vaccine associated benign headache and cutaneous hemorrhage after ChAdOx1 nCoV-19 vaccine: A cohort study.
Journal of Stroke & Cerebrovascular Diseases.
ISSN 1052-3057.
32(1).
doi:
10.1016/j.jstrokecerebrovasdis.2022.106860.
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Objectives Fatal complications have occurred after vaccination with ChAdOx1 nCoV-19, a vaccine against Covid-19. Vaccine-induced immune thrombotic thrombocytopenia (VITT) with severe outcome is characterized by venous thrombosis, predominantly in cerebral veins, thrombocytopenia and anti-PF4/polyanion antibodies. Prolonged headaches and cutaneous hemorrhages, frequently observed after the ChAdOx1 nCoV-19 vaccine, have therefore caused anxiety among vaccinees. We investigated whether these symptoms represent a mild form of VITT, with a potential for aggravation, e.g. in case of a second vaccination dose, or a different entity of vaccine complications<p> <p>Materials and methods We included previously healthy individuals who had a combination of headache and spontaneous severe cutaneous hemorrhages emerging after the 1st dose of the ChAdOx1 nCoV-19 vaccine. Twelve individuals were found to meet the inclusion criteria, and a phone interview, cerebral MRI, assessment of platelet counts, anti PF4/polyanion antibodies and other laboratory tests were performed. <p>Results None of the symptomatic vaccinees had cerebral vein thrombosis, hemorrhage or other pathology on MRI. Platelet counts were within normal range and no anti-PF4/polyanion platelet activating antibodies were found. Moreover, vasculitis markers, platelet activation markers and thrombin generation were normal. Furthermore, almost all symptoms resolved, and none had recurrence of symptoms after further vaccination with mRNA vaccines against Covid-19. <p>Conclusions The combination of headaches and subcutaneous hemorrhage did not represent VITT and no other specific coagulation disorder or intracranial pathology was found. However, symptoms initially mimicking VITT demand vigilance and low threshold for a clinical evaluation combined with platelet counts and D–dimer.
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Hetland, Geir; Fagerhol, Magne Kristoffer; Wiedmann, Markus; Søraas, Arne Vasli; Mirlashari, Mohammad Reza & Nissen-Meyer, Lise Sofie Haug
[Show all 9 contributors for this article]
(2022).
Elevated NETs and Calprotectin Levels after ChAdOx1 nCoV-19 Vaccination Correlate with the Severity of Side Effects.
Vaccines.
10(8).
doi:
10.3390/vaccines10081267.
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ChAdOx1 nCoV-19 vaccination has been associated with the rare side effect; vaccine-induced immune thrombotic thrombocytopenia (VITT). The mechanism of thrombosis in VITT is associated with high levels of neutrophil extracellular traps (NETs). The present study examines whether key markers for NETosis, such as H3-NETs and calprotectin, as well as syndecan-1 for endotheliopathy, can be used as prognostic factors to predict the severity of complications associated with ChAdOx1 vaccination. Five patients with VITT, 10 with prolonged symptoms and cutaneous hemorrhages but without VITT, and 15 with only brief and mild symptoms after the vaccination were examined. Levels of H3-NETs and calprotectin in the vaccinated individuals were markedly increased in VITT patients compared to vaccinees with milder vaccination-associated symptoms, and a strong correlation (r ≥ 0.745, p < 0.001) was found with severity of vaccination side effects. Syndecan-1 levels were also positively correlated (r = 0.590, p < 0.001) in vaccinees to side effects after ChAdOx1 nCoV-19 vaccination. We hypothesize that the inflammatory markers NETs and calprotectin may be used as confirmatory tests in diagnosing VITT.
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Røed-Undlien, Henriette; Schultz, Nina Haagenrud; Lunnan, Asbjørn; Husebråten, Inger; Wollmann, Birgit Malene Tovik & Molden, Espen
[Show all 7 contributors for this article]
(2022).
In Vitro Apixaban Removal By CytoSorb Whole Blood Adsorber: An Experimental Study.
Journal of Cardiothoracic and Vascular Anesthesia.
ISSN 1053-0770.
36(6),
p. 1636–1644.
doi:
10.1053/j.jvca.2022.01.038.
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Objectives The use of unopposed oral anticoagulants while undergoing cardiothoracic surgery is associated with severe bleeding and increased morbidity. The aim of this experimental study was to examine if the apixaban concentration in reconstituted blood could be reduced in an in vitro setup by the use of CytoSorb whole blood adsorber, and to study how this affected global coagulation assays. Design and Setting An experimental study performed in a laboratory. Participants An in vitro setup with reconstituted whole blood. Interventions Reconstituted whole blood spiked with apixaban circulated in an in vitro circuit with the CytoSorb 300 mL device connected. Measurements and Main Results Blood samples were drawn at 0, 5, 15, 30, 60, and 120 minutes of adsorption. The apixaban concentration was measured at each time point. In addition, the global coagulation assays, thromboelastometry clotting time and thrombin generation, were performed, and the results were compared with baseline values obtained before spiking blood with apixaban. After 30 minutes of adsorption, the mean apixaban concentration was reduced from 414.3 (±69.1) ng/mL to 33 (±11.4) ng/mL. Thrombin generation showed maximum effect after 60 minutes, and the thromboelastometry clotting time was close to baseline values after 120 minutes. Conclusions In this in vitro study, apixaban concentrations were effectively reduced, and the clotting time and thrombin generation assays were normalized by the use of CytoSorb whole blood adsorber.
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Schultz, Nina Haagenrud; Fareed, Jawed & Holme, Pål Andre
(2021).
Investigation of the Optimal Dose aPCC in Reversing the Effect of Factor Xa Inhibitors—An In Vitro Study.
Clinical and applied thrombosis/hemostasis.
ISSN 1076-0296.
27,
p. 1–7.
doi:
10.1177/10760296211021156.
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Factor (F) Xa inhibitors are safe and effective alternatives to warfarin. There are concerns about the lack of a reversal strategy in case of serious bleeds or need for emergency surgery in situations when the antidote andexanet alfa is not available. Factor concentrates are widely used, but there are few clinical studies regarding the reversal effect of activated prothrombin complex concentrate (aPCC). Because of the feared thrombogenicity, administration of the lowest effective dose would be desirable. To determine the lowest concentration of aPCC sufficient to reverse the effect of rivaroxaban and apixaban. Blood from 18 healthy volunteers were supplemented with apixaban or rivaroxaban. aPCC was added to obtain 10 different concentrations ranging from 0.08-1.60 U/mL. Thromboelastometry and thrombin generation assay were used to assess the reversal effect. aPCC concentrations of 0.08 and 0.16 U/mL restored thromboelastometry clotting time to baseline in apixaban (P = 1.0) and rivaroxaban (P = 1.0)-containing samples, respectively. The concentrations 0.08 U/mL (P = 0.5) and 0.24 U/mL (P = 0.2) were sufficient to restore thrombin generation. Concentrations of 0.56 U/mL and higher, caused significantly higher ETP than baseline in apixaban-containing samples (P < 0.05). aPCC concentrations lower than previously reported were effective in reversing the effect of FXa inhibitors in vitro.
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Wiedmann, Markus; Skattør, Thor Håkon; Stray-Pedersen, Arne; Romundstad, Luis Georg; Antal, Ellen-Ann & Marthinsen, Pål Bache
[Show all 16 contributors for this article]
(2021).
Vaccine Induced Immune Thrombotic Thrombocytopenia Causing a Severe Form of Cerebral Venous Thrombosis With High Fatality Rate: A Case Series.
Frontiers in Neurology.
12:721146,
p. 1–7.
doi:
10.3389/fneur.2021.721146.
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During a 2-week period, we have encountered five cases presenting with the combination of cerebral venous thrombosis (CVT), intracerebral hemorrhage and thrombocytopenia. A clinical hallmark was the rapid and severe progression of disease in spite of maximum treatment efforts, resulting in fatal outcome in for 4 out of 5 patients. All cases had received ChAdOx1 nCov-19 vaccine 1–2 weeks earlier and developed a characteristic syndrome thereafter. The rapid progressive clinical course and high fatality rate of CVT in combination with thrombocytopenia in such a cluster and in otherwise healthy adults is a recent phenomenon. Cerebral autopsy findings were those of venous hemorrhagic infarctions and thrombi in dural venous sinuses, including thrombus material apparently rich in thrombocytes, leukocytes and fibrin. Vessel walls were free of inflammation. Extra-cerebral manifestations included leech-like thrombi in large veins, fibrin clots in small venules and scattered hemorrhages on skin and membranes. CVT with thrombocytopenia after adenovirus vectored COVID-19 vaccination is a new clinical syndrome that needs to be recognized by clinicians, is challenging to treat and seems associated with a high mortality rate.
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Schultz, Nina Haagenrud; Glosli, Heidi; Bjørnsen, Stine & Holme, Pål Andre
(2021).
The effect of emicizumab and bypassing agents in patients with hemophilia – An in vitro study.
Research and Practice in Thrombosis and Haemostasis (RPTH).
5(5),
p. 1–7.
doi:
10.1002/rth2.12561.
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Background Emicizumab is a nonfactor replacement therapy for hemophilia A (HA) and is a bispecific monoclonal antibody mimicking factor VIII by binding both factors IXa and X. Although it reduces the frequency of bleeding episodes, there is still need for bypassing agents in case of breakthrough bleeds or need for surgery. The HAVEN-1 study showed an increased risk of thrombotic events and episodes of thrombotic microangiopathic hemolytic anemia with simultaneous treatment with emicizumab and activated prothrombin complex concentrate (aPCC) in high doses (>100 U/kg daily) for more than 1 day, and it is suspected that these drugs have a synergistic hemostatic effect. Objectives To evaluate and compare the hemostatic effect of bypassing agents in vitro in people with HA before and after starting treatment with emicizumab to investigate if dosing should be adjusted to optimize treatment. Patients/Methods Blood collected before and after start of treatment with emicizumab was spiked with aPCC and recombinant factor VIIa (rFVIIa) at different concentrations. The effect of aPCC and rFVIIa was assessed by thrombin generation assay and thromboelastometry. Results Six people with HA were included. The response to aPCC in thrombin generation after starting emicizumab was significantly stronger than before. This synergistic effect was less pronounced for emicizumab and rFVIIa. Furthermore, aPCC shortened thromboelastometry clotting time more effectively after starting emicizumab than before starting this treatment. Conclusions We demonstrated a strong synergistic effect of emicizumab and aPCC and a similar but less pronounced effect of rFVIIa in people treated with emicizumab.
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Schultz, Nina Haagenrud; Sørvoll, Ingvild Hausberg; Michelsen, Annika; Munthe, Ludvig Andre; Lund-Johansen, Fridtjof & Ahlen, Maria Therese
[Show all 11 contributors for this article]
(2021).
Thrombosis and thrombocytopenia after CHADOX1 NCoV-19 vaccination.
New England Journal of Medicine.
ISSN 0028-4793.
384(22),
p. 2124–2130.
doi:
10.1056/NEJMoa2104882.
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We report findings in five patients who presented with venous thrombosis and thrombocytopenia 7 to 10 days after receiving the first dose of the ChAdOx1 nCoV-19 adenoviral vector vaccine against coronavirus disease 2019 (Covid-19). The patients were health care workers who were 32 to 54 years of age. All the patients had high levels of antibodies to platelet factor 4–polyanion complexes; however, they had had no previous exposure to heparin. Because the five cases occurred in a population of more than 130,000 vaccinated persons, we propose that they represent a rare vaccine-related variant of spontaneous heparin-induced thrombocytopenia that we refer to as vaccine-induced immune thrombotic thrombocytopenia.
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Holm, Sverre; Kared, Hassen; Michelsen, Annika Elisabet; Kong, Xiang Yi; Dahl, Tuva Børresdatter & Schultz, Nina Haagenrud
[Show all 21 contributors for this article]
(2021).
Immune complexes, innate immunity, and NETosis in ChAdOx1 vaccine-induced thrombocytopenia.
European Heart Journal.
ISSN 0195-668X.
42(39),
p. 4064–4072.
doi:
10.1093/eurheartj/ehab506.
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Aims - We recently reported five cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) 7–10 days after receiving the first dose of the ChAdOx1 nCoV-19 adenoviral vector vaccine against corona virus disease 2019 (COVID-19). We aimed to investigate the pathogenic immunological responses operating in these patients.<p> <p>Methods and results - We assessed circulating inflammatory markers by immune assays and immune cell phenotyping by flow cytometry analyses and performed immunoprecipitation with anti-platelet factor (PF)4 antibody in plasma samples followed by mass spectrometry from all five patients. A thrombus was retrieved from the sinus sagittal superior of one patient and analysed by immunohistochemistry and flow cytometry. Precipitated immune complexes revealed multiple innate immune pathway triggers for platelet and leucocyte activation. Plasma contained increased levels of innate immune response cytokines and markers of systemic inflammation, extensive degranulation of neutrophils, and tissue and endothelial damage. Blood analyses showed activation of neutrophils and increased levels of circulating H3Cit, dsDNA, and myeloperoxidase–DNA complex. The thrombus had extensive infiltration of neutrophils, formation of neutrophil extracellular traps (NETs), and IgG deposits.<p> <p>Conclusions - The results show that anti-PF4/polyanion IgG-mediated thrombus formation in VITT patients is accompanied by a massive innate immune activation and particularly the fulminant activation of neutrophils including NETosis. These results provide novel data on the immune response in this rare adenoviral vector-induced VITT.
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Schultz, Nina Haagenrud; Lundblad, Runar & Holme, Pål Andre
(2018).
Activated prothrombin complex concentrate to reverse the factor Xa inhibitor (apixaban) effect before emergency surgery: A case series.
Journal of Medical Case Reports.
12(138).
doi:
10.1186/s13256-018-1660-9.
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Background The lack of an antidote against factor Xa inhibitors in case of major bleeding or need for urgent surgery is a concern to clinicians. Guidelines on managing major bleeding in patients under anticoagulation with a factor Xa inhibitor suggest several hemostatic agents to reverse the effect, but there is no consensus regarding the choice of drug or appropriate dose. The ability of prothrombin complex concentrate, activated prothrombin complex concentrate, and recombinant factor VIIa to reverse the effect of factor Xa inhibitors has been evaluated in animal studies, in vitro studies, and healthy volunteers, but not yet in randomized clinical studies. Case presentation We report a consecutive case series of patients under factor Xa inhibitor (apixaban) treatment who received activated prothrombin complex concentrate to reverse the anticoagulation effect before emergency cardiovascular surgery. Patient 1, a 63-year-old white man, was operated with replacement of the aortic valve; patient 2, a 65-year-old white man, underwent heart transplantation; patient 3, a 68-year-old white man, was operated for acute type A aortic dissection. They all received activated prothrombin complex concentrate 25 IU/kg immediately before surgery. In two of the cases, the global coagulation assay thromboelastometry (ROTEM™) was performed before and after administering activated prothrombin complex concentrate. The ROTEM™ clotting time was reduced from 1900 seconds to 740 seconds and from 1482 to 807 seconds, respectively, after administering a dose of 25 IU/kg activated prothrombin complex concentrate. The apixaban concentration before reversal was within the range considered to be the therapeutic level in all cases. No bleeding complications occurred during surgery, but one case was complicated with bleeding postoperatively. No thromboembolic complications were observed during or after surgery. Conclusions Activated prothrombin complex concentrate 25 IU/kg reversed the anticoagulation effect of apixaban effectively and safely before emergency cardiovascular surgery.
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Schultz, Nina Haagenrud; Holme, Pål Andre; Bjørnsen, Stine; Henriksson, Carola; Sandset, Per Morten & Jacobsen, Eva-Marie
(2018).
The impact of rivaroxaban on primary hemostasis in patients with venous thrombosis.
Platelets.
ISSN 0953-7104.
doi:
10.1080/09537104.2018.1557618.
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Schultz, Nina Haagenrud; Tran, Hoa Thi Tuyet; Bjørnsen, Stine; Henriksson, Carola; Sandset, Per Morten & Holme, Pål Andre
(2017).
The reversal effect of prothrombin complex concentrate (PCC), activated PCC and recombinant activated factor VII against anticoagulation of Xa inhibitor.
Thrombosis Journal.
15(1).
doi:
10.1186/s12959-017-0129-1.
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Background An increasing number of patients are treated with direct-acting oral anticoagulants (DOACs), but the optimal way to reverse the anticoagulant effect is not known. Specific antidotes are not available and prothrombin complex concentrate (PCC), activated PCC (aPCC) and recombinant factor VIIa (rFVIIa) are variously used as reversal agents in case of a major bleeding. We aimed to determine the most effective haemostatic agent and dose to reverse the effect of rivaroxaban in blood samples from patients taking rivaroxaban for therapeutic reasons. Methods Blood samples from rivaroxaban-treated patients (n = 50) were spiked with PCC, aPCC and rFVIIa at concentrations imitating 80%, 100% and 125% of suggested therapeutic doses. The reversal effect was assessed by thromboelastometry in whole blood and a thrombin generation assay (TGA) in platelet-poor plasma. Samples from healthy subjects (n = 40) were included as controls. Results In thromboelastometry measurements, aPCC and rFVIIa had a superior effect to PCC in reversing the rivaroxaban-induced lenghtening of clotting time (CT). aPCC was the only haemostatic agent that shortened the CT down to below the control level. Compared to healthy controls, patients on rivaroxaban also had a prolonged lag time and decreased peak concentration, velocity index and endogenous thrombin potential (ETP) in platelet-poor plasma. aPCC reversed these parameters more effectively than rFVIIa and PCC. There were no differences in efficacy between 80%, 100% and 125% doses of aPCC. Conclusions aPCC seems to reverse the anticoagulant effect of rivaroxaban more effectively than rFVIIa and PCC by evaluation with thromboelastometry and TGA in vitro.
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Schultz, Nina Haagenrud; Tran, Hoa Thi Tuyet; Bjørnsen, Stine; Henriksson, Carola Elisabeth; Sandset, Per Morten & Holme, Pål Andre
(2017).
The reversal effect of prothrombin complex concentrate (PCC), activated PCC and recombinant activated factor VII in apixaban-treated patients in vitro.
Research and Practice in Thrombosis and Haemostasis (RPTH).
1(1),
p. 49–56.
doi:
10.1002/rth2.12015.
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Røed-Undlien, Henriette; Schultz, Nina Haagenrud; Lunnan, Asbjørn; Husebråten, Inger Marie; Wollmann, Birgit Malene Tovik & Molden, Espen
[Show all 7 contributors for this article]
(2024).
Corrigendum to < IN-VITRO APIXABAN REMOVAL BY CYTOSORB® WHOLE BLOOD ADSORBER. AN EXPERIMENTAL STUDY.> <[Journal of Cardiothoracic and Vascular Anesthesia 36/6 (2024) 1636 – 1644]> (Journal of Cardiothoracic and Vascular Anesthesia (2022) 36(6) (1636–1644), (S1053077022000726), (10.1053/j.jvca.2022.01.038)).
Journal of Cardiothoracic and Vascular Anesthesia.
ISSN 1053-0770.
doi:
10.1053/j.jvca.2024.03.039.
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Schultz, Nina Haagenrud; Bechensteen, Anne Grete; Tjønnfjord, Eirik; Akkøk, Cigdem Ahaein & Berg, Marte Holmboe
(2023).
Ny interessegruppe for rødcellesykdommer.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
143(3).
doi:
10.4045/tidsskr.22.0731.
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Apr. 10, 2026 3:37 PM
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Apr. 10, 2026 3:37 PM
