Pål Andre Holme

• Andersen, May-Linn Fauske; Holme, Pål Andre & Tjønnfjord, Geir Erland (2019). Kirurgiske inngrep hos pasienter med alvorlig blødersykdom 1997–2014. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  139(8), s 709- 712 . doi: 10.4045/tidsskr.18.0592 Show summary

  BAKGRUNN Som følge av god medisinsk behandling er forventet levealder hos pasienter med alvorlig blødersykdom nå nærmest normal. Det medfører et økende behov for behandling av sykdom relatert til livsstil og økt levealder. Vi beskriver kirurgi hos pasienter med alvorlig blødersykdom i perioden 1997–2014. MATERIALE OG METODE Data ble hentet fra registeret knyttet til Nasjonal behandlingstjeneste for kirurgi, intervensjon og avansert diagnostikk ved blødersykdom. Pasientene ble kategorisert etter type blødersykdom og type inngrep i ortopediske og ikke-ortopediske kirurgiske inngrep. RESULTATER 825 kirurgiske inngrep ble utført hos 286 pasienter. Antall inngrep økte fra 21 i 1997 til 66 i 2014. Økningen var knyttet til ikke-ortopediske inngrep: Det ble utført 4 slike inngrep i 1997 og 45 i 2014. Antall ortopediske inngrep varierte en del fra år til år, men viste ingen tydelig trend. FORTOLKNING Med økende levealder sees et økende behov for behandling av sykdommer som ikke er kausalt relatert til blødersykdom. Leger med liten erfaring med pasienter med alvorlig blødersykdom vil måtte forholde seg til sykdom relatert til livsstil og alderdom hos denne pasientgruppen.

• Chowdary, Pratima; Carcao, Manuel; Holme, Pål Andre; Jiménez-Yuste, Victor; Lentz, Steven R.; Møss, Judi; Poulsen, Lone Hvitfeldt; Shen, Chunduo; Tosetto, Alberto; Wheeler, Allison & Santagostino, Elena (2019). Fixed doses of N8-GP prophylaxis maintain moderate-to-mild factor VIII levels in the majority of patients with severe hemophilia A. Research and Practice in Thrombosis and Haemostasis.  ISSN 2475-0379.  3(3), s 542- 554 . doi: 10.1002/rth2.12220
• Curry, Nicola; Albayrak, Canan; Escobar, Miguel; Holme, Pål Andre; Kearney, Susan; Klamroth, Robert; Misgav, Mudi; Negrier, Claude; Wheeler, Allison; Santagostino, Elena; Shima, Midori; Landorph, Andrea; Tønder, Sidsel Marie & Lentz, Steven R. (2019). Once-weekly prophylaxis with glycoPEGylated recombinant factor VIII (N8-GP) in severe haemophilia A: Safety and efficacy results from pathfinder 2 (randomized phase III trial). Haemophilia.  ISSN 1351-8216.  25(3), s 373- 381 . doi: 10.1111/hae.13712 Full text in Research Archive.
• Lalezari, Shadan; Reding, Mark T.; Pabinger, Ingrid; Holme, Pål Andre; Negrier, Claude; Chalasani, Pavani; Shin, Ho-Jin; Wang, Maria; Tseneklidou-Stoeter, Despina & Enriquez, Monika Maas (2019). BAY 94-9027 prophylaxis is efficacious and well tolerated for up to >5 years with extended dosing intervals: PROTECT VIII extension interim results. Haemophilia.  ISSN 1351-8216.  25(6), s 1011- 1019 . doi: 10.1111/hae.13853 Full text in Research Archive.
• Ljungkvist, Marcus; Strandberg, Karin; Berntorp, Erik; Chaireti, Roza; Holme, Pål Andre; Larsen, Ole Halfdan; Lassila, Riita; Jouppila, Annukka; Szanto, Timea & Zetterberg, Eva (2019). Evaluation of a standardized protocol for thrombin generation using the calibrated automated thrombogram: A Nordic study. Haemophilia.  ISSN 1351-8216.  s 1- 9 . doi: 10.1111/hae.13640 Full text in Research Archive.
• Holme, Pål Andre & Tjønnfjord, Geir Erland (2018). Continuous infusion of simoctocog alfa in haemophilia A patients undergoing surgeries. Haemophilia.  ISSN 1351-8216.  s 1- 6 . doi: 10.1111/hae.13625 Full text in Research Archive.
• Qvigstad, Christian; Tait, Robert Cambell; Rauchensteiner, Stephan; Berntorp, Erik; de Moerloose, Philippe; Schutgens, Roger E. & Holme, Pål Andre (2018). The elevated prevalence of risk factors for chronic liver disease among ageing people with hemophilia and implications for treatment. Medicine (Baltimore, Md.).  ISSN 0025-7974.  97:e12551(39), s 1- 7 . doi: 10.1097/MD.0000000000012551 Full text in Research Archive.
• 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
• 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.  ISSN 1752-1947.  12(138) . doi: 10.1186/s13256-018-1660-9
• Yaddehi Gamage, Thilini Hansamali Gamage; Gunnes, Gjermund; Lee, Robert Hugh; Louch, William Edward; Holmgren, Asbjørn; Bruton, Joseph D.; Lengle, Emma; Kolstad, Terje R Selnes; Revold, Tobias; Amundsen, Silja Svanstrøm; Dalen, Knut Tomas; Holme, Pål Andre; Tjønnfjord, Geir Erland; Christensen, Geir Arve; Westerblad, Håkan; Klungland, Arne; Bergmeier, Wolfgang; Misceo, Doriana & Frengen, Eirik (2018). STIM1 R304W causes muscle degeneration and impaired platelet activation in mice. Cell Calcium.  ISSN 0143-4160.  76, s 87- 100 . doi: 10.1016/j.ceca.2018.10.001 Full text in Research Archive. Show summary

  STIM1 and ORAI1 regulate store-operated Ca2+ entry (SOCE) in most cell types, and mutations in these proteins have deleterious and diverse effects. We established a mouse line expressing the STIM1 R304 W gain-of-function mutation causing Stormorken syndrome to explore effects on organ and cell physiology. While STIM1 R304 W was lethal in the homozygous state, surviving mice presented with reduced growth, skeletal muscle degeneration, and reduced exercise endurance. Variable STIM1 expression levels between tissues directly impacted cellular SOCE capacity. In contrast to patients with Stormorken syndrome, STIM1 was downregulated in fibroblasts from Stim1R304W/R304W mice, which maintained SOCE despite constitutive protein activity. In studies using foetal liver chimeras, STIM1 protein was undetectable in homozygous megakaryocytes and platelets, resulting in impaired platelet activation and absent SOCE. These data indicate that downregulation of STIM1 R304 W effectively opposes the gain-of-function phenotype associated with this mutation, and highlight the importance of STIM1 in skeletal muscle development and integrity.

• Berntorp, Erik; Dargaud, Yesim; Hart, Daniel; Lobet, Sébastien; Mancuso, Maria Elisa; d'Oiron, Roseline; Perry, David; Pollard, Debra; van den Berg, Marijke; Blatný, Jan; Chambost, Hervé; Doria, Andrea S.; Holme, Pål Andre; Kaczmarek, Radoslaw; Mantovani, Lorenzo; McLaughlin, Paul; Nanayakkara, Lochana; Petrini, Pia; Sannié, Thomas; Laane, Edward; Maia, Raquel; Dettoraki, Athina; Farrell, Anna; Halimeh, Susan; Raza, Sayma & Taylor, Stephanie (2017). The second Team Haemophilia Education Meeting, 2016, Frankfurt, Germany. European Journal of Haematology.  ISSN 0902-4441.  98, s 1- 15 . doi: 10.1111/ejh.12828
• Holme, Pål Andre; Tjønnfjord, Geir Erland & Batorova, A (2017). Continuous infusion of coagulation factor concentrates during intensive treatment. Haemophilia.  ISSN 1351-8216.  24(1), s 24- 32 . doi: 10.1111/hae.13331
• Osooli, Mehdi; Carlsson, Katarina Steen; Baghaei, Fariba; Holmström, Margareta; Rauchensteiner, Stephan; Holme, Pål Andre; Poulsen, Lone Hvitfeldt; Astermark, Jan & Berntorp, Erik E. (2017). The association between health utility and joint status among people with severe haemophilia A: findings from the KAPPA register. Haemophilia.  ISSN 1351-8216.  23(3), s e180- e187 . doi: 10.1111/hae.13231
• 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.  ISSN 1477-9560.  15(1) . doi: 10.1186/s12959-017-0129-1
• Barratt-Due, Andreas; Fløisand, Yngvar; Lang, Hilde Elisabeth; Kvam, Ann Kristin; Holme, Pål Andre; Bergseth, Grete; Tjønnfjord, Geir Erland & Mollnes, Tom Eirik (2016). Complement activation is a crucial pathogenic factor in catastrophic antiphospholipid syndrome.. Rheumatology.  ISSN 1462-0324. . doi: 10.1093/rheumatology/kew040 Full text in Research Archive.
• Berger, Karin B.; Schopohl, Dorothee; Lowe, Gordon; Holme, Pål Andre; Tait, Robert Cambell; Combescure, Christophe; Rauchensteiner, Stephan & Klamroth, Robert (2016). How to compare cardiovascular disease and risk factors in elderly patients with haemophilia with the general population. Haemophilia.  ISSN 1351-8216.  22(5), s e406- e416 . doi: 10.1111/hae.13069
• HAIG, YLVA; Enden, Tone Rønnaug; Grøtta, Ole Jørgen; Kløw, Nils-Einar; Slagsvold, Carl Erik; Ghanima, Waleed Khalid; Sandvik, Leiv; Hafsahl, Geir; Holme, Pål Andre; Holmen, Lars Olav; Johansen, Anne Mette; Sandbæk, Gunnar & Sandset, Per Morten (2016). Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis (CaVenT): 5-year follow-up results of an open-label, randomised controlled trial. The Lancet Haematology.  ISSN 2352-3026.  3(2), s e64- e71 . doi: 10.1016/S2352-3026(15)00248-3
• Holme, Pål Andre; Combescure, Christophe; Tait, Robert Cambell; Berntorp, Erik E.; Rauchensteiner, Stephan & de Moerloose, Philippe R. (2016). Hypertension, haematuria and renal functioning in haemophilia - a cross-sectional study in Europe. Haemophilia.  ISSN 1351-8216.  22(2), s 248- 255 . doi: 10.1111/hae.12847
• Holstein, K; Batorova, A; Carvalho, M.; Fijnvandraat, K.; Holme, Pål Andre; Kavakli, K; Lambert, T; Rocino, A; Jimenez-Yuste, V & Astermark, J (2016). Current view and outcome of ITI therapy - A change over time?. Thrombosis Research.  ISSN 0049-3848.  148, s 38- 44 . doi: 10.1016/j.thromres.2016.10.015 Show summary

  Introduction Inhibitor development in people with haemophilia is a serious complication that may require intensive and costly interventions. The goal of inhibitor management should be permanent inhibitor eradication through immune tolerance induction (ITI), but well-designed studies are lacking and the management of patients is therefore defined by the experience and views of the clinician. Objectives To explore the current clinical practice and outcome of ITI therapy in Europe and how this may have changed over the last decade, as well as to provide consensus recommendations to guide clinicians in their clinical practice. Methods A survey was conducted among 16 European haemophilia comprehensive care centres to evaluate current ITI treatment regimens and success rates in severe and mild/moderate haemophilia A and haemophilia B. In addition, an updated literature review was performed as guidance for providing recommendations. Results We demonstrated successful inhibitor treatment in 86% of severe haemophilia A patients with low responding (LR) and 59% of patients with high responding (HR) inhibitors. Some new trends in the management of patients with inhibitors were identified, including a tendency to use low-dose regimens (< 50 IU/kg/d) in both children and adults with HR inhibitors possibly based on similar success rates demonstrated in the I-ITI study compared to a high-dose protocol. Data on ITI therapy in mild and moderate haemophilia as well as haemophilia B were limited. Conclusions The outcome of ITI therapy seems to be stable over time, and treatment regimens remain heterogeneous. The use of low dose regimens however is considered more frequently.

• James, PD; Mahlangu, J; Bidlingmaier, C; Mingot-Castellano, María Eva; Chitlur, M; Fogarty, PF; Cuker, A; Mancuso, ME; Holme, Pål Andre; Grabell, J; Satkunam, N; Hopman, WM & Mathew, P (2016). Evaluation of the utility of the ISTH-BAT in haemophilia carriers: a multinational study. Haemophilia.  ISSN 1351-8216.  22(6), s 912- 918 . doi: 10.1111/hae.13089
• Fogarty, Patrick F.; Mancuso, Maria Elisa; Kasthuri, Ram S.; Bidlingmaier, Christoph M.; Chitlur, Meera B.; Gomez, Keith; Holme, Pål Andre; James, Paula D.; Kruse-Jarres, Rebecca; Mahlangu, Johnny Ndoni; Mingot-Castellano, María Eva & Soni, Amit (2015). Presentation and management of acute coronary syndromes among adult persons with haemophilia: Results of an international, retrospective, 10-year survey. Haemophilia.  ISSN 1351-8216.  21(5), s 589- 597 . doi: 10.1111/hae.12652
• Ghanima, Waleed Khalid; Khelif, Abderrahim; Waage, Anders; Michel, Marc; Tjønnfjord, Geir Erland; Romdhan, Neila Ben; Kahrs, Johannes; Darne, Bernadette & Holme, Pål Andre (2015). Rituximab as second-line treatment for adult immune thrombocytopenia (the RITP trial): A multicentre, randomised, double-blind, placebo-controlled trial. The Lancet.  ISSN 0140-6736.  385(9978), s 1653- 1661 . doi: 10.1016/S0140-6736(14)61495-1
• Tran, Hoa Thi Tuyet; Sørensen, B.; Bjørnsen, Stine; Pripp, Are Hugo; Tjønnfjord, Geir Erland & Holme, Pål Andre (2015). Monitoring bypassing agent therapy - a prospective crossover study comparing thromboelastometry and thrombin generation assay. Haemophilia.  ISSN 1351-8216.  21(2), s 275- 283 . doi: 10.1111/hae.12570
• Valentino, Leonard A. & Holme, Pål Andre (2015). Should anti-inhibitor coagulant complex and tranexamic acid be used concomitantly?. Haemophilia.  ISSN 1351-8216.  21(6), s 709- 714 . doi: 10.1111/hae.12723
• Husøy, Magnus Andreas Rognlien; Brinch, Lorentz; Tjønnfjord, Geir Erland; Gedde-Dahl, Tobias Jr.; Heldal, Dag; Holme, Pål Andre; Dybedal, Ingunn; Kolstad, Arne; Akkøk, Cigdem Ahaein; Rollag, Halvor; Gaustad, Peter; Bergan, Stein; Egeland, Torstein; Josefsen, Dag; Kvalheim, Gunnar & Fløisand, Yngvar (2014). Allogen stamcelletransplantasjon hos voksne 1985-2012. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  134(16), s 1569- 1575 . doi: 10.4045/tidsskr.13.1415
• Kristiansen, Annette; Brandt, Linn; Agoritsas, Thomas; Akl, Elie A.; Berge, Eivind; Bondi, Johan Fridtjof; Dahm, Anders Erik A; Granan, Lars-Petter; Halvorsen, Sigrun; Holme, Pål Andre; Jacobsen, Anne Flem; Jacobsen, Eva-Marie; Neumann, Ignacio; Sandset, Per Morten; Sætre, Torunn; Tveit, Arnljot; Vartdal, Trond; Guyatt, Gordon & Vandvik, Per Olav (2014). Adaptation of trustworthy guidelines developed using the GRADE methodology: a novel five-step process. Chest.  ISSN 0012-3692.  146(3), s 727- 734 . doi: 10.1378/chest.13-2828 Show summary

  BACKGROUND: Adaptation of guidelines for use at the national or local level can facilitate their implementation. We developed and evaluated an adaptation process in adherence with standards for trustworthy guidelines and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, aiming for efficiency and transparency. This article is the first in a series describing our adaptation of Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines for a Norwegian setting. METHODS: Informed by the ADAPTE framework, we developed a five-step adaptation process customized to guidelines developed using GRADE: (1) planning, (2) initial assessment of the recommendations, (3) modification, (4) publication, and (5) evaluation. We developed a taxonomy for describing how and why recommendations from the parent guideline were modified and applied a mixed-methods case study design for evaluation of the process. RESULTS: We published the adapted guideline in November 2013 in a novel multilayered format. The taxonomy for adaptation facilitated transparency of the modification process for both the guideline developers and the end users. We excluded 30 and modified 131 of the 333 original recommendations according to the taxonomy and developed eight new recommendations. Unforeseen obstacles related to acquiring a licensing agreement and procuring a publisher resulted in a 9-month delay. We propose modifications of the adaptation process to overcome these obstacles in the future. CONCLUSIONS: This case study demonstrates the feasibility of a novel guideline adaptation process. Replication is needed to further validate the usefulness of the process in increasing the organizational and methodologic efficiency of guideline adaptation.

• Misceo, Doriana; Holmgren, Asbjørn; Louch, William Edward; Holme, Pål Andre; Mizobuchi, Masahiro; Morales, Raul J.; De Paula, André Maues; Stray-Pedersen, Asbjørg; Lyle, Robert; Dalhus, Bjørn; Christensen, Geir Arve; Stormorken, Helge; Tjønnfjord, Geir Erland & Frengen, Eirik (2014). A Dominant STIM1 Mutation Causes Stormorken Syndrome. Human Mutation.  ISSN 1059-7794.  35(5), s 556- 564 . doi: 10.1002/humu.22544
• Tran, Hoa Thi Tuyet; Sørensen, B.; Rea, C.J.; Bjørnsen, Stine; Ueland, Thor; Pripp, Are Hugo; Tjønnfjord, Geir Erland & Holme, Pål Andre (2014). Tranexamic acid as adjunct therapy to bypassing agents in haemophilia A patients with inhibitors. Haemophilia.  ISSN 1351-8216.  20(3), s 369- 375 . doi: 10.1111/hae.12318
• Tran, Hoa Thi Tuyet; Tjønnfjord, Geir Erland & Holme, Pål Andre (2014). Use of thromboelastography and thrombin generation assay to predict clinical phenotype in patients with severe FVII deficiency. Haemophilia.  ISSN 1351-8216.  20(1), s 141- 146 . doi: 10.1111/hae.12256
• Tvedt, Tor Henrik Anderson; Holme, Pål Andre & Bruserud, Øystein (2014). En mann i 80-årene med muskelstivhet og hudblødninger 1058. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  134(10), s 1058- 1061 . doi: 10.4045/tidsskr.13.0817
• WESTBERG, MARIANNE; Paus, Albert Collett; Holme, Pål Andre & Tjønnfjord, Geir Erland (2014). Haemophilic arthropathy: Long-term outcomes in 107 primary total knee arthroplasties. Knee (Oxford).  ISSN 0968-0160.  21(1), s 147- 150 . doi: 10.1016/j.knee.2013.09.010
• Mathijssen, Natascha C.J.; Masereeuw, Roselinde; Holme, Pål Andre; van Kraaij, Marian G.J.; Laros-van Gorkom, Britta A.P.; Peyvandi, Flora & van Heerde, Waander L. (2013). Increased volume of distribution for recombinant activated factor VII and longer plasma-derived factor VII half-life may explain their long lasting prophylactic effect. Thrombosis Research.  ISSN 0049-3848.  132(2), s 256- 262 . doi: 10.1016/j.thromres.2013.05.027
• van Geffen, Mark; Mathijssen, Natascha C.J.; Holme, Pål Andre; Laros-van Gorkom, Britta A.P.; van Kraaij, Marian G.J.; Masereeuw, Roselinde; Peyvandi, Flora & van Heerde, Waander L. (2013). Pharmacodynamics of recombinant activated factor VII and plasma-derived factor VII in a cohort of severe FVII deficient patients. Thrombosis Research.  ISSN 0049-3848.  132(1), s 116- 122 . doi: 10.1016/j.thromres.2013.04.021
• Batorova, A; Holme, Pål Andre; Gringeri, A; Richards, M.; Hermans, C.; Altisent, C.; López-Fernández, M. & Fijnvandraat, K. (2012). Continuous infusion in haemophilia: current practice in Europe. Haemophilia.  ISSN 1351-8216.  18(5), s 753- 759 . doi: 10.1111/j.1365-2516.2012.02810.x
• Enden, Tone Rønnaug; HAIG, YLVA; Klow, Nils-Einar; Slagsvold, Carl Erik; Sandvik, Leiv; Ghanima, Waleed Khalid; Hafsahl, Geir; Holme, Pål Andre; Holmen, Lars Olav; Johansen, Anne Mette; Sandbæk, Gunnar & Sandset, Per Morten (2012). Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial. The Lancet.  ISSN 0140-6736.  379(9810), s 31- 38 . doi: 10.1016/S0140-6736(11)61753-4
• Holmström, M.; Tran, Hoa Thi Tuyet & Holme, Pål Andre (2012). Combined treatment with APCC (FEIBA (R)) and tranexamic acid in patients with haemophilia A with inhibitors and in patients with acquired haemophilia A - a two-centre experience. Haemophilia.  ISSN 1351-8216.  18(4), s 544- 549 . doi: 10.1111/j.1365-2516.2012.02748.x
• Vetlesen, Annette; Holme, Pål Andre; Lyberg, Torstein & Kjeldsen-Kragh, Jens (2012). Recovery, survival, and function of transfused platelets and detection of platelet engraftment after allogeneic stem cell transplantation. Transfusion.  ISSN 0041-1132.  52(6), s 1321- 1332 . doi: 10.1111/j.1537-2995.2011.03442.x
• Lassila, R; Antovic, Jovan P; Armstrong, Elina; Baghaei, Fariba; Dalsgaard-Nielsen, Jørn; Hilllarp, Andreas; Holme, Pål Andre; Holmström, Margareta; Johnsson, Hans; Joutsi-Korhonen, Lotta & Sandset, Per Morten (2011). Practical viewpoints on the diagnosis and management of heparin induced thrombocytopenia. Seminars in Thrombosis and Hemostasis.  ISSN 0094-6176.  37(3), s 328- 335 . doi: 10.1055/s-0031-1274516 Show summary

  Heparin-induced thrombocytopenia (HIT, type II) is an immune-mediated disorder due to antibodies formed against heparin-platelet factor 4 complexes, usually appearing at days 5 to 14 after initiation of heparin. It is important to recognize HIT because heparin prophylaxis or treatment paradoxically associates with new venous and/or arterial thrombosis. Early clinical suspicion and diagnosis together with proper pharmacotherapy and close laboratory monitoring are the cornerstones for successful management. This includes monitoring of Thrombocytopenia, its Timing to heparin administration, appearance of new Thrombosis or resistance to treatment, and differential diagnosis by exclusion of o Ther causes (the 4T's). Specific attention should be paid to the absence or presence of thrombosis and to tailoring thromboprophylaxis or anticoagulant therapy with a nonheparin alternative. Even in the absence of HIT-associated thrombosis, an active policy for prolonged thromboprophylaxis is demanded. Rapid and reliable assays should be developed for diagnosis and anticoagulation monitoring to secure safe management with nonheparins. Semiquantitative testing for on-call hours should be available and later confirmed as clinically needed. Alternative therapeutic options are available, but because their use is infrequent, experienced coagulation treatment centers should provide guidance in the treatment and in laboratory monitoring. Most of the evidence in HIT is grade IC, and thus the best evidence is provided by clinical experience. New anticoagulants and platelet inhibitors may offer future alternatives in the management of HIT, but the current treatment options provide the best experience and benefit. The joint clinical and laboratory guidelines provided in this article along with two practical case scenarios were prepared by a Nordic expert panel. They will be valuable for hematologists and colleagues who do not routinely encounter HIT.

• Lassila, Riita; Holme, Pål Andre; Landorph, Andrea; Petrini, Pia; Onundarson, Páll T. & Hillarp, Andreas (2011). Nordic Haemophilia Council's Practical Guidelines on Diagnosis and Management of von Willebrand Disease. Seminars in Thrombosis and Hemostasis.  ISSN 0094-6176.  37(5), s 495- 502 . doi: 10.1055/s-0031-1281034
• Tran, Hoa Thi Tuyet; Tjønnfjord, Geir Erland; Paus, Albert Collett & Holme, Pål Andre (2011). rFVIIa administered by continuous infusion during surgery in patients with severe congenital FVII deficiency. Haemophilia.  ISSN 1351-8216.  17(5), s 764- 770 . doi: 10.1111/j.1365-2516.2011.02596.x
• Ghanima, Waleed Khalid; Holme, Pål Andre & Tjønnfjord, Geir Erland (2010). Immunologisk trombocytopeni - patofysiologi og behandling :. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  130(21), s 2120- 2123
• Perry, Dewayne; Berntorp, E; Tait, C; Dolan, G; Holme, Pål Andre; Laffan, M; Lassila, R; Mumford, A; Pasi, J; Wilde, J; Will, A & Yee, TT (2010). FEIBA prophylaxis in haemophilia patients: a clinical update and treatment recommendations. Haemophilia.  ISSN 1351-8216.  16(1), s 80- 89 . doi: 10.1111/j.1365-2516.2009.02104.x Show summary

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• Astermark, J; Negrier, C; Hermans, C.; Holme, Pål Andre; Klamroth, R; Kotsi, P; De Moerloose, P; Pasi, J; Rocino, A; Von Depka, M; Windyga, J & Ludlam, CA (2009). European curriculum for thrombosis and haemostasis. Haemophilia.  ISSN 1351-8216.  15(1), s 337- 344 . doi: 10.1111/j.1365-2516.2008.01836.x
• Enden, Tone Rønnaug; Kløw, Nils-Einar; Sandvik, Leiv; Slagsvold, Carl Erik; Ghanima, Waleed; Hafsahl, Geir; Holme, Pål Andre; Holmen, Lars Olaf; Njaastad, AM; Sandbæk, Gunnar & Sandset, Per Morten (2009). Catheter-directed thrombolysis versus anticoagulant therapy alone in deep vein thrombosis: Results of an open randomized, controlled trial reporting on short term patency. Journal of Thrombosis and Haemostasis.  ISSN 1538-7933.  7(8), s 1268- 1275 . doi: 10.1111/j.1538-7836.2009.03464.x Show summary

  Background: Approximately one in four patients with acute proximal deep vein thrombosis (DVT) given anticoagulation and compression therapy develop post-thrombotic syndrome (PTS). Accelerated removal of thrombus by thrombolytic agents may increase patency and prevent PTS. Objectives: To assess short-term efficacy of additional catheterdirected thrombolysis (CDT) compared with standard treatment alone. Patients and methods: Open, multicenter, randomized, controlled trial. Patients (18–75 years) with iliofemoral DVT and symptoms < 21 days were randomized to receive additional CDT or standard treatment alone. After 6 months, iliofemoral patency was investigated using duplex ultrasound and air-plethysmography assessed by an investigator blinded to previous treatment. Results: One hundred and three patients (64 men, mean age 52 years) were allocated additional CDT (n = 50) or standard treatment alone (n=53). After CDT, grade III (complete) lysis was achieved in 24 and grade II (50%–90%) lysis in 20 patients. One patient suffered major bleeding and two had clinically relevant bleeding related to the CDT procedure. After 6 months, iliofemoral patency was found in 32 (64.0%) in the CDT group vs. 19 (35.8%) controls, corresponding to an absolute risk reduction (RR) of 28.2% (95% CI: 9.7%–46.7%; P = 0.004). Venous obstruction was found in 10 (20.0%) in the CDT group vs. 26 (49.1%) controls; absoluteRR29.1%(95%CI: 20.0%–38.0%; P = 0.004). Femoral venous insufficiency did not differ between the two groups. Conclusions: After 6 months, additional CDT increased iliofemoral patency from 36% to 64%. The ongoing long-term follow-up of this study will document whether patency is related to improved functional outcome.

• Negaard, Helene Francisca Stigter; Iversen, Per Ole; Østenstad, Bjørn; Iversen, Nina; Holme, Pål Andre & Sandset, Per Morten (2008). Hypercoagulability in patients with haematological neoplasia: No apparent initiation by tissue factor. Thrombosis and Haemostasis.  ISSN 0340-6245.  99, s 1040- 1048 . doi: 10.1160/TH07-09-0541 Show summary

  Patients with haematological malignancies carry increased risk of venous thrombosis (VT). However, the mechanisms that link these malignancies to activated coagulation have not been fully identified. Since anti-haemostatic agents are studied in clinical trials for their potential to prolong survival in cancer patients, a detailed characterisation of haemostatic markers in cancer subtypes is needed. Hence, in this study, we measured the plasma concentrations and mRNA expression in blood mononuclear cells of haemostatic parameters in 93 patients with haematological neoplasias (acute myeloid leukaemia, chronic lymphatic leukaemia, multiple myeloma, and non-Hodgkin’s lymphoma) before start and after completion of cancer therapy. At diagnosis we found activation of coagulation and fibrinolysis, especially in patients with acute myeloid leukaemia. This hypercoagulation was not associated with increased levels of tissue factor (TF) or factor VII (fVII) antigen or mRNA, or levels of activated fVII. In conclusion we found a hypercoagulable state in patients with haematological malignancy that did not seem to be initiated by TF.

• Enden, Tone; Sandvik, Leiv; Kløw, Nils-Einar; Hafsahl, Geir; Holme, Pål Andre; Holmen, Lars Olaf; Ghanima, Waleed; Johansen, Anne Mette; Sandbæk, Gunnar; Slagsvold, Carl Erik & Sandset, Per Morten (2007). Catheter-directed venous thrombolysis in acute iliofemoral vein thrombosis (CaVenT) study: Rationale and design of a multicenter, randomized, controlled, clinical trial (NCT00251771). American Heart Journal.  ISSN 0002-8703.  154, s 808- 814 . doi: 10.1016/j.ahj.2007.07.010 Show summary

  Background. The conventional treatment of acute deep vein thrombosis (DVT) is anticoagulation and compression therapy, as recommended in the international guidelines. Anticoagulation prevents recurrent venous thrombosis, pulmonary embolism, and death. Compression therapy reduces the risk of developing long-term sequelae, that is, postthrombotic syndrome (PTS). Evaluation of systemic thrombolysis has shown effective thrombolysis and a likely reduction in PTS but at the cost of increased risk of bleeding complications. Catheter-directed thrombolysis (CDT) was introduced for rapid removal of thrombi and salvage of venous valves with less systemic thrombolytic effect, and is being offered to selected patients with iliofemoral DVT to prevent development of PTS. Case series have shown technical and thrombolytic success; however, no randomized studies have evaluated the long-term clinical effects of venous CDT. The aim of the CaVenT study is to investigate the role of adjunctive CDT by evaluating its clinical efficacy and safety compared with conventional treatment alone in patients with acute iliofemoral DVT. Methods. The CaVenT study is an open, randomized, controlled, clinical trial. We plan to include 200 patients who will receive either CDT, in addition to conventional treatment, or conventional treatment alone. The primary outcome measures are patency at 6 months and prevalence of PTS at 2 years. Conclusion. Implementation of the CaVenT study will be a contribution toward evidence-based medicine in the treatment of acute proximal DVT of the leg. Any documentation of improved functional outcome will have a significant impact on clinical practice for this patient group and may lead to a modification of existing international guidelines.

• Holme, Pål Andre; Brosstad, Frank Roger & Tjønnfjord, Geir Erland (2005). Acquired haemophilia: management of bleeds and immune therapy to eradicate autoantibodies. Haemophilia.  ISSN 1351-8216.  11(5), s 510- 515 . doi: 10.1111/j.1365-2516.2005.01136

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• Schultz, Nina Haagenrud; Holme, Pål Andre; Henriksson, Carola; Mowinckel, Marie-Christine; Sandset, Per Morten; Bratseth, Vibeke & Jacobsen, Eva-Marie (2019). The influence of rivaroxaban on markers of fibrinolysis and endothelial cell activation/injury in patients with venous thrombosis. Thrombosis Research.  ISSN 0049-3848.  177, s 154- 156 . doi: 10.1016/j.thromres.2019.03.010
• Holme, Pål Andre; Berntorp, E; De Moerloose, P & Tait, R.C. (2011). Haematuria and hypertension in haemophilia - the H3 study. Haemophilia.  ISSN 1351-8216.  17(2), s 377- 377
• Tran, Hoa Thi Tuyet; Holmström, M. & Holme, Pål Andre (2011). The combined treatment of APCC and tranexamic acid in patients with haemophilia a with inhibitors and in patients with acquired haemophilia a - a two-centre experience. Journal of Thrombosis and Haemostasis.  ISSN 1538-7933.  9, s 219- 219
• Batorova, Angelika; Holme, Pål Andre; Gringeri, Alessandro; Fijnvandraat, K.; Richards, M.; Hermans, C.; Altisent, C. & López-Fernández, M. (2010). Inhibitor incidence in hemophilia A patients intensively treated with continuous infusion of factor VIII. Haemophilia.  ISSN 1351-8216.  16, s 67- 67
• Heldal, Dag; Brinch, Lorentz; Fløisand, Yngvar; Dybedal, Ingunn; Gedde-Dahl, Thobias; Holme, Pål Andre; Tjønnfjord, Geir Erland & Evensen, Stein A. (2010). Long-term (>= 5 years) follow-up of a randomized study of allogeneic stem cell transplantation with stem cells from blood or bone marrow. Bone Marrow Transplantation.  ISSN 0268-3369.  45, s S155- S156
• Brinch, Lorentz; Fløisand, Yngvar; Tjønnfjord, Geir Erland; Gedde-Dahl, Thobias; Heldal, Dag; Holme, Pål Andre & Egeland, Torstein (2009). Allogeneic blood stem cell transplants for AML using the Bu4Cy2 regimen in AML: long term experience. Bone Marrow Transplantation.  ISSN 0268-3369.  43, s S98- S98
• Holme, Pål Andre & Michelsen, Annika (2008). En 40 år gammel kvinne med svimmelhet og oppkast. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  128(1413)

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