Anticoagulation for venous thromboembolism

Summary

Acute venous thromboembolism (VTE) is treated with parenteral administration of heparin or derivatives, in conjunction with oral vitamin K antagonists (VKAs) to reach and maintain INR values between 2.0 and 3.0 for at least 3 months; the duration of a further period of treatment for secondary prevention of recurrences is still matter of debate. If bleeding occurs during treatment the decision will be based on: a) type of bleeding (major or minor), and b) thrombotic risk if anticoagulation is withheld (characteristics of patients and time elapsed from the index VTE). In case of major bleeding anticoagulation should be stopped and reversed. A first but insufficient measure is i.v. vitamin K administration. Fresh frozen plasma is widely used; however, large volumes are needed (at least 15 mL/kg body weight) with risk for fluid overload. Prothrombin complex concentrate infusion, with 3 or (better) the 4 pro-coagulant factors, is a more efficient (fast and safe) measure. In patients at high thrombotic risk (first month or other conditions) and absolute contraindication for anticoagulation a caval filter is recommended, to avoid as much as possible lifethreatening pulmonary embolism.

Zusammenfassung

Die Behandlung der akuten venösen Thromboembolie (VTE) besteht in der parenteralen Gabe von Heparin bzw. -derivaten, zusammen mit oralen Vitamin-K-Antagonisten (VKA), um INR-Werte zwischen 2,0 und 3,0 zu erreichen und für mindestens drei Monate aufrecht zu erhalten. Über die Dauer einer anschließenden sekundären Rezidivprophylaxe wird noch diskutiert. Falls während der Behandlung eine Blutung auftritt, richtet sich die Entscheidung nach: a) Art der Blutung (leichte oder schwere) und b) Thromboserisiko bei Absetzen der Antikoagulation (Patientencharakteristika und Zeitraum seit der Index-VTE). Im Falle einer großen Blutung sollte die Antikoagulation beendet und antagonisiert werden. Eine erste, jedoch unzureichende Maßnahme ist die i.v.- Gabe von Vitamin K. Gefrorenes Frischplasma wird häufig verwendet; es werden jedoch große Mengen benötigt (mindestens 15 ml/kg Körpergewicht), mit dem Risiko der Volumenüberlastung. Die Infusion eines Prothrombinkomplex-Konzentrats mit drei oder (besser) vier Gerinnungsfaktoren ist das effizientere Verfahren (schnell und sicher). Bei Patienten mit einem hohen Thromboserisiko (im ersten Monat oder bei Vorliegen anderer Erkrankungen) und einer absoluten Kontraindikation für eine Antikoagulation wird ein Vena-cava-Filter empfohlen, um möglichst eine lebensbedrohliche Lungenembolie zu vermeiden

Keywords

VTE - anticoagulation - bleeding - haemorrhages

Schlüsselwörter

VTE,Antikoagulation - Blutung - Hämorrhagien

• References

• 1 Palareti G, Cosmi B. Predicting the risk of recurrence of venous thromboembolism. Curr Opin Hematol 2004; 11: 192-197.
• 2 Kahn SR. Natural history of postthrombotic disease: Transition from acute to chronic disease. J Vasc Surg 2010; 52: 62S-64S.
• 3 Kearon C, Kahn SR, Agnelli G. et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence- Based Clinical Practice Guidelines. (8^th ed). Chest 2008; 133: 454S-545S.
• 4 Kearon C. Indefinite anticoagulation after a first episode of unprovoked venous thromboembolism: yes. J Thromb Haemost 2007; 05: 2330-2335.
• 5 Baglin T. Unprovoked deep vein thrombosis should be treated with long-term anticoagulation – no. J Thromb Haemost 2007; 05: 2336-2339.
• 6 Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 03: 692-694.
• 7 Briz M, Talks K, Hanley J. et al. Reversal of warfarininduced over-anticoagulation with individualized dosing of oral vitamin K: a pilot study. J Thromb Haemost 2010; 08: 1123-1125.
• 8 Makris M, Greaves M, Phillips WS. et al. Emergency oral anticoagulant reversal: the relative efficacy of infusions of fresh frozen plasma and clotting factor concentrate on correction of the coagulopathy. Thromb Haemost 1997; 77: 477-480.
• 9 Ansell J, Hirsh J, Hylek E. et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. (8^th edition). Chest 2008; 133: 160S-198S.
• 10 Dentali F, Ageno W, Crowther M. Treatment of coumarin-associated coagulopathy: a systematic review and proposed treatment algorithms. J Thromb Haemost 2006; 04: 1853-1863.
• 11 Ozgonenel B, Omalley B, Krishen P, Eisenbrey AB. Warfarin reversal emerging as the major indication for fresh frozen plasma use at a tertiary care hospital. Am J Hematol 2007; 82: 1091-1094.
• 12 Lee SB, Manno EM, Layton KF, Wijdicks EFM. Progression of warfarin-associated intracerebral hemorrhage after INR normalization with FFP. Neurology 2006; 67: 1272-1274.
• 13 Lankiewicz MW, Hays J, Friedman KD. et al. Urgent reversal of warfarin with prothrombin complex concentrate. J Thromb Haemost 2006; 04: 967-970.
• 14 Leissinger CA, Blatt PM, Hoots WK, Ewenstein B. Role of prothrombin complex concentrates in reversing warfarin anticoagulation: a review of the literature. Am J Hematol 2008; 83: 137-143.
• 15 Baglin TP, Keeling DM, Watson HG. Guidelines on oral anticoagulation (Warfarin): 3^rd ed. – 2005 update. Br J Haematol 2006; 132: 277-285.
• 16 Pabinger I, Brenner B, Kalina U. et al. Prothrombin complex concentrate (Beriplex P/N) for emergency anticoagulation reversal: a prospective multinational clinical trial. J Thromb Haemost 2008; 06: 622-631.
• 17 Holland L, Warkentin TE, Refaai M. et al. Suboptimal effect of a three-factor prothrombin complex concentrate (Profilnine-SD) in correcting supratherapeutic international normalized ratio due to warfarin overdose. Transfusion (Paris) 2009; 49: 1171-1177.
• 18 Boulis NM, Bobek MP, Schmaier A, Hoff JT. Use of factor IX complex in warfarin-related intracranial hemorrhage. Neurosurgery 1999; 45: 1113-1118.
• 19 Hull R, Delmore T, Genton E. et al. Warfarin sodium versus low dose heparin in the long term treatment of venous thrombosis. N Engl J Med 1979; 301: 855-858.
• 20 Nielsen HK, Husted SE, Krusell LR. et al. Anticoagulant therapy in deep venous thrombosis – a randomized controlled study. Thromb Res 1994; 73: 215-226.
• 21 Kearon C, Hirsh J. Current concepts: management of anticoagulation before and after elective surgery. N Engl J Med 1997; 336: 1506-1511.
• 22 Kearon C. Natural history of venous thromboembolism. Circulation 2003; 107: I22-I30.
• 23 Coon WW, Willis 3^rd PW. Recurrence of venous thromboembolism. Surgery 1973; 73: 823-827.
• 24 Eichinger S, Weltermann A, Minar E. et al. Symptomatic pulmonary embolism and the risk of recurrent venous thromboembolism. Arch Intern Med 2004; 164: 92-96.
• 25 Imberti D, Prisco D. Retrievable vena cava filters: key considerations. Thromb Res 2008; 122: 442-449.
• 26 Segal JB, Streiff MB, Hoffman LV. et al. Management of venous thromboembolism: A systematic review for a practice guideline. Ann Intern Med 2007; 146: 211-222.
• 27 Ageno W, Garcia D, Aguilar MI. et al. Prevention and treatment of bleeding complications in patients receiving vitamin K antagonists, part 2: Treatment. Am J Hematol 2009; 84: 584-588.
• 28 Hui AJ, Wong RM, Ching JY. et al. Risk of colonoscopic polypectomy bleeding with anticoagulants and antiplatelet agents: analysis of 1657 cases. Gastrointest Endosc 2004; 59: 44-48.
• 29 Garcia DA, Regan S, Henault LE. et al. Risk of thromboembolism with short-term interruption of warfarin therapy. Arch Intern Med 2008; 168: 63-69.
• 30 Clark NP, Witt DM, Delate T. et al. Thromboembolic consequences of subtherapeutic anticoagulation in patients stabilized on warfarin therapy: The Low INR Study. Pharmacotherapy 2008; 28: 960-967.