Epidemiological features of warfarin overdose and efficacy of prothrombin complex concentrates

Abstract

The aims of this study were to investigate the epidemiological features of warfarin overdose and evaluate the efficacy of prothrombin complex concentrate (PCC) for overdose treatment. The hospital records of 106 patients admitted to the emergency department (ED) for warfarin overdose during a two-year period were evaluated retrospectively. Demographic and epidemiological data as well as treatments were recorded. The data from 15 patients administered PCC were compared with those of other patients. The patient population consisted of 53 (50%) males and 53 (50%) females with a mean age of 70.2±14.5 years. Forty-five (42.4%) patients were admitted to the ED with bleeding disorders; 61 (57.6%) patients were admitted for other symptoms such as headache, syncope, trauma related injuries. Atrial fibrillation (n=50, 47.1%) was the most common indication for treatment with a vitamin K antagonist (VKA). Other common indications were transient ischemic attack, stroke (n=43, 40.5%) and valvular heart disease (n=17, 16%). Vitamin K was the preferred treatment for VKA reversal in 32 (30.2%) patients. Fresh-frozen plasma (FFP) was preferred in 23 (21.7%) patients. Fifteen (14.1%) patients required acute reversal of VKA with PCC. The anticoagulant drug was discontinued in 58 (54.7%) patients. Erythrocyte suspension (ES) and thrombocyte suspension (TS) transfusion rates were higher in the PCC-administered group; hospitalization rates were also higher in this group. ED length of stay (LOS) was shorter in this group. Initial international normalized ratio (INR) levels were significantly higher in the PCC group (5.68±3.74 versus 13.17±5.15). As the elderly population increases, warfarin and VKArelated complications will be a more significant portion of ED practice.ED physicians should be experienced in acute reversal of VKA with PCC, and be familiar with the possible complications of FFP and PCC. J. Exp. Clin. Med., 2013; 30:327-330

Keywords

• Fresh-frozen plasma; prothrombin complex concentrate; vitamin K antagonist; warfarin overdose

References

1. Altunbaş, G., Ercan, S., Davutoğlu, V., Al, B., 2013. Varfarin tedavisine genel bakış ve sorulara cevaplar. ACAD EMERG MED 12, 38-42.
2. Bagot, C.N., Cregg, R., Patel, R.K., Shariff, A., Arya, R., 2007. Perioperative myocar-dial infarction in a patient receiving low-dose prothrombin complex con-centrates. Thromb. Haemost. 98, 1141–1142.
3. Benhamou, D., 2007. The use of Fresh Frozen Plasma (FFP) in 2007 in France. Transfusion Clinique et Biologique. 14, 557-559.
4. Beriplex P/N Anticoagulation Reversal Study Group., 2010. Impact of infusion speed on the safety and effectiveness of prothrombin complex concen-trate: A prospective clinical trial of emergency anticoagulation reversal. Ann Hematol. 89, 309–316.
5. Budnitz, D.S., Shehab, N., Kegler, S.R., Richards, C.L., 2007. Medication use leading to emergency department visits for adverse drug events in older adults. Ann. Intern Med.147, 755-765.
6. Budnitz, D.S., Lovegrove, M.C., Shehab, N., Richards, C.L., 2011. Emergency hospitalizations for adverse drug events in older americans. N. Engl J Med. 365, 2002-2012.
7. Butler, A.C., Tait, R.C., 1998. Management of oral anticoagulant induced intracranial haemorrhage. Blood Reviews. 12, 35-44.
8. Demeyere, R., Gillardin, S., Arnout, J., Strengers, P.F., 2010. Comparison of fresh frozen plasma and prothrombin complex concentrate for the reversal of oral anticoagulants in patients undergoing cardiopulmonary bypass surgery: A randomized study. Vox. Sang. 99, 251-260.

9. Dentali, F., Marchesi, C., Pierfranceschi, M.G., Crowther, M., Garcia, D., Hylek, E., Witt, D.M., Clark, N.P., Squizzato, A., Imberti, D., Ageno, W., 2011. Safety of prothrombin complex concentrates for rapid anticoagulation reversal of vitamin K antagonists. Thromb. Haemost. 106, 429-438.
10. Desmettre, T., Dubart, A.E., Capellier, G., Fanara, B., Puyraveau, M., Kepka, S., Coquart, J., Sheppard, F., Tazarourte, K., 2012. Emergency reversal of anticoagulation: The real use of prothrombin complex concentrates. Thromb. Res. 130, 178-183.
11. Ellis, D.J., Usman, M.H., Milner, P.G., Canafax, D.M., Ezekowitz, M.D., 2009. The first eva-luation of a novel vitamin K antagonist, tecarfarin (ATI-5923), in patients with atrial fibrillation. Circulation. 120, 1029-1035.
12. Erdoğan, M.Ö., Yorulmaz, R., Tayfur, İ., Giritli, Ö., Erdoğan, S.T., 2013. Cortical blindness and bilateral occipital haemorrhage due to warfarin overdose. JAEMCR. 4, 73-75.
13. Garcia, D.A., Regan, S., Crowther, M., Hylek, E.M., 2006. The risk of hemorrhage among patients with warfarin associated coagulopathy. JACC. 47, 804-808.
14. Guyatt, G.H., Akl, E.A., Crowther, M., Gutterman, D.D., Schuünemann, H.J., 2012. American College of Chest Physicians Antithrombotic therapy and prevention of thrombosis panel. Executive summary: Antithrombotic therapy and prevention of thrombosis. 9th Ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 141, 7-47.
15. Hickey, M., Gatien, M., Taljaard, M., Aujnarain, A., Giulivi, A., Jeffrey J. Perry, J.J., 2013. Outcomes of urgent warfarin reversal with frozen plasma versus prothrombin. Circulation. 128,360-364.
16. Kamali, F., Wynne, H., 2010. Pharmacogenetics of Warfarin. Annu. Rev. Med. 61, 63-75.
17. Libby, E.N., Garcia, D.A., 2002. A survey of oral vitamin K use by anticoagulation clinics. Arch. Intern. Med. 162, 1893-1896.
18. Majeed, A., Eelde, A., Agren, A., Schulman, S., Holmström, M., 2012. Thromboembolic safety and efficacy of prothrombin complex concentrates in the emergency reversal of warfarin coagulopathy. Thromb. Res. 129, 146-151.
19. Meeker, E., Dennehy, C.E., Weber, E.J., Kayser, S.R., 2011. Emergency Department management of patients on warfarin therapy. J.annemergmed. 58, 192-199.
20. Meer, S.J.M., Rosendaal, F.R., Brouke, J.P., Briet, E., 1993. Bleeding complications in oral anticoagulant therapy. Archives of Internal Medicine. 153, 1557-1562.
21. Lankiewicz, M.W., Hays, J., Friedman, K.D., Tinkoff, G., Blatt, P.M., 2006. Urgent reversal of warfarin with prothrombin complex concentrate. J. Thromb. Haemost. 4, 967-970.
22. Lin, D.M., Murphy, L.S., Tran, M.H., 2013. Use of prothrombin complex concentrates and fibrinogen concentrates in the perioperative setting. Transfus Med Rev. 27, 91-104.
23. Pabinger I, Tiede A, Kalina U, Knaub S, Germann R, Ostermann H; Beriplex P/N Anticoagulation Reversal Study Group., 2010. Impact of infusion speed on the safety and effectiveness of prothrombin complex concen-trate: A prospective clinical trial of emergency anticoagulation reversal. Ann Hematol. 89, 309-316.
24. Palareti, G., Leali, N., Coccheri, S., Poggi, M., Manotti, C., D’Angelo, A., Pengo, V., Erba, N., Moia, M., Ciavarella, N., Devoto, G., Berrettini, M., Musolefi, S., 1996. Bleeding complications of oral anticoagulant treatment: An inception cohort, prospective collaborative study. Italian study on complications of oral anticoagulant therapy. Lancet. 348, 423-428.
25. Patanwala, A.E., Acquisto, N.M., Erstad, B.L., 2011. Prothrombin complex concentrate for critical bleeding. Ann. Pharmacother. 45, 990–999. Phan, T.G., Koh, M., Wijdicks, E.F., 2000. Safety of discontinuation of anticoagulation in patients with intracranial hemorrhage at high thromboembolic risk. Arch. Neurol. 57, 1710-1713.
26. Preston, F.E., Laidlaw, S.T., Sampson, B., Kitchen, S., 2002. Rapid reversal of oral anticoagulation with warfarin by a prothrombin complex concentrate (Beriplex): Efficacy and safety in 42 patients. British Journal of Haematology. 116, 619-624.
27. Ratnaweera, M., Janowski, W., Simmons, D., 2007. Multiple thrombotic events fol-lowing warfarin reversal. Intern Med J. 37, 580-581.
28. Streiff, M.B., 2011. Prothrombin complex concentrates for reversal of vitamin K antagonists: Assessing the risks. Thromb. Hamost. 106, 389- 390.
29. Sørensen, B., Spahn, D.R., Innerhofer, P., Spannagl, M., Rossaint, R., 2011. Clinical review: Prothrombin complex concentrates: Evaluation of safety and thrombogenicity. Crit Care. 15, 201.
30. Warren, O., Simon, B., 2009. Massive, fatal, intracardiac thrombosis associ-ated with prothrombin complex concentrate. Ann. Emerg. Med. 53, 758-761.