Four-factor prothrombin complex concentrate for life-threatening bleeds or emergent surgery: A retrospective evaluation

Journal of Critical Care

Volumn 36, Issue , 2016, Pages 166-172

  Sin, Jonathan H ^a   Berger, Karen ^a   Lesch, Christine A ^b  

^a WEILL CORNELL MEDICAL CENTER   (United States)

^b New York Presbyterian Morgan Stanley Children's Hospital   (United States)

Author keywords

anticoagulant reversal; anticoagulants; blood coagulation factors; prothrombin complex concentrates; thrombosis; vitamin K

Indexed keywords

BLOOD CLOTTING FACTOR CONCENTRATE; FOUR FACTOR PROTHROMBIN COMPLEX CONCENTRATE; UNCLASSIFIED DRUG; WARFARIN; ANTICOAGULANT AGENT; ANTIFIBRINOLYTIC AGENT; APIXABAN; BLOOD CLOTTING FACTOR; DABIGATRAN; HEMOSTATIC AGENT; HEPARIN; PROTHROMBIN COMPLEX CONCENTRATES; PYRAZOLE DERIVATIVE; PYRIDONE DERIVATIVE; RIVAROXABAN; VITAMIN K GROUP;

ADULT; AGED; ARTERY THROMBOSIS; ARTICLE; BLEEDING; BRAIN ISCHEMIA; CLINICAL PROTOCOL; CONTROLLED STUDY; DORSALIS PEDIS ARTERIAL THROMBOSIS; DRUG EFFICACY; DRUG SAFETY; EMERGENCY SURGERY; FEMALE; HEART INFARCTION; HUMAN; INTERNATIONAL NORMALIZED RATIO; LUNG EMBOLISM; MAJOR CLINICAL STUDY; MALE; OUTCOME ASSESSMENT; RETROSPECTIVE STUDY; RISK ASSESSMENT; RISK FACTOR; THROMBOEMBOLISM; UPPER EXTREMITY DEEP VEIN THROMBOSIS; CHEMICALLY INDUCED; EMERGENCY; GASTROINTESTINAL HEMORRHAGE; HEART SURGERY; HEART TRANSPLANTATION; HEMORRHAGE; INCIDENCE; INTRACRANIAL HEMORRHAGES; LAPAROTOMY; MIDDLE AGED; PREOPERATIVE CARE; PROCEDURES; SURGERY; THROMBOCYTOPENIA; VERY ELDERLY;

AGED; AGED, 80 AND OVER; ANTICOAGULANTS; ANTIFIBRINOLYTIC AGENTS; BLOOD COAGULATION FACTORS; CARDIAC SURGICAL PROCEDURES; DABIGATRAN; EMERGENCIES; FEMALE; GASTROINTESTINAL HEMORRHAGE; HEART TRANSPLANTATION; HEMORRHAGE; HEMOSTATICS; HEPARIN; HUMANS; INCIDENCE; INTERNATIONAL NORMALIZED RATIO; INTRACRANIAL HEMORRHAGES; LAPAROTOMY; MALE; MIDDLE AGED; PREOPERATIVE CARE; PYRAZOLES; PYRIDONES; RETROSPECTIVE STUDIES; RISK FACTORS; RIVAROXABAN; SURGICAL PROCEDURES, OPERATIVE; THROMBOCYTOPENIA; THROMBOEMBOLISM; VITAMIN K; WARFARIN;

EID: 84995611307     PISSN: 08839441     EISSN: 15578615     Source Type: Journal    
DOI: 10.1016/j.jcrc.2016.06.024     Document Type: Article

References (64)

1. [1] Kcentra (prothrombin complex concentrate) prescribing information. 2014, CSL Behring LLC, Kankakee, IL.
2. [2] Hanke, AA, Joch, C, Gorlinger, K, Long-term safety and efficacy of a pasteurized nanofiltrated prothrombin complex concentrate (Beriplex P/N): a pharmacovigilance study. Br J Anaesth 110 (2013), 764–772.
3. [3] Ageno, W, Gallus, AS, Wittkowsky, A, et al. Oral anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 141 (2012), e44S–e88S.
4. [4] Frontera, JA, Lewin, JJ III, Rabinstein, AA, et al. Guideline for reversal of antithrombotics in intracranial hemorrhage: a statement for healthcare professionals from the Neurocritical care society and Society of Critical Care Medicine. Neurocrit Care 24 (2016), 6–46.
5. [5] Keeling, D, Baglin, T, Tait, C, et al. Guidelines on oral anticoagulation with warfarin-fourth edition. Br J Haematol 154 (2011), 311–324.
6. [6] Spahn, DR, Bouillon, B, Cerny, V, et al. Management of bleeding and coagulopathy following major trauma: an updated European guideline. Crit Care, 17, 2013, R76.
7. [7] Tran, HA, Chunilal, SD, Harper, PL, et al. An update of consensus guidelines for warfarin reversal. Med J Aust 198 (2013), 198–199.
8. [8] American Society of Anesthesiologists Task Force of Perioperative Blood Transfusion and Adjuvant Therapies, Practice guidelines for perioperative blood transfusion and adjuvant therapies: an updated report by the American Society of Anesthesiologists Task Force on perioperative blood transfusion and adjuvant therapies. Anesthesiology 105 (2006), 198–208.
9. [9] Sorensen, B, Spahn, DR, Innerhofer, P, et al. Clinical review: prothrombin complex concentrates-evaluation of safety and thrombogenicity. Crit Care, 15, 2011, 201.
10. [10] Cada, DJ, Levien, TL, Baker, DE, Prothrombin complex concentrate. Hosp Pharm 48 (2013), 951–957.
11. [11] Ferreira, J, DeLosSantos, M, The clinical use of prothrombin complex concentrate. J Emerg Med 44 (2013), 1201–1210.
12. [12] Refaai, MA, Goldstein, JN, Lee, ML, et al. Increased risk of volume overload with plasma compared with four-factor prothrombin complex concentrate for urgent vitamin K antagonist reversal. Transfusion 55 (2015), 2722–2729.
13. [13] Demeyere, R, Gillardin, S, Arnout, J, et al. 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 (2010), 251–260.
14. [14] Hickey, M, Gatien, M, Taljaard, M, et al. Outcomes of urgent warfarin reversal with frozen plasma versus prothrombin complex concentrate in the emergency department. Circulation 128 (2013), 360–364.
15. [15] Yanamadala, V, Walcott, BP, Fecci, PE, et al. Reversal of warfarin associated coagulopathy with 4-factor prothrombin complex concentrate in traumatic brain injury and intracranial hemorrhage. J Clin Neurosci 21 (2014), 1881–1884.
16. [16] Joseph, B, Aziz, H, Pandit, V, et al. Prothrombin complex concentrate versus fresh-frozen plasma for reversal of coagulopathy of trauma: is there a difference?. World J Surg 38 (2014), 1875–1881.
17. [17] Karaca, MA, Erbil, B, Ozmen, MM, Use and effectiveness of prothrombin complex concentrates vs fresh frozen plasma in gastrointestinal hemorrhage due to warfarin usage in the ED. Am J Emerg Med 32 (2014), 660–664.
18. [18] Fariborz Farsad, B, Golpira, R, Najafi, H, et al. Comparison between prothrombin complex concentrate (PCC) and fresh frozen plasma (FFP) for the urgent reversal of warfarin in patients with mechanical heart valves in a tertiary care cardiac center. Iran J Pharm Res 14 (2015), 877–886.
19. [19] Sarode, R, Milling, TJ, Refaai, MA, et al. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study. Circulation 128 (2013), 1234–1243.
20. [20] Goldstein, JN, Refaai, MA, Milling, TJ Jr., et al. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial. Lancet 385 (2015), 2077–2087.
21. [21] Eerenberg, ES, Kamphuisen, PW, Sijpkens, MK, et al. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in health subjects. Circulation 124 (2011), 1573–1579.
22. [22] Levi, M, Moore, KT, Castillejos, CF, et al. Comparison of three-factor and four-factor prothrombin complex concentrates regarding reversal of the anticoagulant effects of rivaroxaban in healthy volunteers. J Thromb Haemost 12 (2014), 1428–1436.
23. [23] Barco, S, Whitney Cheung, Y, Coppens, M, et al. In vivo reversal of the anticoagulant effect of rivaroxaban with four-factor prothrombin complex concentrate. Br J Haematol 172 (2016), 255–261.
24. [24] Martin, AC, Gouin-Thibault, I, Siguret, V, et al. Multimodal assessment of non-specific hemostatic agents for apixaban reversal. J Thromb Haemost 13 (2015), 426–436.
25. [25] Cheung, YW, Barco, S, Hutten, BA, et al. In vivo increase in thrombin generation by four-factor prothrombin complex concentrate in apixaban-treated healthy volunteers. J Thromb Haemost 13 (2015), 1799–1805.
26. [26] Marlu, R, Hodaj, E, Paris, A, et al. Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: a randomised crossover ex vivo study in healthy volunteers. Thromb Haemost 108 (2012), 217–224.
27. [27] Jones, GM, Erdman, MJ, Smetana, KS, et al. 3-factor versus 4-factor prothrombin complex concentrate for warfarin reversal in severe bleeding: a multicenter, retrospective, propensity-matched pilot study. J Thromb Thrombolysis 42 (2016), 19–26.
28. [28] Al-Majzoub, O, Rybak, E, Reardon, DP, et al. Evaluation of warfarin reversal with 4-factor prothrombin complex concentrate compared to 3-factor prothrombin complex concentrate at a tertiary academic medical center. J Emerg Med 50 (2016), 7–13.
29. [29] Grandhi, R, Newman, WC, Zhang, X, et al. Administration of a 4-factor prothrombin complex concentrate as an antidote for intracranial bleeding in patients taking direct factor Xa inhibitors. World Neurosurg 84 (2015), 1956–1961.
30. [30] Beynon, C, Nofal, M, Rizos, T, et al. Anticoagulation reversal with prothrombin complex concentrate in aneurysmal subarachnoid hemorrhage. J Emerg Med 49 (2015), 778–784.
31. [31] Soyuncu, AS, Mutlu, H, et al. Prothrombin complex concentrates utility for warfarin-associated hemorrhage. Int J Clin Exp Med 8 (2015), 2778–2783.
32. [32] Ortmann, E, Besser, MW, Sharples, LD, et al. An exploratory cohort study comparing prothrombin complex concentrate and fresh frozen plasma for the treatment of coagulopathy after complex cardiac surgery. Anesth Analg 121 (2015), 26–33.
33. [33] Voils, SA, Holder, MC, Premraj, S, et al. Comparative effectiveness of 3- versus 4-factor prothrombin complex concentrate for emergent warfarin reversal. Thromb Res 136 (2015), 595–598.
34. [34] Beynon, C, Potzy, A, Unterberg, AW, et al. Prothrombin complex concentrate facilitates emergency spinal surgery in anticoagulated patients. Acta Neurochir 156 (2014), 741–747.
35. [35] Arnekeian, V, Camous, J, Fattal, S, et al. Use of prothrombin complex concentrate for excessive bleeding after cardiac surgery. Interact Cardiovasc Thorac Surg 15 (2012), 382–389.
36. [36] Song, MM, Warne, CP, Crowther, MA, Prothrombin complex concentrate (PCC, Octaplex) in patients requiring immediate reversal of vitamin K antagonist anticoagulation. Thromb Res 129 (2012), 526–529.
37. [37] Bruce, D, Nokes, TJ, Prothrombin complex concentrates (Beriplex P/N) in severe bleeding: experience in a large tertiary hospital. Crit Care, 12, 2008, R105.
38. [38] Hedges, A, Coons, JC, Saul, M, et al. Clinical effectiveness and safety outcomes associated with prothrombin complex concentrates. J Thromb Thrombolysis 42 (2016), 6–10.
39. [39] Joseph, R, Burner, J, Yates, S, et al. Thromboembolic outcomes after use of a four-factor prothrombin complex concentrate for vitamin K antagonist reversal in a real-world setting. Transfusion 56 (2016), 799–807.
40. [40] Berndtson, AE, Huang, WT, Box, K, et al. A new kid on the block: outcomes with Kcentra 1 year after approval. J Trauma Acute Care Surg 79 (2015), 1004–1008.
41. [41] Toth, P, van Veen, JJ, Robinson, K, et al. Real world usage of PCC to “rapidly” correct warfarin induced coagulopathy. Blood Transfus 11 (2013), 500–505.
42. [42] Leal-Noval, SR, Lopez-Irizo, R, Bautista-Paloma, J, et al. Efficacy of the prothrombin complex concentrate prothromplex in patients requiring urgent reversal of vitamin K antagonists or presenting with uncontrolled bleeding: a retrospective, single center study. Blood Coagul Fibrinolysis 24 (2013), 862–868.
43. [43] Carvalho, MC, Rodrigues, AG, Conceicao, LM, et al. Prothrombin complex concentrate (Octaplex): a Portuguese experience in 1152 patients. Blood Coagul Fibrinolysis 23 (2012), 222–228.
44. [44] Schick, KS, Fertmann, JM, Jauch, KW, et al. Prothrombin complex concentrate in surgical patients: retrospective evaluation of vitamin K antagonist reversal and treatment of severe bleeding. Crit Care, 13, 2009, R191.
45. [45] Klein, L, Peters, J, Miner, J, et al. Evaluation of a fixed dose 4-factor prothrombin complex concentrate for emergent warfarin reversal. Am J Emerg Med 33 (2015), 1213–1218.
46. [46] Varga, C, Al-Touri, S, Papadoukakis, S, et al. The effectiveness and safety of fixed low-dose prothrombin complex concentrates in patients requiring urgent reversal of warfarin. Transfusion 53 (2013), 1451–1458.
47. [47] Wozniak, M, Kruit, A, Padmore, R, et al. Prothrombin complex concentrate for the urgent reversal of warfarin. Assessment of a standard dosing protocol. Transfus Apher Sci 46 (2012), 309–314.
48. [48] Khorsand, N, Veeger, NJ, Muller, M, et al. Fixed versus variable dose of prothrombin complex concentrate for counteracting vitamin K antagonist therapy. Transfus Med 21 (2011), 116–123.
49. [49] Dentali, F, Marchesi, C, Giorgi Pierfranceschi, M, et al. Safety of prothrombin complex concentrates for rapid anticoagulation reversal of vitamin K antagonists. A meta-analysis. Thromb Haemost 106 (2011), 429–438.
50. [50] Milling, TJ Jr., Refaai, MA, Goldstein, JN, et al. Thromboembolic events after vitamin K antagonist reversal with 4-factor prothrombin complex concentrate: exploratory analyses of two randomized, plasma-controlled studies. Ann Emerg Med 67 (2016), 96–105.
51. [51] Watson, HG, Baglin, T, Laidlaw, SL, et al. A comparison of the efficacy and rate of response to oral and intravenous vitamin K in reversal of over-anticoagulation with warfarin. Br J Haematol 115 (2001), 145–149.
52. [52] Keeling, D, Baglin, T, Tait, C, et al. Guidelines on oral anticoagulation with warfarin - fourth edition. Br J Haematol 154 (2011), 311–324.
53. [53] Tsu, LV, Dienes, JE, Dager, WE, Vitamin K dosing to reverse warfarin based on INR, route of administration, and home warfarin dose in the acute/critical care setting. Ann Pharmacother 46 (2012), 1617–1626.
54. [54] Kalus, JS, Pharmacologic interventions for reversing the effects of oral anticoagulants. Am J Health Syst Pharm 70 (2013), S12–S21.
55. [55] Woo, CH, Patel, N, Conell, C, et al. Rapid warfarin reversal in the setting of intracranial hemorrhage: a comparison of plasma, recombinant activated factor VII, and prothrombin complex concentrate. World Neurosurg 81 (2014), 110–115.
56. [56] Yasaka, M, Sakata, T, Minematsu, K, et al. Correction of INR by prothrombin complex concentrate and vitamin K in patients with warfarin related hemorrhagic complication. Thromb Res 108 (2002), 25–30.
57. [57] Carvalho, MC, Rodrigues, AG, Conceicai, LM, et al. Prothrombin complex concentrate (Octaplex): a Portuguese experience in 1152 patients. Blood Coagul Fibrinolysis 23 (2012), 222–228.
58. [58] Leal-Noval, SR, Lopez-Irizo, R, Bautista-Paloma, J, et al. Efficacy of the prothrombin complex concentrate prothromplex in patients requiring urgent reversal of vitamin K antagonists or presenting with uncontrolled bleeding: a retrospective, single center study. Blood Coagul Fibrinolysis 24 (2013), 862–868.
59. [59] Greinacher, A, Thiele, T, Selleng, K, Reversal of anticoagulants: an overview of current developments. Thromb Haemost 113 (2015), 931–942.
60. [60] Mo, Y, Yam, FK, Recent advances in the development of specific antidotes for target-specific oral anticoagulants. Pharmacotherapy 35 (2015), 198–207.
61. [61] Pollack, CV Jr., Reilly, PA, Eikelboom, J, et al. Idarucizumab for dabigatran reversal. N Engl J Med 373 (2015), 511–520.
62. [62] Siegal, DM, Curnutte, JT, Connolly, SJ, et al. Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med 373 (2015), 2413–2424.
63. [63] Ansell, JE, Bakhru, SH, Laulicht, BE, et al. Use of PER977 to reverse the anticoagulant effect of edoxaban. N Engl J Med 371 (2014), 2141–2142.
64. [64] Hunt, BJ, Bleeding and coagulopathies in critical care. N Engl J Med 370 (2014), 847–859.