Main Article Content
Prothrombin complex concentrate, outcome, predictors
Aim: To compare the demographical profile, indications, efficacy, and contributors to adverse outcome following administration of 4F-PCC in patients on warfarin with supratherapeutic INR.
Methodology: Retrospective cross-sectional study was performed in a community based teaching hospital. All patients 18 years and older on warfarin with supratherapeutic INR, who had received 4F-PCC between January 2014 and December 2018 were eligible and included in the study.
Results: 44 patients were included in the analysis. The mean age of the patients was 79.5 years. The male to female ratio was 1:1. Patients were on warfarin for atrial fibrillation, thromboembolism in 79.5% (N-35), and 20.5% (N-9) respectively. Indications for use of 4F-PCC were active bleeding in 93% (N-41) of patients. The common sites of bleeding were gastrointestinal, intracranial, and musculoskeletal which were seen in 54.5% (N-24), 29.5% (N-13) and 6.8% (N-3) respectively. The median number of doses of 4F-PCC administered was 1 per patient. The mean dose administered was 2,883u. Clinical improvement was documented in 84% (N-37) of patients. Mortality was seen in 16% (N-7) of patients. BMI greater than 30, anemia, hypotension, presence of intracranial bleed, the requirement of blood products, and mechanical ventilation were associated with higher odds for mortality. Hypotension and requirement of mechanical ventilation were statistically significant.
Conclusion: 4F-PCC continues to be an effective agent in the rapid reversal of warfarin therapy in patients with supratherapeutic INR presenting with major bleeding events. Most patients have clinical improvement with a single, weight-adjusted dose.
2. Sarode Ravi, Milling Truman J., Refaai Majed A., Mangione Antoinette, Schneider Astrid, Durn Billie L., et al. Efficacy and Safety of a 4-Factor Prothrombin Complex Concentrate in Patients on Vitamin K Antagonists Presenting With Major Bleeding. Circulation. 2013 Sep 10;128(11):1234–43.
3. Sahu KK, Mishra AK, Lal A, George SV. Retroperitoneal and rectus sheath hematomas: Challenges in diagnosis and management. Am J Surg. 2019 Jun 12;
4. Sridharan M, Wysokinski WE, Pruthi R, Oyen L, Freeman WD, Rabinstein AA, et al. Periprocedural warfarin reversal with prothrombin complex concentrate. Thromb Res. 2016 Mar;139:160–5.
5. Huang W-T, Cang WC, Derry KL, Lane JR, von Drygalski A. Four-Factor Prothrombin Complex Concentrate for Coagulopathy Reversal in Patients With Liver Disease. Clin Appl Thromb Off J Int Acad Clin Appl Thromb. 2017 Nov;23(8):1028–35.
6. Dybdahl D, Walliser G, Chance Spalding M, Pershing M, Kincaid M. Four-factor prothrombin complex concentrate for the reversal of factor Xa inhibitors for traumatic intracranial hemorrhage. Am J Emerg Med. 2019;37(10):1907–11.
7. Barzilai M, Kirgner I, Steimatzky A, Salzer Gotler D, Belnick Y, Shacham-Abulafia A, et al. Prothrombin Complex Concentrate before Urgent Surgery in Patients Treated with Rivaroxaban and Apixaban. Acta Haematol. 2019 Oct 14;1–6.
8. Piran S, Gabriel C, Schulman S. Prothrombin complex concentrate for reversal of direct factor Xa inhibitors prior to emergency surgery or invasive procedure: a retrospective study. J Thromb Thrombolysis. 2018 May;45(4):486–95.
9. Mačiukaitienė J, Bilskienė D, Tamašauskas A, Bunevičius A. Prothrombin Complex Concentrate for Warfarin-Associated Intracranial Bleeding in Neurosurgical Patients: A Single-Center Experience. Med Kaunas Lith. 2018 Apr 25;54(2).
10. Maguire M, Fuh L, Goldstein JN, Marshall AL, Levine M, Howell ML, et al. Thromboembolic Risk of 4-Factor Prothrombin Complex Concentrate versus Fresh Frozen Plasma for Urgent Warfarin Reversal in the Emergency Department. West J Emerg Med. 2019 Jul;20(4):619–25.
11. Sheikh-Taha M. Treatment of apixaban- and rivaroxaban-associated major bleeding using 4-factor prothrombin complex concentrate. Intern Emerg Med. 2019 Mar;14(2):265–9.
12. Fitzgerald J, Lenihan M, Callum J, McCluskey SA, Srinivas C, van Rensburg A, et al. Use of prothrombin complex concentrate for management of coagulopathy after cardiac surgery: a propensity score matched comparison to plasma. Br J Anaesth. 2018 May;120(5):928–34.
13. Sahu KK, Mishra AK, Lal A, George SV, Siddiqui AD. Clinical spectrum, risk factors, management and outcome of patients with retroperitoneal hematoma: a retrospective analysis of 3-year experience. Expert Rev Hematol. 2020 Mar 3;1–11.
14. Sahu KK, Mishra AK, Lal A, Davuluri V. An interesting case of gluteal haematoma. BMJ Case Rep. 2019 Aug;12(8):e230282.
15. Sahu KK, Maradana S, Mishra A, Chastain I. A spontaneous rectus sheath hematoma. Intern Emerg Med. 2018;13(8):1341–3.
16. Quinlan Daniel J., Eikelboom John W., Weitz Jeffrey I. Four-Factor Prothrombin Complex Concentrate for Urgent Reversal of Vitamin K Antagonists in Patients With Major Bleeding. Circulation. 2013 Sep 10;128(11):1179–81.
17. Kushimoto S, Fukuoka T, Kimura A, Toyoda K, Brainsky A, Harman A, et al. Efficacy and safety of a 4-factor prothrombin complex concentrate for rapid vitamin K antagonist reversal in Japanese patients presenting with major bleeding or requiring urgent surgical or invasive procedures: a prospective, open-label, single-arm phase 3b study. Int J Hematol. 2017 Dec;106(6):777–86.
18. Laubham M, Kallwitz E. Coagulation in chronic liver disease and the use of prothrombin complex concentrate for an emergent procedure: a case report and review of literature. J Community Hosp Intern Med Perspect. 2018;8(3):138–41.
19. Mishra AK, Sahu KK, Basaula NP, Lal A. Letter to the Editor Regarding “Management of spinal emergencies in patients on direct oral anticoagulants.” World Neurosurg. 2019;132:446.
20. Smith MN, Deloney L, Carter C, Weant KA, Eriksson EA. Safety, efficacy, and cost of four-factor prothrombin complex concentrate (4F-PCC) in patients with factor Xa inhibitor-related bleeding: a retrospective study. J Thromb Thrombolysis. 2019 Aug;48(2):250–5.
21. Peyko V, Shams D, Urbanski R, Noga J. 4-Factor Prothrombin Complex Concentrate Administration via Intraosseous Access for Urgent Reversal of Warfarin. J Emerg Med. 2019 Jul;57(1):82–4.
22. Unold D, Tormey CA. Clinical Applications of 4-Factor Prothrombin Complex Concentrate: A Practical Pathologist’s Perspective. Arch Pathol Lab Med. 2015 Nov 30;139(12):1568–75.
23. Refaai MA, Goldstein JN, Lee ML, Durn BL, Milling TJ, Sarode R. Increased risk of volume overload with plasma compared with four-factor prothrombin complex concentrate for urgent vitamin K antagonist reversal. Transfusion (Paris). 2015 Nov;55(11):2722–9.
24. Mishra AK, Sahu KK, Siddiqui AD, George SV. Initiation of a fixed- dose four- factor prothrombin complex concentrate protocol. J Thromb Thrombolysis. 2020 Feb;49(2):332–3.
25. Marcos-Jubilar M, García Erce JA, Martínez-Calle N, Páramo JA, Martínez Virto A, Quintana-Díaz M. Safety and effectiveness of a prothrombin complex concentrate in approved and off-label indications. Transfus Med Oxf Engl. 2019 Aug;29(4):268–74.
26. Mitsiakos G, Karametou M, Gkampeta A, Karali C, Papathanasiou AE, Papacharalambous E, et al. Effectiveness and Safety of 4-factor Prothrombin Complex Concentrate (4PCC) in Neonates With Intractable Bleeding or Severe Coagulation Disturbances: A Retrospective Study of 37 Cases. J Pediatr Hematol Oncol. 2019 Apr;41(3):e135–40.
27. Harris JE, Varnado S, Herrera E, Salazar E, Colavecchia AC. Evaluation of postoperative clinical outcomes in Jehovah’s Witness patients who receive prothrombin complex concentrate during cardiac surgery. J Card Surg. 2020 Feb 12;
28. Sahu KK, Mishra AK, Zhang P. Femoral Neuropathy: A Rare Presentation of Retroperitoneal Hematoma with Review of Literature. Indian J Hematol Blood Transfus Off J Indian Soc Hematol Blood Transfus. 2020 Jan;36(1):174–7.
29. Mishra, A. K., Sahu, K. K., & Lal, A. (2020). Stroke Symptoms in a Patient on 4-Factor Prothrombin Complex. Hospital Pharmacy. https://doi.org/10.1177/0018578720910395
30. Peksa GD, Mokszycki RK, Rech MA, Maynard B, Panos NG, Sweis RT, DeMott JM. Reversal of Warfarin-Associated Major Hemorrhage: Activated Prothrombin Complex Concentrate versus 4-Factor Prothrombin Complex Concentrate. Thromb Haemost. 2020 Feb;120(2):207-215. doi: 10.1055/s-0039-3400958. Epub 2019 Dec 14. PubMed PMID: 31837652.
31. Mishra AK, Aaron S, Abhilash K, Iyadurai R, Shaikh A, Lazarus E, et al. Simple telephone call a feasible, useful and acceptable method of following up patients with cerebrovascular accidents: Prospective Cohort study in South India. Int J Stroke Off J Int Stroke Soc. 2016;11(8):NP87–8.
32. Merchan C, Ahuja T, Raco V, Lewis A. High-Dose 4-Factor Prothrombin Complex Concentrate for Warfarin-Induced Intracranial Hemorrhage. Neurohospitalist. 2020;10(1):16–21. doi:10.1177/1941874419844343