Clinical ReviewsThe Clinical Use of Prothrombin Complex Concentrate
Introduction
Vitamin K antagonist (VKA) utilization has steadily risen in the past 20 years, increasing by 300% from 1993 to 2008 alone. VKAs are used for stroke risk reduction in patients with atrial fibrillation and mechanical heart valves, prevention of recurrent embolism after venous thromboembolism, and for treatment of genetic coagulation disorders (1). Trials in a variety of clinical settings have demonstrated a significant risk of bleeding with warfarin, which was as high as 1–3% per year of fatal or life-threatening bleeding in high-risk patients (2). International normalized ratios (INR) > 4 are associated with an increased absolute risk of intracranial hemorrhage (ICH), which can be as much as 2% per year. Continuation of elevated INR values for the initial 20 h post-ICH lead to increased risk of hematoma expansion, an independent risk factor of mortality (3).
Despite the introduction of newer oral anticoagulants, VKAs are still projected to play an important role in anticoagulation; therefore, it is imperative to maintain therapeutic options for bleeding reversal (4). Historically, the preferred method for VKA reversal has been vitamin K supplementation combined with blood products or recombinant factors. Interest has shifted to the potential benefit of using clotting factor concentrate for rapid, reliable, and sustained reversal of life-threatening hemorrhage in these patients.
Guidelines recommend prothrombin complex concentrate (PCC) use for life-threatening bleeds, but little is known concerning the most effective dosing strategies or the effect of presenting INR on response to therapy (5). PCC is an inactivated concentrate of factors II, IX, and X, with variable amounts of factor VII. The aim of this review is to highlight available data concerning PCC, including monitoring techniques, reversal of life-threatening bleeds, and comparison with other therapeutic options. Shortcomings of currently available data will also be addressed.
Section snippets
Warfarin and Reversal Therapies
Warfarin inhibits vitamin K epoxide reductase enzyme, thus preventing reactivation of the vitamin K-dependent clotting factors II, VII, IX, and X, and the endogenous anticoagulant proteins C and S. Reversal of this mechanism is accomplished through administration of vitamin K or exogenous clotting factor supplementation. Vitamin K, administered intravenously or orally, is the treatment of choice for patients presenting with an elevated INR without signs of clinical bleeding. Patients presenting
Conclusion
PCC has identified itself as a potential therapy for critically bleeding patients, but patient-specific factors, product availability, and current data should weigh into this decision. The most documented data exist in the setting of VKA-induced bleeding, specifically ICH, which supports the utilization of PCCs because there was more of a profound and rapid reduction in INR. As health care professionals, we must remain aware of the differences in products and interpret how three- vs.
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Cited by (33)
Hemorrhagic disorders and laboratory assessment
2019, Rodak’s Hematology: Clinical Principles and ApplicationsFour-factor prothrombin complex concentrate for life-threatening bleeds or emergent surgery: A retrospective evaluation
2016, Journal of Critical CareCitation Excerpt :Limitations of FFP include risk of transfusion-related acute lung injury, hypocalcemia, disease transmission, prolonged time required for infusion, and potential for fluid overload, particularly in patients with heart failure, liver cirrhosis, or renal insufficiency. Kcentra is available as a lyophilized powder, allowing for easy reconstitution and rapid intravenous administration in small volumes [9-12]. For example, a 70 kg patient would receive 70 to 140 mL of 4F-PCC depending on the pre-treatment international normalized ratio (INR), as opposed to 700 to 1050 mL of FFP.
Bleeding and coagulation management in clinical practice. Evaluation of the evidence and recommendations using GRADE strategy. First expert meeting
2016, Acta Colombiana de Cuidado IntensivoSuperwarfarin ingestion treated successfully with prothrombin complex concentrate
2016, American Journal of Emergency MedicineLimb-threatening Deep Venous Thrombosis Complicating Warfarin Reversal with Three-factor Prothrombin Complex Concentrate: A Case Report
2016, Journal of Emergency MedicineCitation Excerpt :Data for three-factor PCC reversal of warfarin-related coagulopathy remain scarce, though preliminary results are mixed (10–12). Profilnine, a three-factor PCC that was administered to our patient, does not contain the anticoagulant proteins C and S, or heparin, which are each present in varying amounts in other three- and four-factor PCCs (brand names Bebulin® [Baxter Healthcare Corporation, Westlake Village, CA], Octaplex® [Octapharma Canada, Inc., Toronto, ON, Canada], and Kcentra® [CSL Behring, Kankakee, IL]) in an attempt to combat the postulated risk of thrombosis from rapid and concentrated infusion of procoagulant factors (13,14). Definitive data from high-quality randomized trials comparing thromboembolic risks between PCC and standard therapy with FFP have not been reported.