Clinical Reviews
The Clinical Use of Prothrombin Complex Concentrate

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Abstract

Background

Prothrombin complex concentrate (PCC) is an inactivated concentrate of factors II, IX, and X, with variable amounts of factor VII. Guidelines recommend the use of PCC in the setting of life-threatening bleeds, but little is known on the most effective dosing strategies and how the presenting international normalized ratio affects response to therapy.

Objectives

This review aims to highlight available data on monitoring techniques, address shortcomings of currently available data, the reversal of life-threatening and critical bleeds with PCC, and how this product compares to other therapeutic options used in critically ill patients.

Discussion

PCC has been identified as a potential therapy for critically bleeding patients, but patient-specific factors, product availability, and current data should weigh the decision to use it. Most data exist regarding patients experiencing vitamin K antagonist-induced bleeding, more specifically, those with intracranial hemorrhage. PCC has also been studied in trauma-induced hemorrhage; however, it remains controversial, as its potential benefits have the abilities to become flaws in this setting.

Conclusion

Health care professionals must remain aware of the differences in products and interpret how three- versus four-factor products may affect patients, and interpret literature accordingly. The clinician must be cognizant of how to progress when treating a bleeding patient, propose a supported dosing scheme, and address the need for appropriate factor VII supplementation. At this point, PCC cannot be recommended for first-line therapy in patients with traumatic hemorrhage, and should be reserved for refractory bleeding until more data are available.

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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