Plasma versus prothrombin complex concentrate for warfarin-associated major bleeding: a systematic review

Abstract

Learning Objective• To compare the efficacy and adverse effects of prothrombin complex concentrate and plasma for rapid correction of vitamin K antagonist-associated hemorrhagic emergency Clinical vignetteA 78-year-old female presents to the emergency department with brisk hematochezia, fatigue, and tachycardia. She is receiving chronic oral anticoagulant therapy with warfarin as thromboprophylaxis for a mechanical mitral valve. International normalized ratio (INR) is 4.2. Red blood cell transfusion is ordered, and 10 mg of intravenous vitamin K is given. You are asked whether plasma or prothrombin complex concentrate is more effective for emergent reversal of her warfarin-associated coagulopathy.Warfarin is a vitamin K antagonist (VKA) that has been the mainstay of oral anticoagulant therapy for the prevention and treatment of thromboembolism. Bleeding is the major complication of anticoagulant therapy with rates of major warfarin-related bleeding up to 7% reported depending on the indication for anticoagulation and study design. [1][2][3][4][5] Warfarin use increases the risk of major bleeding by 0.3%-0.5%/year and intracranial hemorrhage (ICH) by 0.2%/year compared to controls in clinical trials. 1 Despite the availability of warfarin-reversal agents, warfarin-associated bleeding leads to significant morbidity and mortality, with case fatality rates of 8%-13%. 5-8 Death in hospital or within 7 days of discharge has been reported in 18% of warfarin-treated atrial fibrillation patients presenting with major bleeding. 9 In patients presenting with warfarin-associated ICH, high mortality rates of 54% and 64% have been reported at 30 days and 6 months, respectively. 10Although direct oral anticoagulants (DOACs) are now approved for several indications, warfarin use is expected to continue for patients who are stably managed on long-term warfarin therapy, conditions in which DOACs are not proven (eg, antiphospholipid antibody syndrome, mechanical heart valves), patients with severe renal failure (creatinine clearance Ͻ30 mL/min), and patients for whom DOACs are cost prohibitive.Warfarin-associated major bleeding complications require urgent reversal of coagulopathy. When given intravenously, the effect of vitamin K on warfarin coagulopathy is evident within 6 hours. Plasma contains all coagulation factors and will correct coagulation factor deficiency attributable to inadequate synthesis. Time to thaw frozen plasma (FP) may in some circumstances be a limitation, but large blood banks typically have a continuous stock of thawed plasma. The infusion time depends on vascular access and volume status of the patient. Fluid overload and mild allergic reactions are the most common adverse reactions to plasma (ϳ1 in 100 transfusions). Serious allergic and transfusion-related acute lung injury reactions are rare (ϳ1 in 10 000 transfusions). [11][12][13][14][15][16] Prothrombin complex concentrates (PCCs) are plasma-derived products containing vitamin K-dependent factors II, VII, IX, and X (4-factor PCC) or II, IX, and X (3-...

Bloodless Management of the Anemic Patient in the Emergency Department

“…17 Prothrombin complex concentrate containing factors II, IX, and X is referred to as "3-factor prothrombin complex concentrate"; these factors, along with factor VII, are also included in the "4-factor prothrombin complex concentrate" currently available in the United States and indicated for the reversal of acute major bleeding associated with the use of vitamin K antagonists (eg, warfarin). 18,19 Advantages of prothrombin complex concentrate over fresh frozen plasma include a lower volume of infusion, lack of blood group specificity, and ease of use (it is stored at room temperature and can be reconstituted quickly). 18,20 Dosing of prothrombin complex concentrate is based on the patient's body weight as well as the international normalized ratio.…”

“…18,19 Advantages of prothrombin complex concentrate over fresh frozen plasma include a lower volume of infusion, lack of blood group specificity, and ease of use (it is stored at room temperature and can be reconstituted quickly). 18,20 Dosing of prothrombin complex concentrate is based on the patient's body weight as well as the international normalized ratio. However, as the coagulation factors contained in prothrombin complex concentrate are derived from human plasma, they are considered as minor blood fractions and may not be acceptable to all bloodless medicine patients.…”