Systematic review: 3-factor versus 4-factor prothrombin complex concentrate for warfarin reversal: does it matter?

Immediate reversal of the anticoagulant effect of vitamin K antagonists, for example in case of intracranial hemorrhage or life-threatening bleeding may be achieved by administration of prothrombin complex concentrate (PCC). There are two types of PCCs: those containing four (vitamin K-dependent) factors II, VII, IX and X, and those containing mainly factors II, IX, and X. Voils and Baird performed a systematic review on the efficacy of these agents in clinical studies, specifically comparing the 3-factor and 4-factor concentrates. They found that INRs ranged from 1.2 to 1.9 after administration of 3-factor concentrates and from 1.0 to 1.9 in the 4-factor concentrate group. A decrease in the INR to levels <1.5 was seen in 6 out of 9 studies with 3-factor concentrates and in 12 out of 13 studies with 4-factor concentrates. The authors conclude that 4-factor PCCs result in a more reliable correction of the INR compared to 3-factor concentrates. The subject of this systematic review is basically important, since reversal of anticoagulant treatment may be important in specific clinical situations. These observations regarding several types of PCCs are also relevant in view of the mounting evidence that PCCs may also reverse the anticoagulant effect of the novel oral factor Xa and IIa inhibitors. A weakness of the review is its focus on correction of the INR. The INR is basically a prothrombin time that is known to be extremely sensitive to factor VII levels. Hence, it is no surprise that 4-factor PCCs do better than 3-factor PCCs (that do not contain factor VII). It is unclear how this translates into clinical efficacy in terms of cessation of bleeding. Therefore, the authors’ conclusion that 4-factor PCCs are more effective than 3-factor PCCs is somewhat premature and more clinical research is required before one type of PCC can be definitively preferred over the other. – Marcel Levi