Prothrombin Complex Concentrates for Warfarin-Related Intracranial Hemorrhage: Should they Replace Fresh Frozen Plasma?

Abstract

Intracranial hemorrhage (ICH) is a medical emergency. Rapid diagnosis and management of patients with ICH is important because rapid deterioration is common in the first few hours after ICH onset. Patients undergoing treatment with oral anticoagulants, mainly warfarin, constitute 12% to 14% of patients with ICH (1,2). Patients with warfarin-related ICH have a high mortality rate close to 60%, compared to about 40% for nonanticoagulated patients with ICH (3,4). The poor outcome in warfarin-related ICH is mainly related to volume of hemorrhage and expansion of the hematoma size after admission (2,5). In addition, early expansion of the hematoma occurs more frequently in anticoagulated (54%) versus nonanticoagulated (16%) patients with ICH (6). A major predictor of mortality and worse outcome is higher initial international normalized ratio (INR). The general recommendation is thus to correct the INR as rapidly as possible (7). Vitamin K and fresh-frozen plasma (FFP) have historically been recommended, but recently, prothrombin complex concentrates (PCCs) have emerged as potential therapies. PCCs are concentrates of the vitamin K-dependent factors II, VII, IX, and X, as well as proteins C and S. PCCs are available with low amounts of factor VII (three factor PCCs, used mainly in the United States) and higher concentrations of factor VII (four-factor PCCs, commonly used in Europe). PCCs have the advantages of rapid reconstitution with high concentrations of coagulation factors