Prothrombin Complex Concentrates Use in Intracerebral Hemorrhage.

We would treat with 4-factor PCCs because otherwise—with an INR of 1.9—there is a high risk of further expansion of an already large ICH. Without reversal of the anticoagulant effects of warfarin, the patient’s life is at stake. At age 65 years, he has a reasonable chance to recover from a right-sided ICH if treated early and aggressively. In our eyes, early withdrawal of care is not an option! Compared with spontaneous ICH, warfarin-associate ICH (WICH) is associated with an increased risk of hematoma expansion and subsequently higher morbidity and mortality. Achieving rapid hematoma stabilization must, therefore, be the therapeutic goal in this case. It is promoted most effectively by administering PCCs, while the risk of prothrombotic effects is low. Because of ventricular involvement of the bleed, the patient is at a high risk of developing occlusive hydrocephalus. This may warrant placement of an external ventricular drain, which should only be undertaken when the INR is within normal range. INR must be monitored closely; ideally shortly after application of 30 U of PCCs per kilogram of body weight and then at least daily until it is definitely stabilized at normal levels. Within the first 3 hours, we would readminister PCCs if the INR remains elevated—the same dose if the INR is ≥2 or 10 U/kg if the INR is >1.2. For sustained reversal effect, we would also administer 10 mg of vitamin K intravenously during or shortly after the acute admission phase. In addition to coagulation management, blood pressure should be controlled and early complications of ICH associated with severely impaired neurological status (eg, aspiration pneumonia) should be treated appropriately. In general, the evidence for treatment with PCCs in WICH is limited because of the absence of prospective clinical end point–driven randomized placebo-controlled trials, which must be considered unethical in the light of today’s knowledge: an association of hematoma expansion with ICH-related mortality is plausible and has been repeatedly established in several studies. Early reversal of coagulopathy, on the other hand, leads to a significant decrease in hematoma expansion. Consequently, international stroke guidelines recommend rapid reversal of anticoagulation in WICH with PCCs. The threshold for treatment, however, is still subject to discussion. Alternative means of achieving a normal coagulation status would be infusion of fresh frozen plasma or rFVIIa (recombinant activated factor VII). Fresh frozen plasma, however, has been proven to be of inferior efficacy regarding INR normalization and hematoma stabilization in several studies, including the randomized INCH trial (International Normalised Ratio Normalisation in Patients With CoumarinRelated Intracranial Hemorrhages). Moreover, the required large fresh frozen plasma infusion volumes may lead to fluid overload and transfusion-related acute lung injury. There is currently no data supportive of rFVIIa use in warfarin-related ICH; it is even suggested that rFVIIa does not have a clinically meaningful effect on hemostasis in warfarin-treated patients. Superiority of 4-factor PCCs over 3-factor PCCs is not established. Presumably, 4-factor PCC should offer a higher efficacy regarding normalization of coagulation status because Prothrombin Complex Concentrates Use in Intracerebral Hemorrhage