Treatment of warfarin-associated intracerebral hemorrhage: literature review and expert opinion.

Wider use of oral anticoagulants has led to an increasing frequency of warfarin-related intracerebral hemorrhage (ICH). The high early mortality of approximately 50% has remained stable in recent decades. In contrast to spontaneous ICH, the duration of bleeding is 12 to 24 hours in many patients, offering a longer opportunity for intervention. Treatment varies widely, and optimal therapy has yet to be defined. An OVID search was conducted from January 1996 to January 2006, combining the terms warfarin or anticoagulation with intracranial hemorrhage or intracerebral hemorrhage. Seven experts on clinical stroke, neurologic intensive care, and hematology were provided with the available information and were asked to independently address 3 clinical scenarios about acute reversal and resumption of anticoagulation in the setting of warfarin-associated ICH. No randomized trials assessing clinical outcomes were found on management of warfarin-associated ICH. All experts agreed that anticoagulation should be urgently reversed, but how to achieve it varied from use of prothrombin complex concentrates only (3 experts) to recombinant factor VIIa only (2 experts) to recombinant factor VIIa along with fresh frozen plasma (1 expert) and prothrombin complex concentrates or fresh frozen plasma (1 expert). All experts favored resumption of warfarin therapy within 3 to 10 days of ICH in stable patients in whom subsequent anticoagulation is mandatory. No general agreement occurred regarding subsequent anticoagulation of patients with atrial fibrillation who survived warfarin-associated ICH. For warfarin-associated ICH, discontinuing warfarin therapy with administration of vitamin K does not reverse the hemostatic defect for many hours and is inadequate. Reasonable management based on expert opinion includes a wide range of additional measures to reverse anticoagulation in the absence of solid evidence.

In vivo efficacy of aerosolized nanostructured itraconazole formulations for prevention of invasive pulmonary aspergillosis.

Aerosolized evaporative precipitation into aqueous solution and spray freezing into liquid nanostructured formulations of itraconazole as prophylaxis significantly improved survival relative to commercial itraconazole oral solution and the control in a murine model of invasive pulmonary aspergillosis. Aerosolized administration of nanostructured formulations also achieved high lung tissue concentrations while limiting systemic exposure.