Hemorrhagic transformation following ischemic stroke: significance, causes, and relationship to therapy and treatment.

Hemorrhagic transformation (HT) is a frequent consequence of ischemic stroke that becomes more prevalent after thrombolytic therapy. Despite concerns about safety parameters, thrombolytic drugs remain the first course of action available to clinicians for stroke management. However, recent efforts in preclinical studies have attempted to discover other drugs that can lessen the risk of hemorrhage associated with thrombolytic administration. This review focuses on three classes of pharmacologic agents that have shown some promise in animal models of stroke, and can thus be considered as possible candidates for coadministration with thrombolytics in the treatment of stroke. These include the following: 1) spin trap agents, such as alpha-phenyl-N-t-butylnitrone (PBN) that scavenge free radicals; 2) matrix metalloproteinase (MMP) inhibitors, such as BB-94, that prevent membrane and vessel remodeling following ischemia; and 3) the novel glycoprotein (GP) IIb/IIIa platelet receptor antagonist SM-20302. Although these drugs affect different mechanisms, the common denominator seemed to be their effectiveness in reducing the incidence of hemorrhage in response to thrombolytic infusion following an embolic stroke.