The Heidelberg Bleeding Classification: Classification of Bleeding Events After Ischemic Stroke and Reperfusion Therapy.

Intracranial hemorrhage is an important safety end point in clinical trials. Yet, not each intracranial hemorrhage detected by computed tomography (CT) or magnetic resonance imaging (MRI) worsens neurological symptoms and impairs outcomes. Consequently, intracranial hemorrhages after ischemic stroke and reperfusion therapy are classified by both imaging characteristics and the association with clinical worsening. Pure radiological classification uses the location, form, and extent of hemorrhage and its relation to ischemic injury to distinguish among hemorrhage subtypes that may differ in impairment of neurological function and prognosis. Mixed radiological–clinical classification adds clinical symptoms to the presence of radiological hemorrhage to classify intracranial hemorrhages as symptomatic or asymptomatic. Historically, modern approaches to classifying hemorrhage after reperfusion therapy began with the emphasis of Pessin et al on the radiographic distinction between hemorrhagic infarction (HI) and parenchymatous hematoma (PH) after embolic stroke. They stated that HI refers to the pathological condition in which petechial or more confluent hemorrhages occupy a portion of an area of ischemic infarction. PH in an area of infarction; in contrast, is a solid clot of blood with mass effect, which displaces and destroys brain tissue. They later proposed that HI (in contrast to PH) could be more of a CT curiosity than a dreaded complication. Wolpert et al defined HI as areas of barely visible increased density with indistinct margins within an infarct or areas of increased density with indistinct margins and a speckled or mottled appearance or multiple areas of coalescent hemorrhage. A mass effect could be present because of the either edema or hemorrhagic component and PH (later named parenchymal hematoma) and as very dense, homogenous region(s) of circumscribed increased density usually with mass effect. Both HI and PH are presumably caused by the same postischemic pathophysiology, bleeding from damaged reperfused arteries, arterioles, capillaries, or venules. Levy et al first used the term symptomatic intracranial hemorrhage (SICH) and distinguished intracerebral hematoma from hemorrhagic conversion by requiring either contemporaneous neurological worsening or a new mass effect on CT for intracerebral hematoma. The European Cooperative Acute Stroke Study (ECASS) group graded each HI and PH into the CT grades 1 and 2 to evaluate with greater nuance the clinical relevance of intracranial hemorrhage as detected on CT after ischemic stroke. In agreement with histological findings, the ECASS protocol adapted pre-existing criteria to define HI 1 as small petechiae along the margins of the infarct, and HI 2 as more confluent petechiae within the infarcted area, but without space-occupying effect. PH 1 was defined as a clot not exceeding 30% of the infarcted area with some mild space-occupying effect. PH 2 represented dense blood clot(s) exceeding 30% of the infarct volume with significant space-occupying effect. Interobserver agreement on these categories was good although the justification for the 30% The Heidelberg Bleeding Classification Classification of Bleeding Events After Ischemic Stroke and Reperfusion Therapy