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  • Updated 07.23.2023
  • Released 02.28.1995
  • Expires For CME 07.23.2026

Hemorrhagic transformation of ischemic stroke



Hemorrhagic transformation after ischemic stroke is an often underdiagnosed phenomenon. With the increasing and widespread use of tPA and with improved imaging capabilities afforded by newer sequences on MRI, it is now possible to predict which patients might be at increased risk of clinically significant hemorrhagic transformation. In this article, the authors have added information about the risk of hemorrhagic transformation with tPA, the use of minocycline to decrease the risk of hemorrhagic transformation, and the predictive value of hemorrhagic transformation in long-term prognosis.

Key points

• Hemorrhagic transformation is a complication of ischemic stroke, occurring in about 10% of patients, although rates depend on the diagnostic method and criteria used.

• The spectrum of hemorrhagic transformation ranges from minor petechial bleeding (hemorrhagic infarct) to major mass-producing hemorrhage (parenchymal hematoma).

• Only parenchymal hematoma, seen in about 3% of patients, is associated with adverse outcomes.

Historical note and terminology

Historically, hemorrhagic infarction, initially designated as "red softening," has long been recognized by neuropathologists to occur as a natural consequence of ischemic brain injury. Several early theories were advanced to explain the pathogenesis of secondary bleeding into a bland (pale, anemic) infarction. Cohnheim proposed that hemorrhagic infarction resulted from the embolic occlusion of end arteries followed by venous reflux into damaged vascular beds (36). “Infarction” to Cohnheim still had the original sense of “stuffing.” In this case, the stuffing was “hemopoietic,” hemorrhagic. He observed two successive events: (1) the retrograde filling and the distension with blood of the venous and capillary void distal to the plug and (2) the subsequent diapedesis of red corpuscles through the vessel wall, damaged secondarily by the loss of their normal blood supply (141). The following year, Liddel recognized that hemorrhagic changes may occur early, often within 2 days, following embolic infarction (112). The role of venous reflux was later discounted by Hiller, who cited the potential importance of collateral circulation in the genesis of secondary bleeding (71).

Fisher and Adams' landmark paper established the special predilection for embolic infarcts to undergo a dynamic process of hemorrhagic transformation (51). The concept of "migratory embolism" rested on their observations that the hemorrhagic portion of an infarction often lay proximal to identified emboli, whereas pale zones of infarction were distal to persisting occlusions. They proposed that the molding and fragmentation of emboli due to hemodynamic forces results in distal clot migration, thereby exposing an ischemically damaged vascular bed to reperfusion and subsequent bleeding.

Hain and colleagues cited two prerequisites for the production of a hemorrhagic infarction: "one, a sufficient volume of blood must flow through the vessels distal to the site of occlusion to produce a hemorrhagic area, and two, there must be sufficient alteration in the permeability of the vessel wall to permit the escape of blood into the tissue" (62).

The current classification of hemorrhagic transformation encompasses a broad spectrum of secondary bleeding ranging from small areas of petechial hemorrhage to massive space-occupying hematomas. The distinction between hemorrhagic infarction and parenchymatous hematoma is important, as the clinical outcome and perhaps the pathogenesis of these two types of hemorrhagic transformation may differ (50). Hemorrhagic infarction on CT scan appears as patchy petechial or more confluent areas of bleeding (increased attenuation), often with indistinct margins and confined within the vascular territory of the infarction. This pattern of hemorrhagic transformation is thought to represent the diapedesis of blood cells through ischemic capillaries without frank rupture of a vessel. Involvement of cortical tissues often appears gyriform in pattern.

Hemorrhagic transformation (CT)
(Left) Gyriform petechial hemorrhagic transformation within the territory of right middle cerebral infarction. (Right) Asymptomatic petechial hemorrhagic transformation confined to cortical gyri. (Contributed by Dr. Philip Teal.)

Parenchymal hematomas, by contrast, are discrete, dense, homogeneous collections of blood (high attenuation on CT) that may extend to the ventricle and often exert mass effect.

Parenchymatous hematoma (CT)
Parenchymal hemorrhage with associated mass effect and clinical deterioration. (Contributed by Dr. Philip Teal.)

In most instances, parenchymatous hematomas are due to the rupture of an ischemic vessel that has been subject to reperfusion pressures. Some hemorrhagic transformations may be indeterminate with overlapping features of both hemorrhagic infarction and parenchymatous hematoma.

Mixed or indeterminate hemorrhages (CT)
(Left) High-attenuation changes due to predominantly gyriform petechial bleeding but accompanied by mass effect and clinical worsening. (Right) Small anterior parenchymal hematoma with subtle petechial gyriform bleeding along post...

The MRI appearance of hemorrhagic infarction varies depending on the stage of hemorrhage; hemosiderin produces T2 shortening with signal loss, whereas methemoglobin results in a high-signal appearance on T1-weighted images. MRI is more sensitive in detecting small areas of hemorrhage than is CT (93; 127).

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