Factors related to intracranial hematoma formation in patients receiving tissue-type plasminogen activator for acute ischemic stroke.

Abstract

Several studies are currently evaluating tissue-type plasminogen activator (TPA) as a potential therapy in acute ischemic stroke. The possibility of inducing intracranial hematomas, however, introduces an important concern into ultimate evaluation of risk and benefit. This retrospective analysis sought to identify factors associated with intracranial hematoma formation in a pilot phase 1 study of TPA for stroke. Ninety-four patients received TPA within 3 hours of the onset of an acute ischemic stroke. Five of these patients developed a symptomatic intracerebral hematoma: 3 of 74 (4%) among patients treated within 90 minutes of stroke onset and 2 of 20 (10%) among those treated at 91 to 180 minutes. Three of the 5 died within 2 weeks. The analysis investigated associations between clinical factors and intracerebral hematomas. Factors significantly related to the development of an intracerebral hematoma were TPA dose and diastolic hypertension. Intracerebral hematomas developed in 4 (18%) of 22 patients given a TPA dose of at least 0.90 mg/kg versus only 1 hematoma in the remaining 72 patients (1%; P < .02, Fisher's exact test). Four (18%) of 22 patients who had initial diastolic blood pressures of at least 100 mm Hg suffered an intracerebral hematoma versus only 1 (1%) of 72 patients (P < .02) with lower initial diastolic pressures. Since the study was not designed to test specific safety hypotheses, results must not be overinterpreted. Nonetheless, these data emphasize the need for caution in both patient and dose selection for further studies of thrombolytic agents in stroke.

Predictors of Hemorrhage Following Intra-Arterial Thrombolysis for Acute Ischemic Stroke: The Role of Pial Collateral Formation

“…[23][24][25] Clinical factors shown to be associated with a higher incidence of HT include profound clinical deficit as represented by a high presenting NIHSS score, longer time to treatment, use of anticoagulants, lower platelet levels, history of diabetes, elevated systolic blood pressure, and elevated presenting glucose levels. 2,5,9,[14][15][16][17][18][19][20][21][22] Imaging findings predictive of HT have included larger territory at risk for infarction as indicated by either a large diffusion abnormality on MR imaging, 4,6 a larger perfusion defect (MR imaging, CT, single-photon emission CT), 3,6 early CT hypoattenuation, 5,7,8,26 or a large infarct volume. 10 Pial collateral flow to an ischemic territory may improve clinical outcomes by sustaining ischemic tissue for longer pe- , D and E).…”

Analysis of Combined Treatment of Embolic Stroke in Rat with r-tPA and a GPIIb/IIIa Inhibitor

“…This suggests that the combination therapy does not increase and may reduce the incidence of hemorrhagic transformation. Furthermore, since 7E3 F(ab 0 ) 2 could amplify the efficacy of fibrinolytic therapy with r-tPA, the dose of r-tPA may be reduced, thereby further reducing the incidence of hemorrhagic transformation (Levy et al, 1994).…”

Spontaneous Intracranial Internal Carotid Artery Dissection Treated by Intra-arterial Thrombolysis and Superficial Temporal Artery-Middle Cerebral Artery Anastomosis in the Acute Stage-Case Report-

“…Early ischemic changes on CT, delayed treatment, advanced age of the patients (aged À70 years), and hypertension are all risk factors for intracerebral hematoma formation after intravenous thrombolysis with recombinant tissue plasminogen activator. 3,12,14,16,27) To reduce the risk of hemorrhagic transformation, we performed thrombolysis (2 hours after the onset) and STA-MCA anastomosis (7 hours after the onset) as soon as possible, confirmed the absence of early ischemic changes on CT before each treatment, and maintained the systolic blood pressure under 140 mmHg and the diastolic pressure under 80 mmHg.…”