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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Levy
D E
DE
Department of Neurology, Cornell University Medical College, New York, NY.
Brott
T G
TG
Haley
E C
EC
Marler
J R
JR
Sheppard
G L
GL
Barsan
W
W
Broderick
J P
JP
D000328:Adult; D000367:Age Factors; D000368:Aged; D000704:Analysis of Variance; D001241:Aspirin / Q000627:therapeutic use; D002545:Brain Ischemia / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D002543:Cerebral Hemorrhage / Q000209:etiology*; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000150:complications; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D012737:Sex Factors; D015912:Thrombolytic Therapy / Q000009:adverse effects*; D010959:Tissue Plasminogen Activator / Q000009:adverse effects* / Q000627:therapeutic use
D011994:Recombinant Proteins; D005340:Fibrinogen; D006493:Heparin; D010959:Tissue Plasminogen Activator; D001241:Aspirin