Intracranial hemorrhage in association with thrombolytic therapy: Incidence and clinical predictive factors

Abstract

In a period of 18 months, 2,469 patients with acute myocardial infarction treated with a thrombolytic agent were prospectively registered in 61 hospitals. Most patients (73%) were treated with streptokinase. Intracranial hemorrhage was observed in 24 patients, corresponding to an incidence rate of 1% (95% confidence interval 0.6% to 1.3%). The median time interval between the start of thrombolytic therapy and the first clinical signs of intracranial bleeding was 16 h (range 3 to 36). In total, 16 (66%) of the 24 patients died as a result of cerebral hematoma. To determine clinical predictive factors, a case-control study was conducted. For every patient with intracranial hemorrhage, two control patients who received thrombolytic therapy because of acute infarction in the same hospital and in the same period were selected. Detailed clinical characteristics of 22 of the 24 patients as well as of 7 other patients with documented intracerebral bleeding from the European Cooperative Study Group and of 2 patients who sustained intracranial hemorrhage outside the registry period were compared with 62 control patients. The results of multivariate logistic regression analysis indicate that patients taking an oral anticoagulant before admission, patients with a body weight less than 70 kg and those greater than 65 years old are at higher risk for intracranial hemorrhage during thrombolytic therapy.

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

“…Although a similar finding was reported in MI patients by Bovill et al, 10 Califf et al, 22 and DeJaegere et al, 15 the failure in these MI studies to base TPA dose on body weight or surface area leaves open the possibility that greater bleeding in lighter patients seen in those studies could simply have been a dose effect. In contrast, our data support the possibility that lighter patients may have a greater risk of bleeding independent of the TPA dose used.…”

“…DeJaegere et al 15 performed a case-control study of MI patients in the Netherlands who had intracranial hemorrhages while being treated with thrombolytic agents. Patients with a body weight less than 70 kg were nearly four times more likely to have an intracranial hemorrhage than heavier patients.…”

Intracranial Hemorrhage Associated With Thrombolytic Therapy for Elderly Patients With Acute Myocardial Infarction

“…Observational studies have not had sufficient power to achieve statistical significance despite at least 1 study with a suggestive trend. 25 Because excessive anticoagulation with warfarin is strongly and consistently related to intracranial hemorrhage and because it is specifically mentioned as a relative contraindication in national guidelines, we believed that its inclusion in the scale was justified.…”

“…7,35,38,43 Recommendation for weight-based dosing became widespread several years before the start of this study, based on results such as the TIMI-II. 29 A lower body weight may result in higher serum concentration of medication, resulting in a greater degree of fibrinolytic activity 25 and an increased risk for hemorrhage. It has been suggested that this effect may be seen with TPA but not streptokinase.…”

“…The generalizability of this low rate of intracranial hemorrhage to a broader population is limited by the highly selected nature of patients enrolled in clinical trials. 24 Trials enrolled healthier subjects compared with the patients in the community 25 ; older patients and women are particularly underrepresented. 26 Higher rates of intracranial hemorrhage have been reported in community-based studies; the Second National Registry of Myocardial Infarction (NRMI-2) reported a rate of intracranial hemorrhage of 0.95%.…”