Intracranial Hemorrhage after Thrombolytic Therapy for MI
Intracranial Hemorrhage after Thrombolytic Therapy for MI
ABSTRACT & COMMENTARY
Synopsis: Although the overall incidence of intracranial hemorrhage after thrombolytic therapy is only about 1%, the risk is higher in elderly patients, those who are underweight, women, and individuals receiving oral anticoagulants; using TPA rather than another agent may also increase the risk.
Source: Conrad AR, et al. Southern Med J 1997;90:5-12.
Conrad et al at nassau county medical center in New York report a case of fatal hemorrhagic stroke complicating thrombolytic therapy for acute myocardial infarction (MI); they also review the literature in an attempt to identify risk factors and possible preventive measures for this devastating complication. Their patient was a previously healthy 71-year-old man who received 1.5 million units of streptokinase intravenously over a one-hour period after presenting with chest pain and ECG evidence of an acute inferolateral MI. He also received aspirin and, beginning four-hours after the streptokinase infusion, subcutaneous heparin at 12,500 units every 12 hours.
Fifteen hours after completion of the thrombolytic therapy, the patient became confused and progressively obtunded. There were no focal neurologic findings but an emergent head CT revealed large intracerebral left frontal and right temporal hemorrhages. Despite infusion of cryoprecipitate and fresh frozen plasma, the patient’s condition deteriorated. His hemorrhages were not considered operable, and he died the following day.
COMMENT BY DAVID J PIERSON, MD
Thromboembolic stroke is reported to occur in about 2% of MI patients, typically 3-14 days after the event and predominantly after large anteroseptal or anterior infarctions in patients with akinetic or dyskinetic areas of cardiac wall motion. In contrast, when intracanial hemorrhage (ICH) occurs following acute MI, it typically presents during or shortly after administration of thrombolytic therapy, in the hours following initial presentation. The incidence of the ICH has ranged between 0.1% and 1.4% in large reported series of MI patients. Conrad et al provide a concise discussion of the factors that have been associated with an increased incidence of ICH, along with possible reasons and/or mechanisms for each. (See Table.)
Table
Risk Factors for Intracranial Hemorrhage with Thrombolytic Therapy
• Low body weight
• Female sex
• Advanced age
• Oral anticoagulation therapy
• Severe hypertension
• Use of a fibrin-specific thrombolytic agent (e.g., TPA)
• Activated PTT > 70 sec with intravenous heparin
The specific thrombolytic agent used may be an important factor, with fibrin-specific substances such as alteplase tissue plasminogen activator (TPA) and anistreplase (APSAC) reported in some series to have twice the incidence of ICH as streptokinase (although not all large studies have documented this difference). The dosage of thrombolytic used is also a factor, and this may explain the fact that patients with low body weight and women are at increased risk. For example, in the TIMI Phase II trial (TIMI Study Group. N Engl J Med 1989;320:618-627), the rate of ICH fell from 1.9% to 0.5% of patients when the dose of TPA was reduced from 150 to 100 mg.
Advanced age has also been a significant risk factor in several studies, presumably because of the increased prevalence of vascular disease in elderly persons. Other risk factors include the use of oral anticoagulants prior to thrombolytic therapy, although reported studies have differed as to whether early heparin therapy also makes ICH more likely. Hypertension (diastolic BP > 110 mmHg) at the time of the thromobolytic therapy has been found to increase the incidence of this complication in at least some studies.
Simoons et al (Lancet 1993;342:1523-1528) analyzed the results of several large trials of thrombolytic therapy, and developed a model to predict the occurrence of ICH. They identified four independent risk factors: age greater than 65 years, body weight less than 70 kg, systolic BP higher than 170 mmHg and/or diastolic BP higher than 95 mmHg on admission, and the use of alteplase rather than another thrombolytic agent. According to the multivariate analysis performed by those investigators, if the overall incidence of ICH is 0.75%, that for a patient with none of these risk factors would be 0.26% as compared to 5% in the presence of all four.
Conrad et al point out that advanced age should not by itself be a contraindication to thrombolytic therapy in patients with acute MI, since the benefits of this therapy may be more pronounced in the elderly. However, when fibrin-specific agents such as TPA are used, weight-adjusting the dosage is advisable in order to reduce the likelihood of ICH.
Patients receiving thrombolytic agents for acute MI should be monitored closely for changes in neurologic status. If these are observed (particularly an intense steady headache or changes in sensorium), the thrombolytic agent should be discontinued immediately along with any concomitant anticoagulant or antithrombolitic agent, and an emergency head CT obtained. If an ICH is documented, the authors of this review recommend the infusion of 10 bags of cryoprecipitate, to be repeated if the plasma fibrinogen level is not raised above 100 mg/dL, and the administration of 2 units of fresh frozen plasma if other factors are also depleted. Platelet transfusions are indicated if bleeding time is also prolonged, and the use of protamine sulfate to reverse the effects of heparin (1.0 mg protamine per 100 units heparin infused in the previous 4 hours). Neurosurgical consultation should be obtained promply, because emergency evacuation of the ICH may be indicated.
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