Risk Factors for Cerebral Bleeding After Thrombolysis for Stroke
The strongest predictor of intracranial hemorrhage after thrombolysis is the NIHSS score, with patients having NIHSS >20 carrying a 17% risk of symptomatic intracranial hemorrhage compared to only 3% in those with NIHSS <10. 1
Primary Risk Factors
Stroke Severity (Most Important)
- NIHSS score is the single most powerful predictor of hemorrhagic transformation 1, 2
- Patients with NIHSS >20 have nearly 6-fold higher risk compared to NIHSS <10 1
- Stroke severity was identified as an independent risk factor in multiple systematic analyses 3
Age
- Age ≥80 years is an independent risk factor for hemorrhagic transformation 2
- Advanced age (>65 years) increases ICH likelihood 4
- However, very old patients (≥80 years) do not have increased rates of symptomatic ICH compared to younger patients (2.6% vs 2.6%), though overall mortality is higher 5
Blood Pressure
- Mean systolic pressure ≥140 mm Hg in the 24 hours after thrombolysis significantly increases hemorrhagic transformation risk 2
- High systolic blood pressure at presentation is an independent risk factor 3
- Blood pressure elevation is consistently associated with increased bleeding risk 1
Glucose and Diabetes
- Elevated serum glucose >200 mg/dL is an independent risk factor 1
- History of diabetes or elevated glucose was identified as a risk factor in six of twelve studies in systematic review 3
Secondary Risk Factors
Imaging Findings
- Extent of hypoattenuation on pretreatment CT (indicating extensive ischemia) is a major independent risk factor 3
- Major early CT changes indicating extensive ischemia increase bleeding risk 1
Coagulation Parameters
- Low fibrinogen concentration before thrombolysis increases hemorrhagic transformation risk 2, 6
- Prolonged activated partial thromboplastin time is associated with increased HT 6
- Low platelet counts (<100,000) increase bleeding risk 6, 3
- Low plasminogen activator inhibitor levels were identified as a risk factor 3
Cardiac Factors
- History of atrial fibrillation increases hemorrhagic transformation risk 2
- History of congestive heart failure is an independent risk factor 3
Protocol Deviations
- Deviation from national treatment protocols significantly increases intracranial hemorrhage risk 1
- Increased time to treatment is associated with higher bleeding risk 3
Additional Considerations
Structural Vascular Abnormalities
- Unruptured intracranial aneurysms or arteriovenous malformations may increase hemorrhage risk, though limited data exists 7
- Five cases with intracranial aneurysm detected after intraarterial thrombolysis resulted in 2 fatal intracranial hemorrhages 7
Other Factors
- Smoking is associated with increased hemorrhagic transformation 6
- Positive urinary protein expression correlates with increased bleeding risk 2
- Low body weight (<70 kg) increases ICH likelihood 4
Clinical Context
The overall rate of symptomatic intracranial hemorrhage ranges from 3-9% in acute ischemic stroke patients treated with tPA 4, with recent large studies showing rates of approximately 6.4-7.3% 1, 7. When symptomatic ICH occurs, mortality rates exceed 60% 1, 4. Patients with multiple risk factors have substantially elevated risk, with likelihood ratios ranging from 0.34 (no risk factors) to 2.89 (three risk factors) 4.