From the Guidelines
The risk of hemorrhagic transformation with tissue plasminogen activator (tPA) in ischemic stroke is approximately 6-7% for symptomatic intracranial hemorrhage, with overall hemorrhagic transformation occurring in up to 30-40% of treated patients, as supported by the most recent and highest quality study 1. This serious complication typically occurs within the first 24-36 hours after tPA administration. The standard dose of tPA (alteplase) is 0.9 mg/kg with a maximum of 90 mg, given as a 10% bolus followed by the remainder infused over 60 minutes. Risk factors that increase hemorrhage risk include:
- Advanced age (>80 years)
- Higher stroke severity
- Elevated blood pressure (>185/110 mmHg)
- Hyperglycemia
- Early ischemic changes on imaging
- Treatment beyond the recommended time window (generally 4.5 hours from symptom onset) Strict blood pressure control before, during, and after tPA administration is essential, typically maintaining systolic BP <180 mmHg and diastolic BP <105 mmHg, as recommended by 1 and 1. The mechanism behind hemorrhagic transformation involves tPA's fibrinolytic effects breaking down clots but also potentially degrading components of the blood-brain barrier, especially in areas where ischemia has already compromised vascular integrity. Despite this risk, when administered within appropriate time windows to eligible patients, the benefits of tPA in reducing disability from ischemic stroke generally outweigh the hemorrhage risk, as demonstrated by the improved outcomes in the NINDS tPA Stroke Study 1. It is crucial to weigh the potential benefits against the risks, considering the individual patient's characteristics and the timing of treatment, to make an informed decision about tPA administration, as emphasized by 1.
From the FDA Drug Label
ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in Section PRECAUTIONS of the label: Bleeding In the clinical trials, the most serious adverse events reported after treatment were sepsis, gastrointestinal bleeding, and venous thrombosis Major hemorrhage was defined as severe blood loss ( > 5 mL/kg), blood loss requiring transfusion, or blood loss causing hypotension. There were no reports of intracranial hemorrhage.
The risk of hemorrhagic transformation with tissue plasminogen activator (tPA) in ischemic stroke is not directly stated in the provided drug label. However, it does mention bleeding and major hemorrhage as adverse reactions, with no reports of intracranial hemorrhage in the trials described 2.
- Bleeding is listed as an adverse reaction.
- Major hemorrhage is defined, but no specific rate or risk is provided for ischemic stroke patients.
- No intracranial hemorrhage cases were reported in the described trials.
Given the information provided, no direct conclusion can be drawn about the specific risk of hemorrhagic transformation in ischemic stroke patients treated with tPA.
From the Research
Risk of Hemorrhagic Transformation with tPA in Ischemic Stroke
The risk of hemorrhagic transformation with tissue plasminogen activator (tPA) in ischemic stroke is a significant concern. According to a study published in 1995 3, symptomatic intracerebral hemorrhage within 36 hours after the onset of stroke occurred in 6.4 percent of patients given tPA, but only 0.6 percent of patients given placebo.
Factors Influencing Hemorrhagic Transformation
Several factors can influence the risk of hemorrhagic transformation, including:
- Higher admission NIHSS score 4
- Higher admission glucose levels 4
- Longer intervals from symptom onset to first digital subtraction angiography runs 4
- Lower preinterventional Alberta Stroke Program Early CT score 4
- Wake-up stroke 4
Management and Prevention of Hemorrhagic Transformation
To balance the risks and benefits of recanalization therapy, it is essential to consider the occurrence of hemorrhagic transformation in acute stroke settings 5. Prevention strategies for the occurrence and enlargement of hemorrhagic transformation include blood pressure control 5.
Barriers to the Use of tPA
Despite the benefits of tPA, there are barriers to its use, including:
Errors in tPA Administration
Errors in tPA administration can occur, including incorrect dosage for body weight 7. These errors can have serious consequences, including systemic hemorrhage or intracerebral hemorrhage 7. Therefore, quality assurance mechanisms are necessary to reduce potentially dangerous, avoidable errors 7.