Can a patient with acute stroke receive Tissue Plasminogen Activator (tPA) if a thorough medical history cannot be obtained?

From the Guidelines

In cases where a complete history cannot be obtained from a stroke patient, tissue plasminogen activator (tPA) can still be administered under certain circumstances, but with caution, as the benefits of timely treatment outweigh the risks, as indicated by the American Heart Association/American Stroke Association guidelines 1. The decision to administer tPA should be based on available information from other sources such as family members, witnesses, EMS personnel, or medical records.

• The standard dose of tPA for acute ischemic stroke is 0.9 mg/kg (maximum 90 mg), with 10% given as an initial bolus and the remainder infused over 60 minutes.
• Critical information needed includes the time of symptom onset (must be within 4.5 hours, although the study referenced was within 3 hours 1), absence of contraindications such as recent surgery, trauma, bleeding disorders, or use of anticoagulants.
• If the time of onset cannot be established, tPA should generally be withheld unless the patient was definitely normal within the treatment window. A non-contrast head CT must be performed before administration to rule out hemorrhage, as the presence of edema or mass effect on baseline CT scan was associated with higher risk of symptomatic intracranial hemorrhage 1. The urgency of treatment is based on the "time is brain" principle, making rapid assessment and decision-making crucial even with incomplete history, as approximately 1.9 million neurons die each minute during an untreated stroke.
• Patients with mild to moderate strokes (NIHSS score <20) and persons younger than 75 years of age had the greatest potential for a favorable response to treatment, as shown in the NINDS rtPA Stroke Study 1.

From the Research

Administration of TPA in Stroke Patients with Unknown Onset

• The administration of tissue plasminogen activator (tPA) in stroke patients is a time-sensitive decision, typically guided by the time of onset of symptoms 2.
• However, in cases where the onset time is unknown, the decision to administer tPA can be challenging.
• Studies have shown that tPA can be safely administered to patients with unknown onset time based on non-contrast head CT (NCCT) findings, with comparable rates of symptomatic intracerebral hemorrhage (sICH) to those with known onset times 2.

Safety and Efficacy of TPA Administration

• A single-center study and meta-analysis found that tPA administration based on NCCT was safe and effective, with no significant difference in sICH rates between patients with unknown onset and those with known onset times 2.
• Another study found that administering tPA prior to mechanical thrombectomy may improve recanalization rates, but did not significantly impact functional and safety outcomes 3.
• The use of multimodal CT scan protocols, including NCCT, arterial-phase CT angiography, and CT perfusion, can aid in decision-making for mechanical thrombectomy and tPA administration 4.

Predicting Hemorrhagic Transformation Risk

• Radiomics features extracted from initial non-contrast CT scans can predict hemorrhagic transformation risk in stroke patients undergoing revascularization, including tPA administration 5.
• A study using the ANGEL-ACT registry found that non-contrast head CT alone can be used for thrombectomy in acute ischemic stroke, with improved procedural outcomes and smaller increases in baseline modified Rankin Scale scores at 90 days 6.

Clinical Implications

• The findings of these studies suggest that tPA can be safely administered to stroke patients with unknown onset time, based on NCCT findings and clinical judgment.
• The use of advanced imaging protocols and radiomics features can aid in predicting hemorrhagic transformation risk and guiding treatment decisions.
• Further studies are needed to clarify the role of tPA in the treatment of acute ischemic stroke, particularly in patients with unknown onset time.