Background: IV tissue plasminogen activator (tPA) is an efficacious treatment of acute ischemic stroke. However, the utilization of tPA has been deterred by its hemorrhagic complications. Our previous exploratory study found that following tPA administration, ischemic stroke patients with hemorrhagic transformation (HT) had a significantly longer prothrombin time (PT) than those without HT. Here we aim to study the effect of post-tPA parenchymal hemorrhage on a wide range of coagulation labs in a lager cohort of patients.
Method: 308 consecutive ischemic stroke patients with IV tPA were recruited in accordance with IRB approval. Clinical coagulation profiles were analyzed at 6, 12, 24, 36, 48 and 72 hr post IV tPA. Patients on anticoagulants or having other conditions (e.g. liver and kidney dysfunctions) that may affect these labs were excluded.
Result: As determined by head CT scan, 16 patients (5.19%) developed post-tPA hemorrhage. Compared to patients without tPA related hemorrhage, patients with hemorrhage had significantly higher levels of PT within the first 24 hr post tPA (Figure 1A), and PT levels at 6 hr have the potential to predict subsequent hemorrhage (Figure 1C, AUC = 0.753, p = 0.003). Moreover, D-Dimer remained at high levels even after 48 hr (Figure 1B), suggesting sustained fibrinolysis abnormality or possibly indicating active bleeding. D-Dimer levels at 24 and 48 hr were also predictive of tPA-induced bleed (Figure 1D, AUC = 0.827, p = 0.007).
Conclusion: Our results suggest PT and D-Dimer as early markers of tPA-induced hemorrhage in ischemic stroke patients. Their differential predictive ability at different time points may offer the possibility to monitor the clinical efficacy of tPA over a longer time window to guide adjunct treatment. Studies in additional coagulation factors in an expanded patient cohort are ongoing.