Background: Intravenous tissue plasminogen activator (tPA) is not routinely followed by blood work due to its reputed short half-life. While there has been a great deal of research on tPA’s extra-vascular effects on the neurovascular unit in the context of hemorrhagic complications, there is little clinical data on the intravascular efficacy of IV tPA - how and where it has its intended effect. Emerging data suggest that tPA may be most effective in the microvasculature and IV therapy may be a good adjunct to intra-arterial (IA) therapy. We previously found through proteomic profiling that the effects of IV tPA can last more than 72 hours. Now, we report that even routine blood labs can potentially help predict hemorrhagic transformation (HT).
Method: 72 stroke patients treated with IV tPA were recruited post IRB approval. Clinical coagulation profiles (PT, PTT, fibrinogen and D-dimer) were performed at 12, 24, 72 hrs post IV tPA. Patients on medications (e.g. anticoagulants) or having other conditions (e.g. liver dysfunction, infection) that may affect these labs were excluded.
Result: Compared to patients without HT, HT patients had significantly higher PT and PTT (Fig. 1 A,B) as early as 12 hrs post tPA administration and throughout the first 3 days of treatment. ROC analysis suggested PT and PTT at 12 and 24 hrs have potential to predict tPA-induced HT (Figure 1C,D. PT: AUC = 0.848, p = 0.001; PTT: AUC = 0.877; p = 0.003).
Conclusion: Higher PT and PTT levels within 72 hours of IV tPA are early markers of HT post IV tPA in acute ischemic stroke. Whether these routine labs have value in symptomatic hemorrhage will require further study in a larger cohort. But this proof-of-concept study suggests that tPA efficacy can potentially be followed in real time, even with routine labs. The development of a reliable blood test would be of clinical utility to gauge thrombolytic efficacy in real time to guide and/or triage adjunct treatments.