Variability of fibrinolytic activity in pregnant patients exposed to tissue plasminogen activator: an in vitro study utilizing rotational thromboelastometry: Fibrinolytic activity in vitro in pregnant patients

Background: The investigation into the variability of fibrinolysis in obstetric patients is notably limited despite its relevance to postpartum hemorrhage. We investigate an in vitro model of fibrinolysis measured by rotational thromboelastrometry (ROTEM) in maternal blood samples with lysis stimulated by tissue plasminogen activator (tPA). Methods: Written informed consent was obtained from 19 patients at term pregnancy during admission to the labor and delivery unit. Patients who were taking medication affecting coagulation were excluded. Tissue plasminogen activator was added to whole blood samples to a final concentration of 100 or 220 ng/mL prior to ROTEM testing. Results: The addition of tPA produced high intra-individual fibrinolytic variability for clot firmness and lysis parameters. Patients responded differently to each tPA dose ranging from clot lysis within the range of 0 ng/mL tPA group to complete clot lysis. The coefficient of variation (CV) values for the 220 ng/mL tPA group were: EXTEM MCF 0.510, EXTEM LI30 1.601, FIBTEM MCF 0.349, FIBTEM LI30 2.097. CV values for the 100 ng/mL tPA group were: EXTEM MCF 0.144, EXTEM LI30 1.038, FIBTEM MCF 0.096, FIBTEM LI30 1.238. Conclusion: We demonstrate a wide range of fibrinolytic response in the obstetric population to exogeneous tPA. We found subgroups of patients that were very responsive to tPA and insensitive to tPA. This study represents a preliminary exploration into classifying the obstetric fibrinolytic phenotypes. Further research will integrate relevant coagulation factors to establish a predictive model for testing susceptibility to lysis that can be applied at the point of care.