Rapid Detection of Fibrinolytic Activation in Postpartum Hemorrhage and Acute Obstetric Coagulopathy Using a Novel Assay Open Access

• The Fibrinolytic Activity Screening Test (FAST) rapidly detects endogenous fibrinolytic activation in plasma

• FAST distinguishes the most severe phenotype of postpartum hemorrhage acute obstetric coagulopathy (AOC)

Postpartum hemorrhage (PPH) remains the leading cause of pregnancy-related mortality worldwide. Regardless of initiating cause, continued bleeding may progress to a systemic coagulopathy. This coagulopathy may be further complicated by profound fibrinolytic activation progressing to systemic hyperfibrinolysis, a condition that we have termed acute obstetric coagulopathy (AOC). Patients with placental abruption or amniotic fluid embolism are among those at highest risk for AOC. In response to the unmet need for a rapid method to detect fibrinolytic activation in this scenario, we developed a novel assay that we have termed the Fibrinolytic Activity Screening Test (FAST). This assay measures endogenously generated plasmin activity in plasma within 5 minutes. Its high sensitivity for the detection of in vivo fibrinolytic activation was confirmed by strong correlation with elevated plasmin-antiplasmin (PAP) complex levels. We analyzed archived plasma samples from 33 women with PPH and 20 pregnant women just prior to elective Cesarean section. Of the 33 subjects with PPH, 12 had PAP complexes >25,000 ng/mL, thereby meeting criteria for the diagnosis of AOC. Plasmin activity measured by the FAST assay differentiated AOC from non-AOC PPH (p=0.0007) and from pregnant non-PPH control groups (p<0.0001), and was strongly correlated with both PAP complexes and D-dimer levels. Among subjects with PPH in whom viscoelastic whole blood testing (ROTEM) was performed, none of the 18 without AOC or 9 of those with AOC had evidence of ROTEM-defined hyperfibrinolysis. The FAST assay is a rapid tool to detect activation of fibrinolysis associated with AOC in women after delivery.