Beyond uterine atony: characterizing postpartum hemorrhage coagulopathy.

BACKGROUND: Postpartum hemorrhage is a leading cause of morbidity and mortality worldwide, yet the associated early coagulopathy is not well defined.

OBJECTIVE: We hypothesize that women who develop postpartum hemorrhage have a distinct derangement of thrombin generation and coagulation factors as compared to postpartum women without postpartum hemorrhage.

STUDY DESIGN: This prospective study of pregnant patients with postpartum hemorrhage was completed at a single urban hospital. Blood was drawn upon postpartum hemorrhage diagnosis and 2 and 4 hours later. Assays included thrombelastography, whole blood thrombin generation, coagulation factor activity, tissue factor levels and activity, and tissue factor pathway inhibitor levels, which were compared to patients without postpartum hemorrhage.

RESULTS: Eighty-one patients were included. Of those, 66 had postpartum hemorrhage, and 15 served as controls. Compared to patients without postpartum hemorrhage, postpartum hemorrhage patients had lower fibrinogen (411.0 versus 469 mg/dL, p=0.02), increased tissue plasminogen activator resistance (fibrinolysis 30 minutes after maximal clot strength [LY30] 4.2% versus 8.7%, p=0.02), decreased peak thrombin (40.7 versus 150.2 nM, p=0.01), and decreased maximal rate of thrombin generation (2.8 versus 60.1 nM/min, p=0.02). Patients with postpartum hemorrhage also had decreased tissue factor levels (267.1 versus 444.3 pg/mL, p=0.02) and increased tissue factor pathway inhibitor levels (0.8 versus 0.6 U/mL, p=0.04), with decreased tissue factor pathway inhibitor ratios (299 versus 624, p=0.01) compared to patients without postpartum hemorrhage.

CONCLUSION: PPH is not merely an issue of uterine tone and mechanical bleeding, but rather is associated with distinct coagulopathy, characterized by decreased fibrinogen, clot breakdown resistance, and markedly low thrombin generation. This pathology appears to be driven by low tissue factor and high tissue factor pathway inhibitor levels.