Failure of recombinant factor VIIa to correct the coagulopathy in a case of severe postpartum hemorrhage

Postpartum hemorrhage (PPH) remains an important cause of maternal morbidity and mortality. Several published reports suggest that recombinant factor VIIa (rFVIIa) is effective in controlling bleeding in PPH. This study reports a case of severe PPH complicated by disseminated intravascular coagulation (DIC), in which early rFVIIa (44 mu g/kg) administration not only failed to control the bleeding in vivo but also, surprisingly, failed to correct the patient's international normalized ratio (INR) in vitro. It was hypothesized that the failure of rFVIIa to correct the INR indicated a deficiency in a downstream coagulation factor(s). To investigate this, coagulation factor levels were measured in blood samples that had been drawn periodically during resuscitation in the operating room. Clinical and laboratory data were extracted from the medical record. Plasma samples that had been obtained during resuscitation were frozen, and activity levels of the following factors were subsequently measured: fibrinogen, FII, FV, FVII, F IX, and FX. After rFVIIa administration, the patient's INR remained elevated at 1.9, and bleeding continued. It was determined that at the time rFVIIa was administered, the patient's fibrinogen level was very low (60 mg/dL). INR normalization and control of bleeding was achieved only after the patient's fibrinogen level was restored to normal. FII, F IX, and FX remained at hemostatic levels throughout resuscitation. In this case of severe PPH complicated by DIC, fibrinogen appears to have been limiting at the time rFVIIa was administered. It is suggested that fibrinogen levels should be corrected during PPH resuscitation before rFVIIa use is considered.