Canadian Hemophilia Carriers Pregnancy Study: Coagulation Factor Levels and Postpartum Blood Loss

Abstract

Hemophilia is an X-linked recessive bleeding disorder caused by a deficiency in Factor VIII (FVIII) or Factor IX (FIX) that was previously thought to only affect men. Women are carriers for this disorder with recent studies showing that they may also be affected by hemophilia. In recent years, it has been consistently reported that hemophilia carriers (HC) experience excessive bleeding versus normal controls. Furthermore, FVIII and FIX levels have been shown to be decreased in HC in comparison to normal controls. HC have been shown to experience increased rates of postpartum hemorrhage (PPH) in comparison to normal controls. Although PPH treatments are available, there is no consensus on protocols. This thesis aims to quantify bleeding during the postpartum period in HC and normal controls and to examine how changes in coagulation factors during and after pregnancy may impact PPH. Five Hemophilia A carriers and 31 normal controls of similar mean ages consented to participate in the study. Quantification of postpartum blood loss using the validated Pictorial Blood Loss Assessment Chart showed that mean estimated postpartum blood loss was not significantly different between HC and normal controls. Significantly more postpartum bleeding occurred within the first week (512 ± 282 mL) versus the following postpartum weeks in normal controls, p<0.01. Plasma FVIII and FIX levels at 37 weeks gestation, admission for delivery, 12-24 hours post-delivery, postpartum day 7±2, 21±3, and 35±4 were assessed. HC had significantly lower FVIII levels versus normal controls (p<0.05) at each timepoint. Interestingly, post-delivery FVIII levels in normal controls was positively correlated with total postpartum blood loss (rs=0.59, p<0.05). We have shown that the majority of postpartum blood loss occurs within the first week after delivery in both HC and normal controls. The ability of normal controls to raise FVIII in response to blood loss may give insight as to why PPH occurs at an increased rate in HC who have previously been shown to have a reduced ability to raise FVIII levels. The results from this study could inform future treatment protocols potentially targeted at the first week of the postpartum period.