High Incidence of Postpartum Hemorrhage Seen in Hemophilia Carriers

To help prevent postpartum hemorrhage (PPH), international guidelines recommend that certain hemophilia carriers (HC) receive supplemental clotting factor at the time of childbirth. At a session at the 66th American Society of Hematology Annual Meeting and Exposition, Anne de Vaan, MD, presented preliminary data exploring the effects of lowering the threshold for giving such factors, but changing measures of PPH may cloud interpretation.¹

The physiologic process of pregnancy naturally shifts the body toward a more procoagulant state, as the body prepares to mitigate the risks of blood loss postpartum. For example, certain coagulation factors increase gradually during pregnancy and peak shortly before delivery, especially factor VIII, which increases two to threefold.²

However, clotting factor levels may not increase adequately in some carriers of hemophilia A and do not increase at all in carriers of hemophilia B. Although concentrations of factors VIII and IX in HCs are often higher than what some guidelines consider to be a hemostatic level (40-50 IU/dL), some HC concentrations dip below this, and even patients who have normal (non-pregnant) levels of clotting factors are at increased risk of PPH.²

Guidelines recommend supplementation with relevant clotting factors for third trimester HCs who have factor concentrations of less than 50 IU/dL. However, optimal dose, duration, and thresholds are not known.²

A retrospective cohort study of HCs and patients with von Willebrand disease in the Netherlands, published in 2015, found that 34% of HCs experienced PPH, and manifestations were severe (defined as estimated blood loss >1,000 mL) in 8%, almost twice the rate seen in the general Dutch population; rates of PPH were highest in those with the lowest factor levels during their third trimester.³ In response, Dutch guidelines on management were revised in 2018; these guidelines recommend clotting factors for HCs in the third trimester if levels are less than 80 IU/dL to reduce the risk of severe PPH.²

Dr. de Vaan, a PhD student at the Center for Benign Hematology, Thrombosis, and Hemostasis at Utrecht University Medical Center in the Netherlands, discussed the incidence of PPH in HCs after this new guideline was introduced. The multicenter observational cohort study, PRIDES, included 170 deliveries from all Dutch hemophilia centers.¹

Dr. de Vaan and colleagues found that rates of PPH remained high following the guideline revision. In the less than 80 IU/dL group (n=34), about three-fourths received prophylactic clotting factors, and the PPH incidence was 29.4% (n=10/34). In the groups whose clotting factors didn’t dip below 80 IU/dL in the third trimester, only 2% received clotting factors, and the incidence of PPH was also quite high at 34.6% (n=47/136). No statistically significant difference was seen between these two groups in overall incidence, even after adjusting for additional factors such as cesarean section, previous history of PPH, and primiparity.¹ The incidence of severe PPH was also similar between both groups (around 12% in both).¹

However, changing practices on assessing PPH may make it challenging to interpret these findings at present. Dr. de Vaan shared preliminary analyses comparing the incidence of severe PPH in the PRIDES study (12.4% overall) versus recent data from the general Dutch population from 2018 to 2024 (7.8%), a higher rate than previously documented. In the past, blood loss was often visually estimated, but blood loss in this study was more precisely measured using weights of products used to absorb blood, Dr. de Vaan explained. “We believe that this is more of the true incidence of PPH, and earlier rates were a bit of an underestimation.”

Thus, further exploration is needed to see if lowering thresholds for administering clotting factors, as in the revised Dutch guideline, does benefit patients.

Any conflicts of interest declared by the authors can be found in the original abstract.

References

1. de Vaan A, Kruip MJHA, Eikenboom J, et al. Postpartum hemorrhage in hemophilia A and B carriers after enhanced prophylactic clotting factor suppletion: the Pregnancy and Inherited Bleeding Disorders Study (PRIDES). Abstract 129. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7, 2024; San Diego, California.
2. Leebeek FWG, Duvekot J, Kruip MJHA. How I manage pregnancy in carriers of hemophilia and patients with von Willebrand disease. Blood. 2020;136(19):2143-2150.
3. Stoof SC, van Steenbergen HW, Zwagemaker A, et al. Primary postpartum haemorrhage in women with von Willebrand disease or carriership of haemophilia despite specialised care: a retrospective survey. Haemophilia. 2015;21(4):505-512.