Impact of Inherited Bleeding Disorders on Peripartum Blood Loss: Insights from a Majority Hispanic Cohort Study

Introduction:

According to the World Health Organization, 25% of pregnancy related deaths were due to severe bleeding occurring in the postpartum period (Khan et al. 2006). Women with inherited bleeding disorders are known to have an increased risk of bleeding complications during delivery (Leebek et al. 2020; Peyvandi et al. 2011). There is a scarcity of published data on obstetric related outcomes in women with congenital bleeding disorders in the US, and even less information on minority ethnic subgroups. Herein we provide bleeding outcomes for a cohort of patients with inherited bleeding disorders, a majority of whom were Hispanic, compared to their age-matched control counterparts.

Methods:

44 patients with bleeding disorders (52 deliveries) were identified at the University of Miami and Jackson Memorial Hospitals. Inclusion criteria included reproductive-age women pregnant from 2012-2024 with a clinician diagnosis of an inherited bleeding disorder (Von Willebrand Disease (VWD), or carrier of hemophilia A or B, or other factor deficiency. Patients were identified through pregnancy and bleeding disorder ICD codes, hematology consult notes, and identification by treating provider. Age-matched controls (n=104) were defined as any delivery by a pregnant woman without a history of bleeding disorder and identified using pregnancy ICD codes. All methods were approved by our institution's IRB. Analysis was performed using unpaired t-testing.

Results:

Of the 52 bleeding disorder deliveries, 36 had clinical diagnosis of VWD (11 with unspecified type, 12 with type 1, 2 with type 2 unspecified, 7 with type 2A, 1 with type 2B, 3 with type 2M), 7 were hemophilia A carriers, 6 hemophilia C /factor XI deficiency carriers, 1 factor VII deficiency carrier, 1 factor XIII deficiency carrier, and 1 platelet storage pool disorder. 104 age-matched controls deliveries were identified, with a 2:1 ratio per bleeding disorder delivery, 3 years within delivery of their counterparts.

Of the 52 deliveries in the bleeding disorder group, 31 (59.6%) were Hispanic. Of the control group, 63 (60.6%) were Hispanic. In the bleeding disorder group of 52 deliveries, 24 (46.2%) were cesarean sections and 28 (53.8%) were vaginal deliveries. In the control group of 104 deliveries, 46 (44.2%) were cesarean sections and 58 (55.8%) were vaginal deliveries.

Average initial hemoglobin (Hgb) for the bleeding disorder group was 11.8 +/- 1.0 g/dL and for the control group was 11.5 +/- 1.4 g/dL. The average Hgb drop (pre vs post-delivery) for the bleeding disorder group was 1.575 +/- 0.95 g/dL and the average Hgb drop for the control group was 1.26 +/- 0.90 g/dL (p = 0.046). Average EBL for the bleeding disorder group was 557.9 +/- 417.7 g/dL and for the control group was 483.85 +/- 296.2 g/dL, which was not statistically significant (p = 0.203).

Subgroup analysis of VWD, hemophilias, and factor deficiencies showed only VWD had a significant Hgb drop, with an average of 1.69 +/- 1.00 g/dL (p = 0.025). EBL difference was unremarkable (p = 0.203). Of note, there was no significant difference in Hgb drop in factor deficiency carriers. Subgroup analysis of cesarean section in the bleeding disorder subjects showed a significant Hgb drop of 1.82 +/- 0.99 g/dL compared to 1.34 +/- 0.87 g/dL in controls who underwent cesarean section (p=0.040). EBL difference was similar, (p = 0.152). In subgroup analysis of Hispanic bleeding disorder subjects compared to non-Hispanic bleeding disorder subjects there was no significant difference in Hgb drop or EBL between the groups.

Conclusions:

Our bleeding disorder cohort consists of a majority of Hispanic patients. Subjects with VWD had objectively more blood loss with a larger Hgb drop than their age-match control counterparts. In addition, cesarean section had a more significant Hgb drop in bleeding disorder subjects than controls. EBL did not correlate with the more objective drop in Hgb and is not likely to be reliable. Underestimation of blood loss could have poor implications for management of bleeding and risk of further hemorrhage. It is important for clinicians to be aware of the risk of underestimation of bleeding in patients with inherited bleeding disorders, and further assess with corresponding clinical signs and lab values.

Bloomberg:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Soff:Sanofi: Consultancy; Alpine Immune Sciences, a Vertex Company: Research Funding; Anthos Therapeutics: Research Funding; Sobi/Dova Pharmaceuticals: Consultancy, Research Funding; Janssen Scientific Affairs: Consultancy; Amgen: Research Funding; Agios Pharmaceuticals: Consultancy. Byrnes:Sanofi: Consultancy; Anthos Therapeutics: Research Funding.