Women who have or are carriers for factor VIII (FVIII) or factor IX (FIX) deficiency often report excessive bleeding, though it is unclear how bleeding risk may vary among females with different factor levels and those with type 1 von Willebrand disease (vWD).
“Hemophilia A and B carriers with normal factor levels are at risk for excessive bleeding, regardless of their factor level, and warrant evaluation by a hematologist,” Robert F. Sidonio Jr., MD, from Emory University in Atlanta, Georgia, and lead author of the study, told told ASH Clinical News. “Our objective was to further characterize the bleeding tendencies in hemophilia A and B carriers and females with type 1 vWD enrolled in a large national dataset.”
Using data from the Universal Data Collection (UDC) project, which was created to monitor bleeding events among women with inherited bleeding disorders, Dr. Sidonio and colleagues conducted a cross-sectional study of women with FVIII or FIX deficiency or type 1 vWD. Results were presented at the Thrombosis and Hemostasis Societies of North America 2016 Summit.
The researchers collected data about the diagnosis subtype, demographics, and bleeding history (including oral, joint, skin, central nervous system, gastrointestinal, post-surgical, muscle, and heavy menstrual bleeding and bruising) of 551 women enrolled at 23 hemophilia centers between 2009 and 2011.
Seventy-three patients had FVIII/FIX deficiencies and 338 had type 1 vWD. Patients’ FVIII/FIX deficiency was defined according to severity: severe/moderate (≤5%), mild (5-40%), and normal (≥40%). Type 1 vWD was defined as a von Willebrand factor (vWF) antigen (VWF:Ag) or vWF ristocetin cofactor levels ≤40 percent.
In the hemophiliac cohort, most patients were FVIII-deficient (75%), Caucasian (76%), and young (median age = 23 years; range = 4-83 years). Thirty-three percent of patients with FVIII/FIX deficiency had normal levels, 49 percent were mildly deficient, 3 percent were moderately/severely deficient, and 15 percent did not have a level reported.
In the type 1 vWD cohort, most were Caucasian (78%) and young (median age = 20 years; range = 0-82 years).
Bleeding symptoms were compared between mild FVIII/FIX-deficient patients and those with normal levels and between FVIII/FIX-deficient patients and those with type 1 vWD.
Many women with FVIII/FIX deficiency (44%) reported four or more bleeding symptoms, and patients with mild FVIII/FIX deficiency and normal levels reported bleeding symptoms with similar frequencies (p>0.05).
These cohorts also reported a similar number of symptoms (mean number of symptoms = 3.4 in mild deficiency vs. 2.3 in normal levels; p=0.11). The most commonly reported symptoms were:
- heavy menstrual bleeding (52%)
- epistaxis (28%)
- post-surgical bleeding (26%)
- joint bleeding (14%)
In the second comparison, between patients with mild FVIII/FIX deficiency or normal levels and those with type 1 vWD, women with vWD reported a significantly higher frequency of epistaxis (52% vs. 28%), skin bleeding (56% vs. 28%), and heavy menstrual bleeding (70% vs. 52%; p<0.05 for all).
However, across all other bleeding symptoms measured, differences between hemophilia A or B carriers and those with vWD did not vary significantly.
On average, women with type 1 vWD reported 4.3 bleeding symptoms (range = 0-12 symptoms), and 84 percent reported four or more bleeding symptoms – nearly double the proportion of FVIII/FIX-deficient patients who reported experiencing four or more bleeding symptoms.
“We demonstrated that hemophilia A and B carriers are at risk for excessive bleeding regardless of their factor level, and females with type 1 vWD have a similar bleeding risk, but are at higher risk for mucocutaneous bleeding,” Dr. Sidonio concluded. “Although there was variability in bleeding symptoms between these patient groups, the majority did report significant bleedings.”
Sidonio RF Jr, Barry V, Byams V, et al. Reported bleeding among females with FVIII or FIX deficiency and type 1 von Willebrand disease: results from the female UDC. Abstract #50. Presented at the 3rd Annual Summit of the Thrombosis and Hemostasis Societies of North America, April 15, 2016; Chicago, Illinois.