Hemophilia A, the result of reduced factor VIII (FVIII) activity, is an X-linked recessive bleeding disorder affecting one in 5,000 males born in the United States (U.S.). Females are designated heterozygous or carriers. While bleeding symptoms have been fully characterized in male patients with Hemophilia A, less is known about the female Hemophilia A carrier bleeding phenotype. Previous reports in Hemophilia A carriers suggest an increased bleeding tendency regardless of residual FVIII activity. Further, small studies suggest that Hemophilia A carriers report excessive bleeding symptoms including, but not limited to menorrhagia, epistaxis, surgical bleeding and hemarthrosis.
To determine the attitudes and understanding of Hemophilia A carrier testing from the perspective of both providers and affected patients. Our global hypothesis is that genetically verified Hemophilia A carriers with normal FVIII activity will have increased clinically relevant bleeding.
We employed a cross-sectional study design, and developed an electronic survey that was emailed to physicians and nurses employed at U.S. Hemophilia Treatment Centers (HTC). The email list was generated from listed current HTC providers on www.cdc.gov. A similar electronic survey was developed and distributed to female Hemophilia A carrier members of Hemophilia Federation of America. Questions were derived from the Female Universal Data Collection project questionnaire, and focused on the clinical understanding and management of Hemophilia A carriers. In addition, questions were developed to assess attitudes regarding the timing and intensity of testing. Data was analyzed using SPSS with descriptive statistics, Wilcoxon rank sum test and Pearson test.
In the provider survey there was a 49%(42/85) response rate from the physicians and 37% response rate (30/80) from nurses. Combined, 64% (47/72) had >10 years of clinical experience, 94% (68/72) work in primarily within an HTC and 97% (69/71) offer carrier testing. In the survey aimed at Hemophilia A carriers, a total of 38 responses were analyzed. The mean age was 35 ± 11 years, 76% (29/38) had a biologic son with Hemophilia A with 65% (24/37), 22% (8/37) and 14% (5/37) being severe, moderate or mild in severity. Carrier testing was performed after the age of 14 in 82% of those queried. When asked about the optimal timing of carrier testing, 78% (31/41) of physicians and 68% (19/28) of nurses recommend testing after 14 years of age while 69% (24/35) of carriers prefer testing to be done prior to this age (p<0.001). Furthermore, patients report that 82% (27/33) were not aware of their carrier status until after 14 years of age.
While 78% (28/36) of the carrier's affected hemophiliac relatives receive care at an HTC only 26% (9/35) receive regular Hemophiliac care, and 67% (6/9) of those receiving regular care are followed at the same location as their affected hemophiliac relative. When queried, 51% (36/51) of providers compared to 78% (28/36) of carriers believe that Hemophilia A carriers with normal FVIII activity have an increased bleeding tendency (p<0.001). Carriers surveyed had a self-reported mean FVIII activity of 48% (range 17–129) and 69% (25/36) report a high frequency of bleeding symptoms including the following: menorrhagia 61% (23/38), recurrent miscarriages 52% (15/29), post-pregnancy bleeding 42% (16/38), oral bleeding 34% (13/38), post-surgical bleeding 32% (12/38), epistaxis 21% (8/38) and joint bleeding 11% (4/38).
Hemophilia A carriers report a higher frequency of bleeding than previously acknowledged. In contrast to preferences of Hemophilia specialists, Hemophilia A carriers prefer to know their carrier status prior to 14 years of age and be cared for in the same location as their affected relatives. Under recognition of Hemophilia A carrier bleeding is common amongst HTC providers, and data collected in a prospective cohort with appropriate controls is warranted.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.