Is Bleeding In Hemophilia Really Spontaneous Or Activity Related: Analysis Of US Patient/Caregiver Data From The Hemophilia Experiences, Results and Opportunities (HERO) Study
Authors: Valentino Leonard A. , Forsyth Angela , Witkop Michelle , Guelcher Christine , Lambing Angela , Cooper David L. 
Published: October 2019

Background

Bleeding in hemophilia is believed to transition from more traumatic etiologies in early childhood to spontaneous bleeding in adolescents and adults as target joints develop and arthropathy progresses. The HERO study examined psychosocial issues impacting adults and children (and their parents) with moderate-severe hemophilia. As part of HERO, adults/parents reported bleed frequency/location, most affected joint, causes of bleeding, and current employment/activities. Prior analyses highlighted differences in bleed frequency by treatment regimen and age, prompting further exploration of potential causes of bleeding.

Methods

People with hemophilia (PWH) (≥18 years) and parents of children with hemophilia (<18 years) (CWH) were recruited in 10 countries. In the US, subjects were recruited online through the National Hemophilia Foundation's Facebook page and eNotes. Following informed consent, adults/parents completed distinct surveys (∼ 45 min).

Results

The 189 US PWH had a median (range) age of 35 (18-74). The 190 US parents of children with hemophilia had a median (range) age of 37 (23-59) years. The mean age of the oldest son <18 years was 8.7 years. Most PWH/parents reported hemophilia A (59%/66%) with (24%/9%) reporting inhibitors. Most parent respondents were female (79%) and were responsible for their son's care (75%).

PWH on likely secondary prophylaxis (PPX) reported higher overall median number of hemorrhages requiring treatment in the prior 12 months compared to those treated on demand (OD); there was little difference seen across employment and age (see table). More unemployed PWH reported a specific joint affected by hemorrhages. The ankle was the most frequently cited affected joint. Repetitive activity was reported as the most common cause of the most recent hemorrhage in those who used PPX and was more common in those working (40%) compared to those unemployed (22%). Spontaneous bleeding was most common in those unemployed (46%) and aged ≥41 years (41%). PWH reported more success in following HTC recommendations around taking medications than exercise.

Parents of CWH on PPX reported fewer hemorrhages than those treated OD, particularly due to differences in hemarthroses (see table). Older children were reported to have more frequent joint and muscle bleeding. A specific joint impacted by hemorrhage was reported more frequently in older compared to younger CWH (57 vs 44%); all groups except inhibitors reported trauma and repetitive activities combined as the most common causes of the last hemorrhage. The knee/elbow was the most commonly reported specific joint in the age 0-6 years group and the ankle in the age 7-17 years group. Parents generally reported good success in following HTC recommendations.

Conclusions

HERO provides unique insight into the causes of bleeding in PWH and CWH. The addition of a category of “repetitive activity” in the HERO study to reflect non-traumatic repetitive work/school/sports activity suggests there might be triggers for bleeding previously described as “spontaneous”. This observation warrants further attention by the HTC team including the physiotherapist, and should be investigated in prospective observational studies.

Disclosures:

Valentino: Baxter Bioscience, Bayer Healthcare, Biogen, CSL Behring, GTC Biotherapeutics, Inspiration: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Forsyth:Novo Nordisk: Consultancy. Witkop:Novo Nordisk: Consultancy. Guelcher:Novo Nordisk: Consultancy. Lambing:Novo Nordisk: Consultancy. Cooper:Novo Nordisk Inc.: Employment.