The Hemostasis and Thrombosis Research Society (HTRS) Registry Study of Acquired Hemophilia: Assessment of AH Patient Demographics in the US

Abstract

4625 Introduction: Acquired hemophilia (AH) is a rare disorder marked by the development of autoantibodies to factor VIII. Patients present with bleeding and a prolonged aPTT that does not correct with prolonged incubation mixing with normal plasma. The Hemophilia Research Society (HRS) Registry was established in 1999 to support the research needs of the society and to monitor post-approval usage of recombinant factor VIIa (rFVIIa). In 2004, the registry was renamed the Hemophilia and Thrombosis Research Society (HTRS) Registry. Since FDA approval of rFVIIa, the HTRS registry has been used to collect demographic and treatment information on US patients with AH. Methods: Following IRB approval, informed consent was obtained prior to data entry. AH patient registration captured age, gender, comorbidities and predisposing conditions, first bleeding location, laboratory parameters, blood product/factor/bypassing agent exposure, and initiation of immune suppression/tolerance. HRS patient records were incorporated into the HTRS registry platform and combined here for descriptive analysis. Results: Of 166 identified AH patients (83 female, 72 male), 21 were entered in HRS (2000–2003) and 145 in HTRS (2004–2011). The mean/median age was 65.3/70 with 3 aged <20, 11 aged 20–40, 28 aged 41–60, and 119 aged 61–92. Race/ethnicity included white non-Hispanic (102, 61%), white Hispanic (15, 9%), black non-Hispanic (38, 23%), black Hispanic (2, 1.2%), and other (4, 2.4%). Functional status at registration was unrestricted in 51 (31%), with limited recreation in 11 (6.6%), limited school/work in 59 (36%) and requiring assistance with no recreation in 27 (16.3%). Antibody titers in Bethesa units (BU) are shown below: Comorbidities included autoimmune disease (39, 27%), malignancy (20, 15%), surgery/intervention (17, 12%), post-partum (5, 3%), trauma (2, 1%), other (26, 18%) and not specified (64, 44%). Autoimmune/malignancy occurrence was similar across gender and race, but was slightly higher in non-hispanics. The most common autoimmune diseases reported were rheumatoid arthritis (10) and SLE (4). The most common malignancies reported were breast (6), leukemia (3), prostate (3), bladder (2), GI (2), and cervix (2). The first sites of bleeding were subcutaneous (46, 28%), mucosal (35, 21%), extremity NOS (12, 7%), muscle (9, 5%), joint (7, 4%), retroperitoneal (4, 2%), surgery/procedure (3, 2%), post partum (3, 2%), head (3, 2%), other (7, 4%), and not specified (27, 16%). Subcutaneous bleeding was more common in females than males (34% vs. 30%), whites than blacks (30% vs. 3%), and non-Hispanics vs. Hispanics (26% vs. 18%). Mucosal bleeding was more common in whites than blacks (21% vs. 6%). Median highest anti-human FVIII titers were similar for subcutaneous bleeding (58.5 BU) and other first bleeding sites (46). Blood product exposure was reported for 48 of 131 (37%) patients where it was known. Patient exposure included PRBCs (83%, mean 3.7 units), whole blood (44%, mean 4.2 units), platelets (10%, mean 21.5 units), and cryoprecipitate (4%, mean 10 units). FVIII exposure was reported for 8 of 120 (7%) patients where FVIII exposure history was known. History of either immune suppression or true immune tolerance was reported for 65/166 (39%). Of the 57 evaluable patients, 26 patients reported success (46%) 13 no success (23%), and 18 (32%) were receiving active treatment at the time of registration. A separate detailed immune tolerance case report form was not completed for most AH cases. Conclusions: The HTRS registry final analysis represents the 2nd largest data set on AH; provides the only comprehensive and current demographic look at AH in the US population; and includes additional details on specific autoimmune diseases and malignancies not reported elsewhere. Interestingly, we see that cutaneous bleeding as a presenting bleeding symptom was most notable in white and non-Hispanic individuals. Post-partum hemorrhage as a presenting symptom and lymphoma as a predisposing condition were less common than in recent European data. As the HTRS registry AH initiative was not restricted to only patients receiving rFVIIa, the AH demographics should not be biased. Disclosures: Kessler: Novo Nordisk: Consultancy, Research Funding. Ma:Novo Nordisk Inc.: Consultancy, Speakers Bureau. Fisher:Novo Nordisk Inc.: Employment. Gut:Novo Nordisk Inc.: Employment. Cooper:Novo Nordisk Inc.: Employment.

Acquired haemophilia: an overview for clinical practice

“…In agreement with previous large collections of patients with AHA , around half of AHA patients in EACH2 had an identifiable underlying clinical condition (malignancies, pregnancy, autoimmune disorders, infections, drug‐induced and dermatological conditions); the remaining cases were idiopathic . Compared with pan‐European databases, such as EACH2, the HTRS registry in the United States (US) derived its observations from a more ethnically diverse population, which included 24% of patients with AHA of black race/ethnicity . The incidence of AHA appears overrepresented compared with the percentage of black people within the US population [13.6% ] and suggests that black individuals could be preferentially affected by AHA, as they are for allo‐FVIII antibodies .…”

“…This is a longitudinal US database established in 1999 to study treatment strategies for patients with bleeding disorders and monitor the postapproval use of rFVIIa, which since 2006 (date of approval of rFVIIa for AHA in the US) has provided postmarketing surveillance on rFVIIa‐treated patients with AHA. We await the full publication of the HTRS data set with interest.…”

Overcoming the diagnostic and monitoring challenges for very rare bleeding disorders in the US: the potential benefits of a centralized laboratory

“…The EACH‐2 registry captured data between 2003 and 2008 and included 501 patients with AH from 117 centres and included data on 474 bleeding episodes, follow‐up for post‐partum haemorrhage and outcomes of immunosuppression . The Hemostasis and Thrombosis Research Society (HTRS) registry captured data between 2000 and 2011 and included 166 patients with AH with 237 bleeding episodes and 58 surgical procedures .…”