Acquired Hemophilia: Analysis of the Experience of a Regional Hemophilia Center.

Acquired hemophilia is a rare but life-threatening bleeding disorder caused by the development of auto-antibodies against Factor VIII. As a regional hemophilia center, we are referred the majority of these patients in our area for management of acute bleeds and eradication of the inhibitor. We report here our clinical experience with 21 consecutive patients over a 57 month period (12/00–10/05).

The median age at diagnosis was 75 (22–95). 12 patients were female and 9 male. Median time to diagnosis from symptom onset was 1 month (0.25–12). Underlying etiologies include: autoimmune (19%), malignancy (10%), pregnancy (4%), and idiopathic (67%). 37/44 bleeding episodes required hospitalization for a median admission length of 12.5 days (1–44); 14 patients required treatment in the ICU. 18 bleeds were spontaneous (41%), 11 traumatic (25%), 9 postoperative (20%), and 6 at IV sites (14%). Primary bleeding sites included: soft tissue (59%), oropharynx (9%), GI (7%), gynecological (7%), hemarthrosis (5%), retroperitoneal (5%), hematuria (4%), compartment syndrome (2%), and extensive bruising (2%). The median FVIII level on presentation was 2 (0–14) and inhibitor titer was 6 BU (0.5–870.4).

Factor VIII concentrates with vWF (Alphanate®, 22%) or without vWF (Recombinate®, 9%), or bypassing agents including rFVIIa (50%) or the activated prothrombin complex concentrate FEIBA® (19%) were chosen as initial treatments for bleeding; some form of therapy was required in all patients. Alphanate® was used most commonly in patients with low-titer inhibitors and was effective 40% of the time in stopping the initial bleed within 72 hours; rFVIIa was most effective in high-titer inhibitors (63%). 9/21 patients (43%) required ≥10 units of PRBCs; only 3 patients were not exposed to at least 1 blood product.

All patients were treated with at least one form of immunosuppression. Patients with low-titer inhibitors only used steroids. Initial choice of medication was a steroid in 64% of patients, cyclophosphamide in 27% and rituximab in 9%; 66% of patients used a combination. Patients who achieved complete remission (CR) were treated on average more aggressively than patients with no response (NR), receiving more doses of cyclophosphamide and rituximab (p=0.01).

Thirteen patients (62%) achieved a CR, 3 patients achieved a partial response (PR), and 5 patients demonstrated no response. Median time to CR was 43 days (10–341). 2/3 patients relapsed but responded again and reached CR. 5/5 patients who demonstrated no response died within 4 months of diagnosis. The overall mortality rate was 38% (8/21) in this elderly cohort with a median follow-up time of 11 months (0–107). Multivariate regression analysis revealed age, FVIII level, and achievement of CR as significant predictors of overall survival. 14/21 patients experienced an adverse event (AE), 3 of which were fatal. 73% of AEs were attributed to immunosuppression. 3/4 patients with thrombosis were using rVIIa at the time; the other patient developed DIC and thrombosis on FEIBA®.

In our experience, the majority of patients with acquired hemophilia are able to achieve a CR (13/21). Patients with high-titer inhibitors required more aggressive therapy than low-titer. Age, FVIII level, and achievement of CR are independent predictors of overall survival. However, a cautious approach is indicated as these results confirm the significant morbidity and mortality associated with acquired hemophilia, especially induced iatrogenically by its treatment.