A bloody maze: Acquired hemophilia a manifesting as a spontaneous intramuscular hematoma
Journal
Journal of the American Geriatrics Society
Journal Volume
62
Journal Issue
1
Pages
205-206
Date Issued
2014
Author(s)
Chang C.-M.
Abstract
To the Editor: Acquired inhibitors against factor VIII (FVIII), also termed acquired hemophilia A (AHA), is a rare autoimmune disorder that may pose a high risk of bleeding and most commonly occurs in elderly adults.1 Herein is presented a case of AHA that was diagnosed promptly and treated successfully. A 94-year-old woman who had not been receiving regular medical consultations presented with a 2-day history of acute progressive right thigh swelling and pain leading to disability in performing her daily activities. On admission, her blood pressure was 137/85 mmHg, pulse 90 beats per minute, temperature 36.2°C, and respiration rate 20 breaths per minute. A physical examination revealed pale conjunctiva and localized ecchymosis over the lateral aspect of her right thigh extending to the upper portion of her right lower leg with mild erythematous changes. On palpation, a firm induration with tenderness and local heat were noted, although capillary refilling time in her right foot was normal. Soft tissue sonography confirmed a hematoma (13 × 5 cm) in her right thigh. According to her medical history, she had given birth to six children through uncomplicated vaginal deliveries with no history of fetal loss. She had undergone orthopedic surgery for a right femoral neck fracture 5 years previously without complications. Except for experiencing easy bruising over the bilateral hands and dorsal feet in the past year, she denied any history of trauma, regular medication use, or family history of bleeding diathesis. Elder abuse was deemed unlikely after a thorough evaluation and history taking. Her hemoglobin was 11.4 g/dL (normal range 11.6–14.8 g/dL), with a mean corpuscular volume of 97 fL (normal range 82.7–95.5 fL). Her platelet count was 184,000/μL, prothrombin time 11.1 seconds (normal range 9.4–12.5 seconds), and activated partial thromboplastin time (APTT) 94 seconds (normal range 26–38 seconds). Electrolytes, liver and renal function tests, and fecal occult blood test were unremarkable. Further surveys yielded an uncorrected APTT on a plasma mixing test and a negative lupus anticoagulant test. FVIII activity was 7% (normal range 58–118%), FIX activity 119% (normal range 58–130%), and von Willebrand factor antigen level 253% (normal range 50–150%). The FXIII inhibitor titer was 11 Bethesda units (BU; normal range 0–0.5 BU) in a Bethesda assay. On the second day of hospitalization, the right thigh hematoma became enlarged, and her hemoglobin dropped to 7.5 g/dL despite a transfusion with fresh frozen plasma and packed red blood cells. She underwent urgent treatment with 90 μg/kg of recombinant activated FVII (rFVIIa) three times at 2-hour intervals with concomitant prednisolone (1 mg/kg/d). The clinical response was good, and she was discharged 13 days later with a gradually normalizing hemoglobin level, APTT, FVIII activity, and FVIII inhibitor titer noted during a follow-up visit at the clinic. Acquired hemophilia A carries a high risk of mortality due to bleeding. The age distribution is biphasic, with a small peak between ages 20 and 30 and a major peak between ages 68 and 80.1 The incidence of AHA in a 2-year national surveillance study in the United Kingdom showed increase with age (1–15, 0.045/million per year; 16–64, 0.29/million per year; 65–84, 5.97/million per year; ≥85, 14.66/million per year).2 More than 85% of the cases were aged 65 and older.2 Half of affected cases are previously healthy, and the remainder may be associated with postpartum period, autoimmune diseases, or malignancies.1 The U.K. cohort showed the likelihood of underlying disease decreases with age,2 which suggests that old age alone is a risk factor for AHA, older adults are investigated less intensively, or both. Unlike with congenital hemophilia, the most common manifestation in AHA is subcutaneous bruising, followed by deep soft tissue hemorrhages, whereas hemarthroses is uncommon. A prolonged APTT that is not corrected by a mixing test in an individual without a history of bleeding diathesis should alert physicians to this disease. Diagnosis is confirmed by a low FVIII level and a high titer of FVIII inhibitor in the Bethesda assay. Treatments are targeted at controlling bleeding and eradicating the inhibitors. To achieve the former, the choice of treatment depends on the severity of bleeding and inhibitor titers and includes desmopressin and FVIII concentrate in cases with a low titer (<5 BU), and rFVIIa or activated prothrombin complex concentrate given until a clinical response is noted in cases with a higher titer. Corticosteroid-based immunosuppressive therapy is effective in eliminating most autoantibodies as first-line therapy, whereas rituximab is another promising agent for nonresponders.1, 3 The selection of immunosuppressive therapy should be customized, weighing the risks and benefits given a lack of randomized controlled trials. Age was associated with mortality during follow-up but also with achieving remission more quickly.2 The current case not only demonstrates a successful treatment model, but also reinforces that early recognition and rapid diagnosis are crucial to minimize bleeding complications and to achieve a favorable outcome when confronted with this uncommon disorder in elderly adults. Conflict of Interest: The authors have no financial or any other personal conflict to report. Author Contributions: Study concept and design: both authors. Acquisition of subjects and data: Li-Tan Yang. Analysis and interpretation of data: both authors. Preparation of manuscript: both authors. Critical review and approval: both authors. Sponsor's Role: None.
SDGs
Type
letter