Venous Thrombosis in Acquired Hemophilia: The Complex Management of Competing Pathologies

Introduction  Venous thrombosis is rare in the setting of factor VIII (FVIII) deficiency. Cases of deep vein thrombosis (DVT) have been described in hemophiliacs after recent major surgery, or in association with the administration of FVIII concentrate and activated prothrombin complex concentrates, but occurrence of spontaneous DVT is even more uncommon. Aim  We describe the challenging management of extensive DVT in a patient with acquired hemophilia A with concurrent hemorrhagic manifestations and review similar published cases. Methods  We summarize a series of 10 cases with the following demographics: 6 males and 4 females; median age at presentation of 65 (21-80); mean inhibitor titer of 68.5 Bethesda Units (BU 1.9 to BU 350). Results  Four cases were idiopathic and six had associated conditions (cancer [two cases], recent pregnancy [two cases], and recent surgery [two cases]). Three cases had an inferior vena cava filter inserted for acute lower limb DVT/pulmonary embolism. Inhibitor eradication was achieved with high-dose steroids with or without cyclophosphamide, and adjunct Rituximab administration was used in three cases. One patient received concurrent therapeutic plasma exchange (TPE). Inhibitor eradication was fastest with concurrent TPE at 6 days (range: 6-733 days). The 30-day survival was 90%. Conclusions  There was adequate response of inhibitors to immunosuppression with steroids and cyclophosphamide therapy. For more refractory disease, Rituximab is emerging as a beneficial and cost-effective adjunct with better rates of complete remission, and the threshold for its use may be lowered in this complex cohort with dual competing pathologies.