Occurrence of thrombosis in rare bleeding disorders.

Paradoxically, there are reports of thrombotic events for some rare bleeding disorders associated with significant bleeding tendency. Afibrinogenemia, factor (F) VII, or FXI deficiencies are those most commonly associated with venous or arterial thrombosis. Pathogenesis is multifactorial and the main conditions associated with this complication relate to the coexistence of inherited or acquired thrombotic risk factors linked to certain specific characteristics of the underlying defect. Patients with afibrinogenemia can develop severe, spontaneous, or recurrent thromboembolic disease. Up to 20% of congenital dysfibrinogenemia patients show predisposition to thrombosis. Thrombotic episodes, particularly deep vein thrombosis, have been reported in 3 to 4% FVII deficient patients, even those who were severely affected. These events have been reported either after infusion of plasma derived FXI concentrate or recombinant activated FVII in FXI deficient patients. So, in addition to factor level, replacement therapy must be individualized and should take into account past personal or family history of bleeding and thrombosis, and other prothrombotic risk factors. Treatment of thrombosis represents a challenge. For mild factor deficiencies, antithrombotic prophylaxis must be considered with or without concomitant use of replacement therapy. For all patients, it is also recommended to control known cardiovascular disease risk factors.