Thrombosis in rare bleeding disorders

Abstract

Inherited deficiencies of blood coagulation factors are usually associated with lifelong bleeding tendency. In addition to Hemophilias A and B and von Willebrand disease, congenital deficiencies of such factors as fibrinogen, prothrombin (FII)), FV, FVII, FX, FXI, FXIII, and combined deficiencies occur and can lead to a diversity of clinical conditions. Paradoxically, for some of these disorders associated with significant bleeding tendency there are reports of thrombotic events, both arterial and venous. Thrombosis in hemophilia patients has a multifactorial pathogenesis and the main conditions associated with this complication are the use of long-term central venous catheters, intensive replacement therapy usually in the setting of surgical procedures, the use of bypassing agents or the coexistence of acquired or inherited prothrombotic risk factors. Regarding other rare bleeding disorders, thrombotic phenomena has been described particularly in patients with afibrinogenemia, FXI and FVII deficiency and the events can occur even in young patients, in the presence of concomitant risk factors or spontaneously. Replacement therapy must be individualized and should take into account past history of haemostatic challenges, family history of bleeding and thrombosis, just like the level of factor. For mild deficiencies when patients are asymptomatic the use of antithrombotic prophylaxis must be considered with or without concomitant use of replacement therapy. In patients with history of thrombosis it may be helpful to perform a thrombophilia screening to exclude coexisting prothrombotic defects and for all patients it is recommended to control known cardiovascular disease risk factors.