Antithrombotic therapy in patients with inherited bleeding disorders: practical considerations.

Abstract

For decades hemophilia and allied bleeding disorders caused by inherited deficiency of clotting factors were considered conditions protecting against thromboembolism (TE). This opinion was coined over 60 years ago, when average life expectancy of people with hemophilia (PWH) was below 30 years, long-term anti-hemorrhagic prophylaxis of bleeding episodes was unattainable, and the main cause of premature death of hemophilia patients were life-threatening bleeds. At that time, arterial or venous thromboembolism were simply not observed among people with inherited bleeding disorders. With the progress of hemophilia management leading to improved hemostasis, resulting in reduction of severity and frequency of bleeding episodes and longer life expectancy it became obvious that hemophilia patients may and do develop TE episodes. This review is focused on how to manage arterial and venous thromboembolism in people with inherited bleeding disorders. Anticoagulant therapy should be avoided in severe or moderate hemophilia without anti-hemorrhagic prophylaxis. Use of anticoagulants in therapeutic doses is safer when FVIII or FIX plasma activity is permanently ≥20 IU/dl rather than <20 IU/dl. Taking into account their efficacy, safety profile and convenience, direct oral anticoagulants are the first choice as oral anticoagulation therapy for stroke prevention in non-valvular atrial fibrillation as well as in venous TE treatment in PWH. People with hemophilia may be offered many treatment options which allow to minimize exposure to antithrombotic agents, e.g. cardioversion, catheter ablation, left atrial appendage occlusion, newer generation drug-eluting stents, bioprosthetic heart valves, mechanical thromboprophylaxis methods.