Occurrence of Thrombosis in Rare Bleeding Disorders

Abstract

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.

Thrombotic Events in Asymptomatic FXII Deficiency versus Symptomatic FXI Deficiency: Surprising Observations

“…The study of thrombosis occurring in congenital bleeding disorders has considerably stimulated our understanding of thrombotic events [11,38,39]. This is also well demonstrated by the recent observation of the low prevalence of venous thrombosis seen in FXI deficiency [7,11], the finding that high levels of FXI are a risk factor for venous thrombosis [40] and that a synthetic anti-FXI compound (FXI antisense oligonucleotides) showed a noninferiority effect in comparison with enoxaparin in the prevention of venous thrombosis after total knee arthroplasty [41].…”

Endoprothetischer Ersatz des oberen Sprunggelenks bei Patienten mit Gerinnungsstörungen

“…In der aktuellen Literatur werden jedoch die thromboembolischen Komplikationen in dieser Patientengruppe beschrieben [51]. Aus diesem Grund empfehlen wir die Thromboprophylaxe für 6 Wochen postoperativ [8].…”

Paradoxical Bleeding and Thrombosis in a Patient With Afibrinogenemia and Fibrinogen Mumbai Mutation

“…1 Although bleeding is the most common presentation, there are few case reports of both arterial and venous thrombotic complications in these patients. 2 Generally, thrombosis is related to substitution therapy 3 or due to the coinherited thrombophilia. 4 We report on a 28-year-old woman with severe abdominal pain and anemia.…”