Coexistence of hypofibrinogenemia and factor V Leiden mutation

Abstract

Congenital hypofibrinogenemia and afibrinogenemia are usually associated with an increased risk of bleeding, but occurrence of arterial or venous thrombosis has also been reported in individuals with fibrinogen deficiency. This study reports on a 25-year-old patient with hypofibrinogenemia (fibrinogen 0.6 g/l) and congenital thrombophilia due to heterozygous factor V Leiden mutation who developed spontaneous deep-vein thrombosis (DVT) in the right lower extremity. Regardless of hypofibrinogenemia, he was receiving anticoagulant therapy over 6 months, with no occurrence of bleeding. His father is also a heterozygous carrier of factor V Leiden, but with normal fibrinogen level and he remained asymptomatic despite having experienced surgery in the past. This case, as well as data from literature, suggests that risk of thrombosis in carriers of factor V Leiden mutation is not counterbalanced by moderate congenital hypofibrinogenemia, and that antithrombotic prophylaxis should not be omitted in high-risk situations for occurrence of thrombosis in patients with coinheritance of hypofibrinogenemia and factor V Leiden mutation.

Management of congenital quantitative fibrinogen disorders: a Delphi consensus

“…To reduce the concomitant risk of bleeding in case of anticoagulation an accurate fibrinogen replacement should be maintained or introduced in afibrinogenaemic patients . Moderate hypofibrinogenaemic patients could be safely anticoagulated . Many anticoagulants have been used for the treatment of venous thromboembolism but low‐molecular‐weight heparin should be the first choice given the difficulty to use the prothrombin time to monitor antivitamin K treatment and the few experiences with oral direct Xa or thrombin inhibitors.…”

Clinical Consequences and Molecular Bases of Low Fibrinogen Levels

“…The low levels of circulating fibrinogen are probably enough to counteract the induced thrombotic phenotype observed in afibrinogenemia. It should be noted that low fibrinogen levels do not compensate a hypercoagulable state [ 37 , 38 ].…”

Clinical Features and Management of Congenital Fibrinogen Deficiencies

“…32,33 Fibrinogen replacement (see later) and genetic polymorphisms (e.g., inherited thrombophilia) may contribute to the increased risk of thrombosis, although in several patients no other thrombotic risk factors are identified. [34][35][36] It is also important to note that both thrombosis and severe bleeding can occur in the same patient leading to catastrophic clinical situations. 37,38 Dysfibrinogenemia and Hypodysfibrinogenemia…”