Hypercoagulability in a Patient with Hypodysfibrinogenemia:Implic ations for Clinical Management

Abstract

Dysfibrinogenemia accounts for approximately 0.7% of thrombophilia in patients with venous thromboembolic disease. In 20% of these patients, plasma thrombophilic dysfibrinogen is below 1.0 mg/ml, defining hypodysfibrinogenemia. We describe a young female patient, in whom hypodysfibrinogenemia was the cause of several severe thromboembolic events which occurred even under oral anticoagulation monitored by a standard prothrombin time (PT) test. In this patient, the standard PT test according to Quick underestimated the plasma coagulability in vivo, presumably due to the low levels of dysfunctional fibrinogen as the substrate of the thromboplastin reagent. A PT test supplemented with bovine plasma fibrinogen (Thrombotest) revealed lower fibrinogen-independent international normalized ratio (INR) values in the proposita on oral anticoagulation compared to a control group with eufibrinogenemia. Monitoring therapy with the fibrinogen-independent Thrombotest secured safe anticoagulation in this patient. We suggest to consider PT tests with exogenous fibrinogen (e.g. Thrombotest) to monitor oral anticoagulation in the rare thrombophilic patients with hypodysfibrinogenemia.

Thrombosis in Inherited Fibrinogen Disorders

“…Reported therapies include anticoagulant, antiplatelet or vasodilatory drugs such as LMWH, rivaroxaban, warfarin, aspirin, clopidogrel, urokinase, phenprocoumon, streptokinase, pentoxifylline, nifedipine, and nafamostat [15,16,18,[38][39][40][41][42][43][44]. Concomitant fibrinogen replacement therapy may be administered to reduce the risk of severe hemorrhage [16,17,38].…”

“…Surgical interventions, including thrombus removal, resection and inferior vena cava filter placement, may be considered. Favorable outcomes have been reported with both pharmacotherapy and surgery in the majority of patients [19,41,42]. In 7 cases (10%), the thrombotic event was fatal, while the rest made a full recovery.…”

Severe hypodysfibrinogenemia in compound heterozygotes of the fibrinogen AαIVS4 + 1G>T mutation and an AαGln328 truncation (fibrinogen Keokuk)

“…Regardless of the precise molecular explanations for thrombogenicity, the near fatal post-surgical thrombosis following the administration of cryoprecipitate to our patient II.2 illustrates the risk associated with aggressive replacement therapy for raising the circulating concentration of fibrinogen without adequately characterizing the nature of the hypodysfibrinogenemia. 42…”

Genetics, diagnosis and clinical features of congenital hypodysfibrinogenemia: a systematic literature review and report of a novel mutation

“…Thrombotic recurrences were frequent ( n = 11/22, 50%), mainly in the venous territory. Available data did not allow determination of whether these events occurred under an appropriate antithrombotic treatment, except for three cases: a young woman with recurrent venous thromboses under oral anticoagulation , a man (Fibrinogen Freiburg I) with recurrent arterial thromboses under low‐molecular‐weight heparin and aspirin and another man with recurrent extensive bilateral pulmonary embolisms and intracardiac thromboses despite therapeutic international normalized ratio (INR) . Eleven patients (22%) were asymptomatic at time of diagnosis.…”