Abstract

Inherited hypofibrinogenemia (hypo-FBG) and dysfibrinogenemia (dys-FBG) are rare blood coagulation disorders caused by quantitative or qualitative defects of fibrinogen. We reviewed the clinical course in 47 individuals with dys-FBG and 16 patients with hypo-FBG with median fibrinogen coagulant/antigen levels of 0.76/2.8 and 1.1/1.2 g/L, respectively. Genetic analysis was performed in 5 families (16 individuals) with dys-FBG and 4 families (8 individuals) with hypo-FBG.

In the dysfibrinogenemia group 21 (45%) individuals were asymptomatic, 24(51%) patients suffered from bleeding and/or prolonged wound healing (only four had serious bleeding) and 2(4%) patients had a history of thrombosis. A total of 96 surgeries were performed without preoperative fibrinogen replacement in 31 dys-FBG patients, only 9 (9%) procedures were complicated with bleeding, two requiring fibrinogen substitution. Genetic analysis in dysfibrinogenemia has revealed heterozygous mutation in FGA exon 2 (Aα Arg16 His) known to cause delayed fibrinopeptide A cleavage by thrombin in 6 individuals (3 families). Five patients from two other families were heterozygous for a novel mutation in FGA exon 2 (Aα Gly13Glu). Fibrinogen coag/Ag median levels were comparable for both mutant genotypes: 0.5/2.9 g/L and 0.56/2.8 g/L, respectively.

In the hypofibrinogenemia group 6/14 (43%) patients had mild spontaneous bleeding, 8/36 (22%) surgeries performed in 12 patients w/o replacement were complicated with bleeding. A novel mutation in FGG exon 1 (Trp3 Stop) was identified in heterozygosity for 3 patients (3 families) with FBG coag/Ag median level of 1.1/1.2 g/L. An additional unrelated patient with a fibrinogen level of 0.7 g/L and serious postpartum bleeding was heterozygous for a novel mutation in FGG exon 7 (Trp253Cys) - Fibrinogen Bratislava.

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