Fibrinogen Bethesda III: A Hypodysfibrinogenemia

Abstract

A qualitative and quantitative defect of fibrinogen in a white female was associated with first trimester abortions and hemorrhage. This congenital hypodysfibrinogenemia was inherited in an autosomal pattern. The functional defect was an abnormality in the fibrin monomer aggregation. Metabolic studies in the propositus revealed that homologous fibrinogen had a normal intravascular survival and fractional catabolic rate, while her fibrinogen, when injected into a normal volunteer, had a very short intravascular survival and high fractional catabolic rate. Coagulation changes were monitored through 36 wk of one pregnancy. The observed coagulation changes included elevation of factors VIII, VII-X, and plasminogen; however, the fibrinogen measured by immunologic or fibrin tyrosine content did not increase during the pregnancy, while the functional fibrinogen assay became undetectable and the thrombin and reptilase times were markedly prolonged. This suggested that this patient either was synthesizing more of her abnormal fibrinogen during pregnancy or that her normal fibrinogen was being catabolized at a different rate than her abnormal fibrinogen. Comparative studies with fibrinogen Philadelphia revealed several similarities in the two fibrinogens; however, significant differences were also noted. This new congenital hypodysfibrinogenemia is designated fibrinogen Bethesda III.