Clinical Manifestations of Patients with Dysfibrinogenemia

Abstract

Congenital dysfibrinogenemias are characterized by structural abnormalities in the fibrinogen molecule that result in tendencies for hemorrhage and/or thrombosis. Acquired dysfibrinogenemia may carry a worse prognosis than the congenital dysfibrinogenemia due to a severely damaged liver [1]. With rare exceptions, the congenital dysfibrinogenemias are inherited in an autosomal dominant or codominant way. Fibrinogen is a 340000 Da protein which is synthesized in hepatocytes. The molecule is a homodimer; each half consists of three non-identical polypeptide chains that have been termed A alpha, B beta and gamma-chains [2]. The genes for all three chains have been localized to the long arm of chromosome 4 [3]. The amino termini of the three pairs of polypeptide chains are symmetrically arranged into a disulphide knot to form a central E-domain that is flanked by two large Ddomains to form a trinodular structure. Approximately 300 abnormal fibrinogens with unique name designations have been reported to date, and about 83 structural defects have been identified [4]. The most common structural defects involve the fibrinopeptides and their cleaving sites, and the second most common involves the gamma-chain polymerization region. Dysfibrinogenemia can also be acquired secondary to liver cirrhosis or use of certain drugs (e.g. asparaginase).