title: Acquired dysfibrinogenemia in a hemophiliac with hepatoma: resolution of fibrinogen dysfunction following chemotherapy.
abstract: A 17-year-old male with previously undiagnosed congenital Factor IX deficiency (13%) presented with gastrointestinal bleeding and a hepatic mass. Prolonged thrombin and Reptilase times, which partially corrected with CaCl2 and a discrepancy between thrombin-clottable and immunoreactive plasma fibrinogen, suggested a dysfibrinogenemia. Laparotomy disclosed metastatic hepatoma. Adequate hemostasis was obtained with clotting factor replacement, but wound healing was delayed. Patient fibrinogen purified with 2.1 M glycine migrated normally on immunoelectrophoresis and 7.5% polyacrylamide-SDS gel electrophoresis. However, fibrin monomers prepared from purified patient fibrinogen displayed impaired aggregation at high and low ionic strengths when compared with fibrin monomers from normal and control Factor IX deficient subjects. Aggregation of normal monomers was delayed when mixed 1:1 with patient monomers. Fibrinopeptide release was normal, and total sialic acid content was similar to that of normal and control fibrinogens. Chemotherapy, consisting of 5-FU given via intra-arterial hepatic infusion, was accompanied by significant transient clinical improvement which coincided with correction of thrombin clotting times and fibrin monomer aggregation. Reappearance of fibrinogen dysfunction occurred with clinical deterioration prior to death from metastatic hepatoma and sepsis. This case is the first to corroborate the postulated tumor marker role of dysfibrinogenemia in a patient with hepatoma by documenting a direct relationship with response to chemotherapy.
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001778:Blood Coagulation Disorders / Q000150:complications*; D006528:Carcinoma, Hepatocellular / Q000150:complications* / Q000188:drug therapy; D005340:Fibrinogen / Q000032:analysis / Q000502:physiology; D006467:Hemophilia A / Q000150:complications*; D002836:Hemophilia B / Q000150:complications; D006801:Humans; D008113:Liver Neoplasms / Q000150:complications* / Q000188:drug therapy; D008297:Male; D009362:Neoplasm Metastasis; D012008:Recurrence
chemical_list: D000970:Antineoplastic Agents; D005340:Fibrinogen