Fibrinogen Baltimore II: congenital hypodysfibrinogenemia with delayed release of fibrinopeptide B and decreased rate of fibrinogen synthesis.

Abstract

A congenital hypodysfibrinogenemia, fibrinogen Baltimore H, was found in a young asymptomatic Caucasian female. Prothrombin, partial thromboplastin, and euglobulin lysis times were normal, as were platelet function and coagulation factor assays. Subnormal plasma fibrinogen levels were found using chronometric, rate-independent, and immunologic assay methods. Kinetic analysis of fibrinopeptide release revealed a delay in the thrombin-catalyzed release of fibrinopeptide B from the abnormal protein. Proteolysis of fibrinopeptide A by thrombin or -Arvin, fibrin monomer polymerization, and fibrin polymer ligation occurred at normal rates. -Catabolism of radiolabeled autologous and homologous fibrinogen was also normal, but the fibrinogen synthetic rate was -less than half the normal value. Tyler (18). Factors VII and X were measured as follows: citrated patient plasma was diluted 1:10 with 0.9% NaCl, and 0.15 ml of this solution was combined with an equal amount of factor-deficient plasma. A onestage PT was then performed as described above. The results were compared with a standard curve generated in the same manner using pooled normal plasma.Platelet aggregometry was performed on a platelet aggregation profiler (BioData, Horsham, PA) at 37C with plateletrich plasma (=300,000 platelets per mm3) and the following as aggregating agents in a final volume of 0.5 ml: 2-10 tLM ADP (Sigma), 1.2 mg of ristocetin (Abbott) per ml, 5.5 and 11 ,uM epinephrine (Ellcins-Sinn, Cherry Hill, NJ), 0.26 mg of collagen (Worthington) per ml, and 0.2-0.4 u of bovine thrombin (Parke-Davis) .per ml.Release The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Fibrinogen Philadelphia, a hypodysfibrinogenemia characterized by abnormal polymerization and fibrinogen hypercatabolism due to γ S378P mutation

“…A second hypodysfibrinogenemia, Bethesda III, 41 exhibits properties similar to those of fibrinogen Philadelphia: no obvious truncations of the constitutive chains, a polymerization defect, a decrease in the concentration of fibrinogen to about one third to one fourth of normal, and a high catabolic rate of only the abnormal fibrinogen. In contrast, 2 other hypodysfibrinogenemias, fibrinogens Baltimore II 42 and Chapel Hill I, 43 manifest a normal catabolic rate of the autologous and homologous fibrinogens, indicating a defect in synthesis, assembly, or secretion. Two other hypodysfibrinogenemias, fibrinogens Marburg 44 and Otago, 45 are structurally characterized by truncations of the A␣ chain that cause delay in fibrin polymerization and the low plasma fibrinogen could be due to impaired synthesis, intracellular assembly, or defects in secretion, as demonstrated with other hypofibrinogenemias.…”

Fibrinogen date: Congenital hypodysfibrinogenemia associated with decreased binding of tissue‐plasminogen activator

“…We investigated abnormal fbg of the patient with episodes of arterial thrombosis and phlebothrombosis. This was a case of hypodysfibrinogenemia, of which there are very few case reports due to difficulty in the isolation of abnormal fbg [ 17,191. This abnormal fbg was characterized not only by a defective polymerization as observed in most cases of dysfibrinogenemia but also by poor t-PA adsorption at the time of fibrin formation.…”

“…Polymerization was initiated by mixing 0.5 ml of fibrin solution with an equal volume of 80 mM Na,HPO, to produce a pH 7.4 solution with an ionic strength of 0.10 [17]. The extent of polymerization was measured by turbidity at 350 nm in a spectrophotometer (Hitachi Model 200-10, Japan.…”

The rate of fibrinopeptide B release modulates the rate of clot formation: a study with an acquired inhibitor to fibrinopeptide B release

“…At least five congenital dysfibrinogenaemias have been due to delayed fibrinopeptide B release (Andes, 1983;Branson ~t ul. 1983; Ebert &Bell, 1983: Borrellet al 1987. Acquired antibodies to fibrinogen are uncommon but can occur after transfusions (Bronnimann.…”