Physiological and Clinical Significance of Disordered Cross-Linking of Fibrin
Disorders of fibrin stabilization are hemorrhagic conditions in which the patient’s plasma clot is lacking in inter-fibrin γ-glutamyl-ε-lysine isopeptide linkages. The primary defect occurs either because no fibrinoligase (FXIIIa) activity can be generated or because the enzyme cannot act on fibrin in the patient’s plasma. Distinction is made between hereditary disorders (Class I) and those appearing later in life because of an acquired inhibitor (Class II) directed against one of the steps on the pathway of fibrin stabilization: Of the genetic deficiencies (Class I), Type I is characterized by a lack of zymogen activity in plasma and Type II by the unreactivity of the cross-linking sites of the patient’s fibrin [“dysfibrin(ogen)emias”] towards fibrinoligase.There are three varieties of Class II abnormalities. In Type I, the acquired inhibitor interferes with zymogen activation. Type II inhibitors affect transamidation by competing against fibrin for the enzyme. The Type III inhibitor combines with fibrin rendering it unreactive towards fibrinoligase. The Type I and III inhibitors appear to be autoimmune antibodies.(Ann. N. Y. Acad. Sei., 202, 6, 1972).Differential diagnostic criteria for this family of molecular disorders will be discussed.