Plasma Fibrin Stabilizing Factor Activity in Various Diseases.

I N 1948, Laki and Lorand1 observed that “fibrin clots” formed by the addition of calcium throm in to purified fibrinogen solutions were readily soluble in 5 NI urea and 1 per cent monochloroacetic acid. “Plasma clots” formed Iw the recalcification of oxalated plasma were insoluble in these solvents. Urea insolube clots could also be prepared 1w the addition of small amounts of plasma to the purified fibrinogen solutions prior to the addition of thrombin and calcium.2 The plasma factor responsible for rendering fibrin clots insoluble in urea and monochloroacetic acid has been called fibrin stabilizing factor ( FSF),2 Laki-Lorand factor or fibrinase. FSF has been indentified as an alpha-2 globulin with a molecular weight of 350,000 and a sedimentation constant of 6.4. The protein exists as three inactive slll)units which aggregate to one active molecule Ill the presence of cvsteine and other sulfhvdryl-containing compounds.3 In this active form, it is capable of converting 11,000 times its own weight of urea soluble fibrin into the insoluble form, presumably by promoting sulfhvdrvl-disulfide exchange,34 and possibly by promoting transpeptidation or transamiclation reactions hetween fibrin monomers.5 An 8000-fold concentration of this protein was achieved by Loewy et al.4’65 Immunologic specificity was also demonstrated. Its pr hable role in fibrin clot formation is illustrated in figure 1. Lorand believes that FSF acts as a copolymer with fibrin monomer.#{176} Loewy and his co-workers proposed that this activity is enzymatic.4 The physiologic significance of FSF and its physical properties are the subjects of a recent extensive review by Lorand.#{176} Uhhizin a plasma assay procedure, Lorand and Dickenman found diminished FSF activity in specimens obtained from 15 of 110 hospitalized patients.1#{176} Duckert et al.1’ and Ikkala and Nevanlinna12 reported their observations on families with the congenital absence of FSF. Weiner and Farhang13 found urea soluble plasma clots in a patient with excessively high levels of fibrinogen. Nussbaum and Morse14 reported decreased levels of FSF activity in the plasma of patients with liver disease, and in rats which were fed carbon tetrachloride. The present study was undertaken to determine the FSF activity in the plasma of patients with various disease states.