Fibrinogen and fibrinolytic activity in hyperthyroidism before and after antithyroid treatment.

Plasma concentration of fibrinogen and B beta 15-42, a specific product of fibrinogen metabolism induced by plasmin, were measured in a group of patients with untreated hyperthyroidism and in controls. Significantly increased plasma levels of both parameters were observed in hyperthyroid patients. The restoration of euthyroidism either by antithyroid drug or by radioiodine caused a significant decrease of fibrinogen and B beta 15-42. These data indicate that hyperthyroidism is another clinical condition associated with increased concentration of fibrinogen and B beta 15-42.

Fibrinopeptide A and fibrinopeptide B beta 15-42 in patients with Behçet's disease.

Plasma levels of FPA and FPB beta 15-42 in patients with Behçet's disease were examined. In the patients, the mean levels of FPA and FPB beta 15-42 were significantly higher than controls (p less than 0.001). Fibrinolysis subsequent to coagulation may be activated in the patients. The levels of both FPA and FPB beta 15-42 were higher during attack than in remission. The caution should be taken these levels to understand the disease activity.

In vitro stability of human fibrinopeptide B.

In anticipation of a future clinical application of plasma fibrinopeptide B (FPB) measurement, we studied the stability of FPB in an ultrafiltrate of normal plasma, normal urine and alkaline buffer by measuring the immunoreactivity of the peptide by FPB radioimmunoassay using anti FPB serum (R-29). FPB was unstable in an ultrafiltrate of plasma and urine and demonstrated a temperature dependent loss of activity. In plasma ultrafiltrate the loss of immunoreactivity was not significant during the first 24 hours, however, 92% of the peptide activity was lost at the end of seven days at 25 degrees C and 37 degrees C. The rate of FPB degradation in urine was comparable. The peptide was stable in an alkaline buffer (pH 8.5) at temperatures ranging from -10 degrees C to 37 degrees C or in plasma ultrafiltrate or urine when incubated at -10 degrees C. Treatment with carboxypeptidase B or leucine aminopeptidase for two hours at 37 degrees C (enzyme/substrate molar ratio of up to 1:100) did not cause a loss of FPB immunoreactivity. EDTA (1.0 mM) and Trasylol (500 units/ml) completely stabilized the peptide in a plasma ultrafiltrate.

Sequence of fibrinogen proteolysis and platelet release after intrauterine infusion of hypertonic saline.

Plasma fibrinopeptide B (Bbeta1-14 or FPB) immunoreactivity was studied by radioimmunoassay in patients who received intrauterine infusion of hypertonic saline to terminate pregnancy. FPB immunoreactivity increased with thrombin treatment (TIFPB) suggesting the presence of a larger FPB-containing peptide, since purified FPB is not altered by thrombin, whereas thrombin increases the immunoreactivity of Bbeta1-42 (which includes FPB) 10-fold. TIFPB immunoreactivity in plasma, drawn 4 h after hypertonic saline infusion eluted from Sephadex G-50 similarly to isolated Bbeta1-42. Streptokinase, incubated with normal plasma progressively generated TIFPB immunoreactivity, which showed a major component which eluted from Sephadex G-50 similarly to Bbeta1-42. Streptokinase generated TIFPB much more rapidly in reptilase-treated plasma that contains fibrin I, (which still includes FPB), indicating that fibrin I is preferred over fibrinogen as a substrate for plasmin cleavage of arginine (Bbeta42)-alanine (Bbeta43). Serial studies were then made in 10 patients receiving intrauterine hypertonic saline. Fibrinopeptide A (FPA) levels rose immediately, reached a peak between 1 and 2 h, were declining at 4 h, and were normal at 24 and 48 h. TIFPB levels rose slightly in the 1st h, reached a peak at 4 h, and had returned to base-line values at 24 h. Serum fibrinogen degradation product levels were unchanged at 1 h, reached their highest level at 4 h, and were still markedly elevated at 24 and 48 h. Fibrinogen levels dropped slightly being lowest at 4 and 24 h. Platelet counts declined in parallel with the fibrinogen levels over the first 4 h, but continued to decrease through 48 h. Beta thromboglobulin (betaTG) levels generally paralleled FPA levels whereas platelet factor 4 (PF4) levels showed only slight changes. The data indicate that immediately after intrauterine hypertonic saline infusion thrombin is formed that cleaves FPA from fibrinogen to produce fibrin I and releases betaTG and PF4 from platelets. Later plasmin cleaves Bbeta1-42 from fibrin I to produce fragment X, which is further degraded to form serum fibrinogen degradation products. This sequence of proteolysis indicates that plasmin action on fibrin I serves as a mechanism that regulates fibrin II formation by removing the Bbeta chain cleavage site, which is required for thrombin action in converting fibrin I to fibrin II.