title: Sequence of fibrinogen proteolysis and platelet release after intrauterine infusion of hypertonic saline.
abstract: 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.
mesh_terms: D000028:Abortion, Induced; D000328:Adult; D001792:Blood Platelets / Q000378:metabolism*; D005260:Female; D005337:Fibrin / Q000096:biosynthesis; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000378:metabolism*; D005342:Fibrinolysis; D005344:Fibrinopeptide A / Q000097:blood; D005345:Fibrinopeptide B / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D007263:Infusions, Parenteral; D011247:Pregnancy; D011863:Radioimmunoassay; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage*; D012965:Sodium Chloride / Q000008:administration & dosage*; D013300:Streptokinase / Q000494:pharmacology; D013917:Thrombin / Q000378:metabolism / Q000494:pharmacology; D014599:Uterus
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D012462:Saline Solution, Hypertonic; D005344:Fibrinopeptide A; D005345:Fibrinopeptide B; D012965:Sodium Chloride; D005337:Fibrin; D005340:Fibrinogen; D013300:Streptokinase; D013917:Thrombin