The role of sodium citrate in the dysfibrinogenaemia of liver disease.
The addition of excess sodium citrate to plasma was found to inhibit fibrin polymerisation (clot opacity) from patients with cirrhosis, hepatitis and hepatoma but not from normal controls. Abnormal clot opacity in plasma from patients with liver disease could be partly or completely abolished by removal of citrate ions by dialysis against citrate-free buffer, but not by dialysis against buffer containing citrate. Similar results were observed in plasma freed of calcium ions by treatment with EGTA. Treatment of plasma with neuraminidase largely abolished the inhibitory effect of excess citrate, and the thrombin times and clot opacity of asialofibrinogen were less affected by citrate than native fibrinogen. In addition, the effects of citrate on the clotting of purified, calcium-free fibrinogen from cirrhotic patients correlated with the sialic acid content. It is concluded that binding of citrate ions to fibrinogen renders the molecule acutely more sensitive to elevations in the sialic acid content, and that a simple plasma clot opacity test in the presence of excess citrate may be a useful aid in the differential diagnosis of liver disease. These findings may also explain why defects in fibrin polymerisation observed in plasma are not always reproduced in purified fibrinogen or fibrin monomer preparations.
D000347:Afibrinogenemia / Q000097:blood* / Q000209:etiology; D001777:Blood Coagulation / Q000187:drug effects*; D002951:Citrates / Q000494:pharmacology*; D019343:Citric Acid; D003937:Diagnosis, Differential; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D008107:Liver Diseases / Q000097:blood* / Q000150:complications; D012794:Sialic Acids / Q000378:metabolism; D013918:Thrombin Time
D002951:Citrates; D012794:Sialic Acids; D019343:Citric Acid; D005340:Fibrinogen