fibrinopeptide-a and Liver-Diseases

Recent advances in the elucidation of the molecular biochemistry of the coagulation proteins have provided the foundation for the development of synthetic substrates. These substrates are oligopeptide with either a chromophore or fluorophore group attached to the C-terminal end. They may be used in the laboratory to assay for a number of the serine proteases involved in either coagulation or fibrinolysis. Also, by suitably modifying the assay system, the various inhibitors can be quantitated. These substrates promise to revolutionize the coagulation laboratory allowing for more precise quantitation of trace enzymes and also improved standardization and precision of coagulation assays. In addition to these substrates, the introduction of a number of immunologic procedures into the diagnostic laboratory have been of major importance in elucidating the heterogeneity of hereditary coagulation defects. By correlating the immunologic assays, coagulation assays and clinical picture, a number of subgroups of hereditary deficiencies have been identified. Also, the immunologic assays have provided a means for identifying the carrier state of hemophilia A and have significantly contributed to the improved diagnosis of von Willebrand's disease. The use of ristocetin cofactor assays, when used in conjunction with the Factor VIII antigens, have enable the laboratory to more accurately diagnose the majority of patients with von Willebrand's disease. Ristocetin cofactor may be assayed utilizing either formalin fixed or washed platelets and recently a snake venom has been introduced to assay for this particular aspect of the Factor VIII complex. Platelet specific proteins (i.e., platelet factor 4 and beta-thromboglobulin) may be assayed utilizing either radioimmunoassays or in the case of platelet factor 4 modified coagulation assays. These proteins provide evidence of in vivo platelet activation and hopefully may, in the future, be correlated with platelet kinetics.

Topics: beta-Thromboglobulin; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Chromogenic Compounds; Factor IX; Factor VII; Factor VIII; Factor X; Fibrinogen; Fibrinopeptide A; Genetic Variation; Humans; Immunologic Techniques; Liver Diseases; Platelet Factor 4; Prothrombin

1. The concentration in plasma of fibrinogen derivatives fibrinopeptide A (FPA) and B beta 1-42 and the platelet release products beta-thromboglobulin (beta TG) and platelet factor 4 (PF4) have been determined in patients with acute and chronic liver disease. 2. In 21 patients with fulmiant hepatic failure on admission in grade III or IV coma the plasma FPA, B beta 1-42, beta TG and PF4 levels were significantly increased compared with those in normal control subjects. On heparinization before haemoperfusion the FPA levels returned to the normal range and during resin and charcoal haemoperfusion there were no significant changes in the coagulation or platelet factors, except for a small increase in FPA with charcoal haemoperfusion. 3. In ten patients with compensated chronic liver disease there was a significant increase in B beta 1-42 and beta TG levels but not FPA and PF4 as compared with normal controls. 4. Interpretation of the results is complicated by the possible reduced clearance of these proteins as a result of renal failure in some of the patients with fulminant hepatic failure and also by the damaged liver itself. However, these results have confirmed that disseminated intravascular coagulation can occur in both acute and chronic liver disease.

Topics: Acute Disease; Adolescent; Adult; Aged; beta-Thromboglobulin; Chronic Disease; Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Fibrinopeptide B; Hemoperfusion; Humans; Liver Diseases; Male; Middle Aged; Peptide Fragments; Platelet Factor 4

Fibrinopeptide A (FPA), released from the fibrinogen A alpha-chain by thrombin, can be resolved by high-performance liquid chromatography (HPLC) into three forms, the intact peptide (A), a modified peptide phosphorylated at the serine in position 3 (AP), and an N-terminally degraded form (AY). A new method has been developed, using HPLC, that allows direct measurement of the proportions of AP, A, and AY released by thrombin from fibrinogen in plasma samples of 200 ul or less. The method was used to examine variations in the proportions of AP and AY expressed as a % of total FPA in a number of patient and control groups. The mean percentages of AP and AY of plasma fibrinogen were found to be 21.7 and 14.2%, respectively, in normal laboratory controls. In older, apparently normal, individuals these figures were 27.0 and 15.5%, respectively. Cord plasma exhibited very high AP and slightly reduced AY levels (41.6 and 12.4%, respectively) compared with normal adults. Patients with liver failure had low AP levels and high AY levels (11.6 and 21.1%, respectively). Patients recovering from major surgery or acute thrombotic stroke showed an acute-phase rise in fibrinogen level that was accompanied by an increase in AP and variable reduction in AY. Incubation of heparinized whole blood for 8 days in vitro demonstrated a gradual decrease in the proportion of AP and increase in AY of plasma fibrinogen. These results provide some support for the idea that an increased "aging" of fibrinogen in the circulation may result in a decrease in the AP content of fibrinogen accompanied by a more variable increase in AY.

Topics: Aged; Aged, 80 and over; Cerebrovascular Disorders; Chromatography, High Pressure Liquid; Female; Fetal Blood; Fibrinogen; Fibrinopeptide A; Humans; Infant, Newborn; Kinetics; Liver Diseases; Macromolecular Substances; Pregnancy; Rectal Neoplasms; Reference Values; Thrombin