fibrinopeptide-a and Liver-Cirrhosis

Cirrhotic patients with a prolonged prothrombin time (PT) are known to have low levels of factor VII. Because the current modalities to correct this problem are not ideal, recombinant factor VIIa (rFVIIa) may be useful in correcting the prolonged PT observed in the coagulopathy of cirrhosis. The aim of this study was to evaluate the effectiveness of rFVIIa in nonbleeding volunteer patients with the coagulopathy of cirrhosis.. A preliminary, single-center, dose-escalation trial was performed. Cirrhotic patients with a PT of > 2 seconds above the upper limit of the reference value received an intramuscular injection of vitamin K. Ten patients whose PT did not correct to within 2 seconds above the control of the upper limit of the reference value were given three successive dosages of rFVIIa (5, 20, and 80 micrograms/kg) during a 3-week period.. The mean PT transiently corrected to normal in all three dosage groups. No adverse effects were noted. There was no evidence of the induction of disseminated intravascular coagulation.. This preliminary trial shows rFVIIa to be effective in transiently reversing the prolonged PT in a select group of nonbleeding cirrhotic patients. These preliminary observations support conducting a large-scale efficacy trial.

Topics: Adult; Dose-Response Relationship, Drug; Factor VIIa; Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Humans; Liver Cirrhosis; Male; Middle Aged; Partial Thromboplastin Time; Prothrombin Time; Recombinant Proteins

To test the hypothesis that disseminated intravascular coagulation contributes to hemostatic failure in liver cirrhosis, fibrinopeptide A and fibrin(ogen) degradation fragment E were measured in 69 patients with stable liver cirrhosis and compared with fibrinopeptide A and fibrin(ogen) degradation fragment E in 32 healthy subjects, 33 patients with thromboembolism, and 10 patients with hypofibrinogenemic disseminated intravascular coagulation. Mean fibrinopeptide A in cirrhosis was slightly increased compared with healthy subjects (2.4 vs. 1.8 ng/ml, p < 0.005), but fourfold lower than in thromboembolism (mean fibrinopeptide A 9.7 ng/ml; p < 0.0001), and tenfold lower than in disseminated intravascular coagulation (mean FPA 24.3 ng/ml; p < 0.0001). Single fibrinopeptide A levels in cirrhosis were within the normal range in 75% of the patients, marginally increased in 9%, and definitely increased in 16%. A definite increase in both fibrinopeptide A and fibrin(ogen) degradation fragment E, which characterized the groups of patients with thromboembolism and disseminated intravascular coagulation, was found in 10% of the cirrhotic patients. Among 17 patients with cirrhosis and hypofibrinogenemia, mean fibrinopeptide A (2.7 ng/ml) was tenfold lower compared with mean fibrinopeptide A in patients with hypofibrinogenemic disseminated intravascular coagulation (p < 0.0001), whereas the frequency of increased single fibrinopeptide A levels (29%) was not significantly different compared with the 52 cirrhotic patients without hypofibrinogenemia (single levels elevated in 23% of the cases). Moreover, the frequency of hypofibrinogenemia, thrombocytopenia, or abnormal clotting times was not significantly different in cirrhotic patients with normal fibrinopeptide A level when compared with cirrhotic patients with increased fibrinopeptide A. These findings do not support an important contribution of disseminated intravascular coagulation to coagulopathy of liver cirrhosis.

Topics: Adult; Aged; Blood Coagulation Disorders; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Humans; Liver Cirrhosis; Male; Middle Aged; Reference Values; Thromboembolism

In order to detect even minimal fibrinolysis activation in liver cirrhosis, we measured fibrinopeptide B beta 15-42 (B beta 15-42), an indicator of plasmin activity in vivo and alpha 2-antiplasmin (alpha 2-AP) in a group of cirrhotic patients. The second goal of this study was to investigate whether an increased fibrinolytic activity is related to a chronic disseminated intravascular coagulation. For this purpose we concomitantly measured fibrinopeptide A (FPA), marker of thrombin activity in vivo. Results show significantly higher levels of B beta 15-42 in cirrhotic patients than in control (p less than 0.01). In patients with high FPA levels we found significantly higher values than in patients with normal FPA (p less than 0.01). alpha 2-AP was lower in patients with high FPA levels than in patients with normal FPA (p less than 0.05). A significant negative correlation was found between FPA and alpha 2-AP only in patients with high FPA (p less than 0.05). There was no relationship between B beta 15-42 and FPA nor between B beta 15-42 and alpha 2-AP when all patients were considered. These findings confirm that in liver cirrhosis fibrinolysis activation may occur. The primary pathogenetic role of DIC may be important in this respect. However the lack of correlation between FPA and B beta 15-42 suggests that other pathogenetic factors may be involved in determining fibrinolysis activation.

Topics: Adult; alpha-2-Antiplasmin; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Fibrinopeptide B; Humans; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Peptide Fragments

Ascitic fluid reinfusion in severe cirrhosis has frequently been associated with intravascular coagulation (DIC). A low-grade DIC has been postulated to be present in liver cirrhosis. PT, APTT, fibrinogen, plasminogen, antiplasmin, fibrin degradation producers (FDP), euglobulin lysis time, tissue plasminogen activator, and fibrinopeptide A were investigated both in the plasma and ascitic fluid of cirrhotic patients before and after the concentration-reinfusion technique. Our results indicate that increased thrombin formation associated with hyperfibrinolysis is present in the plasma of cirrhotic patients. In ascitic fluid very high levels of thrombin and fibrinolysis activation were found. We conclude that (1) a DIC-like picture exists in ascites and (2) after ascites reinfusion procedures, ascitic fluid is the principal factor in the pathogenesis of DIC. During ascitic fluid reinfusion heparin treatment could be used successfully.

Topics: Aged; Ascites; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Fibrinopeptide A; Humans; Liver Cirrhosis; Male; Middle Aged; Partial Thromboplastin Time; Plasminogen; Prothrombin Time; Reference Values; Tissue Plasminogen Activator

Topics: Disseminated Intravascular Coagulation; Fibrinopeptide A; Humans; Liver Cirrhosis

Topics: Aged; Cholinesterases; Female; Fibrinopeptide A; Humans; Liver; Liver Cirrhosis; Male; Middle Aged; Platelet Count; Spleen; Thrombin; Thrombocytopenia

Increased fibrinopeptide A (FPA) levels have been reported in various non-thrombotic disorders, including cancer, acute myocardial infarction, liver cirrhosis and collagen vascular diseases. To investigate the significance of these findings, the present study combined the radioimmunoassay of FPA with that of fibrinogen/fibrin degradation fragment E (FgE) in the aforementioned disorders and compared the results with those observed in healthy subjects as well as in patients with thromboembolism and overt disseminated intravascular coagulation (DIC). Mean FPA and FgE in malignancy were 6.3 and 305 ng/ml, in myocardial infarction 5.6 and 98 ng/ml, in liver cirrhosis 2.7 and 132 ng/ml and in collagen vascular diseases 5.6 and 142 ng/ml. All these values were significantly higher than in healthy controls (mean FPA 1.6 ng/ml, mean FgE 49 ng/ml) but significantly lower than in thromboembolism (mean FPA 10.7 ng/ml, mean FgE 639 ng/ml). and DIC (mean FPA 22.0 ng/ml, mean FgE 1041 ng/ml). The overall correlation between FPA and FgE was highly significant. However, different disorders showed peculiar patterns in FPA, FgE and fibrinogen levels. In malignancy, a definite increase of FPA, FgE and plasma fibrinogen levels was observed. This finding probably indicates a compensated state of (intra- or extravascular) fibrin formation and lysis. Acute myocardial infarction was characterized by a high FPA to FgE ratio, which is interpreted to reflect acute thrombin generation and fibrin formation. FPA in cirrhosis was only marginally elevated with most single values within the normal range, indicating that intravascular coagulation was infrequent and unimportant in quantitative terms.

Topics: Collagen Diseases; Disseminated Intravascular Coagulation; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Humans; Liver Cirrhosis; Myocardial Infarction; Neoplasms; Thromboembolism

Subnormal concentrations of alpha 2 Antiplasmin (alpha 2 AP) in liver cirrhosis may be due to an impaired hepatic synthesis and/or to a fibrinolysis activation in disseminated intravascular coagulation (DIC). In order to clarify this problem, in 26 cirrhotic patients (15 compensated and 11 decompensated) alpha 2 AP plasma activity and plasma Fibrinopeptide A (FPA) were measured. Serum albumin, p-Cholinesterase (p-CHE), Fibrinogen and Fibrinogen Degradation Products (FDP) were also carried out. Our data show that alpha 2 AP and FPA were equally abnormal in compensated and decompensated cirrhosis. The significant negative correlation obtained between alpha 2 AP and FPA as well as the lack of correlation between alpha 2 AP and albumin, alpha 2 AP and p-CHE in both groups suggests that, in our patients, alpha 2 AP decrease may be due to a fibrinolysis activation induced by a DIC which appears chronic since Fibrinogen and FDP were normal. These findings are in agreement with the results obtained in the four subgroups a posteriori selected on the basis of FPA levels: alpha 2 AP in subgroups with high FPA was significantly different from controls while it did not differ in subgroups with normal FPA.

Topics: Adult; alpha-2-Antiplasmin; Cholinesterases; Disseminated Intravascular Coagulation; Female; Fibrinolysis; Fibrinopeptide A; Humans; Liver Cirrhosis; Male; Middle Aged; Serum Albumin

Ascitic fluid from patients with ovarian cancer contains high levels of fibrin(ogen) degradation products (FDP). Crosslinked fibrin derivatives were isolated by precipitation and separated by PAA-gel-electrophoresis. In order to evaluate the submolecular structure the total precipitate and single derivatives were investigated after cleavage of the disulfide bonds. The findings are related to the radioimmunological measurements of certain fibrinopeptides. Tumor ascites contains approximately ten times higher levels of crosslinked fibrin derivatives than cirrhosis ascites. The fibrinopeptide A content is similar, whereas the levels of plasmin-induced alpha-chain fragment are significantly higher in tumor ascites. The findings suggest a catabolism of fibrinogen in ascitic fluid via coagulation and fibrinolysis. In tumor ascites fibrinogen is catabolized to a significantly higher degree via the degradation of crosslinked fibrin. Crosslinked fibrin derivatives may therefore be usable as non-carcinoembryogenic tumor markers.

Topics: Ascites; Ascitic Fluid; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Humans; Liver Cirrhosis; Ovarian Neoplasms

Topics: Adult; Aged; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Female; Fibrinopeptide A; Humans; Liver Cirrhosis; Male; Middle Aged; Platelet Count; Thrombin; Thrombocytopenia

Plasma fibrinopeptide A (FPA) was measured in 50 patients with liver cirrhosis divided into 'moderate' or 'severe' cirrhotics according to standard clinical and laboratory criteria. FPA was significantly higher than in normal controls although no relation to the severity of disease was found. After a single intravenous administration of heparin there was a significant decrease in FPA levels in the patients. High molecular weight fibrinogen (HMWF) was also determined for some of the patients and was significantly greater than in the normal controls. However, there was no correlation between FPA and HMWF. The greater values of FPA and their responses to heparin indicate that there is increased thrombin formation in a number of patients with liver cirrhosis, with no apparent relation to the severity of the disease.

Topics: Female; Fibrinogen; Fibrinopeptide A; Heparin; Humans; Liver Cirrhosis; Male; Molecular Weight

Topics: Animals; Dialysis; Fibrinogen; Fibrinopeptide A; Humans; Immune Sera; Liver Cirrhosis; Rabbits; Radioimmunoassay; Time Factors

In 13 patients with effusions of varying etiology, considerably higher fibrinopeptide A (FPA) immunoreactivity were found in the effusions than in the corresponding plasmas. After instillation of heparin into the effusion the FPA concentration diminished significantly but very slowly. The difference in concentration between plasma and effusion therefore represents a relative FPA accumulation in the effusion. In view of its extremely short half-life in plasma, the FPA produced in the effusions is thought not to contribute to the increased plasma FPA levels. In addition, injection of amounts of FPA into the effusion such as to produce an acute increase of the local FPA level did not lead to a significant change in the FPA level in plasma.

Topics: Breast Neoplasms; Bronchial Neoplasms; Fatty Liver; Female; Fibrinogen; Fibrinopeptide A; Half-Life; Humans; Liver Cirrhosis; Lymphoma, Non-Hodgkin; Pleural Effusion