fibrinopeptide-a and Chronic-Disease

Several prospective studies have demonstrated that high plasma fibrinogen levels are associated with an increased risk of ischemic heart disease. Since in most patients an increased thrombin generation has been reported, we investigated whether the control of thrombin generation could affect plasma fibrinogen levels. Forty male outpatients (20 asymptomatic with previous myocardial infarction and 20 with stable effort angina) were enrolled in a randomized medium-term (6 months) cross-over study. Clottable fibrinogen, according to Clauss, prothrombin fragment 1 + 2, thrombin-antithrombin complex, and fibrinopeptide A were evaluated in relation to treatment with low-dose heparin. After a 15-day wash-out period, during which patients had been treated only with nitrates if needed, patients were allocated to two sequential periods of treatment with standard heparin (12,500 U, subcutaneously daily) plus antianginal treatment or antianginal treatment alone, separated by a second 15-day wash-out period. At the end of the treatment period with low-dose heparin significant decreases in the plasma fibrinogen (2.5 +/- 0.6 g/l vs. 3.3 +/- 0.5 g/l, P < 0.001), prothrombin fragment 1 + 2 (1.4 +/- 0.5 nmol/l vs. 1.9 +/- 0.7 nmol/l, P < 0.001), thrombinantithrombin (4.5 +/- 2.4 ng/ml vs. 9.7 +/- 3.6 ng/ml, P < 0.001), and fibrinopeptide A (2.1 +/- 1.1 ng/ml vs. 3.5 +/- 2.1 ng/ml, P < 0.001) were observed compared with the period without heparin. The present results indicate that low-dose heparin can effectively control the increased abnormal thrombin generation and elevated fibrinogen levels in patients with ischemic heart disease, possibly decreasing the risk of cardiovascular death.

Topics: Aged; Anticoagulants; Antithrombin III; Chronic Disease; Cross-Over Studies; Fibrinogen; Fibrinopeptide A; Heparin; Humans; Male; Middle Aged; Myocardial Ischemia; Peptide Fragments; Peptide Hydrolases; Protein Precursors; Prothrombin; Thrombin

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

The level of urinary FPA was assayed by high performance liquid chromatography (HPLC) in 42 normal controls, 57 cases of chronic glomerulonephritis, including 24 with normal renal function, 12 with renal insufficiency and 21 with uremia. Their levels were 24.40 +/- 10.30 micrograms/L, 26.99 +/- 5.77 micrograms/L, 38.81 +/- 6.28 micrograms/L, 79.74 +/- 18.76 micrograms/L, respectively. The level of urinary FPA in renal insufficiency function group was significantly higher than those of the control group and normal renal function group (P < 0.01). The patients with uremia presented dramatically higher level of urinary FPA than those in the renal insufficiency group (P < 0.01). A positive correlation was found between the level of urinary FPA and the blood creatine (r = 0.9120, P < 0.01). It was suggested that a hypercoagulable state existed in the patients with chronic nephritis with renal failure, in which the severity was closely related with the occurrence and development of the disease. The urinary FPA could serve as a good indicator for renal function.

Topics: Biomarkers; Case-Control Studies; Chronic Disease; Fibrinopeptide A; Humans; Kidney; Nephritis; Renal Insufficiency

Thromboembolism is an important complication of heart failure. To test the hypothesis that heart failure may be associated with hemostatic dysfunction, we studied hemostatic function in 21 patients with stable chronic heart failure and related these measures to the severity of heart failure as assessed by clinical evaluation, neuroendocrine activation, radionuclide ventriculography, and cardiopulmonary exercise testing. Plasma and blood viscosity were elevated; all patients showed evidence of platelet activation, and many had elevated plasma concentrations of fibrinopeptide A, D-dimer, and von Willebrand factor. The plasma concentrations of these variables were poorly interrelated and related poorly to the severity of heart failure. Plasma concentrations of angiotensin II and endothelin were correlated, and the latter was also correlated with the plasma concentration of von Willebrand factor. Patients with chronic heart failure have hemostatic abnormalities that may predispose them to thromboembolic events and may be in part due to neuroendocrine activation.

Topics: Adult; Aged; Angiotensin II; Blood Coagulation; Blood Viscosity; Chronic Disease; Endothelins; Exercise Test; Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Heart Failure; Humans; Male; Middle Aged; Neurosecretory Systems; Platelet Activation; Radionuclide Ventriculography; Thromboembolism; von Willebrand Factor

The development of hemodialysis treatment has remarkably improved the prognosis of chronic hemodialysis (HD) patients. However, as the patient's survival time is prolonged, vascular damages due to the abnormalities of calcium and lipid metabolism and hypertension has become the important complications in HD patients. In addition to coagulation and fibrinolysis, vascular endothelial function has been pursued to clarify the pathogenesis for occurrence of thrombosis in HD patients with more than ten years' duration. Twenty-two HD patients including twelve of less than ten years' duration and ten of more than ten years' were subjected to this study. Twelve healthy controls were also involved in this study. Fibrinopeptide A (FPA) and thrombin-antithrombin III complex (TAT) as indexes of coagulation, antithrombin III (AT III) as an index of coagulation inhibitor and D-dimer as an index of fibrinolysis were measured. A special attention has been focused in changes in the levels of tissue plasminogen activator (t-PA) activity and antigen and plasminogen activator inhibitor-1 (PAI-1) as indexes of fibrinolysis capacity, representing parameters of vascular endothelial functions. Levels of FPA, TAT and D-dimer were significantly higher in HD patients when compared with those in healthy controls. In particular, levels of FPA were significantly higher in HD patients with more than ten years' duration as compared to those in HD patients with less than ten years'. AT III values were significantly lower in HD patients with more than ten years' duration than those in healthy controls. T-PA activity and antigen levels were significantly lower in HD patients than those in healthy controls. T-PA activity levels were lower in HD patients with more than ten years' duration than those in HD patients with less than ten years'. Among HD patients, a significant negative correlation was found between t-PA activity and hemodialysis duration. PAI-1 values in HD patients were not significantly differ from those in healthy controls. These results suggest that in spite of increased coagulability, fibrinolytic capacity of vascular endothelium decreased in HD patients, and that the incidence is accelerated as hemodialysis duration is prolonged. Therefore, it is concluded that long-term HD patients are in the state of a higher risk of thrombosis.

Topics: Adult; Aged; Antithrombin III; Blood Coagulation; Chronic Disease; Endothelium, Vascular; Female; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Fibrinopeptide A; Humans; Male; Middle Aged; Nephritis; Peptide Hydrolases; Renal Dialysis; Time Factors; Tissue Plasminogen Activator

The pathogenesis of chronic subdural hematoma is not fully understood. It is thought that fibrinolytic hyperactivity within the hematoma capsule plays an important role. However, since this hyperactivity has not been found in the systemic blood, accelerated fibrinolysis is thought to occur only locally. To evaluate coagulant and fibrinolytic activities in the peripheral blood, the authors measured fibrinopeptide A (FPA) and fibrinopeptide B beta 15-42 (FPB beta), which are relatively sensitive hematologic factors, in 14 patients with chronic subdural hematoma. Peripheral venous blood was collected within 24 hours before surgery and FPA and FPB beta levels were determined. In the eight cases followed for more than 1 month after surgery, pre- and postoperative FPA and FPB beta values were compared. The possible relationship between preoperative FPB beta and hematoma density as well as elevated intracranial pressure (judged by preoperative computed tomography) was also examined. The following results were obtained: 1) Preoperative FPA and FPB beta values were both statistically significantly elevated suggesting systemic acceleration of coagulant and fibrinolytic activities. FPB beta levels exceeded those of FPA in almost all cases, indicating that fibrinolysis was more dramatically enhanced. 2) Many patients with high FPB beta values had high-density areas on computed tomography scans. 3) Patients with choked disc had high FPB beta values, suggesting a correlation between chronic intracranial hypertension and FPB beta. 4) Postoperatively, there was a marked decrease in FPA values, whereas FPB beta values remained above normal, which may reflect persistence of accelerated systemic fibrinolytic activity in patients with chronic subdural hematoma.

Topics: Adult; Aged; Blood Coagulation; Chronic Disease; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Fibrinopeptide A; Fibrinopeptide B; Hematoma, Subdural; Humans; Middle Aged; Peptide Fragments

A study on the significance of the measurement of fibrinopeptide A (FPA) and fibrinopeptide B beta 15-42 (FPB beta) in urine and plasma before and after urokinase (UK) administration in patients with chronic glomerulonephritis is described. FPA and FPB beta in urine and plasma were measured by radioimmunoassay. The levels of fibrinogen degradation product (FDP) in urine and sera were also determined before and after the UK administration. UK was administered at a dose of 48,000 IU/20 ml in saline intravenously, followed by an intravenous infusion of 250 ml of 5% glucose for one hour. It was demonstrated that the levels of FPB beta in urine and plasma showed a significant increase after UK administration in patients with chronic glomerulonephritis. However, there was no significant difference in the levels of FDP in urine and sera before and after UK administration. It was concluded that the measurement of FPB beta in urine and plasma may be useful for evaluating the efficacy of UK therapy in patients with chronic glomerulonephritis.

Topics: Adult; Chronic Disease; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Fibrinopeptide B; Glomerulonephritis; Glomerulonephritis, IGA; Humans; Peptide Fragments; Urokinase-Type Plasminogen Activator

During 18 hemodialyses of patients with chronic uremia a low molecular weight heparin fraction (mean MW 5000 d) was used as an anticoagulant without complications. For comparison conventional heparin was used during 18 dialyses in the same patients. Equipotent doses, with regard to Xa inhibition of heparin and the 5000d fraction, suppressed FPA generation (fibrin formation) equally. The APT-times were less prolonged by the 5000d fraction. When the 5000d fraction was doubled in relation to conventional heparin with regard to Xa inhibition, the suppression of FPA generation was more effective than with conventional heparin, without more pronounced APTT prolongations. In conclusion this heparin fraction was found to be useful as an anticoagulant during hemodialysis and to give less pronounced APTT prolongation than conventional heparin.

Topics: Adult; Aged; Chronic Disease; Factor X; Factor Xa; Female; Fibrinopeptide A; Heparin; Humans; Male; Middle Aged; Molecular Weight; Partial Thromboplastin Time; Renal Dialysis; Uremia

Topics: Adult; Aged; Chronic Disease; Drug Evaluation; Female; Fibrinogen; Fibrinopeptide A; Fibrinopeptide B; Glomerulonephritis; Humans; Male; Middle Aged; Urokinase-Type Plasminogen Activator

In recipients of renal transplants, the biochemical defect(s) that underlies increased deposition of platelets in the graft and their shortened survival in the circulation are poorly understood. Forty-six recipients of kidney allografts, with and without rejection signs (13 acute rejections (ARs), 15 chronic rejections (CRs), and 18 functioning transplants (FTs), had lower platelet serotonin (5HT) and higher plasma beta-thromboglobulin than normal controls (NCs). These abnormalities were more pronounced in patients with ARs than with CRs but were also present in patients with FTs. All groups of transplant recipients showed an abnormal metabolism of platelet arachidonate, as expressed by low serum levels of thromboxane B2. In AR, plasma fibrinopeptide A (FPA) was significantly high whereas FPA levels were unchanged in CR and in FT. These findings suggest that in patients with renal transplants, the platelet release reaction has occurred in vivo, resulting in the secretion of granule-bound substances and the circulation of partially empty platelets. Vasoactive, mitogenic, and proaggregatory substances released from platelets might damage the graft and aggravate the rejection process.

Topics: Acute Disease; Adolescent; Adult; beta-Thromboglobulin; Blood Platelets; Cell Survival; Child; Chronic Disease; Female; Fibrinopeptide A; Graft Rejection; Humans; Kidney Transplantation; Male; Middle Aged; Platelet Count; Serotonin; Thromboxane B2