fibrinopeptide-a and Diabetic-Angiopathies

Patients suffering from atherosclerosis may have a hypercoagulable state which is further aggravated by surgery. Thrombin, a central enzyme in the coagulation process, cleaves fibrinogen to fibrin. Therefore, inhibition of thrombin is an important anticoagulant mechanism. This is accomplished by heparin in concert with antithrombin III (AT), but vessel wall glycosaminoglycans may act as substitutes for heparin and catalyse thrombin inhibition. The present study examines whether administration of AT or heparin is effective as an anticoagulant during infrainguinal bypass surgery. Preoperatively and during surgery the patients had elevated levels of fibrinogen, fibrinopeptide A (FPA) and thrombin-antithrombin (T-AT) complexes. There were higher levels of FPA in the venous outflow from the ischemic leg than in the arterial inflow. Taken together these measurements indicate ongoing coagulation in the operated leg. Administration of heparin decreased FPA levels and prevented intraoperative graft thrombosis, whereas in patients receiving AT, T-AT levels increased but FPA levels were unchanged. In the latter group, intraoperative graft thrombosis occurred in a high proportion. Based on additional case histories in these patients with hypercoagulability, it is suggested that fibrinogen is a risk factor for thromboembolic complications and that a combination of low dose of heparin and AT might be an effective regimen to prevent intraoperative thrombosis with a low risk of haemorrhage.

Topics: Adult; Aged; Aged, 80 and over; Antithrombins; Arteriosclerosis; Diabetic Angiopathies; Female; Fibrinopeptide A; Graft Occlusion, Vascular; Heparin; Humans; Intermittent Claudication; Ischemia; Leg; Leg Ulcer; Male; Middle Aged; Postoperative Complications; Premedication

Fibrinopeptide A was determined in 75 middle aged male patients, five control subjects and a control group of young medical students, divided into nine subsets. The FPA levels were significantly elevated in the patient group, particularly among the diabetics, when compared with the medical students and also age matched controls. Diabetic patients who smoked and had vascular pathology had high FPA levels even after they stopped smoking.

Topics: Angina Pectoris; Biomarkers; Coronary Artery Disease; Diabetic Angiopathies; Fibrinopeptide A; Humans; Male; Middle Aged; Smoking; Thrombosis

To examine the relationship between diabetic vascular disease and haemostasis, a set of sensitive assays has been used to assess in vivo activation of coagulation in 62 diabetic patients (41 Type 1 and 21 Type 2), aged 19-68 years, who had been screened for the presence of complications. Fibrinopeptide A, an index of thrombin activity, was significantly increased in diabetic patients compared with control subjects (p less than 0.05), in both plasma (with complications mean 8.04 +/- 11.87 (+/- SD); without complications 7.21 +/- 10.13; control subjects 2.11 +/- 1.40 micrograms l-1) and urine (with complications mean 1.48 +/- 0.74; without complications 1.35 +/- 0.62; control subjects 0.98 +/- 0.39 micrograms l-1). Activated factor VII (VIIa ratio 1.21 +/- 0.39; 1.13 +/- 0.23; 1.01 +/- 0.11) and fibrinogen (3.15 +/- 0.59; 3.11 +/- 0.69; 2.70 +/- 0.57 g l-1) were also elevated in diabetic patients with and without complications (VIIa p less than 0.05, fibrinogen p less than 0.01). The only difference between Type 1 and Type 2 patients was in fibrin degradation products (Type 1 0.28 +/- 0.18; Type 2 0.40 +/- 0.18 mg l-1, p less than 0.01). Plasma levels of fibrin degradation products were elevated in diabetic patients (p less than 0.05 vs control subjects), and correlated with age (r = 0.44, p less than 0.01) but were unrelated to the presence of complications. There were no significant differences in any coagulation variables between diabetic patients with and without complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Coagulation; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Factor VII; Factor VIIa; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Glycated Hemoglobin; Hemostasis; Humans; Male; Middle Aged; Smoking

Insulin antibodies and immune complexes (ICs) are present in most patients with diabetes after initiation of conventional insulin therapy. We studied the ability of bovine insulin, porcine insulin, and human insulin ICs to stimulate the procoagulant activity (PCA) of human blood monocytes (HBMs) and human umbilical vein endothelium (HUVE) in vitro. Polyclonal insulin antibodies from patients with insulin antibody-mediated resistance were isolated by immunoabsorption. PCA expressed by isolated adherent HBMs or cultured HUVE was quantified by radioimmunoassay of fibrinopeptide A with a 1:80 dilution of human plasma. Beef, pork, and human insulin, in quantities determined from titration curves, were added to fixed amounts of antibody to obtain equivalent amounts of ICs. For four different antibodies, the ratios of PCA (expressed by HBMs exposed to ICs or to antibodies alone and normalized for cell numbers) to activity expressed by tissue culture medium were as follows: beef insulin ICs, 2.55 +/- 0.41; por insulin ICs, 1.47 +/- 0.16; human insulin ICs, 1.28 +/- 0.19; and antibody, 1.28 +/- 0.32. The differences between beef and pork insulin ICs and antibody controls were significant. For a fifth antibody, a dose response between beef insulin ICs and PCA expression was demonstrated. For a sixth antibody, HBMs could express PCA when stimulated with antibody of a relatively low binding capacity (0.35 ng bovine insulin per microgram of antibody) only in the presence of lymphocytes. Conditioned medium from these cells significantly stimulated endothelial cell procoagulant activity. These observations raise the possibility that insulin ICs, that is, beef insulin ICs, may generate increased PCA and thereby contribute to the vascular complications of diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antigen-Antibody Complex; Blood Coagulation Factors; Cattle; Diabetic Angiopathies; Endothelium, Vascular; Fibrinopeptide A; Humans; Insulin; Monocytes; Swine; Thromboplastin

Plasma and urine fibrinopeptide-A (FPA) levels were investigated in type I and II diabetic patients. Plasma FPA and 24-h urinary excretion of FPA were significantly elevated in diabetic patients compared with normal volunteers, indicating augmented thrombin activity in diabetes. Plasma and urine FPA did not differ between type I and type II diabetic subjects. Comparison of plasma FPA with blood glucose and hemoglobin A1 (HbA1) indicated that elevation of FPA is rapidly reversible and intermittent during hypo- and hyperglycemia. Although elevated plasma FPA was seen in patients of short as well as long duration of diabetes, plasma and urine FPA correlated with duration of diabetes in type I patients. In type I diabetic patients with vascular complications, hyperglycemia induced by an oral glucose challenge was accompanied by elevation of plasma FPA and acceleration of fibrinogen disappearance. These responses were not seen when the patients were treated with intravenous (i.v.) heparin before the glucose challenge. In patients without vascular complications, there was also an acceleration of fibrinogen disappearance and a marginal (not statistically significant) elevation of plasma FPA seen after the FPA response observed in vascular disease patients. In all patients, induced hyperglycemia resulted in a decrease in hematocrit and hemoglobin (blood volume expansion) and an increase in pulse pressure indicating hemodynamic changes. The association of hyperglycemia and hemodynamic changes with augmented thrombin activity is consistent with a mechanism for fibrin formation and deposition based on endothelial injury and/or increased vascular permeability. Fibrin deposition due to such a mechanism may participate in the development of the vascular complications of diabetes.

Topics: Adolescent; Adult; Blood Glucose; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Fibrinogen; Fibrinopeptide A; Glucose; Hemodynamics; Humans; Male; Middle Aged

Plasma thromboglobulin concentrations are raised in diabetes. Although patients with angiopathic complications tend to have the highest thromboglobulin, this distinction is not clearly defined. Diabetic subjects with high thromboglobulin also have increased plasma concentrations of fibrinogen and fibrinopeptide A. Abnormal platelet function, therefore, accompanies changes in the coagulation system and suggests a "prethrombotic" state. Increases in plasma glucose induced by an oral glucose load in diabetics are associated with a decrease in plasma thromboglobulin. The role of these changes in the pathogenesis of microangiopathic complications remains speculative.

Topics: Adolescent; Adult; Aged; Beta-Globulins; beta-Thromboglobulin; Blood Glucose; Diabetes Mellitus; Diabetic Angiopathies; Fibrinogen; Fibrinopeptide A; Humans; Middle Aged