fibrinopeptide-a and Diabetes-Mellitus--Type-2

Platelet aggregation and spontaneous thrombolytic activity were assessed in patients with non-insulin dependent diabetes and stroke using a shear-induced and agonist-induced platelet aggregation test. The Thrombotic Status Analyser (TSA), induces platelet-rich thrombus formation solely by shear forces, while whole blood platelet aggregometry measures platelet reactivity to different agonists. These tests were employed in the present study because in earlier studies they both demonstrated that platelet aggregability in healthy volunteers was unchanged with age. On the other hand, it is known that thrombolytic activity decreases with age in males, but not in females. In diabetic patients shear-induced platelet aggregability varied according to the stage of nephropathy but platelet aggregation to collagen was suppressed at all stages. Platelet reaction to shear stress was enhanced in stroke patients with haemorrhagic episodes but not in patients with lacunar infarction. In contrast, platelet reactivity to collagen was suppressed and changes in ADP-induced platelet aggregability were inconsistent. Suppressed thrombolysis was observed only in diabetes with minor renal defect. Fibrinogen was increased in diabetes with stage III and IV nephropathy. Fibrinopeptide A (FPA) and D-dimer were increased in stroke. Thus, the observed increase in fibrinogen, FPA and D-dimer is inconsistent with changes in platelet aggregability. Our present findings suggest that a shear-induced platelet aggregation test is superior to other tests such as agonist-induced platelet aggregation and thrombotic markers such as fibrinogen, FPA and D-dimer in detecting a prothrombotic state. It is concluded that elderly males may have a prothrombotic state not because of platelet hyper-aggregability but because of suppressed thrombolytic activity. On the other hand, a prothrombotic state in patients with non-insulin dependent diabetes and after stroke may be due to changes in age-independent platelet aggregability.

Topics: Adult; Age Factors; Aged; Antifibrinolytic Agents; Arteriosclerosis; Diabetes Mellitus, Type 2; Female; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinopeptide A; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Function Tests; Stress, Mechanical; Stroke; Thrombophilia

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

Topics: Adult; Blood Coagulation; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; False Positive Reactions; Female; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Fibrinopeptide A; Fibrinopeptide B; Humans; Male; Middle Aged; Peptide Fragments

In vivo study of blood coagulation and fibrinolysis activities in non insulin dependent diabetes mellitus. The aim of the study was to investigate in vivo blood coagulation and fibrinolysis activities in a group of diabetic patients NIDDM with and without vascular complications. For this purpose we determined two sensitive indicators in vivo of blood coagulation and fibrinolytic activities such as fibrinopeptide A and B beta 15-42 respectively. Moreover, we computed the ratio between B beta 15-42 and fibrinopeptide A in order to investigate a possible imbalance in vivo between blood coagulation and fibrinolysis. Control groups were 15 healthy subjects and 28 non diabetic patients affected by atherosclerotic disease. Fibrinopeptide A and B beta values were significantly higher in the diabetic patients than controls but there was no difference between the former group and the atherosclerotic patients. Also, no correlation was found for FPA, B beta, B beta/FPAr and HbAlc, fructosamine and blood glucose levels. There was no difference in B beta, FPA and B beta/FPAr values for patients treated with insulin and for those treated with either hypoglycemic agents or diet. Our data indicate that in diabetic patients fibrinolysis activity is increased, but it cannot counterbalance thrombin activity which appears much more enhanced. Finally, the lack of correlation for FPA, B beta, B beta/FPAr and HbAlc, fructosamine and blood glucose suggests that blood coagulation and fibronolysis abnormalities are not related to the degree of blood glucose control.

Topics: Adult; Aged; Aged, 80 and over; Blood Coagulation; Diabetes Mellitus, Type 2; Female; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Fibrinopeptide A; Fibrinopeptide B; Humans; Male; Middle Aged; Peptide Fragments

Abnormalities of haemostasis are common in diabetes mellitus. As indicators of fibrinolysis and coagulation, plasmin and thrombin activity were assessed by assay of the fibrinogen peptide derivatives B beta 15-42 and fibrinopeptide A respectively in 60 diabetic patients and 50 control subjects in a cross-sectional study. Glycosylated haemoglobin (HbA1) correlated with B beta 15-42 (r = -0.26, p less than 0.05) and fibrinopeptide A (r = 0.30, p less than 0.05) in the diabetic patients suggesting that poor glycaemic control (i.e. high HbA1 levels) was associated with depressed plasmin and enhanced thrombin activity. Compared to controls, fibrinopeptide A levels were increased in diabetics (p less than 0.001) irrespective of sex or type of diabetes. B beta 15-42 levels were normal in diabetic females but increased in diabetic men (p less than 0.001) possibly secondary to the activation of coagulation. These results suggest that in diabetes mellitus activation of coagulation is the dominant haemostatic abnormality and that better glycaemic control could influence in-vivo plasmin and thrombin activity favourably.

Topics: Adult; Aged; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Fibrin Fibrinogen Degradation Products; Fibrinolysin; Fibrinopeptide A; Fibrinopeptide B; Glycated Hemoglobin; Hemostasis; Humans; Male; Middle Aged; Peptide Fragments; Thrombin

Twenty type II (non-insulin-dependent) poorly controlled diabetics had tests of coagulation and platelet function performed while receiving high-dose sulphonylurea therapy and at 1 and 3 months following their conversion to insulin. Although no overall change in glycaemic control (assessed by glycosylated haemoglobin) was noted, a reduction in thrombin generation was observed, as judged by a significant fall in fibrinopeptide A concentrations. No changes in factor VIII coagulant activity (VIII:C), factor VIII-related antigen or antithrombin III were found. Glycosylated haemoglobin concentrations showed significant correlations with antithrombin III and factor VIII:C, suggesting that improved glycaemic control might lead to an improvement of antithrombin III function and lower factor VIII:C concentrations. No changes in platelet function were detected. The introduction of an insulin regimen that improves glycaemic control might lead to a reversal of the 'hypercoagulable state' found in type II diabetes.

Topics: Aged; Antithrombin III; Blood Coagulation; Blood Platelets; Diabetes Mellitus, Type 2; Factor VIII; Female; Fibrinopeptide A; Glycated Hemoglobin; Humans; Insulin; Male; Middle Aged; Sulfonylurea Compounds

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