M. Bazzan

PAI-1 and Factor VII Activity Are Higher in IDDM Patients With Microalbuminuria

Microalbuminuria is associated with an increased risk of cardiovascular disease (CVD) in insulin-dependent diabetes mellitus (IDDM) patients, but the pathophysiological basis of this association is not clear. To see whether or not hemostatic dysfunctions might contribute to explain this association, we measured tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), factor VII activity, plasma fibrinogen, and plasma endothelin-1 (ET-1) in 13 microalbuminuric (albumin excretion rate [AER], 20–200 μg/min) and in 13 comparable normoalbuminuric (< 20 μg/min) IDDM patients. t-PA and ET-1 were similar in the two groups, whereas PAI-1 activity (5.65 ± 1.92 vs. 0.85 ± 0.58 IU/ml, P < 0.05), factor VII (87.85 ± 4.94 vs. 76.54 ± 2.31%, P < 0.05), and plasma fibrinogen (3.38 ± 0.21 vs. 2.65 ± 0.13 g/l, P < 0.05) were significantly higher in microalbuminuric than in normoalbuminuric patients. Plasma fibrinogen was related to AER (r2 = 0.23, P < 0.05), whereas triglycerides and factor VII were related to PAI-1 (r2 = 0.39, P < 0.001 and r2 = 0.10, P < 0.05). These results suggest that microalbuminuria is associated with a hypercoagulative and hypofibrinolytic state. Hemostatic dysfunctions might be a pathogenetic link between microalbuminuria and CVD.

Activated Protein C Resistance in Type I Diabetes

OBJECTIVE To compare activated protein C (aPC) sensitivity in 37 type I diabetic patients and 33 healthy control subjects. RESEARCH DESIGN AND METHODS In this study, 37 type I diabetic patients and 33 healthy control subjects without personal or familial history of venous thrombosis and coagulation disorders, infections, intercurrent conditions, serum lupus anticoagulant, clinical cardiovascular complications, or drugs were examined. RESULTS The aPC ratio (aPTT [activated partial thromboplastin time] with and without aPC) was significantly lower in the type I diabetic patients than in the control subjects (P = 0.005). CONCLUSIONS These results suggest that the final steps of the protein C/S inhibiting system could be abnormal in type I diabetes.

Microalbuminuria in IDDM is associated with increased expression of monocyte procoagulant activity

Summary Microalbuminuria, the early phase of diabetic nephropathy, is associated with an increased risk of atherothrombosis. Monocytes play an important part in the pathogenesis of atherosclerosis and in the activation of haemostasis. However, procoagulant activity is poorly understood in Type I (insulin-dependent) diabetes mellitus, particularly in the presence of microalbuminuria. This study aimed to evaluate spontaneous and endotoxin-induced monocyte procoagulant activity in insulin-dependent diabetic patients with normoalbuminuria or microalbuminuria. Seventeen patients with microalbuminuria, 28 with normoalbuminuria and 26 healthy control subjects matched for age, sex, body mass index and smoking habit were studied. Mononuclear cells from peripheral venous blood were incubated with or without bacterial lypopolysaccharide. Spontaneous procoagulant activity and procoagulant activity after 3 h and 6 h of incubation were calculated. Spontaneous procoagulant activity values were similar in the three groups. After 3 h and 6 h incubation with bacterial lypopolysaccharide, procoagulant activity values were slightly, but not statistically significantly, higher in the normoalbuminuric diabetic group than in control group, and significantly higher in microalbuminuric diabetic group than in control group (p < 0.01). The increased endotoxin-induced monocyte procoagulant activity helps to explain the link between microalbuminuria and the increased risk of atherothrombosis in patients with Type I diabetes. [Diabetologia (1998) 41: 767–771]

DVT exclusion in symptomatic outpatients: use of a rapid D-dimer immunofiltration assay and comparison with three enzyme immuno assays

Summary Many authors have shown that plasma measurement of the degradation products of cross-linked fibrin, D-dimer, may be able to identify patients without DVT. Enzyme Immuno assay (EIA) have shown the best performance characteristics with a sensitivity and a negative predictive value around 100%. These tests are time-consuming and therefor non applicable in the rapid exclusion of DVT. The immunofiltration test we have studied showed a good correlation with three EIA tests of known performance characteristics. This test has a sensitivity and predictive negative value comparable to EIA but is more rapid and thus suitable as a rapid exclusion test for DVT.

Paraproteinaemias and platelet aggregation: Role of whole blood aggregometry

Whole blood and optical platelet aggregation were measured in normals and in patients with paraproteinaemias; extent of aggregation was correlated with paraprotein concentrations in patients and in normals after addition of different doses of paraproteins; threshold aggregating concentrations of several agonists were also determined in whole blood and in PRP from both groups of subjects. The results indicate that patients with macromolecular monoclonal component bear a hyperaggregable state which can be probably ascribed also to plasma hyperviscosity and which is better detected with the impedance aggregometer.

Molecular characteristics of human plasma, platelet and vascular cell PAI-1. Comparison between normal and thrombocytemic subjects

Abstract The recovery and stability of human platelet and plasma PAT activity in 15 thrombocytemic patients and 15 controls was studied. In patients plasma PAI-1 is present at higher concentrations but in a less stable form. A defective stabilization of the molecule could be responsible for the quick inactivation of PAI-1 observed in thrombocytemic patients.

Factor IX propeptide mutation and life threatening bleeding.

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Resistance to activated protein C evaluated with APTT-based methods and DNA analysis

Summary Two approaches are at our disposal for the diagnosis of activated protein C (APC) resistance: 1) the semi-quantitative plasma test based on an aPTT assay and 2) the detection of the factor V gene defect by DNA analysis. In this work we evaluated sensitivity, specificity and diagnostic efficiency of the two plasma clotting tests at present available in Italy: Chromogenix and Behring, in 26 subjects found positive for Arg506 →Gln mutation and in 44 healthy subjects negative for the mutation. A sensitivity of 100% was never achieved; The Chromogenix test choosing 1.88 as ration threshold (corresponding to the mean ratio-2SD), gave a specificity and a predictive positive value of 100%. The same accuracy indexes were achieved by the Behring test when a cut off of 1.43 (corresponding to the mean ratio-2SD) was used. Normalised ratios for both tests yielded similar results. Therefor both test can be used as pre-screening tests in the diagnosis of APC resistance but genotyping investigation is mandatory in the case of border line results.