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In patients with chronic liver disease, the reliability of various criteria generally used to diagnose impaired glucose tolerance and diabetes was evaluated. Twenty-one patients with chronic persistent hepatitis, 68 patients with chronic active hepatitis and 57 patients with liver cirrhosis were studied. All subjects underwent an oral glucose tolerance test (75 g). Impaired glucose tolerance and diabetes were diagnosed according to the criteria established by: the National Diabetes Study Group; Fajans and Conn; the European Diabetes Study Group; Deutsche Diabetes Gesellschaft; Kobberling & Creutzfeld criteria 1 and 2; Wilkerson; and the University Group Diabetes Program. The results obtained are in partial agreement with other reported data, showing a high prevalence of both impaired glucose tolerance and diabetes in chronic liver disease, with a positive correlation to the severity of hepatic involvement. However, our results show that the agreement among the criteria most frequently used for diagnosing impaired glucose tolerance and diabetes is still far from satisfactory.

In Crohn's disease (CD) a condition of hypercoagulability with increased risk for thrombotic events has been reported. In this study we have investigated hemostatic parameters in thirty-one patients affected by CD before, 3 and 12 months after bowel operation, and in thirty healthy controls. Before surgery platelet number (PLT), fibrinogen (Fbg), prothrombin fragment F1 + 2 (F1 + 2), PAI and whole blood-spontaneous platelet aggregation (WB-SPA) were significantly higher (p at least0.0005) in patients than in controls, while factor XIII (F XIII) was significantly lower (p at least0.005). Three and twelve months after surgery PLT, FBG and WB-SPA significantly decreased in comparison to pre-surgery values (respectively p at least0.05 and p0.01), but PLT and Fbg were still significantly higher than in controls at 3 and 12 months (p0.01). At three and 12 months after operation F XIII was significantly higher in comparison with pre-surgery values (p at least0.05). The presence of antiphospholipid antibodies (aPL) was not different between CD patients and controls before surgery, whereas it significantly increased 12 months after surgery (p0.05). Our results suggest that in CD hemostatic changes are only in part influenced by local flogistic processes and that an inflammatory systemic condition may provoke both the bowel and extraintestinal manifestations of CD.

Patients affected by inflammatory bowel disease (IBD) frequently suffer from thromboembolic events. Aims of this study were to investigate hemostatic system and the presence of antiphospholipid antibodies (aPL) in IBD patients. Forty-one patients affected by Crohn's disease (CD) and 19 by ulcerative colitis (UC) were studied, compared to 40 healthy control subjects. Platelet count (PLT), PT, aPTT, fibrinogen (Fib), prothrombin fragment F1+2, antithrombin (AT), protein C (PC), protein S (PS), factor XIII (FXIII), plasminogen (PLG), plasminogen activator inhibitor (PA1), spontaneous platelet aggregation in platelet-rich plasma (PRP-SPA) and in whole blood (WB-SPA), and antiphospholipid antibodies (aPL) were evaluated. PLT, Fib, F1+2 and WB-SPA were significantly increased in IBD patients (p at least0.05) both in active and inactive phases; aPL positivity was more frequent (p0.05) and FXIII was significantly decreased (p0.05) in comparison to control subjects. The thrombophilic state of IBD patients is not related to the degree of activity of the disease or to previous thrombotic events; aPL express the immunological alterations connected with IBD and are not the main cause of thrombotic events.

Plasminogen activator inhibitor-1 plays a major role in the fibrinolytic system as the main physiological inhibitor of both tissue-type and urinary-type plasminogen activators. The inhibitor is present in plasma in small amounts and derives mainly from endothelial cells. Positive correlations have been reported between plasma levels and different parameters, such as serum triglycerides, insulin plasma levels and body mass index. Moreover, high plasma inhibitor concentrations have been observed in different disease states, but it must be stressed that plasminogen activator inhibitor-1 behaves as an acute-phase reactant and measurement of plasma levels is not significant in the acute phase of the disease. A possible predictive value of inhibitor levels for thrombotic events such as deep vein thrombosis and ischemic heart disease has been studied. On the basis of available studies, the predictive value is not clear for venous thrombosis, whereas plasminogen activator inhibitor-1 levels can predict some coronary events, at least in subgroups of young patients with a first myocardial infarction. It remains to be established if treatments able to reduce plasma inhibitor levels lead to a decrease in the risk of thromboembolic events.

Pregnancy is considered as a hypercoagulable state and an increased incidence of thromboembolic phenomena has been reported in pregnant women. Relevant changes in the hemostatic mechanism have been reported during physiological pregnancy: briefly, increased levels of coagulation factors, enhanced thrombin generation and suppression of fibrinolysis are commonly found in women with uncomplicated pregnancy. We recently described progressive increases in fibrinogen and D-dimer plasma levels during normal pregnancy. The increase in D-dimer levels makes difficult their interpretation for the exclusion of thromboembolic phenomena in pregnancy. The behavior of prothrombin fragment 1+2 (F1+2) levels during physiological pregnancy is scarcely known. The aim of this preliminary study was to establish range values of F1+2 plasma levels for different periods of normal pregnancy.

In patients with mitral valve prolapse (MVP) a high incidence of valvular abnormalities with a history of previous cerebrovascular disease has been reported and an embolic mechanism has been proposed. Aim of this study is the study of platelet and coagulation activation in patients with MVP. Fifty-four patients affected by MVP (mean age 46 +/- 15 yrs, 22 males, 32 females) and 50 control subjects, age- and sex-matched, were tested for platelet activation [P-selectin and GpIIb-IIIa platelet surface expression at rest and after stimuli by flow cytometric analysis, Beta-Thromboglobulin (TG) and Platelet Factor 4 (PF4) plasma levels by ELISA, platelet-rich-plasma (PRP) and whole blood spontaneous platelet aggregation (SPA)] and for activation of blood coagulation (Prothrombin activation fragment F1+2 plasma levels by ELISA). P-selectin, GpIIb-IIIa expression, Beta-TG, PF4 and SPA were found similar in MVP patients and in controls. However, in patients with severe mitral regurgitation (MR) the percentage of activated platelets which express P-selectin after stimuli was slightly but significantly (p < 0.05) lower in comparison to MVP patients without or with mild to moderate MR and to controls. Moreover, in patients with severe MR F1+2 levels (median 1.6 nmol/L, range 0.6-2.6 nmol/L) were significantly higher (p < 0.001) than both in controls (median 0.95 nmol/L, range 0.2-1.4 nmol/L) and in patients without or with mild to moderate MR (median 1.0 nmol/L, range 0.4-2.3 nmol/L). Our findings suggest that MVP is not responsible per se for blood clotting activation, but in patients with severe mitral insufficiency an increase in thrombin generation can occur. These alterations in hemostatic system may represent a mechanism by which MR increases the risk of thromboembolic events in patients with MVP.

Platelet hyperactivity has been demonstrated in patients with arterial hypertension and is associated with an increase in platelet cytosolic free calcium concentration. Calcium channel blockers have been shown to decrease platelet aggregation and inhibit the mobilisation of intraplatelet calcium induced by various aggregating agents. However, both platelet aggregation and intraplatelet calcium fluxes are affected only at drug concentrations in excess of those attained in vivo. Ex vivo investigations of the antiaggregatory effects of calcium channel blockers in healthy subjects and hypertensive patients have yielded inconsistent results. In the present investigation, the ex vivo effects of amlodipine on platelet aggregation were evaluated in a placebo-controlled crossover study in 10 WHO class 1 hypertensive patients. Treatment with amlodipine 10mg once daily for 8 days resulted in a significant decrease in arterial blood pressure, with the mean arterial pressure decreasing from 127 ± 4mm Hg to 110 ± 7mm Hg (p