Persistence of hemostatic alterations in patients affected by Crohn's disease after bowel surgery.

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 least < 0.0005) in patients than in controls, while factor XIII (F XIII) was significantly lower (p at least < 0.005). Three and twelve months after surgery PLT, FBG and WB-SPA significantly decreased in comparison to pre-surgery values (respectively p at least < 0.05 and p < 0.01), but PLT and Fbg were still significantly higher than in controls at 3 and 12 months (p < 0.01). At three and 12 months after operation F XIII was significantly higher in comparison with pre-surgery values (p at least < 0.05). The presence of antiphospholipid antibodies (aPL) was not different between CD patients and controls before surgery, whereas it significantly increased 12 months after surgery (p < 0.05). 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.

Blood clotting activation during normal pregnancy.

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.

Platelet and blood clotting activation in patients with mitral valve prolapse.

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.

Hemostatic abnormalities in inflammatory bowel disease.

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 least <0.05) both in active and inactive phases; aPL positivity was more frequent (p<0.05) and FXIII was significantly decreased (p<0.05) 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.

Predictive value for thrombotic disease of plasminogen activator inhibitor-1 plasma levels.

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.

Hepatic antipyrine metabolism in athletes.

The aim of the present study was to investigate the influence of prolonged physical exercise on hepatic metabolism. An oral antipyrine loading test (15 mg/kg body weight) was carried out on 24 healthy male subjects: 8 controls, 8 sprinters (anaerobic activity), 8 long distance runners (aerobic activity). Antipyrine clearance resulted to be significantly higher in athletes vs. controls, without a significant difference between the two groups of athletes. These results put forward the importance of the degree of physical activity (1) for the evaluation of antipyrine-loading-test results as expression of liver function and (2) whenever drugs with a low therapeutic index are used in athletes.

Estimate of prevalence of glucose intolerance in chronic liver disease. Degree of agreement among some diagnostic criteria.

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.

Galactose loading tests in patients with hepatocellular carcinoma for the assessment of chemotherapy.

Patients affected by liver cirrhosis with and without hepatocellular carcinoma (HCC) underwent galactose testing for the assessment of both quantitative liver function and effective blood flow. The galactose elimination capacity (GEC), when investigating the former parameter, resulted in being significantly reduced in cirrhotics (29.5%) and in cirrhotics with HCC (42.9%) when compared to controls. The galactose clearance, expressing the effective blood flow through the liver, showed a significant decrease (34.0%) only in the group with superimposed HCC. Our results pointed out a significant impairment of effective hepatic blood flow and an overall reduction of hepatic metabolic activity in the cirrhotics with HCC. These data suggest that lower amounts of chemotherapeutic agents must be given to patients affected by cirrhosis with HCC, especially when dealing with substances mainly metabolized by the liver. On the basis of our results, such a reduction was evaluated to be around 50% of the total dosage.

Hepatocyte taurocholic acid uptake in the regression of ethinyl estradiol cholestasis. Preliminary results.

Taurocholic uptake in ethinyl estradiol cholestatic rats is significantly lower than in untreated rats. In the days following treatment withdrawal there is only a slow increase in uptake, which is still statistically lower than normal at the 11th day. Taurocholic acid uptake behaves in a different way from biliary flow and the amount of excreted bile acids. The diversity could be attributed to a different behaviour of bile acid carriers at the sinusoidal and biliary membranes in the hepatocyte or to a normalisation of bile acid carriers and Na+,K+,-ATPase activity at different times.

The bromosulphthalein loading test in chronic alcoholic liver diseases.

The BSP loading test was performed in 39 patients affected by alcoholic liver disease. The behaviour of some parameters of the hepatic BSP metabolism was observed(45th min retention percentage, plasma disappearance rate, K1 and K2 exponentials, K21, K12 and K32 transfer rates). The 45th min retention percentage was the most sensitive parameter in detecting liver disease. This parameter, PDR, K1 and K21 were the most reliable parameters in differentiating between the various forms of alcoholic liver disease(alcoholic steatosis, alcoholic chronic hepatitis, alcoholic cirrhosis).

[Bromsulphalein dynamic tests in cholelithias patients before and after long-term treatment with chenodeoxycholic acid]. / Prove dinamiche con BSF in pazienti colelitiasici prima e dopo trattamento a lungo termine con acido chenodesossicolico.

The BSP loading and continuous infusion tests were performed in 31 patients with cholesterol gallstones before and after long-term (6-12 months) treatment with chenodeoxycholic acid. The following parameters were evaluated: 45th minute retention percentage, plasma disappearance rate during the first 16 minutes, compartmental transfer rates, transport maximum and storage. Our results, according to previous findings after short-term treatment, indicate that no cholestatic effects seem to be induced after long-term treatment with chenodeoxycholic acid.

[Dynamic BSP tests in cholelithiasis patients before and during chenodeoxycholic acid therapy; initial results]. / Prove dinamiche con BSF in pazienti colelitiasici prima e durante trattamento con acido chenodesossicolico; primi risultati.

The BSP loading and continuous infusion tests were performed in 7 patients before and after a two-week treatment with chenodeoxycholic acid (10 mg/Kg/die per os). The following parameters were evaluated: 45th minute retention percentage, plasma disappearance rate during the first 16 minutes, compartmental transfer rates, transport maximum and storage. Our results indicated that no cholestatic effects seemed to be induced during the first period of treatment with chenodeoxycholic acid.