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Biomedical subjects

F Violi

Publications and source records attributed to F Violi.

At least 127 records · Page 7Linked to original sources
PubMed1992

Hyperfibrinolysis increases the risk of gastrointestinal hemorrhage in patients with advanced cirrhosis.

Sixty-one patients with different degrees of liver failure, 23 with Child-Pugh class B and 38 with Child-Pugh class C, were studied and observed for 3 yr. Coagulation index analysis showed significantly lower values of prothrombin activity, more prolonged activated partial thromboplastin time, higher bilirubin and fibrinogen degradation products values in class C patients. Among all patients, 28 had fibrinogen degradation products values greater than 10 micrograms/ml, and in these patients a hyperfibrinolytic state was confirmed by higher values of circulating plasminogen activator antigen (17.3 +/- 8.7 ng/ml vs. 5.41 +/- 1.9 ng/ml; p less than 0.0001) and activity (6.6 +/- 2.1 IU/ml vs. 1.92 +/- 1.12 IU/ml; p less than 0.0001) and significantly lower plasminogen activator inhibitor antigen (6.4 +/- 3.5 ng/ml vs. 15.8 +/- 5.6 ng/ml; p less than 0.0001) and activity (3.6 +/- 2.2 IU/ml vs. 8.5 +/- 3.9 IU/ml; p less than 0.0001). Patients with positive fibrinogen degradation products had higher serum bilirubin (6 +/- 4 mg/dl vs. 2 +/- 2 mg/dl; p less than 0.0001) and lower fibrinogen (156 +/- 52 mg/dl vs. 194 +/- 62 mg/dl; p less than 0.02) than patients without hyperfibrinolysis. During the follow-up period, 41 patients died, 22 from fatal gastrointestinal hemorrhage and 19 from liver failure. Thirty patients experienced fatal (22 patients) and nonfatal (8 patients) gastrointestinal hemorrhage. Patients with positive fibrinogen degradation products or class C had a higher risk of gastrointestinal bleeding than patients with negative fibrinogen degradation products (odds ratio = 8) or class B (odds ratio = 3.5), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effect of oral defibrotide on tissue-plasminogen activator and tissue-plasminogen activator inhibitor balance.

Defibrotide, a polydeoxyribonucleotide of mammalian origin, has been shown to reduce the blood level of the plasminogen activator inhibitor, and so to increase the activity of tissue plasminogen activator without any adverse effect. A randomized, double-blind, placebo-controlled study has been done in 22 patients, 14 with peripheral vascular disease, 6 with coronary heart disease and 2 with cerebrovascular disease. Patients were given defibrotide 400 mg b.d. or identical placebo for 30 days and the parameters of fibrinolysis were evaluated before and after the treatment. A significant increase in tissue plasminogen activator activity at rest and after venostasis was observed after defibrotide; tissue plasminogen activator antigen at rest and after venostasis was not affected by either treatment. Defibrotide significantly reduced plasminogen activator inhibitor activity and antigen at rest. Only one patient complained of gastric pain after placebo treatment. The study shows that defibrotide has profibrinolytic property and that it could be used to explore the role of plasminogen activator inhibitor in venous and arterial thrombosis.

Administration, Oral↗
PubMed1992

Reaction of dipyridamole with the hydroxyl radical.

Dipyridamole [2,6-bis-diethanolamino-4,8-dipiperidinopyrimido-(5,4-d)pyri midine], a well known platelet aggregation inhibitor, shows powerful hydroxyl radical scavenging activity by inhibiting OH.-dependent salicylate and deoxyribose degradation. Steady-state competition kinetics experiments with deoxyribose were carried out to evaluate the second-order rate constant for the reaction between hydroxyl radical and dipyridamole. OH. radicals were generated either by a Fenton-type reaction or by X-ray irradiation of water solutions. A second-order rate constant k(Dipyridamole + OH.) of 1.72 +/- 0.11 X 10(10) M-1 s-1 and of 1.54 +/- 0.15 X 10(10) M-1 s-1 was measured by Fenton chemistry and by radiation chemistry, respectively. Mannitol was used as an internal standard for hydroxyl radicals in steady-state competition experiments with deoxyribose. A rate constant K(Mannitol + OH.) of 1.58 +/- 0.13 X 10(9) M-1 s-1 and 1.88 +/- 0.14 X 10(9) M-1 s-1 was measured in the Fenton model and in the water radiolysis system, respectively. Both these rate constants are in good agreement with the published data obtained by the "deoxyribose assay" and by pulse radiolysis.

Deoxyribose↗
PubMed1992

Free radical-mediated platelet activation by hemoglobin released from red blood cells.

It is known that the rate of thrombus formation depends on interaction between platelets and erythrocytes, but the mechanism of this process has remained obscure. We here show that nanomolar levels of hemoglobin released from damaged red blood cells can induce platelet aggregation. The molecular mechanism is not receptor-based, but involves oxidation of oxyhemoglobin by platelet-derived hydrogen peroxide, with subsequent generation of a small unknown free radical species, detected by ESR spectroscopy. Methemoglobin and carbon monoxide-treated hemoglobin are unable to cause platelet activation or radical formation. The aggregation of platelets induced by hemoglobin is completely blocked by catalase or radical scavengers. These findings indicate a role for a novel extracellular free radical second messenger in the activation of platelets.

Carbon Monoxide↗
PubMed1992

Methods for detecting lupus anticoagulants and their relation to thrombosis and miscarriage in patients with systemic lupus erythematosus.

AIMS: To examine the sensitivity and specificity to past thrombotic events of four different coagulation tests, which screen for lupus anticoagulant (LA), and of anticardiolipin antibodies in patients with systemic lupus erythematosus. METHODS: Fifty three consecutive patients with systemic lupus erythematosus were studied of whom three males and 21 females, aged 21-60 years, had a history of venous and arterial thrombosis, or miscarriage, or both. Activated partial thromboplastin time (aPTT), dilute Russell's viper venom time (dRVVT), kaolin clotting time (KCT), dilute aPTT and the circulating titre of anticardiolipin antibodies were investigated in the two groups of patients and in 20 healthy control subjects. RESULTS: The prolonged dilute aPTT was more sensitive to thromboses or miscarriages, or both than dRVVT (p less than 0.05), KCT (p less than 0.01), and aPTT (p less than 0.001). No significant differences in specificity were found among aPTT (100%), dRVVT (93%), KCT (93%) and dilute aPTT (86.2%); but aPTT and dRVVT were significantly more specific (p less than 0.01, p less than 0.05, respectively) than anticardiolipin antibodies. CONCLUSIONS: The study shows a strong association between lupus anticoagulant and thrombosis when a very sensitive test such as the dilute aPTT is used. The combination of this assay with a very specific test such as dRVVT might enable patients with SLE at high risk of thrombosis to be identified.

Abortion, Spontaneous↗
PubMed1992

Clotting abnormalities in chronic liver disease.

In patients with chronic liver disease (CLD), several clotting changes can be observed. The most frequent abnormality is the reduced synthesis of many clotting factors, including vitamin-K-dependent and vitamin-K-independent ones. A low platelet count is another frequent feature of patients with CLD, which, however, is not always associated with the prolongation of bleeding time. Hyperfibrinolytic syndrome is usually seen in patients with decompensated state, and may further deteriorate the clotting abnormalities and favor bleeding complications. The assessment of the clotting system may be a useful approach to evaluate liver function and predict prognosis of patients with CLD.

Blood Coagulation Disorders↗
PubMed1992

1-year survey of patients with advanced liver cirrhosis. Prognostic value of clinical and laboratory indexes identified by the Cox regression model.

The relation between coagulation indexes and survival rate was studied and analyzed in 46 patients with advanced liver cirrhosis (grade B and C Child-Pugh Classification), during a follow-up of 1 year. Twenty-four patients (52%) died of liver failure or fatal haemorrhage within 12 months of follow-up. Prothrombin activity, fibrinogen, fibrin(ogen) degradation products, prekallikrein and factor VII, serum bilirubin, and the degree of liver insufficiency, scored by Child-Pugh classification, proved to be significantly correlated with survival by univariate analysis. A multivariate survival analysis (Cox regression model) disclosed two variables, prekallikrein and factor VII, that predicted survival. The rate ratios of death increased to 2.8 and 7.6 with values of prekallikrein < 26% and factor VII < 39%, respectively. This study shows that some simple laboratory tests exploring the clotting system may identify patients with poor prognosis in severe liver failure.

Adult↗
PubMed1992

High density lipoprotein cholesterol low serum level as the only risk factor in male patients with coronary heart disease.

Forty-three male patients with myocardial infarction, severe angiographic coronary lesions, high or normal low density lipoprotein (LDL) cholesterol serum levels, and without other risk factors for coronary heart disease were selected. In all patients high density lipoprotein (HDL) cholesterol and HDL-cholesterol/total cholesterol ratio were significantly lower than in the control group; in particular, the ratio was below 0.240 which was the median value of normal subjects. Six patients with total cholesterol and LDL-cholesterol below 5.16 and 3.35 mmol/l respectively, had low serum levels of HDL-cholesterol; in 4 of them the value of this risk factor was below 0.9 mmol/l; 2 of 6 patients had a lipoprotein (a) serum concentration above 0.3 g/l but not a premature myocardial infarction or a clinical history of coronary heart disease. Our data confirm that HDL-cholesterol/total cholesterol ratio could be a better marker of coronary heart disease than HDL-cholesterol, total cholesterol or LDL-cholesterol and suggest the importance to check HDL-cholesterol serum levels also in subjects without risk factors for atherosclerotic disease.

Adult↗
PubMed1992

Hydrogen peroxide triggers activation of human platelets selectively exposed to nonaggregating concentrations of arachidonic acid and collagen.

The effects of H2O2 on platelet function were investigated in vitro and ex vivo. H2O2 (0.5 to 5 mumol/L) alone did not influence platelet function, but when it was combined with subthreshold concentrations of arachidonic acid or collagen, it induced platelet aggregation and serotonin release in a dose-dependent fashion. The increase in platelet aggregation was associated with thromboxane A2 production and was prevented by 100 mumol/L aspirin. The amplification of platelet response by H2O2 was also inhibited 2 hours after 300 mg aspirin was given to healthy subjects. H2O2 alone did not affect intraplatelet Ca++ influx or mobilization but, combined with subthreshold concentrations of arachidonic acid, it increased Ca++ mobilization. In platelets prelabeled with tritiated arachidonic acid, H2O2 induced tritium release in a dose-dependent fashion; this effect was prevented by mepacrine, an inhibitor of the phospholipase A2 enzyme. Platelet function was not affected by using H2O2 in combination with other agonists such as thrombin, calcium ionophore, or adenosine diphosphate. This study suggests that H2O2 triggers activation of platelets preexposed to agonists at subthreshold levels by stimulating arachidonic acid metabolism, likely by stimulating the phospholipase A2 enzyme. The stimulation of platelets by concentrations of H2O2 similar to those released by activated leukocytes may give new insights into the functional cooperation between leukocytes and platelets.

Arachidonic Acid↗
PubMed1991

Superoxide dismutase triggers activation of "primed" platelets.

Superoxide dismutase (SOD) triggers activation of human platelets exposed to subthreshold concentrations of arachidonic acid and collagen. The subthreshold concentrations used are not able to activate platelets but "prime" platelets to be activated by SOD. The addition of SOD to arachidonic acid-or collagen-primed platelets induced aggregation, thromboxane A2 production, and release of [3H]serotonin. Superoxide dismutase does not have any effect on resting platelets and ADP-, thrombin-, calcium ionophore A23187-, PAF-, or U46619-stimulated platelets. Furthermore, superoxide dismutase-dependent platelet activation is fully prevented by catalase and/or aspirin, suggesting a role for H2O2 and the involvement of the cyclooxygenase pathway of arachidonic acid in such activation.

Adult↗
PubMed1991

Increased plasminogen activator inhibitor antigen levels in diabetic patients with stable angina.

PAI-1 antigen, tPA antigen and thrombin - antithrombin III complexes (TAT) levels were measured in 10 males with stable angina and type-II diabetes mellitus and in 16 males with stable angina without diabetes or other risk factors (hyperfibrinogenaemia, hyperlipidaemia, diabetes, hypertension, smoking and obesity) known to increase PAI levels. Ten healthy men of equivalent age served as controls. Because only diabetics with coronary artery disease (CAD) showed a decreased fibrinolytic capacity, a second study was performed on the 16 non-diabetic CAD patients to determine whether submaximal workload induces significant changes of tPA and PAI levels. TAT levels were increased in CAD, and significantly so in the diabetic group. tPA levels were increased only in the CAD patients without diabetes. PAI levels were significantly increased in diabetic CAD patients (5.26 +/- 1.96 ng/ml) but not in the stable angina patients without diabetes (2.97 +/- 1.44 ng/ml). Immunologically-reactive tPA released after exercise was higher in the 16 CAD patients without diabetes than in controls. Our data could indicate that in stable angina without diabetes there is no chronic latent activation of the clotting system, with no impairment of fibrinolytic activity. On the other hand, the presence of diabetes mellitus seems to influence the fibrinolytic capacity in CAD, particularly increasing PAI levels.

Adult↗
PubMed1991

Plasma thiobarbituric acid reactive substances a predictive marker of cerebral ischemia in patients at high risk?

The clinical meaning of high values of blood lipid peroxides, assessed as thiobarbituric acid reactive substances (TBA-RS), was investigated in 19 selected high risk patients with transient ischemic attacks (TIA). Patients were checked every 3-6 months and followed-up for 3 years. 8 patients experienced further vascular episodes, 4 having minor stroke and 4 TIA; one of the latter died from myocardial infarction. Unlike blood cholesterol and glucose. TBA-RS values discriminated patients with vascular episodes: they, indeed, showed significant higher values of TBA-RS. Discriminant analysis further indicated that TBA-RS levels differentiate patients with and without vascular accidents, suggesting that high blood values of lipid peroxides could represent a predictive sign of vascular ischemia.

Aged↗
PubMed1991

Hydrogen peroxide as trigger of platelet aggregation.

In order to verify if H2O2 affects platelet function, platelet-rich plasma and human washed platelets were incubated with subthreshold concentrations (STC) of collagen or arachidonic acid or ADP and/or with 75-150 microM H2O2. While H2O2 alone did not affect platelet aggregation, it amplified platelet aggregation response in samples stimulated with STC of arachidonic acid and collagen but not in samples stimulated with STC of ADP. When platelets were preventively treated with aspirin, a cyclooxygenase inhibitor, the platelet activation by H2O2 was not observed. Thromboxane A2 (TxA2) was not produced by human washed platelets stimulated with STC of arachidonic acid, collagen or by H2O2 alone. On the contrary, when STC of agonists were tested on platelets supplemented with H2O2 an evident TxA2 production was seen. This effect was prevented by aspirin pretreatment or by the addition of catalase, an enzyme which destroys H2O2. This study suggests that H2O2 triggers the activation of platelets exposed to STC of collagen and arachidonic acid, via the cyclooxygenase pathway.

Adult↗
PubMed1990

Specificity and sensitivity of diluted aPTT and anticardiolipin antibodies towards thrombosis and miscarriages in patients with systemic lupus erythematosus.

In 36 patients suffering from systemic lupus erythematosus (SLE), lupus anticoagulant (LA), as assessed by aPTT and diluted aPTT, and anticardiolipin antibodies (aCL) were studied. 14 patients, had a clinical history complicated by thrombosis and/or miscarriages. Among patients with thrombosis LA was positive in 42% and in 100% of patients when assessed by aPTT and diluted aPTT respectively; aCL were positive in 85.7% of patients. Among patients without a clinical history of thrombosis, 1 had prolonged aPTT, 3 had prolonged diluted aPTT and 5 had aCL positivity. Diluted aPTT was more sensitive than aPTT and aCL (p less than 0.01) to thrombosis and miscarriages; specificity to thrombosis and miscarriages ranged from 77.3% for aCL and 86.4% for diluted aPTT to 95.5% for aPTT but not significant differences were found. The study suggests that LA, as assessed by a sensitive test like diluted aPTT, is strongly associated to thrombosis and should therefore be considered an important risk factor.

Abortion, Spontaneous↗
PubMed1990

Tissue plasminogen activator inhibitor in patients with systemic lupus erythematosus and thrombosis.

OBJECTIVE: To examine the relations among tissue plasminogen activator antigen, plasminogen activator inhibitor, the lupus anticoagulant, and anticardiolipin antibodies in patients with systemic lupus erythematosus. DESIGN: Prospective study of blood samples (a) from selected patients with systemic lupus erythematosus whose disease was and was not complicated by a history of thrombosis or recurrent abortions, or both, and (b) from a series of healthy controls with a similar age and sex distribution. SETTING: University based medical clinic. SUBJECTS: 23 Patients with definite systemic lupus erythematosus (American Rheumatism Association criteria), of whom 11 (eight women) aged 26-51 had a history of thrombosis or recurrent abortions, or both, and 12 (10 women) aged 23-53 had no such history. 15 Healthy subjects (10 women) aged 25-58 served as controls. MAIN OUTCOME MEASURES: Tissue plasminogen activator concentrations, plasminogen activator inhibitor activities, detection of the lupus anticoagulant, and values of anticardiolipin antibodies in the two groups of patients and in the patients with a history of thrombosis or abortions compared with controls. Other measurements included concentrations of proteins that are known to change during the acute phase of systemic lupus erythematosus--namely, fibrinogen, C3 and C4, and C reactive protein. RESULTS: Patients with a history of thrombosis or abortions, or both, had significantly higher values of tissue plasminogen activator and plasminogen activator inhibitor than patients with no such history. A significant correlation between tissue plasminogen activator and plasminogen activator inhibitor (r = 0.80) was found only in the patients with a history of complications of their disease. The lupus anticoagulant was detected in six of the 11 patients with a history of thrombosis or abortions when tested by measuring the activated partial thromboplastin time but was found in all 11 patients when tested by measuring the diluted activated partial thromboplastin time. Nine of these 11 patients had raised values of anticardiolipin antibodies. The findings showed no relation to the activity of the disease. CONCLUSIONS: A significant correlation between tissue plasminogen activator concentrations and plasminogen activator inhibitor activities was found only in patients whose systemic lupus erythematosus was complicated by a history of thrombosis or recurrent abortions. The findings show that these patients have raised plasminogen activator inhibitor activities, and the frequent association between these raised activities and the presence of the lupus anticoagulant suggests that the two may be linked.

Abortion, Habitual↗
PubMed1990

Dilute aPTT prolongation by antiphospholipid antibodies in patients with liver cirrhosis.

The behaviour of aPTT, as assessed by standard or diluted phospholipid mixture, was investigated in 20 patients suffering from liver cirrhosis. Standard aPTT was prolonged in 13 but it was corrected by 1:1 mixture with normal plasma. Dilute aPTT performed in samples mixed 1:1 with normal plasma and calculated by the difference in time between 1:80 and 1:5 phospholipid mixture was prolonged in 9 patients, who had also significantly higher titre of anticardiolipin antibodies (p less than 0.005). Unlike patients' plasma with normal dilute aPTT, the addition of 0.05 M PC/PS liposomes to patient's plasma with prolonged dilute aPTT significantly shortened dilute aPTT (p less than 0.001). This study shows the presence of antiphospholipid antibodies in some patients with liver cirrhosis; this seems to be responsible for the prolongation of dilute aPTT.

Aged↗
PubMed1990

Inhibition of cyclooxygenase-independent platelet aggregation by low vitamin E concentration.

Platelet aggregation induced by threshold concentrations of agonists such as collagen, PAF or epinephrine was inhibited in vitro by 100 microM aspirin but was restored by stimulating platelets with high concentrations of collagen, PAF or by a combination of epinephrine and PAF. Incubating aspirin-treated platelets with 50-100 microM vitamin E or vitamin E acetate inhibited platelet aggregation by high concentrations of collagen and PAF and by the combination of epinephrine and PAF; platelet thromboxane A2 formation was less than 10% in samples incubated with 100 microM aspirin. Apyrase, added to aspirin-treated platelet, did not influence platelet aggregation induced by epinephrine and PAF. The present study suggests that concentrations of vitamin E as low as 50-100 microM inhibit cyclooxygenase-independent platelet aggregation when combined with an inhibitor of the arachidonate pathway.

Apyrase↗