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Biomedical subjects

R Abbate

Publications and source records attributed to R Abbate.

At least 109 records · Page 6Linked to original sources

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.

Adenosine Diphosphate↗

Antiphospholipid antibodies and pregnancy disorders in women with insulin dependent diabetes.

Insulin dependent diabetes (IDD) is considered to be an immune endocrinopathy as in such patients a disorder of the immune system is involved; however, up to now no data are available on the occurrence of antiphospholipid antibodies (aPL) in IDD pregnant women and on possible correlation between the presence of aPL and the high fetomaternal morbidity reported in these patients. The presence of lupus anticoagulant (LA) and of anticardiolipin antibodies (ACA) was monthly evaluated. In 35 IDD pregnant women referring within the 7 degrees week of pregnancy to the High Risk Pregnancy Medical Unit. Levels of D-dimer, fibrin degradation product, were also assayed. Twelve IDD pregnant women resulted to be aPL positive with a markedly high prevalence of positivity (34%). aPL positive did not significantly differ from aPL negative women in age, duration and severity of diabetes and in metabolic control throughout pregnancy. Pregnancy induced hypertension (PIH) and intrauterin growth retard (IUGR) were observed in 6/12 aPL positive and in only 2/23 aPL negative patients (p < 0.02). A pathological increase in D-dimer levels occurred in 6/12 aPL positive patients and in none aPL negative (p < 0.03). The high frequency of aPL positivity and its strict relation to pregnancy complications strongly support a major role for an autoimmune pathogenetic mechanism in the occurrence of feto-maternal morbidity in IDD pregnant women. The identification of this subgroup at risk for complications may be clinically relevant.

Analysis of Variance↗

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.

Adolescent↗

n-3 PUFA supplementation, monocyte PCA expression and interleukin-6 production.

n-3 polyunsaturated fatty acids (PUFA) can affect several monocyte functions and the biochemistry of blood cells, thus possibly influencing the initiation of thrombosis, inflammatory disease and atherosclerosis. In this study, we have investigated the effect of dietary supplementation with n-3 PUFA ethyl esters on procoagulant activity (PCA) and interleukin-6 (IL-6) production by human mononuclear cells. Nine healthy volunteers received 4 g/d of n-3 PUFA ethyl esters (4 x 1 g capsules with at least 85% eicosapentaenoic + docosahexaenoic acid ethyl esters) for 18 weeks. Before and at the end of the treatment, mononuclear cells were obtained from peripheral citrated blood by Ficoll-Hypaque density gradient centrifugation. Cellular suspensions (10(7) cells/ml) were incubated at 37 degrees C for 4 h in the absence and presence of lipopolysaccharide (10 micrograms/ml); PCA was determined by one-stage clotting assay and IL-6 concentrations were assayed in supernatants by specific ELISA. After 18-week treatment, both unstimulated and stimulated monocyte PCA were significantly reduced by 66% and 63%, respectively (P < 0.01). Similarly, a significant inhibitory effect by n-3 PUFA treatment on basal and LPS-stimulated IL-6 monocyte production was observed (50% and 46%, respectively, P < 0.05). These data indicate that 18-week n-3 PUFA supplementation may influence monocyte activities, which play a specific role in atherosclerosis and its thrombotic complications.

Adult↗

Antiphospholipid antibodies (aPL) increase the potential monocyte procoagulant activity in patients with systemic lupus erythematosus.

Lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) are frequently detected in sera from patients affected by systemic lupus erythematosus (SLE). However, the role of antiphospholipid antibodies (aPL) in thrombus formation has not been defined as yet. Twenty-two patients affected by SLE, all fulfilling the 1982 ARA revised criteria, and twenty healthy subjects were investigated for the presence of LA, aCL and other aPLs. Monocyte procoagulant activity-PCA (Tissue Factor production) was evaluated by one stage plasma recalcification time. In all patients the plasma levels of F1 + 2 and of plasminogen activator inhibitor (PAI) were also determined. Monocyte PCA was significantly higher in SLE patients with LA and/or aCL in comparison to SLE patients without LA and/or aCL (p < 0.01) and to controls (p < 0.05). However, no connection was observed between PCA expression by mononuclear cells and LA or aCL levels. No differences in F1 + 2 and PAI plasma levels were found between SLE patients with or without aPL and controls. In our SLE patients LA and/or aCL positivity appears strictly related to an increased monocyte activation that could play an important role in the occurrence of thrombotic events.

Adult↗

Fibrinogen and factor VIIag in healthy adolescents: the Floren-teen (Florence teenager) Study.

At least five studies based on more than twenty thousand healthy subjects indicated that fibrinogen is an independent risk factor for cardiovascular events; less clear-cut is the relation between factor VII and risk for arterial thrombotic disorders, which was demonstrated in two of the three studies investigating this association. However, no study has investigated the behaviour of fibrinogen and factor VII in an adolescent population. In a study of Preventive Medicine and Education Program, fibrinogen (clotting method) and factor VIIag (ELISA), in addition to other metabolic parameters, life-style and familial history, were investigated in 451 students (313 females and 138 males, age 15-17 years) from two high schools of Florence. Fibrinogen levels were significantly higher in women than in men, whereas factor VIIag levels did not significantly differ. Both fibrinogen and factor VIIag significantly correlated with total cholesterol (p < 0.05) while only fibrinogen correlated with body mass index (p < 0.01). Factor VIIag was significantly correlated with systolic blood pressure (p < 0.001). This study provides information on coagulation risk factors in a population of adolescents which may be of importance in planning coronary heart disease prevention programs.

Adolescent↗

D-Dimer in intra-uterine growth retardation and gestational hypertension.

Pregnancy is sometime related to thromboembolic complications (1) and alterations in different hemostatic parameters have been reported in pregnancy (2-4). In particular, a progressive increase in fibrinogen and D-dimer levels occurs during normal pregnancy (5-9). D-dimer levels may be predictive for some complications such as preeclampsia (10) and they have been also reported to be useful for diagnosis of abruptio placentae (6). However, it remains to be established if common ELISA for D-dimer are able to discriminate pathologic samples in conditions such as intrauterine growth retardation (IUGR) or gestational hypertension (GH). Aim of the present study has been to evaluate the behavior of D-dimer in pregnant women with IUGR and GH.

Adult↗

Th1 and Th2 T-helper cells exert opposite regulatory effects on procoagulant activity and tissue factor production by human monocytes.

The role of T-cell subsets in the induction of tissue factor (TF) production by human monocytes in vitro was investigated. Mitogen stimulation enabled both unfractionated T cells and their CD4+ or CD8+ subsets to promote procoagulant activity (PCA). After mitogen or antigen activation, all seven T-cell clones with Th1 cytokine profile, but none of seven Th2 clones, induced TF production and PCA. T-cell blasts from four Th1 activated clones were fixed with paraformaldehyde and added to monocytes in the presence of medium alone or their supernatants. Addition of either fixed Th1 cells or their supernatants induced low TF production (0.2 to 0.6 ng/mL), whereas addition of both resulted in much higher TF synthesis (1.8 to 3.4 ng/mL). Among Th1-type cytokines, only interferon-gamma (IFN-gamma) induced minimal TF production (0.1 to 0.4 ng/mL). No TF synthesis was induced by activated and fixed Th2 cells and/or their supernatants, whereas combined addition of fixed Th2 cells and Th1 supernatants or IFN-gamma induced noticeable TF production. The addition of either anti-IFN-gamma antibody or Th2 supernatants to monocytes stimulated with activated and fixed Th1 cells plus their supernatant resulted in a dose-dependent inhibition of TF synthesis, which was partially restored by neutralization of interleukin-4 (IL-4) or IL-10. Addition of recombinant IL-4, IL-13, or IL-10, but not IL-5, inhibited the Th1-induced TF production by monocytes. Data indicate that both CD8+ and CD4+ Th1, but not Th2, T cells can help TF production and PCA. Both cell-to-cell contact with activated T cells and Th1-type cytokines, in particular IFN-gamma, are required for optimal TF synthesis, whereas Th2-derived cytokines (IL-4, IL-13, and IL-10) are inhibitory. This may be of potential interest for future therapeutic strategies.

Antigens↗

D-dimer concentrations during normal pregnancy, as measured by ELISA.

In pregnant women a number of changes in blood clotting and fibrinolysis proteins have been reported so indicating the existence of a state of hypercoagulability. In addition to fibrinogen and antithrombin III (AT), D-dimer is frequently checked during pregnancy, in particular during at risk pregnancy, but the exact pattern of D-dimer modifications during uncomplicated pregnancy is not definitively described. The aim of this study was to establish the range values in three different periods of uncomplicated pregnancy (A: 1-20 wks; B: 21-30 wks; C: 31-40 wks). We measured plasma levels of D-dimer, clottable fibrinogen and AT in 108 consecutive normal pregnant women aged 16 to 42 years. In period A, the range of D-dimer values was 43-211 ng/mL, not different from controls, while fibrinogen levels were significantly higher (p < 0.05) than in matched non pregnant women. Mean D-dimer levels were higher in periods B (p < 0.05) and C (p < 0.05) vs period A. Similarly, mean fibrinogen levels were found more elevated in periods B and C vs period A (p < 0.05). A significant correlation was found between fibrinogen and D-dimer levels (p < 0.001). No differences in AT levels were found among the three periods of pregnancy. The results of this study indicate that levels of D-dimer up to 685 micrograms/L may be reached at the end of physiological pregnancy. This fact should be taken into account in the evaluation of hemostatic studies performed in uncomplicated and complicated pregnant women.

Adolescent↗

Fibrin generation and digestion in patients with angina pectoris.

Fibrin generation and lysis were studied in 28 patients with angina pectoris (14 with active disease and 14 with inactive disease) and in 14 normal controls. The fibrinolytic response was evaluated by comparing the ratio between the plasma levels of fibrinopeptide A and fibrin degradation products. Levels of both were higher in patients than in controls (P < 0.001), with higher levels in active than in inactive disease (P < 0.001). The fibrinopeptide A/fibrin degradation products ratio was much higher (P < 0.001) in the active group than in other groups. Thus, in patients with angina pectoris, especially in the active state, the increased thrombin generation is not paralleled by an equivalent increase in fibrinolytic activity.

Adult↗

Platelet activation and platelet lipid composition in pulmonary cancer.

In order to investigate the possible mechanisms underlying platelet functional changes in patients affected by neoplasms, platelet lipid composition, plasma beta-thromboglobulin (Beta-TG) and serum thromboxane B2 (TXB2) were investigated in 16 male patients affected by pulmonary carcinoma and in 16 comparable control subjects. In patients high levels of plasma Beta-TG (67 +/- 9 versus controls 14 +/- 4 ng/ml, p < 0.001) and serum TXB2 (434 +/- 56 versus 223 +/- 48 ng/ml, p < 0.001) were observed. Also platelet lipid composition was found altered in patients with respect to controls (lower percent levels in n-3 fatty acids and in linoleic acid esterified in the main platelet phospholipid fractions: at least p < 0.05). These results indicate that in vivo platelet activation is detectable in neoplastic patients and it is associated with alterations in platelet lipid composition. In the light of the important role played by membrane lipids in platelet functions related to thrombosis and haemostasis we conclude that platelet lipid changes could cooperate in platelet activation and increased thrombotic risk so frequently observed in neoplastic disease.

Adult↗

Defibrotide reduces monocyte PAI-2 and procoagulant activity.

Defibrotide is a polydeoxyribonucleotide-derived anti-ischemic drug with multiple sites of action involving both plasmatic and cellular targets. This agent has been demonstrated to produce profibrinolytic, cytoprotective, and vaso-facilatory actions. Since monocytes are increased in the mediation of some of the pathophysiologic responses seen in ischemic disorders, the functional properties of these cells were investigated in experimental conditions to evaluate their behavior during resting and stimulated states. Defibrotide was supplemented in these systems to determine its modulatory action. In this investigation Defibrotide was found to decrease the PAI-1 levels and may indicate that this may be the mechanism for its profibrinolytic actions. Defibrotide was also found to reduce the procoagulant activity of monocytes in these experimental settings. Both PAI and procoagulant factors play an important role in the pathophysiology of inflammation, DIC, and ischemia. Defibrotide induced reduction of these two factors represents the mechanism whereby this agent produces its therapeutic action.

Blood Coagulation Factors↗

No changes in PAI-1 levels after four-month n-3 PUFA ethyl ester supplementation in healthy subjects.

Recent studies have indicated that diets rich in fish or supplemented with fish oils may increase PAI-1 plasma levels. However, this finding has not been consistent and could be related, at least in part, to the type of supplementation. Aim of this study was to investigate the effects of medium-term treatment with n-3 polyunsaturated fatty acid (PUFA) ethyl esters on fibrinolysis. Twenty normolipemic healthy male subjects (age 27 to 41 yrs) were randomly assigned to receive either 4 x 1 g capsules of n-3 PUFA ethyl esters (ESAPENT, Farmitalia-Carlo Erba, Milan, Italy) or 4 x 1 g capsules of olive oil (as placebo) for 4 months in a double blind study. Blood samples for lipid and hemostatic studies were obtained at 0, 2, and 4 months of treatment and 1, 2 and 3 months of wash-out. Plasma lipids, fibrinolytic system, lipoprotein (a)-Lp(a)-, fibrinogen (Fbg) and prothrombin activation fragment 1+2 (F1+2) were assayed. No changes in these parameters were observed in the group of ten subjects treated with olive oil. After n-3 PUFA supplementation no significant alterations were found in plasma lipids, even if a trend to lower triglyceride and Lp(a) levels was detectable. No changes in either PAI-1 activity or PAI-1 antigen levels or F1+2 plasma levels were observed. A trend to lower Fbg levels was found after n-3 PUFA, but changes were not statistically significant. The results of this study indicate that a 4-month treatment with 4 g daily n-3 PUFA ethyl esters does not affect PAI-1 plasma levels.

Adult↗

Euglobulin lysis time in fresh and stored samples.

Euglobulin lysis time is a global test for the study of fibrinolysis. The aim of this study was to evaluate the influence of storage of plasma and euglobulin precipitates on euglobulin lysis time, by testing samples stored in different conditions. In 20 healthy subjects, euglobulin lysis time was measured by (1) euglobulin precipitates prepared within 90 minutes from blood withdrawal (reference euglobulin lysis time); (2) euglobulin precipitates obtained from platelet-poor plasma stored for 24 hours at either -80 degrees C or at -20 degrees C; (3) euglobulin precipitates frozen for 24 hours at either -80 degrees C or at -20 degrees C; (4) euglobulin precipitates dissolved in Owren's buffer and frozen for 24 hours at either -80 degrees C or at -20 degrees C. Euglobulin lysis time measured on euglobulin precipitates dissolved in Owren's buffer and stored at -20 degrees C and at -80 degrees C, and euglobulin lysis time measured on platelet-poor plasma stored at -20 degrees C were significantly longer than the reference euglobulin lysis time (at least P < .05). On the contrary, no changes were observed in euglobulin lysis time measured on platelet-poor plasma stored at -80 degrees C, and on euglobulin precipitates undissolved and stored at -20 degrees C and at -80 degrees C versus reference euglobulin lysis time. The pattern was similar in samples obtained both before and after venous occlusion. These data indicate that the freezing of samples of platelet-poor plasma or euglobulin precipitates at -80 degrees C and of euglobulin precipitates at -20 degrees C makes the simultaneous determination of a large number of samples collected at different times the previous day possible.

Adult↗

[Antithrombotic agents in pregnancy].

The need for antithrombotic therapy during pregnancy is a challenging problem for the clinician. Pregnancy per se is associated with a prothrombotic state, and some conditions definitely require anticoagulant treatment. However, all three main antithrombotic agents (coumarins, heparin and aspirin) have potential serious adverse effects for the mother and fetus. The aim of this review was to discuss the modifications of the coagulation system during pregnancy, and try to properly state the indications and the best schedule of antithrombotic treatment during pregnancy. Presently heparin is considered the anticoagulant of choice for the treatment and prevention of venous thromboembolic disorders and in patients with congenital or acquired thrombophilic conditions. The use of oral anticoagulants is still preferred in women with prosthetic heart valves or atrial fibrillation, but they cannot be administered between the sixth and twelfth week and in the last month of gestation because of the teratogenic and hemorrhagic risks related to their use. Low-dose aspirin is useful for the prevention of pre-eclampsia, intrauterin growth retardation, and in association with heparin or prednisone, for the prevention of abortion in patients with antiphospholipid antibodies.

Antibodies, Antiphospholipid↗

Age-related changes in the hemostatic system.

The increased incidence of arterial thromboembolism in the elderly has prompted investigation of age-related changes in the hemostatic system. Aging is associated with increased plasma levels of fibrinogen, factor VII and factor VIII, which have been shown to be risk factors for thrombotic disease in five large epidemiological studies. An increased responsiveness to different aggregating stimuli, elevated levels of beta-thromboglobulin and an increased production of thromboxane A2 were reported in the platelets of the elderly. These alterations are associated with modifications of platelet membrane lipid composition (namely an increase in the cholesterol/phospholipid ratio and a decrease in linoleic acid) with possible related changes in membrane fluidity. Moreover, a decrease in the number of platelet prostacyclin and thromboxane A2 receptors was observed with aging. Fibrinolytic activity is impaired in the elderly, probably due to an increase in plasminogen activator inhibitor 1. Interestingly, hypercoagulability has been demonstrated by an increase in the activation markers of the coagulation cascade (mainly fibrinopeptide A and prothrombin activation fragment F 1 + 2). Finally, clinical and experimental evidence suggests that endothelium could play a central role in hemostatic alterations which determine a thrombophilic state in the elderly.

Aged↗

Increased thromboxane A2 production at primary tumor site in metastasizing squamous cell carcinoma of the larynx.

In order to evaluate the possible role of prostaglandins (PG) in invasion and metastasis of malignant cells in larynx carcinoma, arachidonic acid (AA) metabolite production by tumor tissue, peritumor tissue and node metastasis was investigated in comparison to that by healthy mucosa and unaffected lymph nodes. The study was performed by evaluating PGE2, 6ketoPGF1 alpha and thromboxane B2 (TXB2) production by radioimmunoassay in specimens from eight patients who underwent surgical treatment. The highest rate of AA metabolism was observed in peritumor tissue. PGE2 was the main metabolite produced in all tissues and its levels were significantly higher than those of 6ketoPGF1 alpha and TXB2 (p < 0.05). 6ketoPGF1 alpha production was higher (p < 0.01) than that of TXB2 and did not significantly change among the different tissues. TXB2 production was significantly increased (p < 0.05) by peritumor tissue as compared to healthy mucosa. The ratio between TXB2 and 6ketoPGF1 alpha production was found to be almost twofold higher in tumor tissue, peritumor tissue, metastatic and non-metastatic lymph nodes as compared to control tissue. The lowest AA metabolism was found in affected lymph nodes. These findings demonstrate a different AA metabolism at primary tumor sites in comparison to healthy mucosa suggesting a prometastatic role of TXB2 and supporting the hypothesis of the occurrence of an imbalance between TXB2 and 6ketoPGF1 alpha production in favouring metastatic spread.

6-Ketoprostaglandin F1 alpha↗