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Biomedical subjects

D Prisco

Publications and source records attributed to D Prisco.

At least 91 records · Page 5Linked to original sources

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↗

Effect of n-3 fatty acid ethyl ester supplementation on fatty acid composition of the single platelet phospholipids and on platelet functions.

Twenty healthy male volunteers were randomly assigned to receive either four 1-g capsules of n-3 polyunsaturated fatty acids (PUFA) ethyl esters or four 1-g capsules of olive oil (as placebo) for a period of 4 months, followed by a 3-month wash-out period. Fatty acids of platelet phospholipid fractions, platelet aggregation, and thromboxane B2 (TXB2) formation were analyzed at 0, 2, and 4 months of treatment and at 1, 2, and 3 months of wash-out. During n-3 PUFA supplementation, accumulations of eicosapentaenoic (EPA), docosapentaenoic (DPA), and docosahexaenoic (DHA) acids were markedly increased after 2 months, with slight differences in further accumulation up to 4 months among the various phospholipid fractions. Significant decreases in platelet sensitivity to collagen, serum TXB2 levels, and urinary TXB2 metabolites were also observed following n-3 PUFA treatment. During the first and second month of wash-out, slight differences were observed in changes of various fatty acids among different phospholipid fractions, but after 3 months of wash-out, alterations were no longer detectable with respect to pretreatment values. After 3 months of wash-out, platelet function parameters also were returned to baseline. Thus, both platelet lipids and function are influenced by n-3 PUFA ethyl ester supplementation, and significant alterations are still detectable after 2 months of wash-out.

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↗

Physical exercise and hemostasis.

A number of hemostatic changes involving platelets, coagulation and fibrinolysis have been reported after acute physical exercise. Results have sometimes been controversial, due to differences in subjects investigated, type of exercise and methods used for hemostatic evaluation. On the whole, physical exercise has been shown to induce: (1) increases in platelet number and activity, (2) activation of coagulation leading to a slight but significant thrombin generation and (3) activation of fibrinolysis. These changes are short lasting. Less known are hemostatic changes induced by exercise training programs: a few data are available on the effects on platelets and coagulation, whereas studies performed on fibrinolysis show a decrease in plasminogen activator inhibitor-1 levels at rest and an increase in fibrinolytic capacity after training.

Blood Coagulation↗

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↗

Thrombin generation after physical exercise.

Many investigators have studied the influence of physical exercise on hemostatic system and it is well accepted that exercise causes an activation of coagulation as indicated by a shortening of aPTT and by an increase in plasma factor VIII activity and levels. A controversial point remains whether this clotting activation leads to a significant thrombin generation and fibrin formation. The type of physical exercise performed and the methods used to study blood coagulation may be two major sources of discrepancies in different studies. In the last years sensitive and reliable methods became available to evaluate prothrombin activation and thrombin generation. Thus in this study we have investigated the influence of a well standardized treadmill stress test, controlled by the measurement of cardiorespiratory and metabolic parameters, on plasma concentration of different markers of clotting activation in healthy untrained young subjects. Blood samples were also withdrawn just before anaerobic threshold to investigate a possible role of metabolic acidosis in changes of clotting system.

Adult↗

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↗

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.

Female↗

Human prostacyclin platelet receptors in diabetes mellitus.

Conflicting data have been reported about the impaired sensitivity to the inhibitory effect of prostacyclin (PGI2) in platelets from patients with diabetes. In the present paper we investigated binding of and sensitivity to PGI2 of platelets from insulin dependent (IDDM) (n = 9), non insulin dependent (NIDDM) (n = 8) diabetics and two groups of ten healthy subjects of equivalent age in relation to platelet lipidic content. Platelet sensitivity to PGI2 (PGI2 IC50) was found not significantly changed in diabetics as compared to controls; similarly, no significant differences of the number of high affinity receptors for PGI2 in platelets from patients with IDDM and NIDDM were observed. Platelet sensitivity to PGI2 and PGI2 receptors were found to be significantly related to platelet cholesterol content (r = 0.89, p less than 0.001 and r = -0.80, p less than 0.001 respectively). In conclusion platelet PGI2 receptor changes are not detectable in diabetics in good metabolic control, but could take place when platelet lipid composition is altered.

Adolescent↗

Age-related changes in red blood cell lipids.

Red blood cell (RBC) lipid composition was investigated in 81 healthy subjects aged twenty to sixty-nine years, having similar dietary habits, and living in the same geographic area in order to search for changes referable to aging. A significant increase in RBC cholesterol and total phospholipid content with aging was found (p less than 0.001), whereas no differences were observed in cholesterol/phospholipid molar ratio. Significant increases in palmitic acid 16:0 esterified in phosphatidylcholine and in stearic acid 18:0 esterified in phosphatidylethanolamine (p less than 0.001) were observed with aging. Moreover, a decrease in 18:2 n6 was observed in all three phosphoglyceride fractions investigated (p less than 0.001). These results suggest that modifications in RBC lipid composition occur with aging, possibly causing a reduction of membrane fluidity.

Adult↗

Pulmonary hypertension associated with long-standing thrombocytosis.

A case of thromboembolic pulmonary hypertension associated with long-standing thrombocytosis is presented. In this patient we found a significant local pulmonary platelet activation and thrombin generation as indicated by the existence of a transpulmonary gradient for thromboxane A2, beta thromboglobulin and fibrinopeptide A. Prolonged heparin and acetylsalicylic acid treatment resulted in improvement of clinical and hemodynamic conditions. These findings support the usefulness of anticoagulating and antiaggregating therapy in selected cases of pulmonary hypertension.

Adult↗

Evidence for local platelet activation in pulmonary vessels in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease.

To investigate the relationships between local platelet activation in pulmonary vessels and pulmonary artery pressure circulating platelet aggregates and plasma beta-thromboglobulin (beta-TG) levels were evaluated in peripheral venous blood and blood from different sites of pulmonary circulation (right ventricle, pulmonary artery and arteriolo-capillary bed) in 29 patients with COPD. Fifteen had pulmonary hypertension and 14 normal pulmonary artery pressure. In normotensive COPD no significant differences could be found in platelet aggregation and beta-TG levels among different sampling sites. On the contrary in patients with pulmonary hypertension a significant increase of platelet aggregates and beta-TG levels was found in blood withdrawn from the arteriolo-capillary bed. A significant correlation was demonstrated between platelet aggregation and both mean pulmonary artery pressure and pulmonary vascular resistance. These results indicate that in patients with pulmonary hypertension secondary to COPD a local platelet activation in pulmonary vessels does occur and may contribute to the maintainance of elevated pulmonary vascular resistance.

Adult↗

Effects of calcium channel blockers on platelet aggregation and thromboxane A2 formation: an in vivo double blind randomized study.

In this double blind cross over study against placebo the in vivo effects of diltiazem, nifedipine and verapamil on platelet aggregation and Thromboxane A2 (TxA2) formation were evaluated in eighteen healthy adults. No significant inhibition of platelet aggregation or TxA2 formation was found either after acute or short term (8 days) administration of the three calcium channel blockers at the usual therapeutical dosages. Our study indicate that diltiazem, nifedipine and verapamil are unable to significantly affect platelet aggregation and TxA2 formation in healthy subjects.

Adult↗