Relationship between classical FDP test and D-dimer assayed both by latex agglutination and ELISA.
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Adult↗
Biomedical subjects
D Prisco
Publications and source records attributed to D Prisco.
No signs of increased thrombin generation in menopause.
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Adult↗
Sex related differences in platelet TxA2 generation.
Platelet lipid composition, c arachidonic acid (AA) metabolism by platelets (stimulated with thrombin), serum thromboxane (Tx)B2 production and plasma lipid composition were investigated in 53 healthy females (18-45 years) and 65 males (19-45 years) with similar dietary habits. In males, serum TxB2 production and cholesterol platelet membrane levels were found significantly higher (p less than 0.001 and p less than 0.05) than in females. No differences were observed between the two groups in the AA conversion through cyclo-oxygenase and lipoxygenase pathways or in the platelet phospholipid fatty acid composition. These findings indicate that in males the platelet proaggregatory capacity is greater than in females and the higher platelet TxB2 production does not depend on a larger AA availability or on enzyme activation for its conversion. The increased TxB2 production may be, at least in part, induced by functional differences such as a different membrane cholesterol content inducing, in its turn, an increased microviscosity and/or higher number of platelet receptors for thrombin.
8,11,14-Eicosatrienoic Acid↗
Prostaglandins in squamous cell carcinoma of the larynx: tumor and peritumor synthesis.
Prostaglandin (PG) E2, 6ketoPGF1 alpha and Thromboxane B2 (TxB2) production by the tumor, peritumor and control tissue were investigated in specimens from patients (n = 11) with squamous cell carcinoma of the larynx, in relation to the extension and infiltration of the neoplasm and to the presence of inflammation, fibrosis and necrosis. In all specimens detectable amounts of 6ketoPGF1+ and TxB2 were found, but the predominant metabolite was PGE2. No differences in the levels of TxB2 and 6ketoPGF1 alpha were observed, but the only patient with lymphnodal involvement showed the lowest levels of 6ketoPGF1 alpha both in tumor and peritumor tissue. Higher amounts (p less than 0.05) of PGE2 were synthesized by peritumor tissues in comparison to control mucosa and tumor tissue independently of the occurrence of reactive infiltration. PGs synthesis did not correlate with inflammation, fibrosis, necrosis or staging of the neoplasm. However the two cases in stage T4 showed PGE2 generation at the highest levels both in neoplastic and perineoplastic tissue. These findings indicate that in squamous cell carcinoma of the larynx an increased production of PGE2 occurs, stemming not only from inflammatory cells but at least in part from neoplastic cells. This suggests that the study of arachidonic acid metabolism may contribute to characterization of the primary cancer and lead to better understanding of the mechanisms of tumor growth and diffusion.
6-Ketoprostaglandin F1 alpha↗
Physiologic role of coronary PGI2 and PGE2 in modulating coronary vascular response to sympathetic stimulation.
To investigate a physiologic role of coronary prostacyclin (PGI2) and prostaglandin E2 (PGE2) 30 patients who were not affected by coronary heart disease were evaluated for coronary hemodynamics and coronary PGI2 and PGE2 production. Inhibition of coronary prostaglandin biosynthesis by ketoprofen (1 mg/kg) or aspirin (15 mg/kg) administered intravenously did not significantly change coronary hemodynamics in resting conditions. In all patients cold pressor tests induced significant increases in coronary blood flow (p less than 0.001) and decreases in coronary vascular resistance (p less than 0.001) without changes in cardiac oxygen extraction and with consequent increases in calculated myocardial oxygen consumption. Simultaneously, a marked increase in coronary PGI2 (as 6-keto-PGF1 alpha) and PGE2 formation was observed (p less than 0.001). Both ketoprofen (1 mg/kg) and aspirin (15 mg/kg) administration completely abolished PGI2 and PGE2 formation that was induced by cold pressor test and caused a paradoxical increase in coronary vascular resistance (ketoprofen: p less than 0.02; aspirin: p less than 0.05). The results of this study support a physiologic role for the coronary prostaglandins in modulating coronary vascular response to sympathetic stimulation in nonischemic patients.
Adult↗
Low-dose heparin as an antithrombotic agent.
Heparin, after subcutaneous administration, has been found to be able to bind to endothelial receptors both in rabbits and in humans. N-sulphonate 35S-heparin remains bound in rabbits for at least 24 h and is able to enhance the inactivation process of thrombin and factor Xa. Heparin subcutaneously (200 U/kg) injected for 2 weeks resulted in an enhanced inactivation of thrombin and factor Xa by the endothelium. The antithrombin-enhancing activity persists longer than the anti-Xa activity. In man, daily subcutaneous administration of heparin (12,500 U/day) for 2 weeks significantly reduces the increased fibrinopeptide A plasma levels and normalizes the increased 125I-fibrinogen turnover. The present work indicates that heparin administration at a low dose represents a treatment able to remarkably enhance the antithrombotic properties of the vessel wall, independently of the presence of detectable heparin levels in the circulating blood.
Animals↗
Thrombolytic versus fibrinogenolytic activity of rt-PA and streptokinase in patients with acute myocardial infarction.
In this study the concentration of plasma breakdown products of cross-linked fibrin (XDP), serum fibrinogen-fibrin degradation products (FDP), and plasma fibrinogen were measured before and at the end of the administration of single-chain recombinant tissue-type plasminogen activator (rt-PA, 100 mg IV over three hours) or streptokinase (1.5 million units over one hour), respectively, in two groups, each composed of 22 patients with acute myocardial infarction. The XDP concentration was not statistically different between the two groups at the end of thrombolytic treatment, whereas FDP and fibrinogen concentrations were significantly different (FDP: streptokinase 396 +/- 287 vs rt-PA 177 +/- 222 micrograms/mL, p less than 0.01; fibrinogen: streptokinase 71 +/- 43 vs rt-PA 181 +/- 49 mg/dL, p less than 0.001). These results indicate that the two drugs have equipotent thrombolytic activity at this administration regimen but that rt-PA causes a markedly more selective lysis of fibrin in comparison with streptokinase.
Adult↗
Evaluation of new methods for the selective measurement of fibrin and fibrinogen degradation products.
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Adult↗
Red blood cell lipid alterations in type II diabetes mellitus.
Alterations in blood rheological properties have been reported in diabetes mellitus. Changes in lipid composition of red blood cell (RBC) membranes resulting in an impairment of RBC deformability may play a role in the altered blood rheological pattern. The aim of this study was to investigate the lipid composition of RBC membrane in a group of patients affected by type II diabetes (age 21-45 years), selected on the basis of the absence of complications and good metabolic control, and in a group of suitable control subjects. Saturated fatty acid amounts in the different phospholipid fractions were significantly higher in diabetics than in controls (p less than 0.05), whereas polyunsaturated fatty acids were decreased (p less than 0.05). Cholesterol/phospholipid molar ratio was not altered. On the contrary, sphingomyelin/phosphatidylcholine ratio was higher in diabetics than in controls (1.10 +/- 0.08 vs 0.96 +/- 0.10, p less than 0.01) due specially to high levels of sphingomyelin. These alterations could account for the impairement of RBC deformability frequently reported in diabetes mellitus, independently of metabolic control and the presence of severe atherosclerotic lesions.
Adult↗
Altered membrane fatty acid composition and increased thromboxane A2 generation in platelets from patients with diabetes.
Lipid composition of platelet membranes and thromboxane A2 (TxA2) generation by platelets were investigated in 42 diabetic patients (14 with macroangiopathic complications, 10 with microangiopathy and 18 without vascular complications) and in 42 clinically healthy subjects of similar age. All subjects were on a similar dietary regimen and the adherence to diet was checked by analysis of red blood cell lipids. Platelets from all groups of diabetic patients produced increased amounts of TxA2 than platelets from controls (at least p less than 0.01) and patients with macroangiopathy (p less than 0.01). Platelet cholesterol and total platelet phospholipids were higher in patients with macroangiopathy, while the relative percentage of the different phospholipid fractions in platelet membrane and their saturated and unsaturated fatty acids were similar in the different groups. Arachidonic acid (AA) content in phosphatidylcholine (PC) was found to be significantly higher in diabetic patients than in controls (at least p less than 0.005). Moreover patients with macroangiopathy had higher AA (p less than 0.001) and lower eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) levels in PC (p less than 0.001) than the other groups of patients and controls.
Adult↗
Ability of whole blood aggregometer to detect platelet hyperaggregability.
In this study the reliability of platelet aggregation in whole blood (WB) was investigated in clinical conditions associated with thromboembolic complications. Spontaneous (SPA) and collagen-induced platelet aggregation were evaluated both in whole and diluted blood by the impedance method and in platelet-rich plasma (PRP) by the Born aggregometer in 18 healthy subjects, 15 patients with ischemic heart disease (IHD), and 15 patients with insulin-independent diabetes. SPA occurred more often in WB than in PRP, and in WB the occurrence of SPA was significantly more frequent in the patient groups (4 of 15 patients with IHD and 6 of 15 diabetic patients) than in the controls (1 of 18). WB aggregation induced by collagen was significantly higher in patients with IHD and in diabetic patients than in controls (P less than 0.01), whereas diluted WB and PRP aggregation were not statistically different from controls either in patients with IHD or in diabetic patients. WB aggregation values were found to be related, although not very closely, to megathrombocyte count (r = 0.31, P less than 0.05) whereas not at all to platelet count or hematocrit. No relationship was observed between WB aggregation and disease severity (angiographic lesions and number of ischemic attacks) in patients with IHD and between WB aggregation and HbAlc values in diabetic patients.
Blood Cell Count↗
[Critical evaluation of new methods for studying fibrin degradation products].
Tests for measuring fibrinogen/fibrin degradation products (FDP) in serum have been employed for many years to study conditions in which fibrinolysis is activated. However, these tests can not differentiate between products of plasmin action on fibrinogen and fibrin stabilized by activated factor XIII because antibodies employed are not specific. Moreover, there is the possibility of false positive and false negative FDP tests. Recently new tests have been proposed which employ monoclonal antibodies interacting specifically with antigenic sites of cross-linked fibrin and its degradation products, making it possible to distinguish these degradation products from those of fibrinogen and to have a more precise evaluation of fibrinolysis. Some applications are discussed.
Evaluation Studies as Topic↗
Radioimmunoassay of thromboxane B2 in plasma: methodological modifications.
Thromboxane B2 (TxB2) determination is usually performed by using commercial 3H-RIA kits. However, the low amounts of TxB2 present in plasma are not detectable without previous extraction. The aim of this study is the evaluation of 1) plasma protein interferences on the binding and separation steps of bound from free analyte and 2) charcoal efficacy in different experimental conditions. Our results indicate that plasma proteins do not influence the antibody binding, but significantly reduce the efficacy of precipitation of kit dextran-charcoal, so that the supernate radioactivity rises with the protein amount increase (r = 0.99 p less than 0.001). Such greater number of counts in the samples determines a lower estimation of TxB2 concentration in plasma when the calibration curve is set up in buffer. Our findings suggest that, in order to measure low amounts of plasma TxB2 without extraction, it is useful: 1) to refer to a calibration curve set up in buffer-diluted plasma, 2) to use the uncoated charcoal concentration allowing the lowest stripping and 3) to perform all steps at 4 degrees C.
Charcoal↗
Altered lipid composition and thromboxane A2 formation in platelets from patients affected by IIa hyperlipoproteinemia.
Platelets from patients with familial hypercholesterolemia (type IIa hyperlipoproteinemia), a condition associated with high prevalence of atherosclerosis and of its thrombotic complications, are known to be hyperresponsive to aggregating stimuli and to synthesize increased amounts of thromboxane A2 (TxA2) in comparison to platelets from normal subjects. In order to search if these functional alterations are linked to a different platelet lipid composition, we studied a group of young patients affected by IIa hyperlipoproteinemia and a group of suitable controls with similar dietary habits. Both cholesterol and phospholipid content of platelets were higher in patients than in controls with a significant increase of cholesterol/phospholipid molar ratio (at least p less than 0.05). The percent contents of the main platelet phospholipid fractions were not altered, while an increase in saturated fatty acids, both unesterified and esterified in different lipid fractions, was observed. Moreover, an increased TxA2 production by platelets and a significantly increased number of megathrombocytes occur in patients with respect to controls (p less than 0.001). Our results indicates that platelets from patients with IIa hyperlipoproteinemia have an altered lipid composition which could explain, at least in part, the enhanced platelet reactivity reported in these patients.
Adult↗
Decrease in frequency of anginal episodes by control of thrombin generation with low-dose heparin: a controlled cross-over randomized study.
Increased thrombin generation is frequently associated with an increase in anginal activity. A cross-over, single-blind, completely randomized study was planned in order to evaluate whether the control of thrombin generation affected the increase in anginal activity. After discharge from the hospital, 24 patients (18 men and 6 women, aged 40 to 69 years) suffering from spontaneous angina were followed up to 12 months and were alternatively treated during two consecutive 6-month periods with calcium heparin, 12,500 IU by the subcutaneous route, or with placebo by the intramuscular route, in addition to the usual antianginal medications. Thrombin generation and clinical activity of angina were assessed every 15 days by measuring fibrinopeptide A (FPA) plasma levels and by grading in three classes (symptomless, mildly symptomatic, and severely symptomatic) the anginal activity on the basis of the number and the time concentration of the ischemic attacks and ECG changes. Low-dose heparin treatment significantly reduced both the FPA plasma level (from 4.1 +/- 3.7 to 2.3 +/- 1.8 ng/ml, p less than 0.001) and the clinical activity of angina. During heparin treatment, the frequency of the observations in the severely and mildly symptomatic classes decreased, respectively, by 53% and by 30%, whereas that in the symptomless class increased by 23% (p less than 0.001) in comparison with the period on placebo. Present results indicate that the control of thrombin generation obtained by low-dose heparin treatment favorably affects the degree of anginal activity in patients with spontaneous angina.
Aged↗
Platelet synthesis of cyclooxygenase and lipoxygenase products in type I and type II diabetes.
In 24 type I and 22 type II diabetic patients without vascular complications and in 25 controls platelet thromboxane A2 (TxA2) and prostaglandin E2 (PGE2) production (by radioimmunoassay-RIA) and 1-14C arachidonic acid (AA) metabolism (by high pressure liquid chromatography-HPLC) after thrombin stimulation were studied. Platelets both from type I and type II diabetics generated larger amounts of TxB2 (p less than 0.001) and PGE2 (p less than 0.005) than controls, independently of the presence of retinopathy. No significant differences in platelet AA uptake or metabolism via the cyclooxygenase (CO) route, after thrombin stimulation (5 NIH U/ml), were observed in diabetic patients: lipoxygenase metabolites were found to be slightly, but significantly decreased. A positive linear relationship (r = 0.64, p less than 0.001) was found between HbA-1c and TxB2 production, but not with fasting plasma glucose. These results indicate that metabolic alterations can affect platelet function independently of vascular complications. The absence of alterations in intraplatelet 1-14C AA metabolism via CO, in the presence of increased TxB2 and PGE2 production from endogenous AA, suggests that the activation of CO is not the only possible mechanism of platelet activation and that probably an increased availability of platelet AA plays an important role in the enhanced platelet aggregation commonly found in diabetics.
Adult↗
Altered intraplatelet arachidonic acid metabolism during the acute state of unstable angina.
Thromboxane A2 (TxA2) generation and 1-14C arachidonic acid (AA) metabolism by platelets (stimulated with thrombin) were studied in vitro in 16 patients with unstable angina both during the acute and chronic inactive phase of the angina. Eight patients with stable effort angina and 21 controls were also investigated. In acute unstable angina 1-14C AA metabolism was significantly increased through cyclooxygenase pathway resulting in a higher selective TxA2 generation than in stable effort angina and in controls (p less than 0.01). No differences were found between patients with stable effort angina and controls. The alterations in AA metabolism were no longer found when patients reverted to the inactive phase of angina. TxA2 generation by platelets was independent of the number of the daily ischemic attacks (r = 0.17, ns) in patients with unstable angina. Present results indicate that an altered intraplatelet AA metabolism leading to the increased TxA2 synthesis occurs simultaneously with the conversion of angina from the chronic to the acute phase.
Acute Disease↗
Association between time of increased fibrinopeptide A levels in plasma and episodes of spontaneous angina: a controlled prospective study.
Thirty-seven patients affected by spontaneous angina and 15 comparable control subjects were enrolled in a 12-month prospective study to evaluate the relationship between blood clotting activation (assessed by fibrinopeptide A [FPA] plasma concentration) and the occurrence of myocardial ischemic attacks. FPA measurements and clinical examinations in patients were performed every 2 weeks. In control subjects blood sampling was performed every 4 weeks. Data from 28 patients who completed the study and from the 15 control subjects were analyzed. The clinical activity of angina was divided into three classes (asymptomatic, mildly symptomatic, and severely symptomatic) on the basis of the number and time-concentration of the ischemic attacks and ECG changes during the 15 days preceding each clinical examination. In all but one patient, a cyclic pattern of activity of coronary artery disease was observed. During follow-up studies, 624 FPA measurements were performed in patients and 173 in control subjects. Mean values were 4.68 +/- 4.53 and 1.32 +/- 0.60 ng/ml, respectively (p less than 0.001). FPA levels differed markedly in relation to the activity of angina. A relationship between FPA levels and activity of disease (r = 0.54, p less than 0.01) was found in time course. Bolus heparin administration (100 IU/kg) during the active phase of angina sharply but incompletely lowered FPA plasma levels, indicating thrombin formation both intravascularly and extravascularly. Present results indicate that a marked blood clotting activation occurs simultaneously with the outbursts of clinical activity of spontaneous angina.
Adult↗