11-dehydro-thromboxane-b2 and Thrombosis

Topics: Adenosine Diphosphate; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Atherosclerosis; Biomarkers; Biotransformation; Blood Coagulation Tests; Blood Platelets; Cardiovascular Diseases; Clopidogrel; Cyclooxygenase 1; Cyclooxygenase Inhibitors; Drug Interactions; Drug Resistance; Hemorrhage; Humans; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prospective Studies; Randomized Controlled Trials as Topic; Receptors, Purinergic P2; Receptors, Purinergic P2Y1; Receptors, Purinergic P2Y12; Thrombosis; Thromboxane A2; Thromboxane B2; Ticlopidine; Treatment Failure

Aspirin's therapeutic action is via inhibition of platelet cyclooxygenase 1 (COX-1) thromboxane A2 (TxA2) production. The aim of this study was to evaluate TxA2 production, in the absence of platelet COX-1 activity, in coronary atherosclerotic heart disease patients with and without atherothrombotic myocardial infarction (MI).. TxA2 production, in the absence of platelet COX-1 activity, was evaluated in 44 patients taking aspirin on 3 commercially available assays that detect metabolites of TxA2 in the urine. Two assays measure urine 11-dehydro-thromboxane B2 (TxB2) alone and 1 measures urine 11-dehydro-TxB2 plus 11-dehydro-2,3-dinor-TxB2. Platelet COX-1 inhibition was confirmed on <10% platelet aggregation in response to ≥1 mmol/L arachidonic acid. Median urine 11-dehydro-TxB2 was no different in those with and without a diagnosis of atherothrombotic MI (325 vs. 311 pg/mg creatinine, P=0.59 via polyclonal ELISA) and (312 vs. 244 pg/mg creatinine, P=0.11 via LC-MS/MS). Median urine 11-dehydro-TxB2 plus 11-dehydro-2,3-dinor-TxB2, however, was higher in those with vs. those without a diagnosis of atherothrombotic MI (1,035 vs. 606 pg/mg creatinine, P=0.03 via monoclonal ELISA).. Differences in TxA2 production, in the absence of platelet COX-1 activity, between those with vs. without atherothrombotic MI were not observed when TxA2 generation was assessed on 11-dehydro-TxB2 production alone (polyclonal ELISA or LC-MS/MS), but differences were observed when TxA2 generation was assessed using 11-dehydro-TxB2 plus 11-dehydro-2,3-dinor-TxB2 (monoclonal ELISA). These findings highlight important differences between different commercially available assays for TxA2 generation and suggest that 11-dehydro-2,3-dinor-TxB2 may be critical to the biology of atherothrombosis.

Topics: Aged; Aspirin; Blood Platelets; Coronary Artery Disease; Creatinine; Cyclooxygenase 1; Cyclooxygenase Inhibitors; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation; Thrombosis; Thromboxane A2; Thromboxane B2

This trial evaluated the effect of antioxidant supplementation on the urinary excretion of 11-dehydro TXB(2)/2,3 dinor 6 keto PGF(1alpha) ratio, a marker of the pathogenesis of thrombosis and arteriosclerosis.. This study was a randomised, double-blind, placebo-controlled trial involving 186 presumably healthy volunteers. One hundred received a multi-antioxidant supplementation and 86 a placebo for two years. Blood zinc, selenium, beta-carotene, vitamin C and E and urinary excretion of 11-dehydro TXB(2) and 2,3 dinor 6 keto PGF(1alpha) were measured.. Baseline subject characteristics did not differ between the two groups. Blood zinc, selenium, and beta-carotene concentrations significantly increased between baseline and two years in the multi-antioxidant supplementation group supporting subject compliance (p < 0.05). At two years, the median urinary 11-dehydro TXB(2)/2,3 dinor 6 keto PGF(1alpha) ratio was significantly lower in the multi-antioxidant supplementation group (3.4 versus 2.78, p = 0.015). Serum selenium concentration was the only antioxidant studied that was significantly related to the urinary 11-dehydro TXB(2)/2,3 dinor 6 keto PGF(1alpha) ratio.. These results support the hypothesis that a low-dose multi-antioxidant supplementation may contributes to a reduction in platelet activation which is beneficial for cardiovascular function.

Topics: 6-Ketoprostaglandin F1 alpha; Antioxidants; Arteriosclerosis; beta Carotene; Biomarkers; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Patient Compliance; Platelet Activation; Prostaglandins I; Selenium; Thrombosis; Thromboxane B2; Thromboxanes; Trace Elements; Vitamins; Zinc

To investigate the effect of dietary saturated fat (SFA) from animal sources on the urine excretion 11-dehydro thromboxane B2 (TXB2) and 6-keto prostaglandin F 1alpha (PGF 1alpha) in 27 healthy free-living male subjects aged 30 to 55 years.. It was a randomized crossover design. Each volunteer was randomly assigned to one of the two diets (high fat and low fat) for a period of 4 weeks, after which each subject resumed his usual diet for 2 weeks as a 'wash-out period', before being assigned to the other diet for an additional 4 weeks.. Serum proportion of 20:4n-6 was 5% lower in the high fat (6.2% of total fatty acid) than in the low fat diet (6.5% of total fatty acid), which was associated with a significantly decreased ratio of the urinary excretion 11-dehydro TXB2 to 6-keto PGF 1alpha (P < 0.05). However, there was no significant fall in the absolute urinary excretion of 11-dehydro TXB2.. Diet rich in SFA from animal sources may influence TXA2 formation via effect on tissue proportion of 20:4n-6.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Arteriosclerosis; Cross-Over Studies; Dietary Fats; Fatty Acids; Humans; Male; Middle Aged; Thrombosis; Thromboxane B2

Evidence for aspirin efficacy testing in pediatrics is limited, especially outside of cardiology, yet thrombotic events have high morbidity in other areas such as pediatric transplant surgery. Debates about whether thromboembolic events while on aspirin represent "aspirin resistance" or "high on-treatment platelet reactivity" persist, given the poor intertest agreement between testing platforms.. This prospective observational study involved measuring aspirin efficacy using ex vivo testing of platelet aggregation (VerifyNow-Aspirin, VN) and urine 11-dehydrothromboxane B2 (AsprinWorks, UTxB2) contemporaneously at up to three time points after major noncardiac organ transplant surgery. The collection days (CD) were the second and seventh days after stable aspirin dosing and then a convalescent time point 2-9 months later.. Fifty-five participants (age range, 0-21 years) were enrolled, having undergone total pancreatectomy with islet autotransplantation (N = 36), orthotopic liver transplantation (N = 18), and combined liver-kidney transplantation (N = 1). Platelet reactivity measured by VN remained unchanged, whereas UTxB2, which was elevated postoperatively, decreased significantly from CD1 to CD2 and CD3. Discordance in therapeutic efficacy was noted per manufacturer cutoffs, with therapeutic VN results in 86% of tests, whereas 12% of UTxB2 were therapeutic. Age-based stratification of UTxB2 results using previously published pediatric median levels increased overall UTxB2 therapeutic rates (80%) and intertest concordance (67% vs 27% if using adult range). No thrombotic events were observed.. Our data suggest that urine thromboxane production may be an underappreciated reflection of postoperative inflammation. Validation of pediatric normal ranges for UTxB2 is a critical next step.

Topics: Adolescent; Adult; Aspirin; Blood Platelets; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Inflammation; Organ Transplantation; Pediatrics; Platelet Aggregation; Platelet Aggregation Inhibitors; Thrombosis; Thromboxane B2; Young Adult

Fish oil supplementation (FOS) is known to have cardiovascular benefits. However, the effects of FOS on thrombosis are incompletely understood. We sought to determine if the use of FOS is associated with lower indices of atherothrombotic risk in patients with suspected coronary artery disease (sCAD). This is a subgroup analysis of consecutive patients with sCAD (n=600) enrolled in the Multi-Analyte, Thrombogenic, and Genetic Markers of Atherosclerosis study. Patients on FOS were compared with patients not on FOS. Lipid profile was determined by vertical density gradient ultracentrifugation (n=520), eicosapentaenoic acid+docosahexaenoic acid was measured by gas chromatography (n=437), and AtherOx testing was performed by immunoassay (n=343). Thromboelastography (n=419), ADP- and collagen-induced platelet aggregation (n=137), and urinary 11-dehydrothromboxane B2 levels (n=259) were performed immediately before elective coronary angiography. In the total population, FOS was associated with higher eicosapentaenoic acid+docosahexaenoic acid content (p<0.001), lower triglycerides (p=0.04), total very low-density lipoprotein cholesterol (p=0.002), intermediate-density lipoprotein cholesterol (p=0.02), and AtherOx levels (p=0.02) but not in patients on lipid-lowering therapy. Patients not on lipid-lowering therapy taking FOS had lower very low-density lipoprotein cholesterol, intermediate-density lipoprotein cholesterol, remnant lipoproteins, triglycerides, low-density lipoprotein cholesterol, AtherOx levels, collagen-induced platelet aggregation, thrombin-induced platelet-fibrin clot strength, and shear elasticity (p<0.03 for all). In clopidogrel-treated patients, there was no difference in ADP-induced aggregation between FOS groups. Patients on FOS had lower urinary 11-dehydrothromboxane B2 levels regardless of lipid-lowering therapy (p<0.04). In conclusion, the findings of this study support the potential benefit of FOS for atherothrombotic risk reduction in sCAD with the greatest benefit in patients not receiving lipid-lowering therapy. Future prospective studies to compare FOS with lipid-lowering therapy and to assess the independent effects of FOS on thrombogenicity are needed.

Topics: Aged; Atherosclerosis; Biomarkers; Cholesterol; Coronary Artery Disease; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Female; Fish Oils; Humans; Lipoproteins; Male; Middle Aged; Risk Factors; Thrombelastography; Thrombosis; Thromboxane B2; Triglycerides

Anti-platelet therapy with aspirin is the cornerstone of treatment after coronary artery bypass grafting (CABG). Aspirin resistance describes the clinical observation of the inability of aspirin to prevent thrombotic complications or the laboratory phenomenon of absence of the effect of aspirin on platelet inhibition tests. Off-pump CABG (OPCAB) is associated with reduced platelet activation and turnover compared to on-pump surgery which may indicate that aspirin is more effective after OPCAB. Our aim was to evaluate the efficacy of aspirin and incidence of aspirin resistance in patients undergoing OPCAB.. A total of 331 patients was recruited, of which 111 underwent primary OPCAB (group A) and 220 controls with ischaemic heart disease received medical therapy. Arachidonic acid-induced platelet aggregation and urinary 11-dehydro thromboxane B2 (11-dehydroTxB2) were measured at baseline and following aspirin administration on days 1, 4 and 10. A 6-month follow-up was completed in patients who developed aspirin resistance.. On the first postoperative day, 78 patients (70.3%) were aspirin sensitive (AS) and 33 (29.7%) were aspirin resistant (AR). Of the latter, 18 (16.2%) and five (4.5%) patients remained resistant on days 4 and 10, respectively. AR patients had significantly greater platelet aggregation and urinary 11-dehydroTxB2 levels at all time points than those in the AS group. All patients in the AR group were AS by 6 months. All controls were sensitive to aspirin with similar platelet aggregation and 11-dehydroTxB2 to those in the AS group.. Aspirin resistance is a transient phenomenon during the early postoperative period in approximately 30% of patients undergoing OPCAB.

Topics: Aged; Aspirin; Biomarkers; Case-Control Studies; Coronary Artery Bypass, Off-Pump; Drug Administration Schedule; Drug Resistance; Female; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Count; Postoperative Care; Postoperative Period; Thrombosis; Thromboxane B2

Methionine ingestion (100mg/kg) identifies subjects in whom fasting total homocysteine (tHcy) may be normal but the post-methionine load (PML) tHcy is abnormally high.. In 96 subjects [54 M/42 F, 40.4 ± 12.3 yrs old; 28 with the 68 bp844 ins of the cystathionine-β-synthase gene (CBSins+); 20 homozygotes for the C677T mutation of the methylene-tetrahydrofolate reductase gene (MTHFR++); 13 with the combination of the two, and 35 without any of them], we have evaluated in vivo oxidative stress and platelet activation, as reflected by urinary excretions of 8-iso-PGF(2α) and of 11-dehydro-TXB(2) respectively, before and after a methionine load test (PML). A history of early-onset thrombosis (18 arterial, 32 venous, 2 both) was present in 52/96 of them.. Baseline; tHcy was highest in MTHFR++ carriers (p < 0,05); 8-iso-PGF(2α) and 11-dehydro-TXB(2) levels were independent of sex, MTHFR++ and/or CBSins + (p > 0.05). PML; The ~3-fold increase (p < 0.01 vs baseline) in tHcy reached a plateau within 6-8 hrs. Mean PML tHcy was maximal in MTHFR++ carriers (p = 0.000). 8-iso-PGF(2α) and 11-dehydro-TXB(2) increase reached a maximum within 4 hrs. 11-dehydro-TXB(2) increase was highest (p = 0.023 vs baseline) in subjects with a history of thrombosis. Baseline 11-dehydro-TXB(2) and a history of thrombosis independently predicted PML 11-dehydro-TXB(2) (β = 0.287, p = 0.000 and β = 0.308, p = 0.026, respectively).The PML increase in 8-iso-PGF(2α) or in 11-dehydro-TXB(2) were comparable in the different genotypes (p > 0.05).. Regardless genotypes associated with moderate hyperhomocysteinemia, following a methionine loading test, in vivo oxidative stress and platelet activation occur, being the latter maximal in subjects with a history of early-onset thrombosis.

Topics: Adult; Age of Onset; Analysis of Variance; Biomarkers; Case-Control Studies; Chi-Square Distribution; Cystathionine beta-Synthase; Dinoprost; Female; Homocysteine; Homozygote; Humans; Hyperhomocysteinemia; Italy; Linear Models; Male; Methionine; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Oxidative Stress; Phenotype; Platelet Activation; Platelet Function Tests; Thrombosis; Thromboxane B2; Time Factors

Aspirin is often used to prevent thrombosis in pediatric cardiac surgery. The primary study aim was to assess aspirin resistance in this context. Secondary aims were to evaluate (1) the relationship between elevated inflammatory markers and thrombosis and (2) aspirin's effect on these levels.. This was a prospective observational study of children undergoing cardiac surgery managed with and without aspirin. Aspirin response was assessed using the VerifyNow system and urinary 11-dehydrothromboxane B2 (uTxB2) measurements. Laboratory studies of inflammation were also obtained.. 101 subjects were studied; 50 received aspirin. Six subjects (5.9%), 5 aspirin-treated, experienced symptomatic thrombosis. When measured by VerifyNow resistance was 43% after aspirin suppositories and 14% after additional days of oral aspirin. There was no correlation with thrombosis. Upper quartile post-operative day (POD) #5 uTxB2 was correlated with thrombosis in aspirin treated subjects (p<0.01). High risk aspirin-treated subjects who experienced thrombosis had higher POD#5 uTxB2. This finding did not reach statistical significance (p=0.07). Elevated pre-operative C-reactive protein (CRP) was independently associated with thrombosis (p<0.02) in all subjects and in high risk subjects (p=0.01). Inflammatory markers were not affected by aspirin.. Aspirin inhibited ex-vivo platelet function with a low incidence of resistance. Elevated POD#5 uTxB2 and pre-operative CRP were correlated with thrombosis in aspirin treated subjects. Further studies are needed to determine whether children with high levels of uTxB2 despite aspirin therapy and/or those with elevated preoperative CRP are at increased risk for thrombosis.

Topics: Administration, Oral; Administration, Rectal; Aspirin; Biomarkers; C-Reactive Protein; Cardiac Surgical Procedures; Drug Resistance; Fibrinolytic Agents; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Inflammation Mediators; Logistic Models; New York; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prospective Studies; Risk Assessment; Risk Factors; Suppositories; Thrombosis; Thromboxane B2; Time Factors; Treatment Outcome; Up-Regulation

The protective role of folate in vascular disease has been related to antioxidant effects. In 45 patients with previous early-onset (at age <50 years) thrombotic episodes and the 677TT methylenetetrahydrofolate reductase genotype, we evaluated the effects of a 28 d-course (15 mg/d) of 5-methyltetrahydrofolate (MTHF) on homocysteine metabolism and on in vivo generation of 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), a reliable marker of oxidative stress. At baseline, patients' fasting total homocysteine (tHcy) was 11.5 micromol/l (geometric mean) and urinary excretion of 8-iso-PGF2alpha was 304 pg/mg creatinine, with the highest metabolite levels in the lowest quartile of plasma folate distribution (P < 0.05). After 5-MTHF supplementation, plasma folate levels increased approximately 13-fold (P < 0.0001 versus baseline); tHcy levels (6.7 micromol/l, P < 0.0001) and urinary 8-iso-PGF2alpha (254 pg/mg creatinine, P < 0.001) were both significantly lowered, their reduction being proportional to baseline values (r = 0.98 and r = 0.77, respectively) and maximal in patients with the lowest pre-supplementation folate levels (P < 0.05). The effects on folate (P < 0.0001) and tHcy (P = 0.0004) persisted for at least up to 2 months after withdrawing 5-MTHF. In parallel with long-lasting tHcy-lowering effects, a short-course 5-MTHF supplementation reduces in vivo formation of 8-iso-PGF2alpha in this population, supporting the antioxidant protective effects of folate in vascular disease.

Topics: Adult; Age of Onset; Case-Control Studies; Dietary Supplements; Dinoprost; Female; Homocysteine; Humans; Linear Models; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Oxidative Stress; Tetrahydrofolates; Thrombosis; Thromboxane B2

Diabetes mellitus (DM) is associated with enhanced lipid oxidation and persistent platelet activation. We investigated whether oxidant stress (OS) also affects circulating proteins and is associated with an abnormal coagulative pattern. In 72 type 2 DM (T2DM) patients, urinary 8-iso-prostaglandin (PG) F2alpha and 11-dehydro-thromboxane B2 (TXM) were measured as markers of lipid peroxidation and platelet activation, respectively. The carbonyl content of plasma proteins (PCARB) was measured as global index of protein oxidation. 8-Iso-PGF2alpha and PCARB levels were higher in DM patients than in controls (P < 0.05). Likewise, both TXM and prothrombin F1+2 levels were higher in diabetics (P < 0.05). By contrast, anticoagulant markers, such as activated protein C, protein C activation peptide, and soluble thrombomodulin (TM) were depressed in T2DM (P < 0.05). In conclusion, OS in T2DM involves circulating proteins and is associated with an unbalanced promotion of procoagulant reactions. These effects in concert with platelet activation may contribute to atherothrombotic complications in T2DM.

Topics: Aged; Aged, 80 and over; Biomarkers; Blood Proteins; Case-Control Studies; Diabetes Mellitus, Type 2; Dinoprost; F2-Isoprostanes; Female; Hemostasis; Humans; Lipid Peroxidation; Male; Middle Aged; Oxidation-Reduction; Oxidative Stress; Platelet Activation; Thrombosis; Thromboxane B2

Topics: Aspirin; Biomarkers; Cyclooxygenase Inhibitors; Drug Resistance; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Predictive Value of Tests; Risk; Thrombosis; Thromboxane B2; Thromboxanes

Recent studies have shown that patients with antiphospholipid antibodies (aPL) have increased lipid peroxidation. We evaluated the urinary excretion of 11-dehydro thromboxane B2 (11-DH-TXB(2) and isoprostane F(2alpha)III (IPF(2alpha)III), reflecting platelet activation and lipid peroxidation in vivo, and plasma soluble markers of endothelial cell, platelet and blood coagulation activation: soluble vascular cell adhesion molecule-1 (sVCAM-1), P- and E-selectin (sPsel and sEsel), F1 + 2 fragment of prothrombin (F1 + 2), thrombin-antithrombin complexes (TAT) and D-Dimer (DD). We studied 79 patients with aPL (47 with previous thrombosis), 45 healthy volunteers (normal controls, NC), 12 patients with systemic lupus erythematosus (SLE) without aPL and a thrombosis control group (TCG) without thrombophilia (n = 16). Urinary levels (mean, range) of eicosanoids and isoeicosanoids were significantly increased in 39 patients with aPL compared with 25 NC, 11-DH-TXB(2) 164.0 ng/mmol creatinine (9.5-1162.8) versus 43.4 ng/mmol creatinine (4.2-87.6), P < 0.001; IPF(2alpha)III 56.9 pg/mg creatinine (5.5-388.7) versus 27.0 pg/mg creatinine (4.6-87.6), P = 0.03. Both metabolites were significantly correlated (rho = 0.49, P = 0.014), but none correlated with any clinical manifestation or antibody profile. The aPL group presented increased levels of sPsel, sEsel, sVCAM-1, TAT, F1 + 2 and DD, but any soluble marker correlated with IPF2alphaIII. Urinary 11-DH-TXB(2) correlated with sPsel (rho = 0.39, P = 0.04). Compared with SLE controls, the SLE group with aPL had higher levels of F1 + 2. Plasma levels of F1 + 2 and DD were significantly increased and a trend to higher sPsel was found in aPL patients with thrombosis compared with the TCG. Platelet activation, lipid peroxidation and blood coagulation activation seem to be important in the pathophysiology of antiphospholipid syndrome.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Antithrombins; Biomarkers; Blood Coagulation; Case-Control Studies; Chi-Square Distribution; Child; Child, Preschool; E-Selectin; Endothelium, Vascular; Female; Fibrin Fibrinogen Degradation Products; Humans; Isoprostanes; Lipid Peroxidation; Lupus Erythematosus, Systemic; Male; Middle Aged; P-Selectin; Platelet Activation; Prothrombin; Statistics, Nonparametric; Thrombosis; Thromboxane B2; Vascular Cell Adhesion Molecule-1

The aim of this study was to assess thrombosis tendency in subjects who were habitual meat-eaters compared with those who were habitual vegetarians.. Cross-sectional comparison of habitual meat-eaters and habitual vegetarians.. Free living subjects.. One hundred and thirty-nine healthy male subjects (vegans n = 18, ovolacto vegetarians n = 43, moderate-meat-eaters n = 60 and high-meat-eaters n = 18) aged 20-55 y who were recruited in Melbourne.. Dietary intake was assessed using a semi-quantitative Food Frequency Questionnaire. The parameters of thrombosis were measured by standard methods.. Saturated fat and cholesterol intakes were significantly higher and polyunsaturated fat (PUFA) was significantly lower in the meat-eaters compared with vegetarians. In the meat-eaters, the platelet phospholipids AA levels were significantly higher than in the vegetarians, but there was no increase in ex vivo platelet aggregation and plasma 11-dehydro thromboxane B2 levels. Vegetarians, especially the vegans, had a significantly increased mean collagen and ADP stimulated ex vivo whole blood platelet aggregation compared with meat-eaters. The vegan group had a significantly higher mean platelet volume than the other three dietary groups. However, meat-eaters had a significantly higher cluster of cardiovascular risk factors compared with vegetarians, including increased body mass index, waist to hip ratio, plasma total cholesterol (TC), triacylglycerol and LDL-C levels, ratio of TC/HDL-C and LDL-C/HDL-C and plasma factor VII activity.. Consumption of meat is not associated with an increased platelet aggregation compared with vegetarian subjects.

Topics: Adult; Blood Coagulation Factors; Cross-Sectional Studies; Diet, Vegetarian; Fatty Acids; Feeding Behavior; Humans; Lipoproteins; Male; Meat; Middle Aged; Platelet Aggregation; Risk Factors; Thrombosis; Thromboxane B2

Because of the association of oral contraceptives (OC) and cigarette smoking with an increased thrombotic risk, we evaluated thromboxane (TX) and prostacyclin urinary (u) metabolites, as in vivo indices of platelet-vessel wall interactions, in women assigned to third generation OC. Twenty-eight women (15 smokers) underwent a 6-month trial of 30 microg ethinylestradiol plus 0.150 mg desogestrel. Cotinine plasma levels were elevated only in persons classified as smokers and serum TXB2 determination confirmed the absence of cyclooxygenase inhibition throughout the study. u-TXB2 and 11-dehydro-TXB2 were higher in smokers than in non-smokers. OC decreased u-11-dehydro-TXB2 both in smokers (from (pg/micromol creatinine) 35.1+/-6.9 to 15.8+/-2.8; P<0.025) and non-smokers (from 31.7+/-9.8 to 20.6+/-4.8, P = N.S.). u-6-keto-prostaglandin(PG)F1alpha excretion, also higher in smokers compared to non-smokers, was also reduced after OC in smokers (from (pg/micromol creatinine) 24.3+/-5.2 to 14.8+/-2.3; P<0.05). Smokers also had a trend to higher u-2,3-dinor-6-keto-PGF1alpha, marginally reduced by OC. Thus, the OC regimen used here improves - if anything - platelet vessel wall interactions as assessed by prostanoid production in vivo. The prothrombotic tendency associated with the use of OC in smokers does not appear to be mediated by changes in platelet-vessel wall interactions.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Blood Platelets; Blood Vessels; Contraceptives, Oral; Female; Humans; Risk Factors; Smoking; Thrombosis; Thromboxane B2

We describe variations of 11-dehydrothromboxane B2(11-dehydro-TXB2) levels in human urine samples. Retinal vein occlusion (RVO) is a thrombotic disease in which the retinal vein is blocked by blood aggregations. We considered the possibility that 11-dehydro-TXB2 plays an important role in the formation of RVO. Thus, we determined the 11-dehydro-TXB2 levels in patients with RVO using gas chromatography/selected ion monitoring (GC/SIM) and compared them with those of healthy volunteers. The thromboxane levels in patients with RVO, who did not also have diabetes, were significantly higher than those in healthy volunteers. One cause of RVO may be the variation of thromboxane production. Furthermore, this GC/SIM method can be applied to the prevention and treatment of not only RVO, but also of general thrombosis.

Topics: Adult; Aged; Chromatography, Gas; Female; Humans; Male; Middle Aged; Retinal Vein Occlusion; Thrombosis; Thromboxane B2

Prostacyclin (PGI2) and thromboxane A2 (TXA2) play an important role in the pathophysiology of various cardiovascular diseases. The balance between PGI2 and TXA2 regulates the interaction between platelets and the vessel wall in vivo. In this study we measured PGI2 and TXA2 synthesis by analysing their urinary index metabolites 2,3-dinor-6-keto-PGF1 alpha and 11-dehydro-TXB2, respectively, in acute (10 patients) and chronic (10 patients) lower limb ischaemia. Both PGI2 and TXA2 synthesis were increased about two-fold in patients with acute lower limb ischaemia compared to chronic lower limb ischaemia. However, the PGI2/TXA2 ratio was more or less the same in acute and chronic lower limb ischaemia. In patients with acute lower limb ischaemia caused by thrombotic occlusion, PGI2 and TXA2 formation were about two times higher than in patients with acute lower limb ischaemia caused by embolic occlusion. Elevation of PGI2 and TXA2 synthesis in acute lower limb ischaemia may reflect increased platelet-vascular wall interactions without changing the PGI2/TXA2 ratio.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Aged, 80 and over; Chronic Disease; Creatinine; Epoprostenol; Extremities; Female; Humans; Ischemia; Male; Middle Aged; Thrombosis; Thromboxane A2; Thromboxane B2