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The thromboxane A2 pathway plays a major role in governing the reactions involved in both the inflammatory and hemostatic biological mechanisms. Cyclooxygenases 1 & 2 act to convert arachidonic acid to thromboxane A2. Scientific studies report cyclooxygenase-2 is up-regulated in many different chronic disease states as well as in chronic inflammation. This explains one major causes of residual thromboxane risk, “aspirin resistance.” Levels of urinary 11-dehydrothromboxane B2 reflect activity of components of the thromboxane A2 pathway that result n thromboxane A2 generation. The assay is normalized to the patient’s urine creatinine concentration and is non-invasive and normalized utilizing standard controls.

Cyclooxgenase-1 mediated platelet reactivity in young male smokers

"Collagen-induced platelet aggregation and plasma/urinary thromboxane B2 (TXB2) and 11-dehydroxythromboxane B2 levels were higher in cigarette smokers compared to nonsmokers."

"The levels of plasma/urinary TXB2 were significantly increased an hour after cigarette smoking."

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Cardiovascular biomarkers in groups of established smokers after a decade of smoking

"Significant statistical differences between smokers with approximately 10 years of smoking history and non-smokers in white cell count, hemoglobin and thromboxane turnover were seen, although they did not reach levels associated with overt diseases."

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Effects of smoking cessation and nicotine substitution on systemic eicosanoid production in man

"This study investigated the effects of smoking cessation with and without nicotine substitution on the excretion of major urinary metabolites of thromboxane A2 and prostacyclin; 11-dehydrothromboxane B2 and 2, 3-dinor-6ketoprostaglandin F1 alpha, respectively, as well as on the excretion of leukotriene E4 in man."

"The fact that eicosanoid production remains at pre-cessation levels in volunteers who quit smoking but use nicotine substitution may be involved in the risk of cardiovascular complications reported during nicotine replacement therapy."

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Cigarette smoking is associated with increased circulating proinflammatory and procoagulant markers in patients with chronic coronary artery disease; effects of aspirin treatment

"Smoking is associated with endothelial dysfunction.  Cytokines released by injured endothelium promote vascular interactions with leukocytes and platelets.  We investigated whether (a) cigarette smoking is linked to increased cytokine production, which may mediate platelet activation and thrombin generation in chronic coronary artery disease (CAD), and (b) aspirin treatment inhibits smoking-related changes on cytokines, platelets, and thrombin."

"After aspirin treatment, M-CSF, CRP, 11-dehydro-TXB2, and prothrombin fragments 1 + 2 remained higher in smokers compared with non smokers despite a significant reduction of these markers by aspirin."

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Synthetic analogues of flavonoids with improved activity against platelet activation and aggregation as novel prototypes of food supplements

"We investigated the ability of quercetin and apigenin to modulate platelet activation and aggregation, and compared the observed efficacy with that displayed by their synthetic analogues (2-phenyl-4Hpyrido, etc.) Platelet aggregation was explored through a spectorphotometric assay on platelet-rich-plasma treated with the thromboxane A2 mimetic, collagen and thrombin in presence/absence of various bioisosteres of flavanoids."

"The inhibitory effect of these compounds might rely on TXA2 antagonism."

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Citrus flavanoids and human cancers

"Nowadays cancers pose a great threat to the health of human beings.  Based on studies on the flavonoids and other bioactive compounds of citrus fruits in current literature, it was widely suggested that the consumption of citrus fruits is beneficial to the prevention and treatment of human chronic diseases including cancers. In the past decades, the study concerning citrus flavonoids has covered various areas including the type, content and distribution of flavonoids in fruits; their variation between wild and cultivated genotypes; their antioxidant, anti-inflammation, anti-aging, antimicrobial and anticarcinogenic activities."

"Nuclear factor kappa B (NF-κB) transcription factors regulate several important physiologic processes of the cell, e.g., cell growth, and apoptosis. Thus, inhibition of NF-κB activation offers a potential strategy for treatment of different malignancies."

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Reduction of thromboxane A2 synthesis in pregnancy by polyunsaturated fatty acid supplements

"High-dose supplements of fish oil reduce thromboxane synthesis in nonpregnant human subjects and were therefore proposed as a means of preventing various small-vessel disorders, including preeclampsia.  The effect of fish oil on thromboxane metabolism in pregnancy was investigated in our study."

"A decrease ranging from 32% to 71%, in 24-hour urinary 11-dehydro-thromboxane B2 excretion (mean reduction from 1606 pg/mg creatinine to 779 pg/mg creatinine, p < 0.001) was found among the 11 fish oil-treated women. No change in excretion was found among the control women. No maternal, fetal, or neonatal bleeding disturbances occurred, and no laboratory changes in coagulation markers were observed.”

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Dietary fish oil alters the lysophospholipid metabolomic profile and decreases urinary 11-dehydro-thromboxane B2 concentration in healthy Beagles

"After dietary treatment with different amounts of fish oil, age (increases 11-dehydro TXB2) was followed by EPA concentration as a significant negative predictor of urine 11-dehydro TXB2 concentration (increasing serum concentrations of EPA decrease 11-dehydro TXB2), and then lean-body mass (decreases 11-dehydro TXB2)."

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Mediterranean diet reduces thromboxane A2 production in atrial fibrillation patients

"Platelet activation plays a major role in cardiovascular events.  Mediterranean diet reduces the incidence of stroke and myocardial infarction but it is still unclear if it affects platelet activation.  Aim of the study was to evaluate the effect of Mediterranean diet on the urinary excretion of 11-dehydro-thromboxane (TX) B2, a marker in vivo platelet activation, in patients with atrial fibillation."

"Med diet adherence is inversely associated to urinary excretion of 11-dehydro-TXB2, suggesting that Med-Diet may favorably affect platelet function in AF patients."

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Casual chocolate consumption and inhibition of platelet function

"Observational studies have associated reduced cardiovascular mortality with chocolate consumption.  Feeding studies of high-dose, flavanol-rich chocolate show antiplatelet effects, but the effect of casual chocolate consumption on platelet function is unknown."

"Despite having similar baseline characteristics, chocolate consumers had longer PFA closure times (130 vs 123 seconds, P=05) and decreased Tx-M levels (175 vs 290 ng/molcreatinine, P=.03). Chocolate remained a significant independent predictor of both ex-vivo and in vivo platelet function testing after adjusting for confounders."

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