In vivo thromboxane-dependent platelet activation is persistently enhanced in subjects with impaired glucose tolerance.

Background: Impaired glucose tolerance (IGT) is associated with increased cardiovascular morbidity and mortality. Enhanced thromboxane (TX)-dependent platelet activation plays a pivotal role in atherothrombosis and characterizes type 2 diabetes mellitus (DM). Whether this also pertains to IGT is currently unknown.

Patient-independent variables affecting the assessment of aspirin responsiveness by serum thromboxane measurement.

The serum TXB (sTXB) assay reflects the pharmacodynamics of platelet inhibition by low-dose aspirin. However, different studies reported variable sTXB values. sTXB assay requires whole blood incubation at 37 °C as a condition for optimal thrombin generation, arachidonic acid release and its metabolism by platelet cyclooxygenase-1 to form TXA.

In Vivo Platelet Activation and Aspirin Responsiveness in Type 1 Diabetes.

Platelet activation is persistently enhanced, and its inhibition by low-dose aspirin is impaired in type 2 diabetes mellitus. We investigated in vivo thromboxane (TX) and prostacyclin (PGI2) biosynthesis and their determinants, as well as aspirin responsiveness, in young adult subjects with type 1 diabetes mellitus (T1DM) without overt cardiovascular disease and stable glycemic control. The biosynthesis of TXA2 was persistently increased in subjects with T1DM versus matched healthy subjects, with females showing higher urinary TX metabolite (TXM) excretion than male subjects with T1DM.

Stability of urinary thromboxane A2 metabolites and adaptation of the extraction method to small urine volume.

Background: Thromboxane (TX) A2 is a pro-thrombotic prostanoid synthesized by activated platelets, biotransformed into 11-dehydro-TXB2, measurable in urines. Eleven-dehydro-TXB2 excretion is increased in high risk cardiovascular diseases; however, this cardiovascular biomarker awaits validation in large trials. The need of large urine volume (8 - 10 mL) and the unknown stability of 11-dehydro-TXB2 in urine after collection might limit its implementation.

Identifying determinants of variability to tailor aspirin therapy.

Once-daily, low-dose aspirin is a cornerstone in the prophylaxis and treatment of cardiovascular diseases. Aspirin 'resistance' still lacks definition, a standardized reference assay, underlying mechanisms, clinical impact or efficacy of alternative antiplatelet drugs. Aspirin response in several studies has been measured by different platelet function tests, not always reflecting aspirin pharmacodynamics, thus generating significantly heterogeneous results.

Aspirin-insensitive thromboxane biosynthesis in essential thrombocythemia is explained by accelerated renewal of the drug target.

Essential thrombocythemia (ET) is characterized by enhanced platelet generation and thrombotic complications. Once-daily low-dose aspirin incompletely inhibits platelet thromboxane A(2) (TXA(2)) in the majority of ET patients. In the present study, we investigated the determinants of aspirin-insensitive platelet TXA(2) biosynthesis and whether it could be further suppressed by changing the aspirin dose, formulation, or dosing interval.