11-Dehydro-Thromboxane B2, Urine
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Antiplatelet medications are frequently utilized in the prevention of stroke, myocardial infarction, and vascular thrombotic diseases due to the fundamental role of platelet aggregation in a variety of atherothrombotic processes. Modulation of the prostaglandin thromboxane A2 (TxA2) pathway is 1 of the pivotal routes of activation involved in stimulating platelet aggregation. Synthesis of TxA2 is mediated in platelets by the cyclooxygenase 1 (COX-1) enzyme, which must be functional for stimulating the production of TxA2 from arachidonic acid.
The importance of TxA2 is demonstrated by the reduction in risk of myocardial infarction (MI) or death in patients with acute coronary syndrome (ACS) following administration of aspirin, which irreversibly inhibits platelet COX-1 and inhibits the production of TxA2. TxA2 has an extremely short half-life, converting to 2 stable, inactive metabolites: 11-dehydro-thromboxane B2 (TxB2) and 2, 3-dinor-11-dehydrothromboxane B2. Excretion of TxB2 in the urine has been shown to reflect in vivo platelet activation. Elevated concentrations of TxB2 have been noted in up to 85% of patients with acute ischemic stroke and demonstrate further diagnostic and prognostic utility in patients with ACS.
Aspirin therapy has been reported to reduce cardiovascular events in men and women by up to 40%. However, use of aspirin is not without risk and is associated with higher frequencies of gastrointestinal bleeding and hemorrhagic stroke. Identification of patients most likely to benefit from antiplatelet therapy with aspirin or other pharmaceutical agents has great clinical utility.
Quantitation of urinary TxB2 offers an advantage over platelet-activation markers measured in plasma or blood because measurements are not subject to interference from in vitro platelet activation, which commonly occurs as a result of preanalytical variables such as local vein trauma or insufficient anticoagulation during phlebotomy. Measurement of urine TxB2 may be performed in patients to assess the effectiveness of specific inhibition in the TxA2 pathway, along with identification of a patientâ€™s ability to benefit from antiplatelet therapy, and their associated risk for developing future cardiovascular events.
Assessing if a patient will derive benefit from aspirin therapy
Determining an individualâ€™s risk of coronary heart disease and stroke
Identifying the effectiveness of antiplatelet therapies
The normal reference range was derived from an in-house normal donor study with individuals who were self-reported as not taking any aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), or other lipid-lowering therapies. Elevated concentrations of urine thromboxane B2 (TxB2) may indicate an increase in platelet activation and thrombosis resulting from atherosclerotic deposits or other vascular obstructions and may identify those individuals who may be at increased risk for an ischemic cardiovascular event. Elevations of TxB2 in patients already receiving antiplatelet therapies suggest a failure in the suppression of laboratory-assessed platelet function, a continued hypercoagulable state, and alternative antithrombotic or antiplatelet therapies may be considered.The liquid chromatography-tandem mass spectrometry method is specific for TxB2 and is not subject to interference from the other metabolite of thromboxane A2, the 2,3-dinor-TxB2 component.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
A variety of tests are available to assess platelet function and interpretation of results from 1 platform to another is confounded by the lack of standardization, because the tests quantitate different aspects of platelet function and use different cutoffs for determining appropriate response to the various antithrombotic therapies. Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit inflammation via the cyclooxygenase 1 pathway, will lower thromboxane B2 concentrations and prevent an accurate baseline assessment of platelet reactivity and response. Patients should not take NSAIDs within 72 hours or aspirin within 2 weeks prior to providing a urine specimen for analysis.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
> or =18 years: 0-2,211 pg/mg creatinine
Reference values have not been established for patients who are <18 years of age.
Reference intervals apply to patients not taking agents known to influence platelet function (aspirin or other nonsteroidal anti-inflammatory drugs, thienopyridines, etc). Healthy individuals taking aspirin typically have 11-dehydro-thromboxane B2 concentrations below 500 pg/mg creatinine using this method.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Patrono C, Garcia Rodriguez LA, Landolfi R, Baigent C: Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med 2005;353:2373-2383
2. Gluckman TJ, McLean RC, Schulman SP, et al: Effects of aspirin responsiveness and platelet reactivity on early vein graft thrombosis after coronary artery bypass graft surgery. J Am Coll Cardiol 2011; 57:1069-1077
3. Pignone M, Williams CD: Aspirin for primary prevention of cardiovascular disease in diabetes mellitus. Nature 2010;6:619-628
4. Eikelboom JW, Hankey GJ, Thom J, et al: Incomplete inhibition of thromboxane biosynthesis by acetylsalicylic acid: determinants and effect on cardiovascular risk. Circulation 2008;118:1705-1712
5. Armstrong PC, Truss NJ, Ali FY, et al: Aspirin and the in vitro linear relationship between thromboxane A2-mediated platelet aggregation and platelet production of thromboxane A2. J Thromb Haemost 2008;6:1933-1943