Identification of functional polymorphisms of the thromboxane A2 receptor gene in healthy volunteers

SummaryThromboxane A2 receptor (TP) is an important actor in vascular physiology and plays a crucial role in the platelet activation process. Genetic polymorphisms of the gene coding for the TP have been described, but their impacts on platelet function tests are unknown. The aim of this study was to investigate the relationship between genetic polymorphisms of the coding sequence of the TP gene and platelet function tests. We investigated 100 healthy volunteers twice, one week apart by performing platelet aggregation and secretion tests. We sequenced the coding region of the TP gene and confronted the genetic variants with the phenotypic results. We identified five single nucleotide polymorphisms (SNP); one of them, T1712C, replaces Leu by Pro at position 133 of the isoform β of the TP. Homozygosity for the minor allele of the C795T, C924T or the G1686A SNP was associated with a decreased expression of CD62P when platelets were stimulated with the TP agonist U46619. As C795T and C924T have been linked to clinical disorders in which TxA2 plays a key role, the possible role of the G1686A and T1712C SNP should also be examined in selected diseases.

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Faculty Opinions recommendation of Precision and reliability of 5 platelet function tests in healthy volunteers and donors on daily antiplatelet agent therapy.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.720923959.793501646 ◽

2014 ◽

Author(s):

Davide Cattano

Keyword(s):

Healthy Volunteers ◽

Platelet Function ◽

Antiplatelet Agent ◽

Platelet Function Tests ◽

Function Tests

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Aspirin - resistance? A few critical considerations on definition, terminology, diagnosis, clinical value, natural course of atherosclerotic disease, and therapeutic consequences

VASA ◽

10.1024/0301-1526/a000145 ◽

2011 ◽

Vol 40 (6) ◽

pp. 429-438 ◽

Cited By ~ 8

Author(s):

Berent ◽

Sinzinger

Keyword(s):

Platelet Function ◽

Point Of Care ◽

Aspirin Resistance ◽

Point Of View ◽

Evidence Based ◽

Platelet Function Tests ◽

Clinical Value ◽

Vascular Events ◽

Therapeutic Consequences ◽

Function Tests

Based upon various platelet function tests and the fact that patients experience vascular events despite taking acetylsalicylic acid (ASA or aspirin), it has been suggested that patients may become resistant to the action of this pharmacological compound. However, the term aspirin resistance was created almost two decades ago but is still not defined. Platelet function tests are not standardized, providing conflicting information and cut-off values are arbitrarily set. Intertest comparison reveals low agreement. Even point of care tests have been introduced before appropriate validation. Inflammation may activate platelets, co-medication(s) may interfere significantly with aspirin action on platelets. Platelet function and Cox-inhibition are only some of the effects of aspirin on haemostatic regulation. One single test is not reliable to identify an altered response. Therefore, it may be more appropriate to speak about treatment failure to aspirin therapy than using the term aspirin resistance. There is no evidence based justification from either the laboratory or the clinical point of view for platelet function testing in patients taking aspirin as well as from an economic standpoint. Until evidence based data from controlled studies will be available the term aspirin resistance should not be further used. A more robust monitoring of factors resulting in cardiovascular events such as inflammation is recommended.

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Faculty Opinions recommendation of Assessment of platelet function in healthy cats in response to commonly prescribed antiplatelet drugs using three point-of-care platelet function tests.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726356134.793518643 ◽

2016 ◽

Author(s):

Davide Cattano

Keyword(s):

Platelet Function ◽

Point Of Care ◽

Antiplatelet Drugs ◽

Platelet Function Tests ◽

Function Tests

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LACK OF CORRELATION BETWEEN INTRAPLATELET cAMP INCREASE AND SYSTEMIC CIRCULATORY EFFECTS

10.1055/s-0038-1644532 ◽

1987 ◽

Author(s):

W Haarmann ◽

H Weisenberger

Keyword(s):

Platelet Function ◽

Circulatory System ◽

Human Platelets ◽

Platelet Function Tests ◽

Inotropic Effects ◽

Circulatory Effects ◽

Function Tests ◽

Drug Concentrations ◽

Camp Metabolism ◽

The Difference

Compounds inhibiting platelet function by acting on platelet cAMP metabolism usually also have effects on the circulatory system, i.e. they decrease systemic blood pressure (bp) and are positive inotropic. For several compounds selected because of their distinct platelet inhibitory effects, the influence on these parameters in animals and on the cAMP metabolism in human platelets was determined.Inotropic effects and bp were measured via an indwelling catheter in anestetised cats after i.v. application of the test compounds. The inhibition of platelet PDEs was measured in freeze-thaw homogenates of human platelets using 3H-cAMP as substrate. Intraplatelet cAMP changes were measured by prelabelling the ATP pool with 3H-adenine and isolation of 3H-cAMP. Linear regression analysis of the drug concentrations causing a doubling of intraplatelet cAMP levis and the % difference in bp or the % difference in dp/dt, resp., by i.v. application of 0.3 mg/kg test compound yielded the following results:cAMP vs % diff. bp : r=0.02, N=18cAMP vs % diff. dp/dt: r = 0.02 , N = 15In contrast to a good correlation between intraplatelet cAMP levels and inhibition of platelet function tests, no obvious relationship was seen between cAMP and decrease in bp and positive initropic effects. It is not known whether the lack of correlation could be due to a different drug access to platelets and the bp regulatory system.A biochemical parameter, i.e. intraplatelet cAMP increase by inhibition of PDEs correlates reasonably well with the inhibition of platelet function tests. This parameter is not useful, however, to predict the effects on the heart and the circulatory system.

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