scholarly journals Response to clopidogrel therapy in patients after PCI changes over time as evidenced by different platelet function tests

2016 ◽  
Author(s):  
Jacek Golański ◽  
Kamila Syska ◽  
Krzysztof Chiżynski ◽  
Hassan Kassasir ◽  
Cezary Watała ◽  
...  
Keyword(s):  
Platelet Function ◽  
Platelet Function Tests ◽  
Function Tests ◽  
Clopidogrel Therapy ◽  
Changes Over Time ◽  
Over Time

Comparison of current platelet functional tests for the assessment of aspirin and clopidogrel response

2016 ◽  
Vol 116 (10) ◽  
pp. 638-650 ◽  
Author(s):  
Jean-Claude Bordet ◽  
Claude Negrier ◽  
Yesim Dargaud ◽  
Sandra Le Quellec
Keyword(s):  
Platelet Function ◽  
Light Transmission ◽  
Platelet Response ◽  
Platelet Function Tests ◽  
Clopidogrel Resistance ◽  
Function Tests ◽  
Function Analyzer ◽  
Clopidogrel Therapy ◽  
Whole Blood Aggregometry ◽  
Platelet Function Analyzer

SummaryThe two most widely used antiplatelet drugs in the world are aspirin and clopidogrel. However, some patients on aspirin and/or clopidogrel therapy do not respond appropriately to either aspirin or clopidogrel. This phenomenon is usually called “aspirin/clopidogrel resistance”. Several platelet function tests have been used in various studies for the assessment of aspirin and clopidogrel resistance in healthy individuals and patients admitted in cardiology departments. An accurate assessment of platelet response to aspirin/clopidogrel could benefit patients by proposing tailored-antiplatelet therapy based on test results. However, there is a clear lack of standardisation of such techniques and their analytical variability may induce misinterpretation. After a quick report of the mechanisms responsible for aspirin/clopidogrel resistance, we describe the pre-analytical aspects and the analytical performances of current platelet function tests (Light-transmission aggregometry, whole-blood aggregometry, VerifyNow®, Platelet Function Analyzer®, thromboelastography, VASP assay) that are used for the assessment of aspirin/clopidogrel resistance in clinical studies. Considering the different variables that have to be taken into account with each of the platelet function tests, a particular attention should be paid when interpreting results.

Platelet Function in ITP, Independent of Platelet Count, Is Consistent Over Time and Is Associated with Both Current and Subsequent Bleeding Severity

2018 ◽  
Vol 118 (01) ◽  
pp. 143-151 ◽  
Author(s):  
A. Frelinger ◽  
R. Grace ◽  
A. Gerrits ◽  
S. Carmichael ◽  
E. Forde ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Function ◽  
Bleeding Tendency ◽  
Platelet Function Tests ◽  
Platelet Surface ◽  
Function Tests ◽  
Immature Platelet Fraction ◽  
Bleeding Score ◽  
Over Time ◽  
Bleeding Severity

Background Treatment decisions for patients with immune thrombocytopenia (ITP) are difficult because patients with similarly low platelet counts differ in their bleeding tendency. We recently reported that platelet function tests, independent of platelet count, are associated with concurrent bleeding severity, suggesting that these tests may be useful indicators of future bleeding in ITP. Objectives To test this hypothesis, we evaluated the consistency of these platelet function tests over time and their association with subsequent bleeding severity. Methods Bleeding score and platelet biomarkers were evaluated in a cross-sectional study of children with ITP at two visits separated by a median of 10 months. Results and Conclusions Correlations between Visit 1 and Visit 2 results for immature platelet fraction, circulating and agonist-stimulated platelet surface P-selectin, and activated GPIIb–IIIa and GPIbα indicated consistency of the platelet phenotype over time. Consistent with our previous findings, platelet biomarkers at each visit were significantly associated with the concurrent bleeding score. Furthermore, increased P-selectin on circulating platelets and reduced agonist-stimulated P-selectin and activated GPIIb–IIIa-positive platelets at Visit 1 were significantly associated with bleeding scores at Visit 2 and remained significantly associated with bleeding severity after adjustment for platelet count. These results suggest a mechanistic link between desensitization of agonist receptors and increased bleeding severity. In summary, platelet function in ITP, independent of platelet count, is consistent over time and is associated with both concurrent and subsequent bleeding severity. These findings support further evaluation of platelet function testing to help guide patient management in ITP.

scholarly journals The Platelet Phenotype of Children with ITP Is Consistent over Time and Is Associated with Both Concurrent and Subsequent Bleeding Severity

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2550-2550
Author(s):  
Andrew L. Frelinger ◽  
Rachael F Grace ◽  
Anja J. Gerrits ◽  
Sabrina L Carmichael ◽  
Emma E Forde ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Function ◽  
Research Funding ◽  
Platelet Function Tests ◽  
Platelet Surface ◽  
Function Tests ◽  
Grade 3 ◽  
Bleeding Score ◽  
Over Time ◽  
Bleeding Severity

Abstract Background. Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder that results in thrombocytopenia and the risk of bleeding. Severe bleeding, while uncommon, is partially associated with the degree of thrombocytopenia. However it remains unclear why some thrombocytopenic patients with ITP have significant bleeding while others have minimal or no bleeding manifestations. We hypothesized that differences in platelet function between ITP patients contribute to the variation in bleeding tendency and these differences can be used to identify children at the highest risk for bleeding. We recently reported (Frelinger et al. Blood 2015;126:873-879) that platelet tests related to platelet age (immature platelet fraction [IPF], forward light scatter [FSC]) and activation through the PAR1 thrombin receptor (TRAP-stimulated P-selectin, activated GPIIb-IIIa, and GPIba) are associated with concurrent bleeding severity in ITP, independent of the platelet count. Aims. 1) Determine the association of platelet function tests with subsequent bleeding severity. 2) Determine the consistency of the platelet function phenotype over time. Methods. At two study visits separated by at least 1 month, bleeding severity (graded by the Buchanan and Adix Score) and platelet function tests were evaluated in a single center cross-sectional study of patients ≥6 months of age with a diagnosis of ITP or Evans syndrome. Platelet function was assessed by whole blood flow cytometric analysis of platelet surface P-selectin, activated GPIIb-IIIa (measured by monoclonal antibody PAC1), and GPIbα with and without in vitro agonist (ADP or thrombin receptor activating peptide [TRAP]) stimulation. Complete blood cell counts, including IPF, were obtained in a Sysmex XN-1000. Results. Fifteen patients (9.5 ± 5.2 [mean ± SD] years of age, 4 male) were evaluated with a median interval between visits of 10.1 months (interquartile range 2.3 - 23.9 months). Bleeding severity was lower at Visit 2 compared to Visit 1 (Visit 1: Grade 0, n=4, Grade 1, n=4, Grade 2, n=6, Grade 3, n=1 vs. Visit 2: Grade 0, n=7, Grade 1, n=6, Grade 2, n=1, Grade 3, n=1, p = 0.0107). At Visit 2 mean platelet count was higher and IPF was lower than at Visit 1 (111 vs. 69 x 109 platelets/L, p = 0.06 and 10.7 vs. 14.3% IPF, p = 0.04). Nevertheless, platelet count and IPF at Visit 1 were both strongly correlated with platelet count and IPF, respectively, at Visit 2. At each visit, % P-selectin-positive platelets with 20 µM ADP, % PAC1-positive with 20 µM ADP, and GPIba mean fluorescence with 1.5 and 20 µM TRAP, were associated by univariate analysis with the concurrent bleeding score (Figure). Platelet function in patients with ITP was consistent over time as demonstrated by: a) significant correlations between platelet count, IPF, and circulating or agonist-stimulated platelet surface P-selectin, activated GPIIb-IIIa, and GPIba at Visit 1 vs. Visit 2; b) significant associations between platelet markers at each visit with bleeding scores at each visit; and c) a significant association of platelet markers at Visit 1 with bleeding scores at Visit 2 (Figure). Conclusions. Platelet function tests identify a platelet phenotype in children with ITP that is consistent over time and is associated with bleeding severity at both concurrent and subsequent visits. These results suggest the platelet phenotype contributes to the bleeding risk in children with ITP and supports further evaluation of platelet function testing to help guide patient management. Figure Univariate association of platelet tests with bleeding score at concurrent and subsequent visits. Tests significantly associated with bleeding score in all comparisons are highlighted. Figure. Univariate association of platelet tests with bleeding score at concurrent and subsequent visits. Tests significantly associated with bleeding score in all comparisons are highlighted. Disclosures Frelinger: Sysmex: Research Funding. Grace:Agios Pharmaceuticals: Other: Scientific Advisor, Research Funding. Michelson:Sysmex: Research Funding.

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

VASA ◽  
2011 ◽  
Vol 40 (6) ◽  
pp. 429-438 ◽  
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.

LACK OF CORRELATION BETWEEN INTRAPLATELET cAMP INCREASE AND SYSTEMIC CIRCULATORY EFFECTS

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.

Standardization of platelet function tests

1981 ◽  
Vol 11 (2) ◽  
pp. 183-203 ◽  
Author(s):  
Pamela R. Roper-Drewinko ◽  
Benjamin Drewinko ◽  
Gail Corrigan ◽  
Dennis Johnston ◽  
Kenneth B. McCredie ◽  
...  
Keyword(s):  
Platelet Function ◽  
Platelet Function Tests ◽  
Function Tests

Platelet function tests during major operation for gastro-intestinal carcinoma

1977 ◽  
Vol 64 (2) ◽  
pp. 147-149 ◽  
Author(s):  
J. A. Kokores ◽  
T. C. Economopoulos ◽  
C. Alexopoulos ◽  
J. Pyrovolakis ◽  
A. G. Papayannis
Keyword(s):  
Platelet Function ◽  
Platelet Function Tests ◽  
Function Tests ◽  
Major Operation

Point-of-Care Platelet Function Tests

2014 ◽  
pp. 45-63
Author(s):  
Gabriele Casso ◽  
Fabio Lanzi ◽  
Carlo E. Marcucci
Keyword(s):  
Platelet Function ◽  
Point Of Care ◽  
Platelet Function Tests ◽  
Function Tests
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