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.

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.

Association Of Platelet Function Markers, Independent Of Platelet Count, With Bleeding Score In Patients With Immune Thrombocytopenia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3534-3534
Author(s):  
Andrew L. Frelinger ◽  
Anja J Gerrits ◽  
Michelle A. Berny-Lang ◽  
Travis Brown ◽  
Sabrina L. Carmichael ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Activation ◽  
Platelet Function ◽  
Research Funding ◽  
Immune Thrombocytopenia ◽  
Univariate Analysis ◽  
Blood Draw ◽  
Platelet Surface ◽  
Platelet Counts ◽  
Bleeding Score

Abstract Background Immune thrombocytopenia (ITP) patients with similarly low platelet counts differ in their tendency to bleed. Aim To determine if differences in platelet function in ITP patients with similarly low platelet counts partly account for the variation in bleeding tendency. Methods The relationship between bleeding scores and platelet function markers was investigated in a single center cross-sectional study of pediatric patients with ITP. Following informed consent, blood was collected from ITP patients and bleeding was graded using the Buchanan and Adix Score (J Pediatr 2002) at routine clinic visits or while admitted to the hospital. Bleeding scores were obtained by one of three hematologists blinded to platelet function results, and investigators performing platelet function tests were blinded to clinical results. Platelet function was assessed by whole blood flow cytometric measurement of unstimulated, ADP- or TRAP-stimulated platelet surface activated GPIIb-IIIa (as measured by PAC1 binding), P-selectin, and GPIb and by unstimulated, convulxin-, or ADP plus TRAP-stimulated platelet surface phosphatidylserine expression (as determined by annexin V binding). Platelet count, immature platelet fraction (IPF) and mean platelet volume (MPV) were determined by a Sysmex XE-2100, and platelet forward angle light scatter (FSC) was measured by flow cytometry. Results Platelet function and bleeding scores were evaluated in 34 consecutive consenting pediatric ITP patients (16 female, 18 male, age 9.7 ± 5.7 years [mean ± SD]). ITP was newly diagnosed (< 3 months) in 10 patients, persistent (3 -- 12 months) in 7 patients, and chronic (>12 months) in 17 patients. Platelet count at the time of the blood draw was 47 ± 55 x 109/L. The median bleeding score on day of blood draw was 1 (range 0 to 4). By univariate analysis, higher IPF, and lower platelet count were significantly associated with a higher bleeding score (odds ratio [OR] >1, p<0.05) but MPV was not. Multiple measures of platelet function were associated with bleeding scores by univariate analysis: higher levels of platelet FSC (a measure affected by multiple variables including size) surface GPIb on unstimulated, ADP- or TRAP-stimulated platelets, surface P-selectin on unstimulated platelets, and platelet FSC were associated with increased odds for higher bleeding scores (ORs each >1, p<0.05), while higher ADP- and TRAP-stimulated platelet surface activated GPIIb-IIIa and P-selectin were associated with reduced odds of higher bleeding scores (ORs each <1, p<0.05). After adjustment for platelet count, higher levels of platelet surface P-selectin on unstimulated platelets, GPIb on TRAP-stimulated platelets, and FSC remained significantly associated with increased odds for higher bleeding scores (Figure), but IPF did not. Similarly, after adjustment for platelet count, higher TRAP-stimulated percentage of P-selectin and activated GPIIb-IIIa positive platelets remained significantly associated with reduced odds of higher bleeding scores (Figure). These findings were independent of recent ITP-related treatment. Conclusions In this study of pediatric ITP patients, we identified selected platelet function markers which, independent of platelet count, are associated with increased (platelet FSC, platelet surface P-selectin on unstimulated platelets, and GPIb on TRAP-stimulated platelets) or decreased (TRAP-stimulated percent P-selectin and GPIIb-IIIa positive platelets) odds of high bleeding scores. Possible hypotheses to explain these associations are as follows: 1) Increased P-selectin on unstimulated platelets demonstrates in vivo platelet activation, possibly as a consequence of the recent bleeding. 2) Because platelet activation results in a reduction in platelet surface GPIb and increases in platelet surface activated GPIIb-IIIa and P-selectin, the ORs associated with all of these markers could be explained by reduced ability of platelets in patients with higher bleeding scores to respond to agonists. 3) While platelet FSC is partly related to size, the finding that MPV and IPF, adjusted for platelet count, were not associated with bleeding score suggests that factors other than size account for the association of platelet FSC with higher bleeding scores. Further study is required to validate these findings and determine if differences in platelet function are associated with future risk for bleeding. Disclosures: Off Label Use: Eltrombopag was given to WAS/XLT patients for treatment of thrombocytopenia. Neufeld:Shire: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Apopharma: Consultancy. Michelson:Sysmex: Honoraria.

scholarly journals Platelet function tests, independent of platelet count, are associated with bleeding severity in ITP

Blood ◽  
2015 ◽  
Vol 126 (7) ◽  
pp. 873-879 ◽  
Author(s):  
Andrew L. Frelinger ◽  
Rachael F. Grace ◽  
Anja J. Gerrits ◽  
Michelle A. Berny-Lang ◽  
Travis Brown ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Function ◽  
Treatment Decisions ◽  
Platelet Function Tests ◽  
Platelet Counts ◽  
Function Tests ◽  
Key Points ◽  
Bleeding Severity

Key Points ITP patients differ in their tendency to bleed despite similarly low platelet counts, thereby confounding treatment decisions. Platelet function tests, independent of platelet count, are associated with bleeding severity in ITP patients.

The Behaviour of Various Platelet Function Tests During Long-Term Prostacyclin Infusion in Patients with Peripheral Vascular Disease

1983 ◽  
Vol 50 (04) ◽  
pp. 885-887 ◽  
Author(s):  
H Sinzinger ◽  
A K Horsch ◽  
K Silberbauer
Keyword(s):  
Platelet Count ◽  
Vascular Disease ◽  
Peripheral Vascular Disease ◽  
Platelet Function ◽  
Peripheral Vascular ◽  
Platelet Function Tests ◽  
Function Tests ◽  
Induced Aggregation ◽  
Significant Activation

SummaryIn 20 patients with peripheral vascular disease treated with prostacyclin (5 ng/kg/min) we observed a significant activation of platelet function as measured by platelet proteins, ADP- induced aggregation platelet sensitivity and platelet count. Only the platelet survival was significantly prolonged by the treatment.

scholarly journals Glycoside Residues on Platelet's Surface Regulate Platelet Function, Apoptosis and Binding of Coagulation Complexes in Patients with Immune Thrombocytopaenia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-11
Author(s):  
Nora V. Butta ◽  
María Teresa Alvarez Román ◽  
Elena Monzón Manzano ◽  
Paula Acuña ◽  
Mónica Martín ◽  
...  
Keyword(s):  
Platelet Count ◽  
Sialic Acid ◽  
Platelet Function ◽  
Research Funding ◽  
Platelet Rich Plasma ◽  
University Hospital ◽  
Activation Markers ◽  
Platelet Surface ◽  
Prothrombinase Complex ◽  
Platelet Disorder

Introduction: Platelet surface glycoproteins (GPs) are highly glycosylated and are key elements for platelet function since most of them constitute receptors for adhesion ligands. However, exact role of their glycan composition is not clear. Under normal conditions, platelets contain sialic acid in the carbohydrate side chains of their GPs, and it has been described that alterations in the degree of their sialinization can affect the clearance of platelets. This mechanism has been proposed as involved in etiopathogenesis of immune thrombocytopaenia (ITP), mainly in those patients who do not respond to treatments. Thus, after the loss of sialic acid, there would be a greater exposure of galactose and of N-acetyl-glucosamine residues on the surface of circulating platelets to hepatic Ashwell-Morell receptors, which could induce their phagocytosis and platelet clearance. On the other hand, procoagulant platelets, defined as the platelet subpopulation that binds functional prothrombinase, exposed on their surface increased levels of P-selectin and GPIb, two glycan rich GPs. So, it is tempting to speculate that changes in glycan residues on platelet surface may induce changes in their function. Aim: We aimed to assess in ITP patients whether changes in platelet glycosylation, mainly the loss of sialic acid, may condition platelet function, apoptosis and binding of prothrombinase complex. Methods: This is an observational, prospective and transversal study approved by Ethics Committee from La Paz University Hospital. One hundred and eight patients with chronic primary ITP (68 with a platelet count ≥30x103 platelets/µL and 40 with a platelet count &lt;30x103 platelets/µL) and 132 healthy controls were included after signing the informed consent. Platelet activation markers were determined in platelet rich plasma; whereas platelet glycosylation, binding of prothrombinase, annexin V and caspase's activities were assayed in washed platelets. Samples were analyzed by flow cytometry. Table 1 shows lectins tested and their sugar-binding specificity. Data were analyzed with GraphPad Prism 6.0 software. Results: Platelets from ITP patients with a platelet count &lt;30x103/µL exposed less sialic acid in correspondence to an enhanced binding of lectins to non-sialylated residues. Moreover, levels of α1,6-Fucose, a glycan residue which could directly regulate antibody-dependent cellular cytotoxicity, and of α-Mannose, which could be recognized by the mannose binding lectin and activate complement pathway, were increased in platelets from these ITP patients. In accordance, sialic acid loss and consequent platelet surface exposure of other glycoside residues were inversely related to platelet count and ability to be activated (Table 1). These differences in glycosylation observed in ITP patients with a platelet count &lt;30x103/µL were accompanied by a less ability of platelets to be activated (Figure 1), an increased exposure of phosphatidylserine and higher caspase activites (Figure 2). Moreover, increased exposure of phosphatidylserine and of N-acetyl-glucosamine residues (measured through the binding of WGA) enhanced binding of prothrombinase complex (Figure 3). Conclusion: Changes in glycoside composition of GPs on platelet's surface impaired their functional capacity, increases their apoptosis and modifies conditions for the binding of coagulation proteins. These modifications in platelet's glycoside residues seem to be related to severity of ITP. This work was supported by grants from FIS-FONDOS FEDER (PI19/00772) and and Platelet Disorder Support Association. EMM holds a predoctoral fellowship from Fundación Española de Trombosis y Hemostasia (FETH-SETH). Disclosures Butta: Grifols: Research Funding; Novartis: Speakers Bureau; ROCHE: Research Funding, Speakers Bureau; Pfizer: Speakers Bureau; SOBI: Speakers Bureau; Takeda: Research Funding, Speakers Bureau; NovoNordisk: Speakers Bureau. Alvarez Román:Grifols: Research Funding; Bayer: Consultancy; Novartis: Speakers Bureau; Roche: Speakers Bureau; Pfizer,: Research Funding, Speakers Bureau; SOBI,: Consultancy, Research Funding, Speakers Bureau; Takeda: Research Funding, Speakers Bureau; NovoNordisk,: Research Funding, Speakers Bureau. Martín:SOBI: Research Funding; Pfizer: Research Funding, Speakers Bureau; Roche: Speakers Bureau; Novartis: Speakers Bureau; NovoNordisk: Speakers Bureau. Rivas Pollmar:Novartis: Speakers Bureau; Roche: Speakers Bureau; Pfizer: Speakers Bureau. Justo Sanz:Takeda: Current Employment. García Barcenilla:NovoNordisk: Research Funding, Speakers Bureau; Takeda: Research Funding, Speakers Bureau; Pfizer,: Speakers Bureau; Roche: Speakers Bureau; Bayer: Speakers Bureau; Novartis: Speakers Bureau. Canales:Celgene: Honoraria; Janssen: Speakers Bureau; Novartis: Honoraria; Roche: Honoraria; Gilead: Honoraria; Sandoz: Honoraria; iQone: Honoraria; Takeda: Speakers Bureau; Sandoz: Speakers Bureau; Roche: Speakers Bureau; Janssen: Speakers Bureau; Sandoz: Honoraria; Roche: Honoraria; Takeda: Speakers Bureau; Novartis: Honoraria; Sandoz: Speakers Bureau; Karyopharm: Honoraria; Roche: Speakers Bureau; Janssen: Honoraria; Karyopharm: Honoraria; Janssen: Honoraria. Jimenez-Yuste:F. Hoffman-La Roche Ltd, Novo Nordisk, Takeda, Sobi, Pfizer, Grifols, Octapharma, CSL Behring, Bayer: Honoraria; F. Hoffman-La Roche Ltd, Novo Nordisk, Takeda, Sobi, Pfizer: Consultancy; Grifols, Novo Nordisk, Takeda, Sobi, Pfizer: Research Funding.

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

Effects Of Eltrombopag On Thrombocytopenia, Platelet Function and Bleeding In Patients With Wiskott-Aldrich Syndrome/X-Linked Thrombocytopenia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3536-3536
Author(s):  
Anja J Gerrits ◽  
Emily Leven ◽  
Andrew L. Frelinger ◽  
Michelle A. Berny-Lang ◽  
Hannah Tamary ◽  
...  
Keyword(s):  
Platelet Count ◽  
Board Of Directors ◽  
Platelet Function ◽  
Research Funding ◽  
Annexin V ◽  
Surface Expression ◽  
Advisory Committees ◽  
Platelet Surface ◽  
Platelet Size ◽  
Equity Ownership

Abstract Introduction Patients with Wiskott-Aldrich syndrome (WAS) including X-linked thrombocytopenia (XLT) have microthrombocytopenia, and hemorrhage is a major problem. Current management options in WAS/XLT patients include splenectomy, human stem cell transplant (HSCT) and gene therapy. In this study, we asked whether eltrombopag, a thrombopoietin mimetic, would increase platelet counts, improve platelet function, and/or reduce bleeding in WAS/XLT patients. Methods In 9 WAS/XLT patients and 8 age-matched healthy control subjects, flow cytometry was used to assess platelet function by surface expression of activated GPIIb-IIIa (reported by PAC1) and P-selectin in whole blood after stimulation with low and high concentrations of ADP or thrombin receptor activating peptide (TRAP), and by annexin V binding (a measure of surface phosphatidylserine) in platelet-rich plasma after stimulation with convulxin. Eltrombopag was administered to 5 WAS and 3 XLT patients (50 mg in 2 adults, and 1 mg/kg in 6 children up to 75 mg/day) with a goal platelet count ≥50k. Results High concentration ADP- or TRAP-induced PAC1 mean fluorescence intensity (MFI) was significantly reduced in WAS/XLT patients compared to healthy controls (Figure). Platelet surface P-selectin MFI in response to TRAP was also significantly reduced. In contrast, annexin V binding to platelets was not different between WAS/XLT and controls. As expected, platelet size of WAS/XLT patients was smaller than controls. WAS protein (which is deficient in WAS/XLT), is important for cytoskeletal movement and could therefore be involved in trafficking of surface proteins. However, surface expression of activated GPIIb-IIIa and P-selectin were no longer different in WAS/XLT patients vs. controls when corrected for size by platelet surface CD41 MFI. In 3 WAS/XLT patients whose platelet count improved on eltrombopag, platelet function did not improve. The table summarizes the results of eltrombopag treatment in 5 responders (2 WAS, 3 XLT patients) and 3 non-responders (3 WAS patients). Comparison of baseline, peak and change in immature platelet fraction in 5 WAS/XLT responders to eltrombopag vs. 7 pediatric chronic immune thrombocytopenia (ITP) patients responding to eltrombopag showed a significant decrease in all three measures, suggesting that platelet production in WAS/XLT patients is more difficult to increase than in ITP patients. Long term eltrombopag use in WAS/XLT patients showed no tachyphylaxis, transaminitis or induction of malignancy. Conclusions 1) Baseline platelet function in WAS/XLT is reduced compared to healthy age-matched controls, as measured by agonist-induced platelet surface activated GPIIb-IIIa and P-selectin. 2) This reduction is proportional to the reduced platelet size in WAS/XLT compared to controls. 3) In contrast, annexin V binding (a measure of platelet procoagulant activity) showed no differences between WAS/XLT and controls. 4) Eltrombopag has beneficial effects on the thrombocytopenia and bleeding, but not platelet function, in the majority of WAS/XLT patients. 5) This eltrombopag-induced reduction in bleeding is presumably primarily the result of the increased platelet count, but it was also observed in 2 eltrombopag “non-responders” (i.e. patients whose platelet counts did not increase after eltrombopag). 6) The production of new platelets with eltrombopag is less in WAS/XLT than in ITP. Disclosures: Off Label Use: Eltrombopag was given to WAS/XLT patients for treatment of thrombocytopenia. Michelson:Sysmex: Honoraria. Bussel:GlaxoSmithKline: Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Amgen: Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; Genzyme: Research Funding; IgG of America: Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Eisai: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Shionogi: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Sysmex: Research Funding; Symphogen: Membership on an entity’s Board of Directors or advisory committees.

“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.

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