Effects of Antiplatelet Treatment with Aspirin (ASA) on Platelet Reactivity in Patients with Essential Thrombocythemia

Abstract INTRODUCTION: Essential Thrombocythemia (ET) is a myeloproliferative neoplasm characterized by an increased rate of thrombotic complications. Antithrombotic prophylaxis with aspirin (ASA), alone or in combination with cytoreduction with hydroxyurea (HU), is widely utilized in ET patients. However, thrombosis occurrence/recurrence in spite of antithrombotic prophylaxis remains a relevant issue. Growing data support the possible contribution to this failure of the inter-individual variability of pharmacological ASA response. AIM: Aim of this study was to characterize, in a group of ET patients receiving 100 mg/d ASA, the platelet reactivity in terms of platelet aggregation and activation properties. MATERIALS AND METHODS: Venous blood samples were obtained from 77 ET patients (26M/51F), and two control groups, i.e., one including 72 non-ET patients receiving chronic ASA prophylaxis, and the other including 111 healthy control subjects (57M/54F). The mutational status of ET was: 35 patients were JAK2V617F⁺, 22 CALR⁺, 3 MPL⁺, and 17 triple negative. Thirty-three ET patients were on ASA+HU, 23 on ASA alone, 5 on HU alone, and 16 were not receiving any of these drugs. Platelet aggregation was assessed in whole blood by the Multiplate® analyzer (Roche). The platelet response to the thrombin receptor activating peptide (TRAP) trigger was the measure of the overall platelet aggregation capacity, while the response to the arachidonic acid (AA) trigger was the measure of ASA effect on platelet aggregation. A normalized AA-induced aggregation (r-AA-agg), defined as AA/TRAP ratio, was calculated for each sample to reflect the individual variation of platelet inhibition by ASA. The platelet activation status was evaluated before and after aggregation by measuring the surface expression of CD62P (P-selectin) by flow cytometry (Accuri™ C6, BD Bioscience). RESULTS: The analysis of subgroups according to treatments shows that AA-induced platelet aggregation in ASA- and ASA+HU-treated ET patients was significantly lower compared to non-ASA ET subjects (p<0.001), and was significantly greater compared to ASA-treated non-ET patients (145±85 AU; p<0.001). The same results were observed with TRAP-induced platelet aggregation. Accordingly, the r-AA-agg. was greater in ET subjects on ASA (=53%) or ASA+HU (=50%) as compared to non-ET ASA-treated individuals (=19%). Furthermore, among ET patients on ASA±HU, those with platelet >450x109/L showed AA-induced aggregation significantly greater than subjects with platelet <450x109/L. The increment of platelet surface CD62P expression after AA stimulation (as a marker of platelet activation) was not influenced by anti-platelet therapy, but was significantly associated with JAK2V617F mutation. CONCLUSIONS: Our data show that in more than 70% of ET patients, in spite of ASA intake, the platelet reactivity remains higher than in non-ET patients receiving the same drug regimen. This phenomenon, together with the so-called "turnover" resistance, i.e. increased platelet turnover associated to short aspirin half-life, may contribute to aspirin failure in ET. Studies are necessary to evaluate the efficacy and safety of a different dose or timing of ASA administration in these patients. Project funded by "AIRC-IG2013" grant Nr. 14505 from the "Italian Association for Cancer Research" (A.I.R.C.). Disclosures Falanga: Pfizer: Speakers Bureau; Aspen: Speakers Bureau; Janssen: Speakers Bureau.

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Prostaglandin E2 potentiates platelet aggregation by priming protein kinase C

Blood ◽

10.1182/blood.v82.9.2704.2704 ◽

1993 ◽

Vol 82 (9) ◽

pp. 2704-2713 ◽

Cited By ~ 53

Author(s):

R Vezza ◽

R Roberti ◽

GG Nenci ◽

P Gresele

Keyword(s):

Protein Kinase C ◽

Platelet Aggregation ◽

Protein Kinase ◽

Prostaglandin E2 ◽

Platelet Activation ◽

Human Platelets ◽

Platelet Surface ◽

Kinase C ◽

Activated Platelets ◽

Induced Aggregation

Abstract Prostaglandin E2 (PGE2) is produced by activated platelets and by several other cells, including capillary endothelial cells. PGE2 exerts a dual effect on platelet aggregation: inhibitory, at high, supraphysiologic concentrations, and potentiating, at low concentrations. No information exists on the biochemical mechanisms through which PGE2 exerts its proaggregatory effect on human platelets. We have evaluated the activity of PGE2 on human platelets and have analyzed the second messenger pathways involved. PGE2 (5 to 500 nmol/L) significantly enhanced aggregation induced by subthreshold concentrations of U46619, thrombin, adenosine diphosphate (ADP), and phorbol 12-myristate 13-acetate (PMA) without simultaneously increasing calcium transients. At a high concentration (50 mumol/L), PGE2 inhibited both aggregation and calcium movements. PGE2 (5 to 500 nmol/L) significantly enhanced secretion of beta-thromboglobulin (beta TG) and adenosine triphosphate from U46619- and ADP-stimulated platelets, but it did not affect platelet shape change. PGE2 also increased the binding of radiolabeled fibrinogen to the platelet surface and increased the phosphorylation of the 47-kD protein in 32P- labeled platelets stimulated with subthreshold doses of U46619. Finally, the amplification of U46619-induced aggregation by PGE2 (500 nmol/L) was abolished by four different protein kinase C (PKC) inhibitors (calphostin C, staurosporine, H7, and TMB8). Our results suggest that PGE2 exerts its facilitating activity on agonist-induced platelet activation by priming PKC to activation by other agonists. PGE2 potentiates platelet activation at concentrations produced by activated platelets and may thus be of pathophysiologic relevance.

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Platelet activation in cystic fibrosis

Blood ◽

10.1182/blood-2004-06-2098 ◽

2005 ◽

Vol 105 (12) ◽

pp. 4635-4641 ◽

Cited By ~ 69

Author(s):

Brian P. O'Sullivan ◽

Matthew D. Linden ◽

Andrew L. Frelinger ◽

Marc R. Barnard ◽

Michele Spencer-Manzon ◽

...

Keyword(s):

Cystic Fibrosis ◽

Platelet Aggregation ◽

Platelet Activation ◽

Platelet Reactivity ◽

Cyclic Adenosine Monophosphate ◽

Adenosine Monophosphate ◽

Gene Encoding ◽

Platelet Surface ◽

Beneficial Effects ◽

Plasma Factor

Abstract Cystic fibrosis (CF) is caused by a mutation of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). We examined platelet function in CF patients because lung inflammation is part of this disease and platelets contribute to inflammation. CF patients had increased circulating leukocyte-platelet aggregates and increased platelet responsiveness to agonists compared with healthy controls. CF plasma caused activation of normal and CF platelets; however, activation was greater in CF platelets. Furthermore, washed CF platelets also showed increased reactivity to agonists. CF platelet hyperreactivity was incompletely inhibited by prostaglandin E1 (PGE1). As demonstrated by Western blotting and reverse-transcriptase-polymerase chain reaction (RT-PCR), there was neither CFTR nor CFTR-specific mRNA in normal platelets. There were abnormalities in the fatty acid composition of membrane fractions of CF platelets. In summary, CF patients have an increase in circulating activated platelets and platelet reactivity, as determined by monocyte-platelet aggregation, neutrophil-platelet aggregation, and platelet surface P-selectin. This increased platelet activation in CF is the result of both a plasma factor(s) and an intrinsic platelet mechanism via cyclic adenosine monophosphate (cAMP)/adenylate cyclase, but not via platelet CFTR. Our findings may account, at least in part, for the beneficial effects of ibuprofen in CF. (Blood. 2005;105:4635-4641)

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Platelet Activation and Aggregation in Patients with Advanced Adenocarcinoma Undergoing Chemotherapy: Correlation with a Validated Venous Thromboembolism Risk Score

Blood ◽

10.1182/blood.v126.23.3445.3445 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3445-3445 ◽

Cited By ~ 2

Author(s):

Arnab Basu ◽

Rohit Gosain ◽

Udaya Tantry ◽

Kenneth Miller ◽

Paul A Gurbel

Keyword(s):

Arachidonic Acid ◽

Risk Factor ◽

Venous Thromboembolism ◽

Platelet Aggregation ◽

Cancer Patients ◽

Platelet Activation ◽

Platelet Reactivity ◽

Risk Scores ◽

Platelet Surface ◽

Thrombotic Risk

Abstract Background: Cancer is known to increase risk of venous thromboembolism (VTE), which is associated with considerable mortality and morbidity. Chemotherapy is an independent risk factor for thrombosis in cancer patients. We examined platelet activation and reactivity based on the Khorana Score, a validated scoring model for VTE risk in patients receiving chemotherapy. Materials and Methods: Patients (n=25) with advanced stage adenocarcinomas (TNM stage III or greater), were enrolled in this study. Patients on antiplatelet therapy or on anticoagulation were excluded. Approximately 10 ml of Citrated blood samples were collected from central access catheters after discarding initial 5 ml to minimize iatrogenic platelet activation. 1μMol, 2μMol, 5μMol of ADP-induced, 2μMol Arachidonic Acid (AA)-induced and 4μMol Collagen-induced platelet aggregation in Platelet Rich plasma (PRP) was assessed with a light transmission aggregometry assay. Maximal aggregation and aggregation velocity were recorded. Concurrent flowcytometry analysis was done to assess the expressions of CD41 (Glycoprotein GpIIb), CD62p (platelet surface p-Selectin), and PAC-1(Activated GP IIb/IIIa). Thromboembolic risk scores (Khorana Scores, KS) were calculated based on a validated scoring system (Khorana AA, et al. Blood. 2008;111:4902-7) as follows: Table 1.Very high risk cancers (pancreatic or gastric)+2 pointsHigh risk cancers (lung, ovarian, or bladder cancer)+1 pointPlatelet count ≥350 x 109/L+1 pointHemoglobin < 10 gm/dL or use of erythropoietin+1 pointLeukocytosis >11 x 109/L+1 pointBMI > 35+1 point Results: Mean values for maximum platelet aggregation were calculated by groups and compared between patient with KS < 3 and KS > = 3 by two sample t-tests. Differences were statistically significant for all concentrations of ADP and collagen, with a positive trend for Arachidonic acid (Table). A significant linear relationship between maximal platelet aggregation and higher KS was observed. However there were no significant differences observed in the expression of platelet surface p-selectin, CD41 or PAC-1 when comparing patients at Khorana scores 0, 3 or more than 3 (not shown). Table 2.Agonist ConcentrationKhorana Score <3Khorana Score >= 3P valueADP 1μMol20.8%28.14%0.02ADP 2μMol38.6%67%0.002ADP 5μMol66.5%79.85%0.006Arachidonic acid 2μMol61.6%73.85%0.12Collagen 4μMol78.6%90.14%0.01 Discussion: The mechanism of cancer-related thromboembolism is not well understood. Chemotherapy is an added risk factor for the development of VTEs. Several new markers such as soluble p-selectin and mean platelet volume have been investigated as adjunct factors to improve predictive ability. Although our study did not find a correlation of some common platelet surface markers for activation with thrombotic risk scores; we find a strong positive correlation of future thrombotic risk derived via Khorana scores with heightened platelet reactivity. Platelet reactivity may mediate a final common pathway for venous thromboembolism in cancer patients and should be validated further as an adjunctive marker in a large scale study. Disclosures No relevant conflicts of interest to declare.

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JAK2V617F Mutation and Thrombosis History Are Determinants of Mean Platelet Volume (MPV) in Essential Thrombocythemia Patients

Blood ◽

10.1182/blood.v128.22.2606.2606 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2606-2606

Author(s):

Marina Marchetti ◽

Cristina Verzeroli ◽

Cinzia Giaccherini ◽

Sara Gamba ◽

Alfonso Vignoli ◽

...

Keyword(s):

Multivariate Analysis ◽

Platelet Activation ◽

Essential Thrombocythemia ◽

Mean Platelet Volume ◽

Jak2v617f Mutation ◽

Platelet Volume ◽

Platelet Surface ◽

Positive History ◽

Mutational Status ◽

History Of

Abstract Introduction and aim: Persistently enhanced platelet activation has been described in patients with myeloproliferative neoplasms, i.e. essential thrombocythemia (ET) and polycythemia vera (PV), which carry a high thrombotic risk. Different studies suggest that mean platelet volume (MPV) and immature platelet fraction (IPF) can serve as useful markers of platelet activation and increased thrombosis rate in various diseases. In a previous study of ET and PV patients, we demonstrated that JAK2V617F mutation and hydroxyurea (HU) treatment determine the IPF parameters (Panova-Noeva et al, Blood 2011). In this study of ET patients, we aimed to investigate on whether MPV values are influenced by pathogenic factors, such as JAK2V617F mutation, previous thrombotic events, HU treatment, and features of platelet activation. Methods: Eighty-nine consecutive patients with ET (56F/33M; median age 60 yrs) were recruited after written informed consent. Venous blood samples were collected at enrollment and clinical data recorded. Ninety healthy subjects acted as a control group. The mutational status was as follows: 46 patients (51.6%) were JAK2V617F+, 23 (25.8%) CALR+, and 3 (3.4%) MPL+. Thirty eight patients were receiving HU cytoreductive therapy plus ASA, 6 patients HU alone, and 20 patients none of these drugs. Fifteen patients (16.8%) had a positive history of thrombosis. MPV was measured by an automated hematology analyzer (CELL-DYN Ruby System). Platelet surface P-selectin was measured by flow cytometry. Plasma levels of platelet-released proteins, i.e. soluble (s)P-selectin, sGPV, PF4, βTG, were measured by commercial ELISA (Stagò, France). Results: The study shows that in ET patients, the MPV values were inversely related to platelet count (p=0.005, by a multivariate analysis). The analysis according to mutational status indicates that MPV was greater in JAK2V617F+ carriers compared to JAK2 wild type (p<0.05) or other mutation carriers. In addition, MPV was greater in subjects with a positive history of thrombosis versusthose without (p<0.05) and results remained significant after multivariate analysis (p<0.05). Differently, HU treatment did not correlate with MPV values. Also, the platelet activation parameters, including the levels of platelet surface P-selectin and the plasma circulating markers, i.e. sP-selectin, sGPV, PF4, βTG, showed no relation with MPV. Conclusions: Our data provide evidence that the presence of JAK2V617F mutation or of a positive history of thrombosis are linked to MPV values in ET patients, which might contribute to the prothrombotic phenotype in these patients. In view of the increasing importance of MPV as a marker of platelet reactivity, prospective studies are warranted to evaluate the usefulness of MPV as a cellular marker to predict thrombosis in MPN patients. Project funded by "AIRC-IG2013" grant Nr. 14505 from the "Italian Association for Cancer Research" (A.I.R.C.). Disclosures Falanga: Pfizer: Speakers Bureau; Aspen: Speakers Bureau; Janssen: Speakers Bureau.

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Simvastatin Effects on Inflammation and Platelet Activation Markers in Hypercholesterolemia

BioMed Research International ◽

10.1155/2018/6508709 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 16

Author(s):

Cristina Barale ◽

Chiara Frascaroli ◽

Rouslan Senkeev ◽

Franco Cavalot ◽

Isabella Russo

Keyword(s):

Oxidative Stress ◽

Platelet Aggregation ◽

Platelet Activation ◽

Ldl Cholesterol ◽

Platelet Reactivity ◽

Lipid Lowering ◽

Cholesterol Levels ◽

Anti Inflammatory ◽

Induced Aggregation ◽

Progression Of Atherosclerosis

Background. Beside the lipid-lowering effect, statins slow the progression of atherosclerosis by exerting anti-inflammatory and platelet inhibiting effects. We investigated whether platelet inhibition by simvastatin correlates with the statin effects on lipid lowering, inflammation, oxidative stress, and endothelial and platelet activation. Methods. In hypercholesterolemic patients allocated to diet (n=20) or a 2-month treatment with diet plus 40 mg simvastatin (n=25), we evaluated platelet aggregating responses to ADP, collagen, and arachidonic acid (AA), the effect of aspirin on AA-induced aggregation, pro- and anti-inflammatory and atherogenic mediators (IL-1β, -5, -6, -7, -8, -9, -10, -12, and -13, IFN-γ, IP-10, Eotaxin, and sRAGE), markers of endothelium (sE-selectin, VEGF, and MCP-1) and platelet activation (sP-selectin, sCD-40L, RANTES, and PDGF-bb), and oxidative stress (8-OH-2’-deoxyguanosine). Results. After treatment, beside the improvement of lipid profile, we observed the following: a reduction of platelet aggregation to ADP (p=0.0001), collagen (p=0.0001), AA (p=0.003); an increased antiaggregating effect of aspirin in the presence of AA (p=0.0001); a reduction of circulating levels of IL-6 (p=0.0034), IL-13 (p<0.0001), IFN-γ (p<0.0001), VEGF (p<0.0001), sE-selectin (p<0.0001), sCD-40L (p<0.0001), sP-selectin (p=0.003), and 8-OH-2’-deoxyguanosine (p<0.0001); an increase of IL-10 and sRAGEs (p=0.0001 for both). LDL-cholesterol levels (i) positively correlated with IL-6, IFN-γ, E-selectin, sCD-40L, 8-OH-2’-deoxyguanosine, platelet aggregation to ADP, collagen, AA, and aspirin IC-50 and (ii) negatively correlated with IL-10 and sRAGE. In multiple regression analyses, LDL-cholesterol was the strongest predictor for most parameters of platelet reactivity. Conclusion. In primary hypercholesterolemia, simvastatin treatment reduced platelet activation and subclinical inflammation and improved endothelial dysfunction. LDL-cholesterol levels were the major correlate of platelet reactivity; however, other effects of statins may contribute to reducing the progression of atherosclerosis.

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Platelet activation induces metalloproteinase-dependent GP VI cleavage to down-regulate platelet reactivity to collagen

Blood ◽

10.1182/blood-2004-07-2842 ◽

2005 ◽

Vol 105 (1) ◽

pp. 186-191 ◽

Cited By ~ 60

Author(s):

Gillian Stephens ◽

Yibing Yan ◽

Martine Jandrot-Perrus ◽

Jean-Luc Villeval ◽

Kenneth J. Clemetson ◽

...

Keyword(s):

Platelet Aggregation ◽

Platelet Activation ◽

Immune Modulation ◽

Soluble Fraction ◽

Platelet Reactivity ◽

Cleavage Product ◽

Platelet Surface ◽

Variable Expression ◽

Collagen Receptor ◽

Stimulation Of

Abstract Glycoprotein (GP) VI, the primary collagen receptor on platelets, has been shown to have variable expression, possibly as a consequence of immune modulation. The present study was designed to determine the mechanism by which GP VI clearance occurs. We found that direct activation of GP VI both by a GP VI–specific antibody and by GP VI ligands (collagen and convulxin) reduced binding of biotinylated convulxin to the stimulated platelets. Analysis of immunoblots of platelets and supernatants showed that the stimulated platelets contained less GP VI, while the soluble fraction contained a 57-kDa cleavage product. Stimulation of platelets with PAR-1 agonists (TRAP peptide and thrombin) also caused GP VI cleavage, although the amount of GP VI loss was less than that observed with direct GP VI ligands. The metalloproteinase (MMP) inhibitors GM6001 and TAPI prevented both the clearance of GP VI from the platelet surface and the appearance of the soluble cleavage product. Induction of GP VI cleavage caused specific down-regulation of collagen-induced platelet aggregation, providing a mechanism for the modulation of platelet responsiveness to this important platelet agonist.

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Prostaglandin E2 potentiates platelet aggregation by priming protein kinase C

Blood ◽

10.1182/blood.v82.9.2704.bloodjournal8292704 ◽

1993 ◽

Vol 82 (9) ◽

pp. 2704-2713

Author(s):

R Vezza ◽

R Roberti ◽

GG Nenci ◽

P Gresele

Keyword(s):

Protein Kinase C ◽

Platelet Aggregation ◽

Protein Kinase ◽

Prostaglandin E2 ◽

Platelet Activation ◽

Human Platelets ◽

Platelet Surface ◽

Kinase C ◽

Activated Platelets ◽

Induced Aggregation

Prostaglandin E2 (PGE2) is produced by activated platelets and by several other cells, including capillary endothelial cells. PGE2 exerts a dual effect on platelet aggregation: inhibitory, at high, supraphysiologic concentrations, and potentiating, at low concentrations. No information exists on the biochemical mechanisms through which PGE2 exerts its proaggregatory effect on human platelets. We have evaluated the activity of PGE2 on human platelets and have analyzed the second messenger pathways involved. PGE2 (5 to 500 nmol/L) significantly enhanced aggregation induced by subthreshold concentrations of U46619, thrombin, adenosine diphosphate (ADP), and phorbol 12-myristate 13-acetate (PMA) without simultaneously increasing calcium transients. At a high concentration (50 mumol/L), PGE2 inhibited both aggregation and calcium movements. PGE2 (5 to 500 nmol/L) significantly enhanced secretion of beta-thromboglobulin (beta TG) and adenosine triphosphate from U46619- and ADP-stimulated platelets, but it did not affect platelet shape change. PGE2 also increased the binding of radiolabeled fibrinogen to the platelet surface and increased the phosphorylation of the 47-kD protein in 32P- labeled platelets stimulated with subthreshold doses of U46619. Finally, the amplification of U46619-induced aggregation by PGE2 (500 nmol/L) was abolished by four different protein kinase C (PKC) inhibitors (calphostin C, staurosporine, H7, and TMB8). Our results suggest that PGE2 exerts its facilitating activity on agonist-induced platelet activation by priming PKC to activation by other agonists. PGE2 potentiates platelet activation at concentrations produced by activated platelets and may thus be of pathophysiologic relevance.

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Platelet Function and Turnover in Essential Thrombocythemia: A Systematic Review

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0040-1718873 ◽

2021 ◽

Vol 47 (01) ◽

pp. 090-101

Author(s):

Joachim Kvernberg ◽

Erik Lerkevang Grove ◽

Hans Beier Ommen ◽

Anne-Mette Hvas

Keyword(s):

Platelet Aggregation ◽

Platelet Activation ◽

Platelet Function ◽

Essential Thrombocythemia ◽

Meta Analysis ◽

Myeloproliferative Neoplasm ◽

Exclusion Criteria ◽

Thromboembolic Risk ◽

Platelet Counts ◽

Support Decision Making

AbstractEssential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by increased platelet counts. ET has an incidence of 0.6 to 2.5 per 100,000 per year in Europe and North America. The disease is characterized by an increased thromboembolic risk, possibly caused by increased platelet counts. Furthermore, increased platelet function and/or increased platelet turnover may play a role. We aimed to explore: (1) whether platelet function and platelet turnover are increased in ET patients compared with healthy controls, and (2) whether these parameters are associated with increased thromboembolic risk and, therefore, may support decision-making on treatment in ET patients. We performed a systematic literature search on March 20, 2020 in Embase and PubMed following the Preferred Reporting Items for Systematic and Meta-Analysis (PRISMA) guidelines. In total, 1,923 articles were identified, 38 of which were included according to prespecified inclusion and exclusion criteria. Among the 38 studies, platelet activation (CD36 and CD62P) was investigated in 18 studies and was found to be increased in 12 of these. Platelet aggregation was investigated in 21 studies and was reported to be reduced in 20 of them. Platelet turnover (immature platelet count and mean platelet volume) was investigated in five studies with inconclusive results. No parameters were reported to predict the risk of thromboembolic events. In conclusion, platelet activation was increased in ET patients, but platelet aggregation was reduced. Future studies exploring markers of thromboembolic risk in ET patients are warranted.

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Soluble but Not Platelet P-selectin Correlates With Spontaneous Platelet Aggregation: A Pilot Study

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029607305915 ◽

2008 ◽

Vol 14 (2) ◽

pp. 227-233 ◽

Cited By ~ 6

Author(s):

Marcus Cleanthis ◽

Jonathan Smout ◽

Vishwanath Bhattacharya ◽

Hamdy Ashour ◽

Alexander Dyker ◽

...

Keyword(s):

Platelet Aggregation ◽

Platelet Activation ◽

Pearson Correlation ◽

Venous Blood ◽

Arterial Disease ◽

Stroke Patients ◽

Platelet Surface ◽

Peripheral Arterial ◽

Spontaneous Platelet Aggregation ◽

Exact Relationship

Background. P-selectin (PS) is a marker of platelet activation measured on the platelet surface as platelet PS (pPS) or in serum as soluble PS (sPS). Controversy remains over the exact relationship between sPS, pPS, and other markers such as spontaneous platelet aggregation (SPA). Objective. To investigate correlations between pPS, sPS, and SPA in patients with peripheral arterial disease. Methods. SPA, pPS, and sPS levels were measured in venous blood sampled from patients following intermittent claudication (n = 18) or an acute stroke (n = 18). Results. SPA and sPS correlated significantly in the claudicants (Pearson correlation coefficient, r = 0.661; P = .0020) and stroke patients ( r = 0.514; P = .020). No significant correlation was identified between pPS and SPA, or sPS and pPS. Conclusions. The 2 methods of assessing PS are not comparable. Although pPS is accepted as a platelet activation marker, sPS may be a better indicator of aggregation represented by SPA.

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On The Mechanism Of Heparin-Induced Potentiation Of Platelet Aggregation

10.1055/s-0038-1652598 ◽

1981 ◽

Author(s):

M Yamamoto ◽

K Watanabe ◽

Y Ando ◽

H Iri ◽

N Fujiyama ◽

...

Keyword(s):

Platelet Aggregation ◽

Platelet Activation ◽

Coagulation Factors ◽

Marked Enhancement ◽

Matrix Bound ◽

Induced Aggregation ◽

Aggregation Of Platelets ◽

Plasma Heparin

It has been suggested that heparin caused potentiation of aggregation induced by ADP or epinephrine. The exact mechanism of heparin-induced platelet activation, however, remained unknown. In this paper, we have investigated the role of anti-thrombin III ( AT ) in heparin-induced platelet activation using purified AT and AT depleted plasma. When ADP or epinephrine was added to citrated PRP one minute after addition of heparin ( 1 u/ml, porcine intestinal mucosal heparin, Sigma Co. USA ), marked enhancement of platelet aggregation was observed, compared with the degree of aggregation in the absence of heparin. However, in platelet suspensions prepared in modified Tyrode’s solution, heparin exhibited no potentiating effect on platelet aggregation induced by epinephrine or ADP. Potentiation of epinephrine- or ADP-induced platelet aggregation by heparin was demonstrated when purified AT was added to platelet suspensions at a concentration of 20 μg/ml. AT depleted plasma, which was prepared by immunosorption using matrix-bound antibodies to AT, retained no AT, while determination of α1-antitrypsinα2- macroglobulin and fibrinogen in AT depleted plasma produced values which corresponded to those of the original plasma when dilution factor was taken into account. The activities of coagulation factors were also comparable to those of the original plasma. Heparin exhibited potentiating effect on ADP- or epinephrine-induced aggregation of platelets in original plasma, but no effect in AT depleted plasma. When purified AT was added back to AT depleted plasma at a concentration of 20 μg/ml, potentiation of platelet aggregation by heparin was clearly demonstrated.Our results suggest that effect of heparin on platelet aggregation is also mediated by anti-thrombin III.

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