Circulating procoagulant microparticles and soluble GPV in myocardial infarction treated by primary percutaneous transluminal coronary angioplasty. A possible role for GPIIb‐IIIa antagonists

Summary.  Circulating procoagulant microparticles (MP) were measured as markers of vascular damage and prothrombotic risk in patients undergoing ST‐segment myocardial infarction (STEMI) treated by primary percutaneous transluminal coronary angioplasty (PTCA) and additional GPIIb‐IIIa antagonists. Cells possibly more responsive to GPIIb‐IIIa (αIIbβ3) antagonists were evidenced through MP phenotypes by comparison with healthy volunteers (HV) and STEMI patients treated by PTCA without GPIIb‐IIIa antagonist (CP). In 50 STEMI patients, blood samples were collected at day 1 and day 6. Circulating procoagulant MP were captured on annexin V and quantified by prothrombinase assay as nanomolar phosphatidylserine equivalents (nm PhtdSer). Platelet activation by thrombin was confirmed through independent measurement of soluble GPV (sGPV). With respect to HV, procoagulant MP levels were high in patients with STEMI or unstable angina, platelet‐derived MP and elevated sGPV testifying to significant platelet activation. A substantial release of endothelial‐derived MP was evidenced simultaneously. In abciximab‐treated patients, procoagulant MP, mainly of platelet origin, decreased precociously at day 1 (4.2 ± 0.6 vs. CP 15.5 ± 2.1 nm PhtdSer; P = 0.001) together with sGPV (36 ± 3 vs. CP 58 ± 8 ng mL−1; P = 0.02). Leukocyte‐derived MP decreased at day 6 (0.12 ± 0.04 vs. CP 0.56 ± 0.12 nm PhtdSer; P = 0.01) suggesting a possible effect on underlying inflammatory status. In patients presenting cardiovascular events at 6‐month follow‐up, procoagulant MP levels at day 1 could be indicative of a worsened outcome. MP could constitute a relevant parameter for the follow‐up of STEMI patients treated by GPIIb‐IIIa antagonists.

[1]  M. Mesri,et al.  Leukocyte Microparticles Stimulate Endothelial Cell Cytokine Release and Tissue Factor Induction in a JNK1 Signaling Pathway* , 1999, The Journal of Biological Chemistry.

[2]  F. Neumann,et al.  Antiplatelet effects of abciximab, tirofiban and eptifibatide in patients undergoing coronary stenting. , 2001, Journal of the American College of Cardiology.

[3]  F. Dignat-George,et al.  Interaction of endothelial microparticles with monocytic cells in vitro induces tissue factor-dependent procoagulant activity. , 2002, Blood.

[4]  R. Califf,et al.  Does eptifibatide confer a greater benefit to patients with unstable angina than with non-ST segment elevation myocardial infarction? Insights from the PURSUIT Trial. , 2002, European heart journal.

[5]  M. Mesri,et al.  Endothelial cell activation by leukocyte microparticles. , 1998, Journal of immunology.

[6]  C. Hack,et al.  Human cell‐derived microparticles promote thrombus formation in vivo in a tissue factor‐dependent manner , 2003, Journal of thrombosis and haemostasis : JTH.

[7]  D. Phillips,et al.  Inhibitory Effects of Glycoprotein IIb/IIIa Antagonists and Aspirin on the Release of Soluble CD40 Ligand During Platelet Stimulation , 2003, Circulation.

[8]  M. Graham,et al.  Abciximab Attenuates Coronary Microvascular Endothelial Dysfunction After Coronary Stenting , 2002, Circulation.

[9]  C. Bode,et al.  The GP IIb/IIIa inhibitor abciximab (c7E3) inhibits the binding of various ligands to the leukocyte integrin Mac-1 (CD11b/CD18, αMβ2) , 2002 .

[10]  David P Miller,et al.  Long-term mortality benefit with abciximab in patients undergoing percutaneous coronary intervention. , 2001, Journal of the American College of Cardiology.

[11]  D. Kereiakes,et al.  IIb's are not IIb's. , 2000, The American journal of cardiology.

[12]  H. Weiss,et al.  Greater inhibition of platelet procoagulant activity by antibody‐derived glycoprotein IIb–IIIa inhibitors than by peptide and peptidomimetic inhibitors , 2001, British journal of haematology.

[13]  K. Ray.  Abciximab suppresses the rise in levels of circulating inflammatory markers after percutaneous coronary revascularization. , 2002, Circulation.

[14]  G. Maurer,et al.  Coronary no-reflow is caused by shedding of active tissue factor from dissected atherosclerotic plaque. , 2002, Blood.

[15]  S. Nomura,et al.  High-shear-stress-induced activation of platelets and microparticles enhances expression of cell adhesion molecules in THP-1 and endothelial cells. , 2001, Atherosclerosis.

[16]  I. Peake.  International Society on Thrombosis and Haemostasis , 1974, Thrombosis and Haemostasis.

[17]  R. Jordan,et al.  An Additional Mechanism of Action of Abciximab: Dispersal of Newly Formed Platelet Aggregates , 2002, Thrombosis and Haemostasis.

[18]  K. Clemetson,et al.  The GPIb thrombin-binding site is essential for thrombin-induced platelet procoagulant activity. , 2000, Blood.

[19]  J. Haga,et al.  Comparison of Shear Stress–Induced Platelet Microparticle Formation and Phosphatidylserine Expression in Presence of &agr;IIb&bgr;3 Antagonists , 2003, Journal of cardiovascular pharmacology.

[20]  C. Paweletz,et al.  Serum-derived protein S binds to phosphatidylserine and stimulates the phagocytosis of apoptotic cells , 2003, Nature Immunology.

[21]  C. Bode,et al.  The GP IIb/IIIa inhibitor abciximab (c7E3) inhibits the binding of various ligands to the leukocyte integrin Mac-1 (CD11b/CD18, alphaMbeta2). , 2002, Thrombosis research.

[22]  O. Morel,et al.  Protective effects of vitamin C on endothelium damage and platelet activation during myocardial infarction in patients with sustained generation of circulating microparticles , 2003, Journal of thrombosis and haemostasis : JTH.

[23]  M. Furman,et al.  GPIIb-IIIa Antagonist-induced Reduction in Platelet Surface Factor V/Va Binding and Phosphatidylserine Expression in Whole Blood , 2000, Thrombosis and Haemostasis.

[24]  L. Horstman,et al.  High levels of circulating endothelial microparticles in patients with acute coronary syndromes. , 2003, American heart journal.

[25]  R. Califf,et al.  Multi-year follow-up of abciximab therapy in three randomized, placebo-controlled trials of percutaneous coronary revascularization. , 2002, The American journal of medicine.

[26]  J. Freyssinet,et al.  Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thrombogenicity. , 1999, Circulation.

[27]  F. Picard,et al.  Flow Cytometry Detection of Platelet Procoagulant Activity and Microparticles in Patients with Unstable Angina Treated by Percutaneous Coronary Angioplasty and Stent Implantation , 2001, Thrombosis and Haemostasis.

[28]  F. Neumann,et al.  Platelet function in acute myocardial infarction treated with direct angioplasty. , 1996, Circulation.

[29]  G. Lip,et al.  Increased Platelet Glycoprotein V Levels in Patients with Coronary and Peripheral Atherosclerosis , 2001, Thrombosis and Haemostasis.

[30]  M. Li,et al.  Different effects of various anti‐GPIIb‐IIIa agents on shear‐induced platelet activation and expression of procoagulant activity , 2003, Journal of thrombosis and haemostasis : JTH.

[31]  M. Sefton,et al.  Platelet-derived microparticle formation involves glycoprotein IIb-IIIa. Inhibition by RGDS and a Glanzmann's thrombasthenia defect. , 1993, The Journal of biological chemistry.

[32]  A. Tedgui,et al.  Current perspective on the role of apoptosis in atherothrombotic disease. , 2001, Circulation research.

[33]  P. Armstrong,et al.  Outcome of urgent and elective percutaneous coronary interventions after pharmacologic reperfusion with tenecteplase combined with unfractionated heparin, enoxaparin, or abciximab. , 2003, Journal of the American College of Cardiology.

[34]  C. Yeh,et al.  Accutin, a new disintegrin, inhibits angiogenesis in vitro and in vivo by acting as integrin alphavbeta3 antagonist and inducing apoptosis. , 1998, Blood.

[35]  R. Ahmadi,et al.  Abciximab Reduces Monocyte Tissue Factor in Carotid Angioplasty and Stenting , 2003, Stroke.

[36]  Assent investigators.  Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction , 2001, The Lancet.

[37]  E. Bramucci,et al.  Thrombogenic potential of human coronary atherosclerotic plaques. , 2001, Blood.

[38]  R. Lassila,et al.  Abciximab inhibits procoagulant activity but not the release reaction upon collagen‐ or clot‐adherent platelets , 2003, Journal of thrombosis and haemostasis : JTH.

[39]  J. Freyssinet,et al.  Elevated levels of circulating procoagulant microparticles in patients with paroxysmal nocturnal hemoglobinuria and aplastic anemia. , 1999, Blood.

[40]  T. Shimazu,et al.  Activated polymorphonuclear leukocytes enhance production of leukocyte microparticles with increased adhesion molecules in patients with sepsis. , 2002, The Journal of trauma.

[41]  R. Peters,et al.  Procoagulant and proinflammatory activity in acute coronary syndromes. , 1998, Cardiovascular research.

[42]  Judy A Craft,et al.  Increased generation of platelet-derived microparticles following percutaneous transluminal coronary angioplasty , 2002, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[43]  T. Byzova,et al.  Networking in the hemostatic system. Integrin alphaiibbeta3 binds prothrombin and influences its activation. , 1997, The Journal of biological chemistry.

[44]  J. Freyssinet,et al.  The significance of shed membrane particles during programmed cell death in vitro, and in vivo, in HIV-1 infection. , 1997, The Journal of clinical investigation.

[45]  U. Ikeda,et al.  Procoagulant and proinflammatory activity in acute coronary syndromes. , 1998, Cardiovascular research.

[46]  H. Hemker,et al.  Inhibition of platelet-mediated, tissue factor-induced thrombin generation by the mouse/human chimeric 7E3 antibody. Potential implications for the effect of c7E3 Fab treatment on acute thrombosis and "clinical restenosis". , 1996, The Journal of clinical investigation.

[47]  C. Yeh,et al.  Accutin, a New Disintegrin, Inhibits Angiogenesis In Vitro and In Vivo by Acting as Integrin vβ3 Antagonist and Inducing Apoptosis , 1998 .

[48]  G. FitzGerald,et al.  Modulation of monocyte-endothelial cell interactions by platelet microparticles. , 1998, The Journal of clinical investigation.

[49]  J. Chou,et al.  Accumulation of Tissue Factor into Developing Thrombi In Vivo Is Dependent upon Microparticle P-Selectin Glycoprotein Ligand 1 and Platelet P-Selectin , 2003, The Journal of experimental medicine.

[50]  K. Preissner,et al.  Intravascular tissue factor initiates coagulation via circulating microvesicles and platelets , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[51]  A. Tedgui,et al.  Circulating Microparticles From Patients With Myocardial Infarction Cause Endothelial Dysfunction , 2001, Circulation.

[52]  J. Freyssinet,et al.  Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes. , 2000, Circulation.

[53]  S. Goto,et al.  Abciximab not RGD peptide inhibits von Willebrand factor-dependent platelet activation under shear , 1999, The Lancet.

[54]  D. Wagner,et al.  P-selectin and leukocyte microparticles are associated with venous thrombogenesis. , 2003, Journal of vascular surgery.