Increased leukocyte-platelet adhesion in patients with graft occlusion after peripheral vascular surgery

Summary

Graft occlusion following peripheral vascular surgery is attributable to some combination of acute thrombosis, and progression of atherosclerosis: interactions between leukocytes and activated platelets may play a role in both of these processes. This investigation measured perioperative leukocyte-platelet conjugate formation, and leukocyte and platelet activation in 46 patients undergoing surgery for lower extremity peripheral vascular disease (PVD). All patients were followed for graft patency over the next 6 months; 27 patients had grafts that remained patent while 19 had graft occlusion. On postoperative day #1 (POD#1), the graft occlusion group demonstrated a significantly greater increase in circulating levels of both mono-cyteplatelet and neutrophil (PMN)-platelet conjugates compared to the patent graft patients (p=0.015 and 0.018, respectively). PMN activation, assessed by increases in surface CD11b expression, was also significantly increased on POD#1 in the graft occlusion group compared to the patent group (p=0.026). The percentage of circulating activated (CD62P+) platelets did not differ between groups, but patients with graft occlusion demonstrated a higher percentage of younger, reticulated platelets throughout the study period (p=0.008), indicating increased platelet turnover.

We conclude that in the early postoperative period, leukocyte-platelet adhesion, PMN activation, and platelet turnover are significantly greater in PVD patients who go on to develop later graft occlusion. Cellular activation and heterotypic cell interactions in peripheral vascular surgery patients may be important in the etiologies of thrombosis and/or accelerated atherosclerosis leading to graft loss.

Keywords

Cell-cell interactions - clinical/epidemiological studies - platelet activation markers - vasculopathies

• References

• 1 Cimminiello C. Peripheral arterial disease: Epidemiology and pathophysiology. Thromb Res 2002; 106: V295-V301.
• 2 Constantini V, Lenti M. Treatment of acute occlusion of peripheral arteries. Thromb Res 2002; 106: V285-V295.
• 3 Group DBOAS: Efficacy of oral anticoagulants compared with aspirin after infrainguinal bypass surgery (The Dutch Bypass Oral anticoagulants or Aspirin study): a randomized trial. Lancet 2000; 355: 6-51.
• 4 Holdsworth R, McCollum P. Results and resource implications of treating end-stage limb ischaemia. Eur J Vasc Endovasc Surg 1997; 13: 164-73.
• 5 Violi F, Criqui M, Longoni A. et al. Relation between risk factors and cardiovascular complications in patients with peripheral vascular disease. Atherosclerosis 1996; 120: 25-35.
• 6 Kantonen I, Lepantalo M, Luther M. et al. Factors affecting the results of surgery for chronic leg ischemia - a nationwide survey. J Vasc Surg 1998; 27: 940-7.
• 7 Matsagas M, Geroulakos G, Mikhailidis M. The role of platelets in peripheral arterial disease: Therapeutic implications. Ann Vasc Surg 2002; 16: 246-58.
• 8 Woodburn K, Lowe G, Love J. et al. Clinical, biochemical, and rheologic factors affecting the outcome of infrainguinal bypass grafting. J Vasc Surg 1996; 24: 639-46.
• 9 Tsakiris D, Tschopl M, Jager K. et al. Circulating adhesion molecules and endothelial markers before and after trans-luminal angioplasty in peripheral arterial occlusive disease. Atherosclerosis 1999; 142: 193-200.
• 10 Rinder C, Bonan J, Rinder H. et al. Cardiopulmonary bypass induces leukocyte-platelet adhesion. Blood 1992; 79: 1201-5.
• 11 Rinder H, Munz U, Ault K. et al. Reticulated platelets in the evaluation of thrombopoietic disorders. Arch Pathol Lab Med 1993; 117: 606-10.
• 12 Rinder H, Bonan J, Anandan S. et al. Noninvasive measurement of platelet kinetics in normal and preeclamptic pregnancies. Am J Obstet Gynecol 1994; 170: 117-22.
• 13 Rinder H, Schuster J, Rinder C. et al. Correlation of thrombosis with increased platelet turnover in thrombocytosis. Blood 1998; 91: 1288-94.
• 14 Bonan J, Rinder H, Smith B. Determination of the percentage of thiazole orange (TO)-positive, “reticulated” platelets using autologous erythrocyte TO fluorescence as an internal standard. Cytometry 1993; 14: 690-4.
• 15 Ault K, Rinder H, Mitchell J. et al. The significance of platelets with increased RNA content (reticulated platelets). Am J Clin Pathol 1992; 98: 637-46.
• 16 Wang C, Smith B, Ault K. et al. Reticulated platelets predict platelet count recovery following chemotherapy. Transfusion 2002; 42: 368-74.
• 17 Tangelder M, Lawson J, Algra A. et al. Systematic review of randomized controlled trials of aspirin and oral anticoagulants in the prevention of graft occlusion nd ischemic events after infrainguinal bypass surgery. J Vasc Surg 1999; 30: 701-9.
• 18 Rutherford R, Baker J, Ernst C. et al. Recommended standards for reports dealing with lower extremity ischemia: Revised version. J Vasc Surg 1997; 26: 517-38.
• 19 Evangilista V, Manarini S, Sideri R. et al. Platelet/polymorphonuclear leukocyte interaction: P-selectin triggers protein-tyrosine phosphorylation-dependent CD11b/CD18 adhesion: role of PSGL-1 as a signaling molecule. Blood 1999; 93: 876-85.
• 20 Kazuya I, Hidari J, Weyrich A. et al. Engagement of P-selectin glycoprotein ligand-1 enhances tyrosine phosphorylation and activates mitogen-activated protein kinases in human neutrophils. J Biol Chem 1997; 272: 28750-6.
• 21 Nagata K, Tsutomu T, Todoroki N. et al. Activated platelets induce superoxide anion release by monocytes and neutrophils through P-selectin (CD62P). J Immunol 1993; 151: 3267-73.
• 22 Weyrich A, McIntyre T, McEver R. et al. Monocyte tethering by P-selectin regulates monocyte chemotactic protein-1 and tumor necrosis factor secretion. J Clin Invest 1995; 95: 2297-303.
• 23 Weyrich A, Elstad M, McEver R. et al. Activated platelets signal chemokine synthesis by human monocytes. J Clin Invest 1996; 97: 1525-34.
• 24 Ott I, Neumann FJ, Gawaz M. et al. Increased neutrophil-platelet adhesion in patients with unstable angina. Circulation 1996; 94: 1239-46.
• 25 Furman M, Frelinger A, Goldberg R. et al. Circulation monocyte-platelet aggregates are an early marker of acute myocardial infarction. JACC 2001; 38: 1002-6.
• 26 Mickelson J, Lakkis N, Villarreal-Lavy G. et al. Leukocyte activation with platelet adhesion after coronary angioplasty: a mechanism for recurrent disease?. JACC 1996; 28: 345-53.
• 27 Rinder C, Gaal D, Student L. et al. Platelet-leukocyte activation and modulation of adhesion receptors in pediatric patients with congenital heart disease undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg 1994; 107: 280-8.
• 28 Peyton B, Rohrer M, Benoit S. et al. Patients with venous stasis ulceration have increased monocyte-platelet aggregation. J Vasc Surg 1998; 27: 1109-16.
• 29 Freedman J, Loscalzo J. Platelet-monocyte aggregates: Bridgin thrombosis and inflammation. Circulation 2002; 105: 2130-2.
• 30 Rinder H, Bonan J, Rinder C. et al. Dynamics of leukocyte-platelet adhesion in whole blood. Blood 1991; 78: 1730-7.
• 31 Michelson A, Barnard M, Hechtman H. In vivo tracking of platelets: circulating degranu-lated platelets rapidly lose surface P-selectin but continue to circulate and function. Proc Natl Acad Sci USA 1996; 93: 11877-82.
• 32 Michelson A, Barnard M, Krueger L. et al. Circulating monocyte-platelet aggregates are a more sensitive marker of in vivo platelet activation than platelet surface P-selectin. Circulation 2001; 104: 1533-7.
• 33 Michelson A, Furman M. Laboratory markers of platelet activation and their clinical significance. Curr Opin Hematol 1999; 6: 342-8.
• 34 May A, Neumann FJ, Gawaz M. et al. Reduction of monocyte-platelet interaction and monocyte activation in patients receiving antiplatelet therapy after coronary stent implantation. Eur Heart J 1997; 18: 1913-20.
• 35 Koksch M, Zeiger F, Wittig K. et al. Coagulation, fibrinolysis and platelet P-selec-tin expression in peripheral vascular disease. Eur J Vasc Endovasc Surg 2001; 21: 147-54.
• 36 Zeiger F, Stephen S, Hoheisel G. et al. P-selectin expression, platelet aggregates, and platelet-derived micropartical formation are increased in peripheral arterial disease. Blood Coag & Fibrinol 2000; 11: 723-8.
• 37 Samama C, Thiry D, Elalamy I. et al. Perioperative activation of hemostasis in vascular surgery patients. Anesthesiology 2001; 94: 74-8.
• 38 Brothers T, JG R, Elliott B. et al. Preoperative thromboxane A2/prostaglandin H2 receptor activity predicts early graft thrombosis. J Vasc Surg 1998; 27: 317-28.
• 39 Rinder H, Tracey J, Recht M. et al. Differences in platelet α-granule release between normals and immune thrombocytopenic patients and between young and old platelets. Thromb Haemost 1998; 80: 457-62.
• 40 Bonomini M, Stuard S, Carreno M. et al. Neutrophil reactive oxygen species production during hemodialysis: role of activated platelet adhesion to neutrophils through P-selectin. Nephron 1997; 75: 402-11.
• 41 Smith C. Leukocyte-endothelial cell interactions. Semin Hematol 1993; 30 (04) Suppl 45-53.
• 42 Gawaz M, Loftus J, Bajt M. Ligand bridging mediates integrin alpha IIb beta 3 (platelet GPIIB-IIIA) dependent homotypic and hetero-typic cell-cell interactions. J Clin Invest 1991; 88: 1128-34.
• 43 Schini-Kerth V, Bassus S, Fisslthaler B. et al. Aggregating human platelets stimulate the expression of thrombin receptors in cultured vascular smooth muscle cells via the release of transforming growth factor-β1 and platelet-derived growth factorAB. Circulation 1997; 96: 3888-96.
• 44 Gunsilius E, Stockhammer P, Nussbaumer G. et al. Thrombocytes are the major source for soluble vascular endothelial growth factor in peripheral blood. Oncology 2000; 58: 169-74.
• 45 Brunetti M, Martelli N, Manarini S. et al. Polymorphonuclear leukocyte apoptosis is inhibited by platelet-released mediators, role of TGFβ-1. Thromb Haemost 2000; 84: 478-83.
• 46 Rinder C, Student L, Bonan J. et al. Aspirin does not inhibit adenosine diphosphate-induced platelet α-granule release. Blood 1993; 82: 505-12.
• 47 Hou Y, Schober A, Forlow S. et al. Circulating activated platelets activate atherosclerosis in mice deficient in apolipoprotein E. Nature Med 2003; 9: 61-7.