Soluble P-Selectin During a Single Hemodialysis Session in Patients With Chronic Renal Failure and Erythropoietin Treatment

Abstract

In several studies, hemodialysis (HD) patients treated with recombinant human erythropoietin (rHuEPO) because of renal anemia showed increased levels of soluble adhesion molecules. The purpose of the study was to investigate the changes of soluble P-selectin (sSELP) and its relationship to platelet activation during a single HD session in patients with long-term rHuEPO treatment. Fifty-two HD patients with chronic renal failure were involved—26 with rHuEPO treatment (EPO group) and 26 without (non-EPO group). Thirty healthy subjects served as the control group. The sSELP, β-thromboglobulin, and platelet factor 4 plasma levels were measured before and after a single 4-hour HD session on a cuprophane dialyzer. The basal β-thromboglobulin and platelet factor 4 plasma levels were significantly increased in both HD groups compared with healthy controls but did not change after a single HD session, except for a significant decrease of platelet factor 4 in the non-EPO group. The predialysis sSELP plasma levels did not differ significantly compared with those of the healthy controls, but there was a significant increase of sSELP levels after a single HD session in both groups (EPO, P < .005; non-EPO, P < .05, respectively). These results suppose that the increased sSELP level was released from platelets during the course of a single HD session. The more significant increase of the sSELP plasma levels in EPO group during HD indicates that platelets are more activated in patients with long-term rHuEPO treatment, and this fact could partially explain the suspected tendency for thrombosis in these patients.

Keywords

Soluble P-selectin β-Thromboglobulin Platelet factor 4 Hemodialysis Recombinant human erythropoietin.

References

Polgar J. , Matuskova J. , Wagner DD The P selectin, tissue factor, coagulation triad. J Thromb Haemost. 2005;3:1590.

McEver RP Adhesive interactions of leucocytes, platelets, and the vessel wall during hemostasis and inflammation. Thromb Haemost. 2001;86:746.

Frenette P. , Johnson R. , Hynes R. , et al. Platelets roll on stimulated endothelium in vivo: An interaction mediated by endothelial sP-selectin. Proc Natl Acad Sci USA . 1995; 92:7450.

Blann AD , Lip Gyh. Hypothesis: Is soluble P-selectin a new marker of platelet activation . Atherosclerosis. 1997;128:135.

Nadar SK , Lip Gyh , Blann AD Platelet morphology, soluble P selectin and platelet P-selectin in acute ischaemic stroke: The West Birmingham stroke project. Thromb Haemost. 2004;92:1342.

6. Tan K, Tayebjee M, Lynd C, Blann AD, et al. Platelet microparticles and soluble P selectin in peripheral artery disease: Relationship to extent of disease and platelet activation markers. Ann Med. 2005;37:61.

Nurden AT Qualitative disorders of platelets and megakaryocytes. J Thromb Haemost. 2005;3:1773.

Sirolli V. , Strizzi L. , Di Sante S. , et al. Platelet activation and platelet-erythrocyte aggregates in end-stage renal disease patients on hemodialysis. Thromb Haemost. 2001;86:834.

Bonomini M. , Dottori S. , Amoroso L. , et al. Increased platelet phosphatidylserine exposure and caspase activation in chronic uraemia. J Thromb Haemost. 2004 ;2:1275.

10.

López JA , Del Conde I , Shrimpton CN Receptors, rafts, and microvesicles in thrombosis and inflammation . J Thromb Haemost. 2005;3:1737.

11.

Tassies D. , Reverter JC , Cases A. , et al. Effect of recombinant human erythropoietin treatment on circulating reticulated platelets in uremic patients: Association with early improvement in platelet function. Am J Hematol. 1998; 59:105.

12.

Zwaginga JJ Hemodialysis, erythropoietin and megakaryocytopoiesis: Factors in uremic thrombocytopathy and thrombophilia. J Thromb Haemost. 2004;2:1272.

13.

European Best Practice Guidelines Expert Group on Hemodialysis, European Renal Association. European Best Practice Guidelines for Haemodialysis (Part 1): Section III: Biocompatibility. Nephrol Dial Transplant. 2002; 17(suppl 7):32.

14.

Bonomini M. , Reale M. , Santarelli P. , et al. Serum levels of soluble adhesion molecules in chronic renal failure and dialysis patients . Nephron. 1998;79:399.

15.

Musiał K. , Zwolinska D. , Polak-Jonkisz D. , et al. Soluble adhesion molecules in children and young adults on chronic hemodialysis. Pediatr Nephrol. 2004;19:332.

16.

Kawabata K. , Nagake Y. , Shikata K. , et al. Soluble P-selectin is released from activated platelets in vivo during hemodialysis. Nephron. 1998;78:148.

17.

de Sa HM , Freitas LA , Alves VC , et al. Leukocyte, platelet and endothelial activation in patients with acute renal failure treated by intermittent hemodialysis. Am J Nephrol. 2001;21:264.

18.

Canadian Erythropoietin Study Group. Association between recombinant human erythropoietin and quality of life and exercise capacity of patients receiving hemodialysis . Br Med J. 1990;300:573.

19.

Tobu M. , Iqbal O. , Fareed D. , et al. Erythropoietin-induced thrombosis as a result of increased inflammation and thrombin activatable fibrinolytic inhibitor. Clin Appl Thromb Hemost. 2004;10:225.

20.

Ikegaya N. , Yamamoto T. , Takeshita A. , et al. Elevated erythropoietin receptor and transforming growth factor-β1 expression in stenotic arteriovenous fistulae used for hemodialysis. J Am Soc Nephrol. 2000;11:928.

21.

Grandaliano G. , Teutonico A. , Allegretti A. , et al. The role of hyperparathyroidism, erythropoietin therapy, and CMV infection in the failure of arteriovenous fistula in hemodialysis . Kidney Int. 2003;64:715.

22.

Van Geet C. , Van Damme-Lombaerts R. , Vanrusselt M. , et al. Recombinant human erythropoietin increases blood pressure, platelet aggregability and platelet free calcium mobilisation in uraemic children: Possible link? Thromb Haemost. 1990;64:7.

23.

Stenver D. , Jeppesen L. , Nielsen B. , et al. The effect of erythropoietin on platelet function and fibrinolysis in chronic renal failure. Int J Artif Organs. 1994;17:141.

24.

Bellon JL , Castellanos C. , Acevedo L. , et al. Measurement of beta-thromboglobulin and platelet factor 4 to follow up patients with artificial heart valves. Semin Thromb Hemost. 1993;19(suppl 1):178.

25.

Clyne N. , Egberg N. , Lins LE Effects of hemodialysis and long-term erythropoietin treatment on protein C, and on free and total protein S. Thromb Res. 1995;80:161.

26.

Kappelmayer J. , Nagy B. Jr , Miszti-Blasius K. , et al. The emerging value of P-selectin as a disease marker. Clin Chem Lab Med. 2004;42:475.

27.

Barbaux SC , Blankenberg S. , Rupprecht HJ , et al. Association between P-selectin gene polymorphisms and soluble P-selectin levels and their relation to coronary artery disease. Arterioscler Thromb Vasc Biol. 2001;21:1668.

28.

Ridker PM , Buring JE , Rifai N. Soluble P-selectin and the risk of future cardiovascular events. Circulation. 2001; 103:491.

29.

Kahraman S. , Yilmaz R. , Kirkpantur A. , et al. Impact of rHuEPO therapy initiation on soluble adhesion molecule levels in haemodialysis patients . Nephrology. 2005;10:264.

30.

Malyszko J. , Malyszko JS , Mysliwiec M. Endothelial cell injury markers in chronic renal failure on conservative treatment and continuous ambulatory peritoneal dialysis. Kidney Blood Press Res. 2004;27:71.

31.

Seyfert UT , Helmling E. , Hauck W. , et al. Comparison of blood biocompatibility during haemodialysis with cuprophane and polyacrylonitrile membranes. Nephrol Dial Transplant. 1991;6:428.

32.

Sultan Y. , London GM , Goldfarb B. , et al. Activation of platelets, coagulation and fibrinolysis in patients on long-term haemodialysis: Influence of cuprophan and polyacrylonitrile membranes . Nephrol Dial Transplant. 1990;5:362.

33.

Ivanovich P. , Hammerschmidt E. , Quintanilla A. , et al. Behaviour of platelets and β-thromboglobulin . Nephrol Dial Transplant. 1993;8(suppl 2):15.

34.

Sagedal S. , Hartmann A. , Sundstrøm K. , et al. Anticoagulation intensity sufficient for haemodialysis does not prevent activation of coagulation and platelets. Nephrol Dial Transplant. 2001;16:987.