Abbate, Rosanna

Bertoni, E.

Caroti, L.

Cerini, G.

Cesari, Francesca

Cioni, G.

Farsetti, S.

Gori, Anna Maria

Rosso, G.

Salvadori, M.

Zanazzi, M.

English

Florence Research

20 December 2021Reticulated platelets and platelet reactivity in renal transplant recipients receiving antiplatelet therapy / M. Zanazzi; F.Cesari; G. Rosso; S. Farsetti; L. Caroti; A.M. Gori; G. Cerini; G. Cioni; E. Bertoni; R. Abbate; M. Salvadori. - In:TRANSPLANTATION PROCEEDINGS. - ISSN 0041-1345. - STAMPA. - 42(2010), pp. 1156-1157.[10.1016/j.transproceed.2010.03.042.]Original Citation:Reticulated platelets and platelet reactivity in renal transplant recipients receivingantiplatelet therapyPublished version:10.1016/j.transproceed.2010.03.042.Terms of use:Publisher copyright claim:(Article begins on next page)La pubblicazione è resa disponibile sotto le norme e i termini della licenza di deposito, secondo quanto stabilito dallaPolicy per l'accesso aperto dell'Università degli Studi di Firenze (https://www.sba.unifi.it/upload/policy-oa-2016-1.pdf)Availability:This version is available at: 2158/393412 since: 2018-02-28T14:23:18ZQuesta è la Versione finale referata (Post print/Accepted manuscript) della seguente pubblicazione:FLORERepository istituzionale dell'Università degli Studi diFirenzeOpen AccessDOI:RRMROfmhtsptapeatawaMTo0d1eticulated Platelets and Platelet Reactivity in Renal Transplantecipients Receiving Antiplatelet Therapy. Zanazzi, F. Cesari, G. Rosso, S. Farsetti, L. Caroti, A.M. Gori, G. Cerini, G. Cioni, E. Bertoni,. Abbate, and M. SalvadoriABSTRACTIntroduction. Renal transplant recipients are at increased risk of cardiovascular morbidity andmortality. We assessed platelet reactivity and reticulated platelets (RPs) in 90 recipients, 51 (56.6%)of whom were not receiving acetylsalicylic acid (ASA) therapy (group A) and 39 (43.3%) who werereceiving ASA therapy, 100 mg (group B), and in 60 healthy controls (group C).Methods. Reticulated platelets were measured using a hematology automated analyzer(XE-2100; Sysmex Corp, Kobe, Japan) and were expressed as the percentage of RPs in thetotal optical platelet count (immature platelet fraction [IPF]), as the percentage of highlyfluorescent RPs, and as the absolute number of RPs (IPF#). Platelet function was assessedusing optical aggregometry (platelet aggregation) induced using 1 mmol/L of arachidonicacid, 2 or 10 mol/L of adenosine diphosphate, or 2 g/mL of collagen.Results. Group A demonstrated significantly higher values of RP compared with group B orgroup C. Group B demonstrated a substantially higher percentage of RPs compared with group C,which was significant only for the IPF parameter. Multiple regression analysis demonstrated thatIPF and IPF# were significantly and positively related to collagen-induced platelet aggregation.Conclusion. We documented the presence of higher concentrations of RPs in transplantrecipients compared with a control population, and a significant association between RPsand platelet function.lmrcmhmaplCltaGFFCVER THE LAST YEARS, a number of studies havedemonstrated the importance of some classic riskactors such as hyperlipidemia and hypertension in deter-ining cardiovascular disease in renal transplant recipients;owever, the presence of risk factors did not enable predic-ion of patient survival.1 Various mechanisms can be re-ponsible for cardiovascular complications in renal trans-lant recipients. Their platelets demonstrate enhancedhromboxane biosynthesis,2 and some immunosuppressiongents such as cyclosporine are associated with increasedlatelet procoagulant activity.3,4 However, to our knowl-dge, no data on the presence of reticulated platelets (RPs),nd in particular platelet activity, are available. The objec-ive of the present study was to assess RPs and plateletggregation (PA) in renal transplant recipients who were orere not receiving acetylsalicylic acid (ASA) therapy and inpopulation of healthy controls.ETHODShe study population included 90 renal transplant recipientsbserved according to American Society of Nephrology guiide- I041-1345/10/$–see front matteroi:10.1016/j.transproceed.2010.03.042156ines.5 Fifty-nine patients were men, and 31 were women, withedian (range) age of 55 (20–70) years. Group A included 51ecipients (56.6%) not receiving ASA therapy, and group B in-luded 39 recipients (43.3%) receiving ASA therapy for at least 6onths posttransplantation. Group C (control group) included 60ealthy individuals. Forty-one were men, and 19 were women, withedian (range) age of 52 (21–72) years, who were free of vascularnd renal diseases. All 3 groups were comparable for age and sex.Venous blood samples were obtained from each study partici-ant in the morning, after an overnight fast, and were anticoagu-ated using 0.129 mol/L of sodium citrate, and examined usingFrom the Renal Unit, Department of Medical and Surgicalritical Care, Thrombosis Centre; Center for the Study at Mo-ecular and Clinical Level of Chronic, Degenerative and Neoplas-ic Diseases to Develop Novel Therapies, University of Florence;nd Careggi University Hospital (M.Z., F.C., G.R., S.F., L.C.,.C., G.C., E.B., R.A., M.S.), and Centro S. Maria agli Ulivi,ondazione Don Carlo Gnocchi Onlus IRCCS, Impruneta (A.M.G.),lorence, Italy.Address reprint requests to Maria Zanazzi, MD, Renal Unit,areggi University Hospital, 18 Via le Pieraccini, 50134 Florence,taly. E-mail: mariazanazzi@libero.it© 2010 by Elsevier Inc. All rights reserved.360 Park Avenue South, New York, NY 10010-1710Transplantation Proceedings, 42, 1156–1157 (2010)pmrdapuKocRsIwmrtasRGcsClsaHasrcaHC1[crPDTiappgpdisooiotcadbtetatsaeRcrRpJennppootpTaJaeeRETICULATED PLATELETS AND ANTIPLATELET THERAPY 1157latelet aggregometry and ethylenediamine tetraacetic acid, 0.17ol/L.Turbidimetric PA was used to measure agonist-induced PA inesponse to various stimuli including 2 or 10 mol/L of adenineiphosphate (ADP2-PA and ADP10-PA, respectively), 1 mmol ofrachidonic acid (AA-PA), or 2 g/mL of collagen (Coll-PA), asreviously described.6Reticulated platelets were measured as previously described6sing a hematology automated analyzer (XE-2100; Sysmex Corp,obe, Japan). They were expressed as a percentage of the totalptical platelet count (immature platelet fraction [IPF]), the per-entage of highly fluorescent RPs (H-IPF), or absolute number ofPs (IPF#).Statistical analysis was performed using commercially availableoftware (SPSS version 13.0 for Windows; SPSS, Inc, Chicago,llinois). Data are given as median (range). The Mann-Whitney testas used to compare unpaired data between the various groups. Aultivariate linear regression model adjusted for cardiovascularisk factors; hematocrit; ASA, erythropoietin, and cyclosporineherapy; and glomerular filtration rate was used to test independentssociations of RPs with platelet reactivity. P  .05 was consideredignificant.ESULTSroup A demonstrated significantly higher values for RPsompared with groups B or C. Group B demonstrated aignificantly higher percentage of RPs compared with group, which was significant only for the IPF parameter.To evaluate the influence of RPs on PA, we performed ainear regression analysis. In the univariate model, IPF wasignificantly and positively related to PA by arachidoniccid (AA) ( [SE], 1nAA and 1nIPF, 0.42 [0.16]; P  .01).owever, in the multivariate model, after adjusting for agend sex; hypertension, dyslipidemia, and diabetes mellitus;moking status; hematocrit; ASA, cyclosporine, and eryth-opoietin therapy; and glomerular filtration rate, the asso-iation lost its significance. Insofar as the association of RPsnd Coll-PA, the univariate model demonstrated that IPF,-IPF, and IPF# were positively and significantly related tooll-PA ( [SE]: 1nColl and 1nIPF, 0.30 [0.06], P  .01;nColl and 1nH-IPF, 0.18 [0.07]; 1nColl and 1nIPF#, 0.250.07]). A multiple regression analysis adjusted for allonfounding factors demonstrated that these associationsemained significant ( [SE]: 1nColl and 1nIPF, 0.25 [0.06, .05; 1nColl and 1nIPF#, 0.18 [0.07], P  .05).ISCUSSIONhis article provides new information about the presence ofncreased platelet turnover in renal transplant recipientsnd the relationship between the presence of RPs andlatelet reactivity induced by AA or collagen. Reticulatedlatelets are immature platelets with a greater mass andreater prothrombotic potential compared with smaller klatelets. They aggregate more rapidly with collagen, andemonstrate a higher concentration of thromboxane A2 andncreased concentrations of procoagulant surface proteinsuch as P-selectin and glycoproteins IIb and IIIa.7 More-ver, RPs are associated with diminished antiplatelet effectsf ASA and increased ASA resistance, possibly because ofncreased reactivity and the presence of uninhibited cyclo-xygenase-1 and cyclooxygenase-2 activity.8We documented the presence of the higher concentra-ions of RPs in renal transplant recipients compared with aontrol population of healthy individuals, and a significantssociation between RPs and platelet function.The number of newly produced circulating plateletsepends on stimulation of the thrombopoietic capacity ofone marrow and on the degree of platelet removal fromhe bloodstream via activation-dependent mechanisms thatnhance platelet turnover. Both mechanisms may be impor-ant in determining the number of RPs. Some cytokinesugment megakaryopoiesis quantitatively, and in renalransplant recipients, higher concentrations of tumor necro-is factor-, a cytokine that can act to promote commitmentlong the megakaryocytic lineage to increased thrombopoi-sis, have been reported.9In conclusion, the presence of an increased percentage ofPs may be another mechanism involved in the increasedardiovascular risk profile documented in renal transplantecipients.EFERENCES1. Kasiske BL, Chakkera HA, Roel J: Explained and unex-lained ischemic heart disease risk after renal transplantation.Am Soc Nephrol 11:1735, 20002. Averna M, Barbagallo CM, Ganci A, et al: Determinants ofnhanced thromboxane biosynthesis in renal transplantation. Kid-ey Int 59:1574, 20013. Malyszko J, Malyszko JS, Takada A, et al: Effects of immu-osuppressive drugs on platelet aggregation in vitro. Ann Trans-lant 7:55, 20024. Tomasiak M, Rusak T, Gacko M, et al: Cyclosporine enhanceslatelet procoagulant activity. Nephrol Dial Transplant 22:1750, 20075. Kasiske BL, Vazquez MA, Harmon WE, et al; American Societyf Transplantation: Recommendations for the outpatient surveillancef renal transplant recipients. J Am Soc Nephrol 11:S1, 20006. Cesari F, Marcucci R, Caporale R, et al: Relationship be-ween high platelet turnover and platelet function in high-riskatients with coronary artery disease on dual antiplatelet therapy.hromb Haemost 99:930, 20087. Tschoepe D, Roesen P, Kauffmann L, et al: Evidence forbnormal platelet glycoprotein expression in diabetes mellitus. EurClin Invest 20:166, 19908. Guthikonda S, Lev EI, Patel R, et al: Reticulated plateletsnd uninhibited COX-1 and COX-2 decrease the antiplateletffects of aspirin. J Thromb Haemost 5:490, 20079. Cottone S, Palermo A, Vaccaro F, et al: Inflammation andndothelial activation are linked to renal function in long-termidney transplantation. Transplant Int 20:82, 2007

Reticulated platelets and platelet reactivity in renal transplant recipients receiving antiplatelet therapy

https://flore.unifi.it/bitstream/2158/393412/1/sdarticle.pdf

Reticulated platelets and platelet reactivity in renal transplant recipients receiving antiplatelet therapy

Abstract

Similar works

Full text

Available Versions

Florence Research