Platelet Volume is Increased in Patients with Slow Coronary Flow

ORİJİNAL ARAŞTIRMA Platelet Volume is Increased in Patients with Slow Coronary Flow Ercan VAROL, MD, a Habil YÜCEL, MD, a Mehmet ÖZAYDIN, MD, a Abdullah DOĞAN, MD, a Doğan ERDOĞAN, MD a a Department of Cardiology, Süleyman Demirel University Faculty of Medicine, Isparta Ge liş Ta ri hi/re ce i ved: 03.07.2010 Ka bul Ta ri hi/ac cep ted: 13.10.2010 Ya zış ma Ad re si/cor res pon den ce: Ercan VAROL, MD Süleyman Demirel University Faculty of Medicine, Department of Cardiology, Isparta, TÜRKİYE/TURKEY drercanvarol@yahoo.com ABS TRACT Ob jec ti ve: Slow co ro nary flow (SCF) is cha rac te ri zed by de la yed opa ci fi ca ti on of co - ro nary ves sels in a nor mal co ro nary an gi og ram. Alt ho ugh cli ni cal and pat ho lo gi cal fe a tu res ha ve be - en pre vi o usly des cri bed, the un derl ying pat hoph ysi o logy has not be en fully un ders to od. The pla te let func ti on di sor ders ha ve be en sug ges ted to play a ro le in the pat ho ge ne sis of SCF. The aim of this study was to as sess the me an pla te let vo lu me (MPV), an in di ca tor of pla te let ac ti va ti on in pa ti ents with SCF. Ma te ri al and Met hods: The study gro up con sis ted of 35 pa ti ents with SCF. An age and gen der matc hed con trol gro up was com po sed of 35 he althy vo lun te ers. We me a su red se rum MPV va lu es in pa ti ents and con trol sub jects. Re sults: The throm boly sis in myo car di al in farc ti on (TI MI) fra me co unt for all the epi car di al co ro nary ar te ri es and the me an TI MI fra me co unt we re sig ni fi - cantly hig her in the SCF gro up than con trol gro up. MPV was sig ni fi cantly hig her among pa ti ents with SCF when com pa red with con trol gro up (8.6 ± 0.9 vs. 8.1 ± 0.5 fl res pec ti vely; p= 0.004). The only uni va ri a te pre dic tor of SCF was MPV (p= 0.007; OR, 2.58; CI, 1.29 to 5.15). The only mul ti - va ri a te pre dic tor of SCF was MPV (p= 0.01 ; OR, 2.43; CI, 1.20 to 4.87). Conc lu si on: We ha ve shown that MPV was sig ni fi cantly ele va ted in pa ti ents with SCF com pa red to con trol sub jects. Key Words: Pla te let ac ti va ti on; co ro nary cir cu la ti on ÖZET Amaç: Ya vaş ko ro ner akım (YKA) nor mal ko ro ner an ji yog ra fi de ko ro ner da mar la rın ge cik - miş bo yan ma sı dır. Her ne ka dar kli nik ve pa to lo jik özel lik le ri da ha ön ce ta nım lan sa da alt ta ya tan pa to fiz yo lo ji ke sin ola rak an la şı la ma mış tır. Trom bo sit fonk si yon bo zuk luk la rı nın YKA nın pa to je - ne zin de rol oy na dı ğı sa nıl mak ta dır. Bu ça lış ma nın ama cı YKA lı has ta lar da trom bo sit ak ti vas yo - nun bir gös ter ge si olan or ta la ma trom bo sit hac mi ni (OTH) de ğer len dir mek ti. Ge reç ve Yön tem ler: Ça lış ma gru bu YKA lı 35 has ta dan oluş tu. Yaş ve cin si yet eşit len miş 35 sağ lık lı bi rey kon trol gru - bu nu oluş tur du. Has ta ve kon trol gru bun da OTH de ğer le ri öl çül dü. Bul gu lar: Bü tün ko ro ner da mar - la rın Throm boly sis in Myo car di al In farc ti o n (TI MI) ka re sa yı la rı ve TI MI ka re sa yı sı or ta la ma sı YKA lı has ta lar da kon trol le re gö re an lam lı de re ce de yük sek bu lun du. OTH YKA lı has ta lar da kon - trol gru bun dan an lam lı de re ce de yük sek ti (8.6 ± 0.9 ve 8.1 ± 0.5 fl; sırayla; p= 0.004). YKA nın tek üni va ri yat belirteci OTH idi (p= 0.007; OR, 2.58; GA, 1.29-5.15). YKA nın tek mul ti va ryat belirteci OTH idi (p= 0.01; OR, 2.43; GA, 1.20-4.87). So nuç: Biz bu ça lış ma da, YKA lı has ta lar da OTH nin kon trol gru buy la kar şı laş tı rıl dı ğın da an lam lı ola rak art mış ol du ğu nu gös ter dik. Anah tar Ke li me ler: Trombosit ak ti vas yo nu; ko ro ner do la şım Turkiye Klinikleri J Cardiovasc Sci 2010;22(3):279-83 Cop yright 2010 by Tür ki ye Kli nik le ri low coronary flow (SCF) is an angiographic finding characterized by slow antegrade progression of contrast agent to the distal branch of a coronary artery in the absence of obstructive coronary artery disease. 1 Several mechanisms have been proposed for the etiology of SCF, including microvascular and endothelial dysfunction, small-vessel disease, diffuse at- Turkiye Klinikleri J Cardiovasc Sci 2010;22(3) 279

Ercan VAROL ve ark. TROMBOSİT HACMİ YAVAŞ KORONER AKIMLI HASTALARDA ARTMIŞTIR he rosc le ro sis and inf la ma ti on. 1-5 Its eti o pat ho ge ne - sis is not still cle ar. The im por tan ce of SCF phe no - me non re sults from its as so ci a ti on with an gi na pec to ris, acu te myo car di al in farc ti on, hyper ten si - on and sud den car di ac de ath. 6 Pla te lets ha ve an im por tant ro le in the pat hoph ysi o logy of car di o vas cu lar di se a ses. 7 Me an pla te - let vo lu me (MPV) is a simp le and easy met hod of as ses sing pla te let func ti on. 8,9 In com pa ri son to smal ler ones, lar ger pla te lets ha ve mo re gra nu les, ag gre ga te mo re ra pidly with col la gen, ha ve hig her throm bo xa ne A2 le vel and ex press mo re glycop ro - te in Ib and IIb/II I a re cep tors. 10-12 The re fo re lar ger pla te lets ha ve hig her throm bo tic po ten ti al. In pre vi o us stu di es, in cre a sed pla te let ac ti va ti - on 13,14 and in cre a sed MPV 14-16 ha ve be en re por ted in pa ti ents with SCF. In this study, we ai med to inves ti ga te MPV va lu es pros pec ti vely in pa ti ents with SCF. MA TE RI AL AND MET HODS The study gro up con sis ted of 35 pa ti ents with SCF (19 fe ma les, 16 ma les, me an age 51.8 ± 8.7 ye ars). An age and gen der matc hed con trol gro up was com po sed of 35 he althy vo lun te ers (18 fe ma les, 17 ma les with a me an age 51.0 ± 10.1 ye ars). The in dica ti on for co ro nary an gi og raphy was eit her the pre sen ce of typi cal an gi na or po si ti ve or equ i vo cal re sults of no nin va si ve scre e ning tests for myo car - di al isc he mi a in both of the gro up. The con trol subjects we re se lec ted in a con se cu ti ve man ner from the cat he te ri zed pa ti ents du ring the sa me study peri od and who pro ved to ha ve nor mal co ro nary angi og rams. Hyper ten si on was con si de red to be pre sent if the systo lic pres su re was >140 mmhg and/or di as to lic pres su re was >90 mmhg or if the in di vi du al was ta king an tihy per ten si ve me di ca ti - ons. Di a be tes mel li tus was de fi ned as a fas ting blo - od glu co se le vel >126 mg/dl or cur rent use of a di et or me di ca ti on to lo wer blo od glu co se. Pa ti ents who we re smo king be fo re hos pi ta li za ti on we re ac cep - ted as smo kers Exc lu si on cri te ri a we re co ro nary ar tery di se a - se, pri or myo car di al in farc ti on, val vu lar he art di - se a se, he art fa i lu re, pe rip he ral vas cu lar di se a se, co ro nary ar tery ec ta si a, di a be tes mel li tus, hyper - ten si on, re nal and he pa tic dysfunc ti on, he ma to lo - gi cal di sor ders, his tory of ma lig nancy, acu te or chro nic in fec ti on and stro ke. No ne of the sub jects we re on an tihy per ten si ve and an ti ag gre ga ti on the - rapy inc lu ding as pi rin. The re is only one pa ti ent using sta tin in pa ti ents gro up. The study was appro ved by the ins ti tu ti o nal et hics com mit te e, and in for med con sent was ob ta i ned from all pa ti - ents. CO RO NARY AN GI OG RAPHY Co ro nary an gi og raphy was ro u ti nely per for med wit ho ut the use of nit rogl yce rin. Se lec ti ve co ro nary an gi og raphy was per for med by me ans of the Judkins tech ni qu e in mul tip le pro jec ti ons. We used iohe xol (Om ni pa qu e) as con trast agent du ring co ro nary an gi og raphy in all pa ti ents and con trol sub jects. Co ro nary blo od flow was me a su red qu an - ti ta ti vely using the throm boly sis in myo car di al infarc ti on (TI MI) fra me co unt which was de ri ved from the num ber of ci ne-fra mes re cor ded from the first en tran ce of con trast to its ar ri val at the dis tal end of eit her the left an te ri or des cen ding ar tery (LAD), cir cumf lex ar tery (Cx), or right co ro nary artery (RCA). The last fra mes used for the LAD, Cx, and RCA we re tho se in which the dye first en te - red the mus tac he seg ment, dis tal bi fur ca ti on segment, and first branch of the pos te ro la te ral ar tery, res pec ti vely. The TI MI fra me co unt of the LAD artery was cor rec ted by di vi ding the fi nal co unt by 1.7. The me an TI MI fra me co unt for each pa ti ent and con trol sub ject was cal cu la ted by ad ding the TI MI fra me co unts for LAD, CFX and RCA and then di vi ding the ob ta i ned va lu e in to thre e. Co ro - nary an gi og rams and TI MI fra me co un ting we re analy sed by two blin ded in ter ven ti o nal car di o lo - gists wit ho ut know led ge of the cli ni cal sta tus and la bo ra tory me a su re ments of the sub jects. BLO OD SAMP LING Blo od samp les we re drawn from the an te cu bi tal ve - in by ca re ful ve in punc tu re in a 21 G ste ri le syrin - ge wit ho ut sta sis at 08.00-10.00 AM af ter a fas ting pe ri od of 12 h. Glu co se, cre a ti ni ne, and li pid pro fi - les we re de ter mi ned by stan dard met hods. MPV was me a su red in a blo od samp le col lec ted in di po - tas si um ED TA tu bes. An au to ma tic blo od co un ter 280 Turkiye Klinikleri J Cardiovasc Sci 2010;22(3)

PLATELET VOLUME IS INCREASED IN PATIENTS WITH SLOW CORONARY FLOW Ercan VAROL et al (Beck man Co ul ter) was used for who le blo od co - unts. MPV was me a su red wit hin an ho ur af ter samp ling. STA TIS TI CAL ANALY SIS Da ta we re analy zed with the SPSS soft wa re ver si - on 10.0 for Win dows. Con ti nu o us va ri ab les from the study gro ups we re re por ted as me an ± 1 standard de vi a ti on, ca te go ri cal va ri ab les as per cen ta ges. To com pa re con ti nu o us va ri ab les, the Stu dent t-test or Mann-Whit ney U test we re used whe re ap prop ri a te. Ca te go ri cal va ri ab les we re com pa red with the chi-squ a red test. Sta tis ti cal sig ni fi can ce was defi ned as p< 0.05. De mog rap hic cha rac te ris tics, cli - ni cal and an gi og rap hic pro fi le we re eva lu a ted in a uni va ri a te analy sis, and tho se with p< 0.15 (BMI and MPV) we re then en te red in to a Mul ti va ri a te lo gis tic reg res si on analy sis. Strength of as so ci a ti on bet we en va ri ab les and oc cur ren ce of SCF was repre sen ted by odds ra ti os (ORs) and the ir ac com pan - ying 95% con fi den ce in ter vals (CIs). RE SULTS Cli ni cal and la bo ra tory cha rac te ris tics of the pa ti - ents with SCF and con trol gro up are pre sen ted in Tab le 1. The re we re no sta tis ti cally sig ni fi cant diffe ren ces bet we en the two gro ups with res pect to age, gen der, systo lic and di as to lic blo od pres su res and le vels of glu co se, cre a ti ni ne, to tal cho les te rol, trigl yce ri de, low-den sity li pop ro te in (LDL) cho les - te rol, high den sity li pop ro te in (HDL) cho les te rol, he mog lo bin, whi te blo od cell and pla te let co unt. The TI MI fra me co unt for all the epi car di al co ro - nary ar te ri es and the me an TI MI fra me co unt we - re sig ni fi cantly hig her in the SCF gro up than con trol gro up. MPV was sig ni fi cantly hig her among pa ti ents with SCF when com pa red with con trol gro up (8.6 ± 0.9 vs. 8.1 ± 0.5 fl res pec ti vely; p= 0.004). The only uni va ri a te pre dic tor of SCF was MPV (p= 0.007; OR, 2.58; CI, 1.29 to 5.15). The only mul ti va ri a te pre dic tor of SCF was MPV (p= 0.01 ; OR, 2.43; CI, 1.20 to 4.87). DIS CUS SI ON In this study, we fo und that MPV was sig ni fi - cantly hig her in pa ti ents with SCF com pa red to TABLE 1: Comparison of the clinical and laboratory characteristics of the slow coronary flow (SCF) and the control groups. SCF Control (n= 35) (n= 35) P value Age (years) 51.8 ± 8.7 51.0 ± 10.1 0.06 Sex (M/F) 16/19 17/18 0.75 Smoking (%) 6(17%) 7(20%) 0.75 BMI (kg/m 2 ) 27.7 ± 3.1 26.6 ± 2.7 0.13 SBP (mmhg) 121.6 ± 7.3 120.8 ± 10.6 0.71 DBP (mmhg) 75.8 ± 8.2 75.7 ± 9.8 0.96 Heart rate (beats/min) 73.5 ± 3.8 72.2 ± 4.3 0.17 Glucase (mg/dl) 97.2 ± 8.0 93.3 ± 11.8 0.11 Creatinin (mg/dl) 0.91 ± 0.15 0.87 ± 0.17 0.36 Total cholesterol (mg/dl) 190.1 ± 29.2 187.9 ± 48.3 0.82 Triglycerides (mg/dl) 139.7 ± 56.4 121.4 ± 52.7 0.16 LDL-cholesterol (mg/dl) 111.0 ± 27.0 112.2 ± 36.7 0.87 HDL-cholesterol (mg/dl) 49.3 ± 14.3 49.9 ± 12.9 0.85 Hemoglobin (g/dl) 14.2 ± 1.3 14.3 ± 1.3 0.75 WBC ( 103 mg/dl) 7.5 ± 2.1 7.7 ± 1.9 0.72 Platelet count ( 109) 259.6 ± 59.1 263.2 ± 94.3 0.84 MPV (fl) 8.6 ± 0.9 8.1 ± 0.5 0.004 TIMI frame count LADc 33.0 ± 8.1 16.0 ± 4.5 < 0.001 Cx 27.9 ± 10.4 17.8 ± 7.3 0.006 RCA 20.7 ± 4.9 15.3 ± 6.2 0.006 Mean 27.6 ± 6.1 16.2 ± 5.1 < 0.001 M/F: ma le to fe ma le, BMI: body mass in dex, SBP: systo lic blo od pres su re, DBP: di as - to lic blo od pres su re, LDL-cho les te rol: low den sity li pop ro te in cho les te rol, HDL-cho les - te rol: high den sity li pop ro te in cho les te rol, WBC: whi te blo od cells, MPV: me an pla te let vo lu me. TI MI: Throm boly sis in Myo car di al In farc ti on, c: Cor rec ted TI MI fra me co unt, P va lu e is for com pa ri son bet we en con trol and study po pu la ti on. con trol sub jects. Se ve ral mec ha nisms ha ve be en pro po sed for the eti o logy of SCF, inc lu ding occ - lu si on of small ves sels, in cre a sed mic ro vas cu lar re sis tan ce, and dif fu se at he rosc le ro sis. 1-4 Ho we ver, the exact un derl ying pat hoph ysi o lo gi cal mec ha - nisms as well as the cli ni cal im por tan ce of this angi og rap hic phe no me non are not fully un ders to od at pre sent. In pre vi o us stu di es, the pla te let func ti on di sorders ha ve be en sug ges ted to play a ro le in the pat - ho ge ne sis of SCF. 13,14 Gok ce et al. fo und that the ra ti o of pla te let ag gre ga bi lity was sig ni fi cantly hig - her in the pa ti ents with SCF than that in the control sub jects, sug ges ting that pla te let func ti on di sor der may play a ro le in the pat ho ge ne sis in Turkiye Klinikleri J Cardiovasc Sci 2010;22(3) 281

Ercan VAROL ve ark. TROMBOSİT HACMİ YAVAŞ KORONER AKIMLI HASTALARDA ARTMIŞTIR SCF. 13 Ce lik et al fo und that MPV and sp-se lec tin le vels of the pa ti ents with SCF we re sig ni fi cantly hig her com pa red to tho se of the sub jects with normal co ro nary flow. 14 In cre a sed MPV ha ve be en repor ted in pa ti ents with SCF al so in so me ot her stu di es. 15,16 The de ter mi na ti on of pla te let si ze, usu ally vi a qu an ti fi ca ti on of MPV is a simp le and easy met hod of ac cu ra tely as ses sing pla te let func ti on. Pla te lets are he te ro ge ne o us in si ze, den sity, and re ac ti vity. Me ta bo li cally and enz yma ti cally lar ger pla te lets are mo re ac ti ve than smal ler pla te lets. 9 Ele va ti on of MPV va lu es has be en shown in acu te co ro nary syndro mes and acu te myo car di al in farc ti on. 17-19 The in cre a sed MPV has be en re por ted in a num ber of pa ti ent gro ups with known co ro nary ar tery di se a - se risk fac tors, such as smo king, 20 di a be tes mel li - tus, 21 obe sity, 22 hyper ten si on, 23 and in cre a sed cho les te rol 24 when com pa red with he althy controls. The dif fe ren ce of our study from pre vi o us stu di es is that we exc lu ded the pa ti ents with hyper ten si on and di a be tes mel li tus. Be ca u se of this exc lu si on our samp le si ze was small. The re was al - so no sig ni fi cant dif fe ren ce bet we en SCF and control gro ups with res pect to body mass in dex, the per cen ta ges of smo king and le vels of cho les te rol in the pre sent study. So we conc lu ded that MPV va l- u es in cre a sed in pa ti ents with SCF re gard less of the se fac tors. Alt ho ugh the pat hoph ysi o lo gic mec ha nisms for in cre a sed pla te let ac ti va ti on in pa ti ents with SCF re ma ins to be lar gely unk nown, the ab nor mal slow flow pat tern in a co ro nary ar tery might le ad to throm bus for ma ti on and, hen ce, dis tal em bo li - za ti on or myo car di al in farc ti on. In a pre vi o us study, we ha ve shown that, MPV was sig ni fi cantly hig her in pa ti ents with co ro nary ar tery ec ta si a when com pa red with con trol sub jects. 25 In this previ o us study, we tho ught the si mi lar mec ha nism. In cre a sed pla te let ag gre ga bi lity and MPV was al so fo und in pa ti ents with car di ac syndro me X in which exer ci se in du ced myo car di al isc he mi a and an gi na co uld be se en wit ho ut obs truc ti ve co ro nary ar tery di se a se li ke SCF. 26,27 The re sults of the se stu - di es sup port our fin dings. The re can be an as so ci a ti on bet we en pla te let func ti on and co ro nary en dot he li al dysfunc ti on or im pa i red co ro nary flow. Inf lam ma ti on has al so be en sug ges ted to be invol ved in the pat hoph ysi o logy of SCF. Tur han et al. per for med a study, eva lu a ting plas ma so lub le adhe si on mo le cu les; in ter cel lu lar ad he si on mo le cu - le-1 (ICAM-1), vas cu lar cell ad he si on mo le cu le-1 (VCAM-1) and E-se lec tin as pos sib le in di ca tors of en dot he li al ac ti va ti on or inf lam ma ti on in pa ti ents with SCF, but with an gi og rap hi cally pro ven normal co ro nary ar te ri es. They sho wed that se rum ICAM-1, VCAM-1, and E-se lec tin con cen tra ti ons of pa ti ents with SCF we re fo und to be sig ni fi cantly hig her than tho se of con trol sub jects with nor mal co ro nary flow sug ges ting the pre sen ce of a mo re se ve re and ex ten si ve chro nic inf lam ma ti on in the co ro nary cir cu la ti on in the se pa ti ents. 5 In an ot her study, Li et al sho wed that plas ma le vels of inf lam - ma tory fac tors, CRP and IL-6 in pa ti ents with SCF we re fo und to be sig ni fi cantly hig her than tho se of con trol sub jects. 28 Pla te let si ze is re gu la ted at the le vel of the me - ga kar yocy te. It has be en shown that inf lam ma tory cyto ki nes such as in ter le u kin-3 or in ter le u kin-6 inf lu en ce me ga kar yocy te plo idy and can le ad to the pro duc ti on of mo re re ac ti ve and lar ger pla te lets. 29 The re fo re, IL-6, a ma jor inf lam ma tory cyto ki ne which in cre a sed in pa ti ents with SCF can ca u se an in cre a se in MPV va lu es by sti mu la ting the me ga - kar yocy te plo idy. As a re sult, inf lam ma tory pro cess in pa ti ents with SCF might be ca u se of in cre a sed MPV. MPV in cre a ses over ti me in ED TA-an ti co a gu - la ted samp les, 30 and this in cre a se was shown to be pro por ti o nal with the ti me pe ri od bet we en samp le col lec ti on and la bo ra tory analy sis. The re fo re, who - le blo od co unt inc lu ding MPV was de ter mi ned in less than one ho ur. Re cently, MPV has be en an in te res ting to pic in car di o vas cu lar re se arch. It is a simp le la bo ra tory me a su re ment which can be me a su red in al most all la bo ra to ri es and it can gu i de us to iden tify high risk pa ti ents with SCF. 282 Turkiye Klinikleri J Cardiovasc Sci 2010;22(3)

PLATELET VOLUME IS INCREASED IN PATIENTS WITH SLOW CORONARY FLOW Ercan VAROL et al The re are so me li mi ta ti ons of this study that sho uld be con cer ned. The small num ber of pa ti ents was the li mi ta ti on of the study. We exc lu ded the fac tors li ke hyper ten si on and di a be tes mel li tus that co uld af fect MPV. Be ca u se of that our samp le si ze was small. Anot her li mi ta ti on of this study is that analy sis was ba sed on a simp le ba se li ne de ter mi na - ti on that may not ref lect the pa ti ent sta tus over long pe ri ods. CONC LU SI ON In this study, we fo und that MPV, an in di ca tor of pla te let ag gre ga ti on, was sig ni fi cantly hig her in pati ents with SCF when com pa red with con trol gro - up. Furt her pros pec ti ve stu di es are ne e ded to es tab lish the pat hoph ysi o lo gi cal and cli ni cal sig ni - fi can ce of in cre a sed MPV and to in ves ti ga te the effect of an ti-pla te let agents in pa ti ents with SCF. 1. Tam be AA, De many MA, Zim mer man HA, Mas ca ren has E. An gi na pec to ris and slow flow ve lo city of dye in co ro nary ar te ri es-a new an gi og rap hic fin ding. Am He art J 1972;84(1): 66-71. 2. Mos se ri M, Ya rom R, Gots man MS, Ha sin Y. His to lo gic evi den ce for small-ves sel co ro nary ar tery di se a se in pa ti ents with an gi na pec to - ris and pa tent lar ge co ro nary ar te ri es. Cir cu - la ti on 1986;74(5):964-72. 3. Sez gin AT, Si gir ci A, Ba rut cu I, To pal E, Sezgin N, Oz de mir R, et al. Vas cu lar en dot he li al func ti on in pa ti ents with slow co ro nary flow. Co ron Ar tery Dis 2003;14(2):155-61. 4. Pek de mir H, Cin VG, Ci cek D, Cam sa ri A, Ak - kus N, Dö ven O, et al. Slow co ro nary flow may be a sign of dif fu se at he rosc le ro sis. Con tri bu - ti on of FFR and IVUS. Ac ta Car di ol 2004;59 (2):127-133. 5. Tur han H, Say dam GS, Er bay AR, Ayaz S, Ya sar AS, Ak soy Y, et al. In cre a sed plas ma so lub le ad he si on mo le cu les; ICAM-1, VCAM- 1, and E-se lec tin le vels in pa ti ents with slow co ro nary flow. Int J Car di ol 2006;108(2):224-30. 6. Fra gas so G, Chi erc hi a SL, Ari o li F, Ca ran - den te O, Ge ro sa S, Car li no M, et al. Co ro nary slow-flow ca u sing tran si ent myo car di al hypo - per fu si on in pa ti ents with car di ac syndro me X: long-term cli ni cal and func ti o nal prog no sis. Int J Car di ol 2009;137(2):137-44. 7. Tsi a ra S, Eli saf M, Jag ro op IA, Mik ha i li dis DP. Pla te lets as pre dic tors of vas cu lar risk: is the - re a prac ti cal in dex of pla te let ac ti vity? Clin Appl Thromb He most 2003;9(3):177-90. 8. Park Y, Scho e ne N, Ha ris W. Me an pla te let vo lu me as an in di ca tor of pla te let ac ti va ti on: met ho do lo gi cal is su es. Pla te lets 2002;13(5-6):301-6. 9. Bo os CJ, Lip GY. As sess ment of me an pla te - let vo lu me in co ro nary ar tery di se a se - what do es it me an? Thromb Res 2007;120(1):11-3. 10. Mar tin JF, Trow brid ge EA, Sal mon GL, Plumb J. The bi o lo gi cal sig ni fi can ce of pla te let vo lu - me: its re la ti ons hip to ble e ding ti me, pla te let REFERENCES throm bo xa ne B2 pro duc ti on and me ga kar - yocy te nuc le ar DNA con cen tra ti on. Thromb Res 1983;32(5):443-60. 11. Ja ku bows ki JA, Thomp son CB, Va il lan co urt R, Va le ri CR, Dey kin D. Arac hi do nic acid meta bo lism by pla te lets of dif fe ring si ze. Br J Ha - e ma tol 1983;53(3):503-11. 12. Gi les H, Smith RE A, Mar tin JF. Pla te let glycop ro te in IIb-II I a and si ze are in cre a sed in acu - te myo car di al in farc ti on. Eur J Clin In vest 1994;24(1):69-72. 13. Gok ce M, Kap lan S, Te ke li og lu Y, Er do gan T, Ku cu kos ma nog lu M. Pla te let func ti on di sor der in pa ti ents with co ro nary slow flow. Clin Car di - ol 2005;28(3):145-8. 14. Ce lik T, Yuk sel UC, Bu gan B, Iyi soy A, Ce lik M, De mir kol S, et al. In cre a sed pla te let ac ti - va ti on in pa ti ents with slow co ro nary flow. J Thromb Throm boly sis 2010;29(3):310-5. 15. Sen N, Ba sar N, Ma den O, Oz can F, Oz lu MF, Gun gor O, et al. In cre a sed me an pla te let vo l- u me in pa ti ents with slow co ro nary flow. Pla - te lets 2009;20(1):23-8. 16. Nur ka lem Z, Al per AT, Or han AL, Zen cir ci AE, Sa ri I, Erer B, et al. Me an pla te let vo lu me in pa ti ents with slow co ro nary flow and its re la ti - ons hip with cli ni cal pre sen ta ti on. Turk Kar di - yol Dern Ars 2008;36(6):363-7. 17. Jag ro op IA, Mik ha i li dis DP. Me an pla te let vo l- u me is an in de pen dent risk fac tor for myo car - di al in farc ti on but not for co ro nary ar tery di se a se. Br J Ha e ma tol 2003; 120(1):169-70. 18. Va rol E, Ic li A, Ozay din M, Er do gan D, Ars lan A. Me an pla te let vo lu me is ele va ted in pa ti ents with myo car di al in farc ti on with nor mal co ro nary ar te ri es, as in pa ti ents with myo car di al in farc ti - on with obs truc ti ve co ro nary ar tery di se a se. Scand J Clin Lab In vest 2009;69(5):570-4. 19. Yil maz MB, Ci han G, Gu ray Y, Gu ray U, Ki sa - cik HL, Sas maz H, et al. Ro le of me an pla te - let vo lu me in tri ag ging acu te co ro nary syndro mes. J Thromb Throm boly sis 2008;26 (1):49-54. 20. Ka ri o K, Mat su o T, Na ka o K. Ci ga ret te smo k- ing in cre a ses the me an pla te let vo lu me in el d- erly pa ti ents with risk fac tors for at he ros- cle rosis. Clin Lab Ha e ma tol 1992;14(4):281-7. 21. Pa pa nas N, Syme o ni dis G, Mal te zos E, Mav - ri dis G, Ka ra va ge li E, Vos na ki dis T, et al. Me - an pla te let vo lu me in pa ti ents with type 2 di a be tes mel li tus. Pla te lets 2004;15(8):475-8. 22. Co ban E, Oz do gan M, Ya zi ci og lu G, Ak cit F. The me an pla te let vo lu me in pa ti ents with obesity. Int J Clin Pract 2005;59(8):981-2. 23. Na dar S, Blann AD, Lip GY. Pla te let morp ho - logy and plas ma in di ces of pla te let ac ti va ti on in es sen ti al hyper ten si on: ef fects of am lo di pi - ne-ba sed an tihy per ten si ve the rapy. Ann Med 2004;36(7):552-7. 24. Pat han sa li R, Smith N, Bath P. Al te red me gakar yocy te-pla te let ha e mos ta tic axis in hyperc - ho les te ro la e mi a. Pla te lets 2001;12(5):292-7. 25. Va rol E, Ak cay S, Ozay din M, Er do gan D, Do - gan A. Me an pla te let vo lu me in pa ti ents with co ro nary ar tery ec ta si a. Blo od Co a gul Fib ri - noly sis 2009;20(5):321-4. 26. Cay S, Bi yi kog lu F, Ci han G, Kork maz S. Me - an pla te let vo lu me in the pa ti ents with car di ac syndro me X. J Thromb Throm boly sis 2005;20 (3):175-8. 27. Lan za GA, An dre ot ti F, Ses ti to A, Sci ah ba si A, Cre a F, Ma se ri A. Pla te let ag gre ga bi lity in car di ac syndro me X. Eur He art J 2001;22(20): 1924-30. 28. Li JJ, Qin XW, Li ZC, Zeng HS, Ga o Z, Xu B, et al. In cre a sed plas ma C-re ac ti ve pro te in and in ter le u kin-6 con cen tra ti ons in pa ti ents with slow co ro nary flow. Clin Chim Ac ta 2007;385(1-2):43-7. 29. De bi li N, Mas se JM, Katz A, Gu ic hard J, Breton-Go ri us J, Va inc hen ker W. Ef fects of the re com bi nant he ma to po i e tic growth fac tors inter le u kin-3, in ter le u kin-6, stem cell fac tor, and le u ke mi a in hi bi tory fac tor on the me ga kar - yocy tic dif fe ren ti a ti on of CD34s cells. Blo od 1993;82(1):84-95. 30. Bath PM, But ter worth RJ. Pla te let si ze: me a - su re ment, physi o logy and vas cu lar di se a se. Blo od Co a gul Fib ri noly sis 1996;7(2):157-61. Turkiye Klinikleri J Cardiovasc Sci 2010;22(3) 283