1. Russian Cardiology Research and Production Complex 2. Petersburg Nuclear Physics Institute; North-Western State Medical University 3. Petersburg Nuclear Physics Institute
Increased mean platelet volume (MPV) is an independent risk factor of thrombotic events in patients with cardiovascular diseases. Interactions of MPV with platelet aggregation activity and contents of glycoprotein (GP) IIb-IIIa (aIIb/b3 integrin, fibrinogen receptor) and GP Ib (von Willebrand factor receptor) were investigated in this study. Investigation was performed in a group of healthy volunteers (n = 38) and in a group of patients with acute coronary syndrome (ACS). In patients blood was collected at days 1, 3-5 and 8-12 after ACS development. As an antiaggregant therapy all patients received acetylsalicylic acid (ASA, inhibitor of thromboxane A2 synthesis) and most of them – clopidogrel (ADP receptor antagonist) with the exception of part of the patients (n=44) at day 1 who had not taken clopidogrel before first blood collection. In volunteers platelet aggregation was stimulated by 1.25, 2.5, 5 and 20 M ADP, and in patients – by 5 and 20 M ADP. GP IIb-IIIa and GP Ib content on platelet surface was measured using 125I-labelled monoclonal antibodies. GP IIb-IIIa and GP Ib genetic polymorphisms were determined in ACS patients. In healthy donors significant correlations between MPV and aggregation levels were revealed at 1.25 and 2.5 M ADP (coefficients of correlation (r) - 0.396 and 0.373, p<0.05) and at 5 and 20 those interactions did not reach significant level (r - 0.279 and 0.205, p>0.05). Correlations between MPV and aggregation levels were observed at day 1 of ACS in a subgroup of patients who received ASA but had not started clopidogrel treatment (r - 0.526, p<0.01 and 0.368, p<0.05 for 5 and 20 M ADP respectively). Interactions between these parameters were not registered upon combined treatment with ASA and clopidogrel. Strong direct correlations between MPV and GP IIb-IIIa and GP Ib contents were detected in healthy donors and ACS patients (at all time points) – r from 0.439 to 0.647 (p£0.001 for all correlations). Genetic polymorphisms of GP IIb-IIIa (GP IIIa Leu33Pro) and GP Ib ((-5)T/C ( Kozak ) and Thr145Met) identified in ACS patients did not affect expression levels of corresponding glycoproteins. The data obtained indicated that increased MPV values correlate with increased platelet aggregation activity and enhanced GP IIb-IIIa and GP Ib expression.
Khaspekova S.G., Zyuryaev I.T., Yakushkin V.V., Naimushin Ya.A., Sirotkina O.V., Zaytseva N.O., Ruda M.Ya., Mazurov A.V. (2014) Mean platelet volume: interactions with platelet aggregation activity and glycoprotein IIb-IIIa and Ib expression levels. Biomeditsinskaya Khimiya, 60(1), 94-108.
Khaspekova S.G. et al. Mean platelet volume: interactions with platelet aggregation activity and glycoprotein IIb-IIIa and Ib expression levels // Biomeditsinskaya Khimiya. - 2014. - V. 60. -N 1. - P. 94-108.
Khaspekova S.G. et al., "Mean platelet volume: interactions with platelet aggregation activity and glycoprotein IIb-IIIa and Ib expression levels." Biomeditsinskaya Khimiya 60.1 (2014): 94-108.
Khaspekova, S. G., Zyuryaev, I. T., Yakushkin, V. V., Naimushin, Ya. A., Sirotkina, O. V., Zaytseva, N. O., Ruda, M. Ya., Mazurov, A. V. (2014). Mean platelet volume: interactions with platelet aggregation activity and glycoprotein IIb-IIIa and Ib expression levels. Biomeditsinskaya Khimiya, 60(1), 94-108.
Klovaite J., Benn M., Yazdanyar S., Nordestgaard B.G. (2011) J. Thromb. Haemost., 9, 49-56. Scholar google search
Goncalves S.C., Labinaz M., Le May M., Glover C., Froeschl M., Marquis J.F., O’Brien E., Shukla D., Ruchin P., Sookur D., Ha A., Sop D. (2011) Am. J. Cardiol., 107, 204-209. Scholar google search
Thompson C.B., Jakubowsky J.A., Quinn P.G., Deykin D., Valeri C.R. (1983) J. Lab. Clin. Med., 101, 205-213. Scholar google search
Martin J.F., Trowbridge E.A., Salmon G., Plumb J. (1983) Thromb. Res., 32, 443-460. Scholar google search
Wong T., Pedvis L., Frojmovic M. (1989) Thromb. Haemost., 62, 733-741. Scholar google search
Varga-Szabo D., Pleines I., Nieswandt B. (2008) Arterioscler. Thromb. Vasc. Biol., 28, 403-412. CrossRef Scholar google search
Ikeda Y., Matsubara Y., Kamata T. (2008) In: Platelets in hematologic and cardiovascular disorders. (Gesele P., Fuster V., Lopez J.A., Page C.P., Vermylen J., eds.). Cambridge: Cambridge University Press. pp. 21-36. Scholar google search
Evangelista V., Smyth S.S. (2013) In: Platelets. Third edition. (Michelson A.D., ed.). Amsterdam, Boston, Heidelberg et al: Academic Press, Elsevier Inc. pp. 295-312. Scholar google search
O’Halloran A.M., Curtin R., O’Connar F., Dooley M., Fitzgerald A., O’Brian J.K., Fitzgerald D.I., Shields D.C. (2006) Br. J. Haematol., 132, 494-502. Scholar google search
Kunucki T.J., Williams S.A., Nugent D.J., Yeager M. (2012) Atherioscler. Thromb. Vasc. Biol., 32, 147-152. CrossRef Scholar google search
Afshar-Kharghan V., Li C.Q., Khoshnevis-Asi M., Lopez J.A. (1999) Blood, 94, 186-191. Scholar google search
Jilma-Stohlawetz P., Homoncik M., Jilma B., Knechtelsdorfer M., Unger P., Mannhalter C., Santoso S., Panzer S. (2003) Br. J. Haematol., 120, 652-655. CrossRef Scholar google search
Corral J., Lozano M.L., Gonzalez-Conejero R., Martinez C., Iniesta J.A., Rivera J., Vicente V. (2000) Thromb. Haemost., 83, 23-28. Scholar google search
Joutsi-Korhonen L., Smethurst P.A., Rankin A., Gray E., Jsseldijk M., Onley C.M., Watkins N.A., Williamson L.M., Goodall A.H., de Groot P.G., Farndale R.W., Ouwehand W.H. (2003) Blood, 101, 4372-4379. CrossRef Scholar google search
Furihata K., Clemetson K.J., Deguchi H., Kunicki T.J. (2001) Artherioscler. Thromb. Vasc. Biol., 21, 1857-1863. CrossRef Scholar google search
Roest M., Sixma J.J., Wu Y.P., Ijsseldijk M.J., Tempelman M., Slootweg P.J., de Groot P.G., van Zanten G.H. (2000) Blood, 96, 1433-1437. Scholar google search
Kunicki T.J., Kritzik M., Annis D.S., Nugent D.J. (1997) Blood, 89, 1939-1943. Scholar google search
Kunicki T.J., Orchekowski R., Honda Y. (1993) Blood, 82, 2693-2703. Scholar google search
Best D., Senis Y.A., Jarvis G.E., Eagleton H.J., Roberts D.J., Saito T., Jung S.M., Moroi M., Harrison P., Green F.R., Watson S.P. (2003) Blood, 102, 2811-2818. CrossRef Scholar google search
Douglas H., Michaelides K., Gorog D.A., Durante-Mangoni E., Ahmed N., Davies G.J., Tuddenham E.G.D. (2002) Heart, 87, 70-74. CrossRef Scholar google search
Khaspekova S.G., Sirotkina O.V., V Shimanova Yu. V., Mazurov A.V. (2008) Biomeditsinskaya Khimiya, 54(3), 361-371 Scholar google search
