Letter to the Editor

Plateletcrit May Not be a Marker for Recurrent Pregnancy Loss

Clinical and Applied Thrombosis/Hemostasis 1-2 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/1076029615579100 cat.sagepub.com

Cengiz BEYAN, MD1, and Esin BEYAN, MD2 Keywords abortion, habitual, biological markers, blood platelets, mean platelet volume, platelet count

We read with a great interest the article of Aynioglu et al about plateletcrit (PCT) and recurrent pregnancy loss (RPL).1 We would like to comment on this study. Firstly, the authors suggested that methylenetetrahydrofolate reductase (MTHFR) gene mutations were the most common hereditary thrombophilia for thrombosis in pregnancy. However, Leiden Multiple Environmental and Genetic Assessment (MEGA) study which performed on 4375 patients with venous thrombosis or pulmonary embolism and from 4856 controls showed no association between the common MTHFR 677CT polymorphism and venous thrombosis.2 According to the results of other studies, MTHFR mutations do not seem the predisposing cause of venous thromboembolism in either or no pregnant women, too.3-5 Thus, the American College of Obstetricians and Gynecologists and the Royal College of Obstetricians and Gynecologists do not recommend assessing MTHFR polymorphisms for evaluation of etiology of thrombophilia for venous thromboembolism in pregnancy.6,7 Secondly, the authors alleged that mean platelet volume (MPV), platelet distribution width (PDW), and PCT are predictive for platelet aggregation. Now, platelet indices are not used as platelet function tests. Turbidometric platelet aggregometry is the gold standard test for platelet functions. Platelet indices do not correlate with optical platelet aggregation responses usage with turbidometric platelet aggregometry.8-10 Moreover, Beyan et al found that severe platelet aggregation abnormalities were absent in patients with RPL.11 Additionally, PCT does not predict more than MPV. Determinations of complete blood count were done using a Beckman Coulter LH 780 analyzer (Beckman Coulter, Miami, Florida) in this study. According to operator’s guide of this analyzer, PCT and PDW parameters are derived parameters and are for research use only. They should not be used in diagnostic procedures.12 The MPV is measured directly from analysis of the platelet distribution curve, and PCT is calculated according to the following formula: PCT ¼ platelet count  MPV/10 000. So reliability of PCT is directly related to MPV. Another critical issue is that MPV has technological limitations and variations in measurement procedure. Platelet size progressively increases with time using EDTA as an anticoagulant. Jackson and Carter notified that MPV increased up to 30% within 5 minutes of exposure and further by 10% to 15% over the next 2 hours.13 Lance et al presented that timing was important when measuring

MPV and optimal measuring time with EDTA should be 120 minutes after venipuncture.14 Because the measurement time of samples was unknown in this retrospective study, reliability of data was questionable. As a result, PCT may not be a marker for RPL. References 1. Aynıoglu O, Isık H, Sahbaz A, et al. Can plateletcrit be a marker for recurrent pregnancy loss [published online December 29, 2014]? Clin Appl Thromb Hemost. 2014. 2. Bezemer ID, Doggen CJ, Vos HL, et al. No association between the common MTHFR 677CT polymorphism and venous thrombosis: results from the MEGA study. Arch Intern Med. 2007;167(5): 497-501. 3. Simone B, De Stefano V, Leoncini E, et al. Risk of venous thromboembolism associated with single and combined effects of factor V Leiden, prothrombin 20210A and methylenetethraydrofolate reductase C677T: a meta-analysis involving over 11,000 cases and 21,000 controls. Eur J Epidemiol. 2013;28(8):621-647. 4. Hickey SE, Curry CJ, Toriello HV. ACMG practice guideline: lack of evidence for MTHFR polymorphism testing. Genet Med. 2013;15(2):153-156. 5. McColl MD, Ellison J, Reid F, et al. Prothrombin 20210 G–>A, MTHFR C677T mutations in women with venous thromboembolism associated with pregnancy. BJOG. 2000;107(4):565-569. 6. American College of Obstetricians and Gynecologists Women’s Health Care Physicians. ACOG practice bulletin No. 138: inherited thrombophilias in pregnancy. Obstet Gynecol. 2013;122(3):706-717. 7. Reducing the risk of thrombosis and embolism during pregnancy and puerperium. Green-top Guideline No. 37a. Published November 2009. Website: https://www.rcog.org.uk/globalassets/documents/ guidelines/gtg37areducingriskthrombosis.pdf. Accessed January 08, 2015.

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Department of Hematology, Gulhane Military Medical Academy, Ankara, Turkey 2 Department of Internal Medicine, Kecioren Training and Research Hospital, Ankara, Turkey Corresponding Author: Cengiz Beyan, Department of Hematology, Gulhane Military Medical Academy, Etlik, 06018 Ankara, Turkey. Email: [email protected]; [email protected]

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Clinical and Applied Thrombosis/Hemostasis

8. Ho CH, Chan IH. The influence of time of storage, temperature of storage, platelet number in platelet-rich plasma, packed cell, mean platelet volume, hemoglobin concentration, age, and sex on platelet aggregation test. Ann Hematol. 1995;71(3):129-133. 9. Beyan C, Kaptan K, Ifran A. Platelet count, mean platelet volume, platelet distribution width, and plateletcrit do not correlate with optical platelet aggregation responses in healthy volunteers. J Thromb Thrombolysis. 2006;22(3):161-164. 10. De Luca G, Verdoia M, Cassetti E, et al. Mean platelet volume is not associated with platelet reactivity and the extent of coronary artery disease in diabetic patients. Blood Coagul Fibrinolysis. 2013;24(6):619-624.

11. Beyan C, Kaptan K, Ifran A. Platelet aggregation abnormalities in patients with recurrent fetal losses. Thromb Res. 2007;121(3): 327-331. 12. Research use only (RUO) options for COULTER LH series hematology systems. Published 2006. Website: http://www.yeec.com/ uploadimages1/forum/2008-1/2008119485325988.pdf. Accessed January 09, 2015. 13. Jackson SR, Carter JM. Platelet volume: laboratory measurement and clinical application. Blood Rev. 1993;7(2):104-113. 14. Lance´ MD, van Oerle R, Henskens YM, et al. Do we need time adjusted mean platelet volume measurements? Lab Hematol. 2010;16(3):28-31.

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Plateletcrit May Not be a Marker for Recurrent Pregnancy Loss.

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