The relationship of pregnancy losses with frequently-used hematologic parameters

Atakan Turgutkaya; Ayşe Hilal Eroğlu Küçükdiler; Alper Seyhan; Ali Bolaman; Zehra Manav Yiğit; Gökay Bozkurt; İrfan Yavaşoğlu

doi:10.19161/etd.1549581

TR EN

Gebelik kayıplarının sık kullanılan hematolojik parametrelerle ilişkisi

Öz

Amaç: Tekrarlayan gebelik kaybı (TGK), hematoloji ve obstetrik alanında sık karşılaşılan ve endişe verici bir konudur; patogenezi belirsizdir. Bu çalışma, TGK ile potansiyel olarak ilişkili hematolojik faktörleri, özellikle trombofiliyi araştırmayı amaçlamaktadır. Gereç ve Yöntem: 2012-2024 yılları arasında en az bir gebelik kaybı yaşamış 170 kadın hastayı retrospektif olarak analiz ettik; antiphospholipid antikorları veya tanımlanabilir nedenleri olanlar dışlandı. Hastalar, bir veya iki düşük yapmış olanlar (grup A) ve ikiden fazla düşük yapmış olanlar (grup B) şeklinde iki gruba ayrıldı. Trombofili tarama testleri, hemogram ve koagülasyon parametrelerini değerlendirdik; analiz için SPSS 25.0 sürümü kullanıldı ve p < 0,05 değeri anlamlı kabul edildi. Bulgular: Dokuz hastanın (%5,3) bir, 71 hastanın (%41,8) iki, 60 hastanın (%35,3) üç, 21 hastanın (%12,4) dört, dört hastanın (%2.4) beş ve beş hastanın (%2.9) altı düşük öyküsü mevcuttu. Trombofili, protein C, S ve antitrombin seviyeleri açısından araştırılan genetik mutasyonlar ile her iki gruptaki gebelik kaybı sayısı arasında anlamlı bir fark bulunamadı. Hemogram parametreleri ve koagülasyon parametreleri arasında, her iki grup için aPTT dışında anlamlı bir fark yoktu. Grup B'nin aPTT değeri, grup A'nınkinden anlamlı derecede düşük bulundu (p = 0,04). Sonuç: TGK durumunda hematolojik parametrelerde çelişkili sonuçlar yaygındır ve homojen sonuçlar elde etmek kolay değildir. Kolay ve hızlı bir şekilde ölçülebilen düşük bir aPTT değeri, TGK'nın öngörülmesine yardımcı olabilecek bir parametre olabilir.

Anahtar Kelimeler

The relationship of pregnancy losses with frequently-used hematologic parameters

Abstract

Aim: Recurrent pregnancy loss (RPL) is a common and undesirable condition in hematology and obstetrics practice. Pathogenesis for most cases remains undetermined. Thrombophilia may be a potential factor for these patients. Here, we aimed to investigate hematological parameters that have the potential to contribute to or predict RPL and to present our data as a single-center experience. Materials and Methods: One hundred seventy female patients with at least one pregnancy loss between the years 2012 and 2024 were included retrospectively. The mean age of the patients was 34.48 ± 6.02. Patients with antiphospholipid antibodies and miscarriage due to an identifiable etiology (maternal anatomic and endocrine abnormalities, infectious causes, trauma, chromosomal abnormalities) were excluded from the study. Patients were divided into two groups, defined as patients with one or two miscarriages and more than two miscarriages, respectively. Thrombophilia screening tests (mutations and protein C/S/antithrombin levels), blood count and coagulation parameters were recorded and investigated whether there was a significant correlation in terms of miscarriage in the two groups. Results: Nine patients (5.3%), 71 patients (41.8%), 60 patients (35.3%), 21 patients (12.4%), four patients (2.4%), and five patients (2.9%) had a history of one, two, three, four, five, and six miscarriages, respectively. No significant difference was found between the genetic mutations investigated in terms of thrombophilia, protein C, S, and antithrombin levels, and the number of pregnancy losses in both groups. There was no significant difference between hemogram parameters and coagulation parameters except aPTT for both groups. The aPTT value of group B was found to be significantly lower than that of group A (p=0.04). Conclusion: Conflicting results in hematologic parameters in case of RPL are common and it is not easy to obtain homogeneous results. However, a low aPTT value, a parameter that can be easily and quickly measured, may be a parameter that can help predict RPL.

Keywords

Destekleyen Kurum

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Etik Beyan

Ethical committee approval has been obtained (Aydın Adnan Menderes University Date: 20.11.2023-Number: 453317)

Teşekkür

Thanks to Dr Kübra Ecem Turgutkaya from Aydın Adnan Menderes University Public Health Department for making statistical analysis of the study.

Kaynakça

Diejomaoh MF: Recurrent spontaneous miscarriage is still a challenging diagnostic and therapeutic quagmire. Med Princ Practice, 2015; 24: 38–55
Practice Committee of American Society for Reproductive Medicine: Definitions of infertility and recurrent pregnancy loss. Fertil Steril, 2013; 99: 63
Jauniaux E, Farquharson RG, Christiansen OB, Exalto N: Evidence-based guidelines for the investigation and medical treatment of recurrent miscarriage. Hum Reprod, 2006; 21: 2216–22.
Kamal AH, Tefferi A, Pruthi RK. How to interpret and pursue an abnormal prothrombin time, activated partial thromboplastin time, and bleeding time in adults. Mayo Clin Proc. 2007 Jul;82(7):864-73. doi: 10.4065/82.7.864
Jiang L, Du Y, Lu Y, Wu X, Tong X. Monitoring of hemostatic parameters for early prediction of first-trimester miscarriage. Biomarkers. 2021 Sep;26(6):532-538. doi: 10.1080/1354750X.2021.1933592.
Cui C, Yang S, Zhang J, Wang G, Huang S, Li A, et al. Trimester-specific coagulation and anticoagulation reference intervals for healthy pregnancy. Thromb Res. 2017 Aug;156:82-86. doi: 10.1016/j.thromres.2017.05.021.
Abortion care guideline, World Health Organization, Geneva 2022. Available at: https://www.who.int/publications/i/item/9789240039483. Last access: 18.12.2024.
American College of Obstetricians and Gynecologists' Committee on Practice Bulletins—Gynecology. ACOG Practice Bulletin No. 200: Early Pregnancy Loss. Obstet Gynecol .2018 Nov;132(5):e197-e207. doi: 10.1097/AOG.0000000000002899.

Quenby S, Gallos ID, Dhillon-Smith RK, Podesek M, Stephenson MD, Fisher J, et al. Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss. Lancet. 2021 May 1;397(10285):1658-1667. doi: 10.1016/S0140-6736(21)00682-6.
Turesheva A, Aimagambetova G, Ukybassova T, Marat A, Kanabekova P, Kaldygulova L, et al. Recurrent Pregnancy Loss Etiology, Risk Factors, Diagnosis, and Management. Fresh Look into a Full Box. J Clin Med. 2023 Jun 15;12(12):4074. doi: 10.3390/jcm12124074.
Tulandi T, Al-Fozan HM. Recurrent pregnancy loss: Management. https :// www.uptodate.com/contents/recurrent-pregnancy-loss-management. Last access: 18 July 2024
Quenby S, Booth K, Hiller L, Coomarasamy A, de Jong PG, Hamulyák EN, Scheres LJ, van Haaps TF, Ewington L, Tewary S, Goddijn M, Middeldorp S; ALIFE2 Block Writing Committee; ALIFE2 Investigators. Heparin for women with recurrent miscarriage and inherited thrombophilia (ALIFE2): an international open-label, randomised controlled trial. Lancet. 2023 Jul 1;402(10395):54-61. doi: 10.1016/S0140-6736(23)00693-1
Schleussner E, Kamin G, Seliger G, Rogenhofer N, Ebner S, Toth B, Schenk M, Henes M, Bohlmann MK, Fischer T, Brosteanu O, Bauersachs R, Petroff D; ETHIG II group. Low-molecular-weight heparin for women with unexplained recurrent pregnancy loss: a multicenter trial with a minimization randomization scheme. Ann Intern Med. 2015 May 5;162(9):601-9. doi: 10.7326/M14-2062.
Sever Erdem, Z., Cayir, Y., Kosan, Z., Erdem, H. B. (2020). Is There Any Relation Between Recurrent Miscarriage and Complete Blood Count Values? A Case-Control Study. Konuralp Medical Journal, 12(1), 39-43. https://doi.org/10.18521/ktd.518494
Al-Husban N, Al-Atrash H, Alhayek N, Al-Soud K, Alhusban M. Platelet and White Blood Cell (WBC) Counts in the First Trimester and Pregnancy Outcome: Prospective Controlled Study. J. Fetal Med. (June 2019) 6:89–94. DOI: 10.1007/s40556-019-00202-0.
Ogasawara M, Aoki K, Katano K, Aoyama T, Ozaki Y, Suzumori K. Activated partial thromboplastin time is a predictive parameter for further miscarriages in cases of recurrent fetal loss. Fertil Steril. 1998 Dec;70(6):1081-4. doi: 10.1016/s0015-0282(98)00336-7.
Yao, H., Ji, Y., & Zhou, Y. (2022). Analysis of blood coagulation indexes, thromboelastogram and autoantibodies in patients with recurrent pregnancy loss. Pakistan journal of medical sciences, 38(7), 2005–2010. https://doi.org/10.12669/pjms.38.7.6284
Ali A, Mohan P, Kareem H, Muhammed MK. Elevated Factor VIII Levels and Shortened APTT in Recurrent Abortions. J Clin Diagn Res. 2016 Jan;10(1):EC04-6. doi: 10.7860/JCDR/2016/17841.7080. Epub 2016 Jan 1. PMID: 26894070; PMCID: PMC4740597.
Lockwood CJ, Bauer, KA. Inherited thrombophilias in pregnancy. Available at: https://www.uptodate.com/contents/inherited-thrombophilias-in-pregnancy. Last access 18.12.2024
Sergi C, Al Jishi T, Walker M. Factor V Leiden mutation in women with early recurrent pregnancy loss: a meta-analysis and systematic review of the causal association. Arch Gynecol Obstet. 2015 Mar;291(3):671-9. doi: 10.1007/s00404-014-3443-x.
Gao H, Tao FB. Prothrombin G20210A mutation is associated with recurrent pregnancy loss: a systematic review and meta-analysis update. Thromb Res. 2015 Feb;135(2):339-46. doi: 10.1016/j.thromres.2014.12.001,
Fakhr-Eldeen, Abeer & Badawy, A & Als, Baraah & Fawzy, Manal. (2017). Factor V Leiden G1691A and Prothrombin G20210A mutations are associated with repeated spontaneous miscarriage in Northern area of Saudi Arabia. Genetics and Molecular Research. 16. 10.4238/gmr16039810.
Bigdeli R, Younesi MR, Panahnejad E, Asgary V, Heidarzadeh S, Mazaheri H, et al. Association between thrombophilia gene polymorphisms and recurrent pregnancy loss risk in the Iranian population. Syst Biol Reprod Med. 2018 Aug;64(4):274-282. doi: 10.1080/19396368.2018.1456576.
Jusić A, Balić D, Avdić A, Pođanin M, Balić A. The association of factor V G1961A (factor V Leiden), prothrombin G20210A, MTHFR C677T and PAI-1 4G/5G polymorphisms with recurrent pregnancy loss in Bosnian women. Med Glas (Zenica). 2018 Aug 1;15(2):158-163. doi: 10.17392/948-18.
Perés Wingeyer S, Aranda F, Udry S, Latino J, de Larrañaga G. Inherited thrombophilia and pregnancy loss. Study of an Argentinian cohort. Med Clin (Barc). 2019 Apr 5;152(7):249-254. English, Spanish. doi: 10.1016/j.medcli.2017.12.019.
Parand A, Zolghadri J, Nezam M, Afrasiabi A, Haghpanah S, Karimi M. Inherited thrombophilia and recurrent pregnancy loss. Iran Red Crescent Med J. 2013 Dec;15(12):e13708. doi: 10.5812/ircmj.13708.
Yengel I, Yorulmaz T, Api M. Association between FVL G1691A, FII G20210A, and MTHFR C677T and A1298C polymorphisms and Turkish women with recurrent pregnancy loss. Med Glas (Zenica). 2020 Feb 1;17(1):129-135. doi: 10.17392/1062-20.
Preston FE, Rosendaal FR, Walker ID, Briët E, Berntorp E, Conard J, et al. Increased fetal loss in women with heritable thrombophilia. Lancet. 1996 Oct 5;348(9032):913-6. doi: 10.1016/s0140-6736(96)04125-6
Liu X, Chen Y, Ye C, Xing D, Wu R, Li F, et al. Hereditary thrombophilia and recurrent pregnancy loss: a systematic review and meta-analysis. Hum Reprod. 2021 Apr 20;36(5):1213-1229. doi: 10.1093/humrep/deab010.
Dizon-Townson D, Miller C, Sibai B, Spong CY, Thom E, Wendel G Jr, et al. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. The relationship of the factor V Leiden mutation and pregnancy outcomes for mother and fetus. Obstet Gynecol. 2005 Sep;106(3):517-24. doi: 10.1097/01.AOG.0000173986.32528.ca.
Said JM, Higgins JR, Moses EK, Walker SP, Borg AJ, Monagle PT, et al. Inherited thrombophilia polymorphisms and pregnancy outcomes in nulliparous women. Obstet Gynecol. 2010 Jan;115(1):5-13. doi: 10.1097/AOG.0b013e3181c68907.
Lindqvist PG, Svensson PJ, Marsaál K, Grennert L, Luterkort M, Dahlbäck B. Activated protein C resistance (FV:Q506) and pregnancy. Thromb Haemost. 1999 Apr;81(4):532-7. PMID: 10235434.
Silver RM, Zhao Y, Spong CY, Sibai B, Wendel G Jr, Wenstrom K, et al. Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (NICHD MFMU) Network. Prothrombin gene G20210A mutation and obstetric complications. Obstet Gynecol. 2010 Jan;115(1):14-20. doi: 10.1097 / AOG.0b013e3181c88918
Dimitriadis, E., Menkhorst, E., Saito, S. et al. Recurrent pregnancy loss. Nat Rev Dis Primers 6, 98 (2020). https://doi.org/10.1038/s41572-020-00228-z

Ayrıntılar

Birincil Dil

İngilizce

Konular

Klinik Tıp Bilimleri (Diğer) , Kadın Hastalıkları ve Doğum

Bölüm

Araştırma Makalesi

Yazarlar

Atakan Turgutkaya ^*
0000-0001-8428-4730
Türkiye

Ayşe Hilal Eroğlu Küçükdiler
0000-0002-2604-3127
Türkiye

Alper Seyhan
0000-0003-0543-6180
Türkiye

Ali Bolaman
0000-0003-0651-5462
Türkiye

Zehra Manav Yiğit
0000-0002-9505-0371
Türkiye

Gökay Bozkurt
0000-0002-6963-3186
Türkiye

İrfan Yavaşoğlu
0000-0003-1703-2175
Türkiye

Yayımlanma Tarihi

10 Haziran 2025

Gönderilme Tarihi

13 Eylül 2024

Kabul Tarihi

3 Mart 2025

Yayımlandığı Sayı

Yıl 2025 Cilt: 64 Sayı: 2

DOI

https://doi.org/10.19161/etd.1549581

IZ

https://izlik.org/JA96YL28FT

Kaynak Göster

RIS / Bibtex

Vancouver

1.Atakan Turgutkaya, Ayşe Hilal Eroğlu Küçükdiler, Alper Seyhan, Ali Bolaman, Zehra Manav Yiğit, Gökay Bozkurt, İrfan Yavaşoğlu. The relationship of pregnancy losses with frequently-used hematologic parameters. ETD. 01 Haziran 2025;64(2):310-8. doi:10.19161/etd.1549581