EFFICACY OF THE METHOD OF SCREENING FOR THROMBOPHILIA IN WOMEN WITH RECURRENT PREGNANCY LOSS

Thrombophilia is known for its role in the pathogenesis of spontaneous loss of pregnancy. However, in-depth hemostasis tests are costly, and cannot be routinely used. Therefore, the aim of this study was to develop a method adjustable to screening for thrombophilia in women with recurrent pregnancy loss and also to evaluate its efficacy.

Materials and methods. A comprehensive examination – clinical, laboratory and instrumental – was performed in 103 women with spontaneous pregnancy loss in the past and 33 women (control) with two or more spontaneous deliveries without significant complications. Diagnosis of thrombophilia was made on the basis of full scale hemostasis tests performed for all patients. The tests included measurements and analyses of 30 standard parameters of hemostasis. Statistical processing of the results was carried out using parametric and nonparametric methods.

Results. A thorough assessment of medical history and medical records together with the current results of clinical, instrumental  and laboratory examination allowed us to determine10  major criteria (markers)  for predicting the presence of thrombophilia. These included certain details of medical history, as well as the family and obstetric-gynecological background. The developed markers laid the groundwork for the proposed screening method, where each of the markers gave 1 point to the total score. As part of the screening data analysis, we developed a matrix for the probable risk of having thrombophilia. Selection of patients with a total screening score of 3 or more points allowed increasing 2.6-fold (by 53.4%) the efficacy of laboratory diagnosis of thrombophilia in women with recurrent pregnancy loss.

Conclusion. The novelty of the proposed screening method is that the analysis begins at the stage of pregnancy planning and it precedes the laboratory tests; the approach does not require additional expenses. According to our estimate, the use of this method increased the rate of thrombophilia detection by 160%.

1. Obstetrics: national guideline [Akusherstvo: nacional'noe rukovodstvo (Pod red. E.K. Ajlamazyana, V.I. Kulakova, V.E. Radzinskogo, G M. Savel'evoj]. Moskva: GEOTAR-Media. 2014: 1200 s (in Russian).

2. Pestrikova T.Yu., Yurasova E.A., Butko T.M. Perinatal loss. Reserves of decline [Perinatal'nye poteri. Rezervy snizheniya]. Moskva: Litterra. 2008: 199 s (in Russian).

3. Strizhakov A.N., Ignatko I.V. Loss of pregnancy [Poterya beremennosti]. Moskva: MIA. 2007: 223 s (in Russian).

4. Makatsariya A.D., Bitsadze V.O. Antiphospholipid syndrome, genetic thrombophilia in the pathogenesis of the main forms of obstetric pathology [Antifosfolipidnyj sindrom, geneticheskie trombofilii v patogeneze osnovnyh form akusherskoj patologii]. Russkij medicinskij zhurnal. 2006: 2-10 (in Russian).

5. Cunningham F.G., Leveno K.J., Bloom S.L. et al. Williams Obstetrics. 24th ed. New York: McGraw-Hill Education Medical. 2014: 2994 р.

6. Bitsadze V.O., Makatsariya A.D., Khizroeva D. Kh. et al. Thrombophilia as the most important link in the pathogenesis of pregnancy complications [Trombofiliya kak vazhnejshee zveno patogeneza oslozhnenij beremennosti]. Prakticheskaya medicina. 2012; 5: 22-9 (in Russian).

7. Kharkevich O.N., Mirov A.I. The role of hereditary and acquired thrombophilia in the pathogenesis of spontaneous abortion and habitual loss of pregnancy [Rol' nasledstvennyh i priobretennyh trombofilij v pato-geneze samoproizvol'nogo aborta i privychnoj poteri beremennosti]. Tavricheskij mediko-biologicheskij vestnik. 2015; 18 (1): 127-31 (in Russian).

8. Cleary-Goldman J., Bettes B., Robinson J.N., Schulkin J. Thrombophilia and the obstetric patient. Am J Obstet Gynecol. 2007; 110 (3): 669-74.

9. Jivraj S., Makris M., Saravelos S., Li T.C. Pregnancy outcome in women with factor V Leiden and recurrent miscarriage. Br J Obstet Gynecol. 2009; 116: 995-8.

10. Robertson L., Wu O., Langhorne P. et al. Thrombophilia in pregnancy: a systematic review. Br J Haematol. 2006; 132: 171-96.

11. Inherited thrombophilias in pregnancy. Practice Bulletin № 138. American College of Obstetricians and Gynecologists. Am J Obstet Gynecol. 2013; 122 (3): 706-17.

12. Lund M., Nielsen H.S., Hviid T.V. et al. Hereditary thrombophilia and recurrent pregnancy loss: a retrospective cohort study of pregnancy outcome and obstetric complications. Hum Reprod. 2010; 25 (12): 2978-84.

13. Norrie G., Farquharson R.G., Greaves M. Screening and treatment for heritable thrombophilia in pregnancy failure: inconsistencies among UK early pregnancy units. Br J Haematol. 2009; 144 (2): 241-4.

14. Mashkova T.Ya. Thrombophilia and failure of IVF [Trombofiliya i neudachi EKO]. Akusherstvo, ginekologiya i reprodukciya. 2015; 3: 17-21 (in Russian).

15. Bitsadze V.O., Akinshina S.V., Makatsaria A.D., Andreeva M.D. Auxiliary reproductive technologies and iatrogenic thrombotic complications [Vspomogatel'nye reproduktivnye tekhnologii i yatrogennye tromboticheskie oslozhneniya]. Voprosy ginekologii, akusherstva i perinatologii. 2014; 1: 49-59 (in Russian).

16. Mirov A.I., Golofast O.E., Kharkevich O.N. Comparative characteristics of thrombophilic conditions in women with single and recurrent pregnancy loss [Sravnitel'naya harakteristika trombofilicheskih sostoyanij u zhenshchin s odnokratnymi i recidiviruyushchimi poteryami beremennosti]. Zhurnal nauchnyh statej «Nauka i obrazovanie v XXI veke». 2017; 19 (6): 79-87 (in Russian).

17. Bates S.M., Greer I.A., Middledorp I.S et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (9th Edition). J Hirsh Chest. 2012; 141 (2 Suppl): 691-736.

18. Kharkevich O., Mirov A., Kovalenko M. Role of the hereditary and acquired thrombophilia in pregnancy loss pathogenesis, correction of complications. Abstract Book of The 12 World Congress of Perinatal Medicine. Madrid. November 3-6, 2015; O-0090: 249.

19. Robertson L., Wu O., Langhorne P. et al. Thrombophilia in pregnancy: a systematic review. Br J Haematol. 2006; 132: 171-96.

20. Order of Health Ministry of RF from November 1, 2012, № 572n «On the Approval of the Procedure for the provision of medical assistance in "obstetrics and gynecology (excluding the use of assisted reproductive technologies)"» (with amendments and additions [Prikaz Ministerstva zdravoohraneniya RF ot 1 noyabrya 2012 g. № 572n «Ob utverzhdenii Poryadka okazaniya medicinskoj pomoshchi po profilyu "akusherstvo i ginekologiya (za isklyucheniem ispol'zovaniya vspomogatel'nyh reproduktivnyh tekhnologij)"» (s izmeneniyami i dopolneniyami)]. URL: https://normativ.kontur.ru/document?moduleId=1&documentId=239049 (in Russian) [Accessed: 24.08.2017].

21. Zubovskaya E.T., Svetlitskaya S.G. Hemostasis. Theoretical bases and methods of research: a practical guide [Sistema gemostaza. Teoreticheskie osnovy i metody issledovaniya: prakticheskoe posobie]. Minsk: BGUFK. 2009: 287 s (in Russian).

22. Momot A.P., Tsyvkina L.P., Taranenko I.A. et al. Modern methods of recognition of the state of thrombotic readiness [Sovremennye metody raspoznavaniya sostoyaniya tromboticheskoj gotovnosti]. Barnaul: Izd-vo AltGU. 2011: 138 s (in Russian).

23. Kharkevich O.N., Kurlovich I.V., Bekasova Т.V. Diagnosis and therapy of hemostasis disorders in women with complicated pregnancy and reproductive losses: instruction for use, approved by Health Ministry of Republic of Belarus [Diagnostika i terapiya narushenij gemostazau zhenshchin s oslozhnennym techeniem beremennosti i reproduktivnymi poteryami: instrukciya po primeneniyu, utverzhdeno MZRB]. RUP «Izdatel'skij centr BGU». 2008: 17 s (in Russian).

24. Antiphospholipid syndrome. Practice Bulletin № 132. American College of Obstetricians and Gynecologists. Am J Obstet Gynecol. 2012; 120 (6): 1514-21.

25. Carbone J.F., Rampersad R. Prenatal screening for thrombophilias: indications and controversies. J Clin Lab Med. 2010; 30 (3): 747-60.

26. Heit J.A. Thrombophilia: common questions on laboratory assessment and management. Hematology Am Soc Hematol Educ Program. 2007; 1: 127-35.

27. Miyakis S., Lockshin M.D., Atsumi T. et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006; 4: 295-306.

28. Vasilyev S.A., Vinogradov V.L. Role of heredity in thrombosis development [Rol' nasledstvennosti v razvitii tromboza]. Tromboz, gemostaz i reologiya. 2007; 3: 3-14 (in Russian).

29. Putilova N.V., Bashmakova N.V., Mazurov A.D. A method for predicting complications of pregnancy in patients with thrombophilia [Sposob prognoza oslozhnenij beremennosti u pacientok s trombofiliej]. Patent RF № 2429478 ot 20.09.2011. Byul. № 26: 6 c. URL: http://www.freepatent.ru/patents/2429478 (in Russian) [Accessed: 24.08.2017].