Opravdanost primjene heparina male molekulske mase u trudnica s nasljednom trombofilijom kao uzrokom opetovanih zadržanih pobačaja [Adequacy of low-molecural-weight heparin prophylaxis in pregnant women with hereditary trombophilia as a cause of recurrent pregnancy loss]

Sokol Karadjole, Vesna (2018) Opravdanost primjene heparina male molekulske mase u trudnica s nasljednom trombofilijom kao uzrokom opetovanih zadržanih pobačaja [Adequacy of low-molecural-weight heparin prophylaxis in pregnant women with hereditary trombophilia as a cause of recurrent pregnancy loss]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

INTRODUCTION: Approximately 1% of women trying to conceive experience recurrent miscarriage. In 50% of the cases, the etiology of preceding miscarriages remains unknown. For this reason, the appropriate treatment and medical approach to these women are very challenging. Over the last 20 years, many studies have been analyzing the association between inherited thrombophilia and recurrent miscarriages. The main goals of this research were to investigate the perinatal outcome in hereditary thrombophilic patients with recurrent missed abortions after treatment with low molecular weight heparin. Nevertheless, this study evaluates the perinatal outcome in asymptomatic mutation carriers without LMWH prophylaxis. MATERIALS AND METHODS: The prospective study was conducted at the Department of Gynaecology and Obstetrics, University Hospital Centre Zagreb, from 2011 to January 2018. The research covered three groups of women: the first group (LMWH+) included 133 pregnant women with the history of two or more early recurrent pregnancy loss and hereditary trombophilia who were treated with a prophylactic dose of LMWH, the second group (LMWH-) enrolled 35 women with habitual abortions and hereditary thrombophilia who were not treated with a prophylactic dose of LMWH and, finally, the third (control) group covered 55 healthy pregnant women (with a negative personal venous thromboembolism and obstetric uteroplacental vascular insufficiency history) with hereditary thrombophilia who were not treated with a prophylactic dose of LMWH. The definition of inherited thrombophilia included the FVL, prothrombin G20210A mutation, antithrombin deficiency, protein C and protein S deficiency, MTHFR mutation and PAI-1 mutation. RESULTS: Pregnant women with inherited thrombophilia and habitual abortions who were treated with prophylactic doses of LMWH heparin showed a statistically significant reduction in miscarriages compared to women with inherited thrombophilia and two or more previous early pregnancy loss who were not administered the prophylactic dose of LMWH (P= 0,001). For a good perinatal outcome, it seems that application of LMWH is not necessary in the group of asymptomatic carriers of mutations with hereditary thrombophilia and negative personal and obstetric history. CONCLUSION: LMWH has a role in preventing further pregnancy losses in patients with hereditary thrombophilias and recurrent miscarriages. Nevertheless, the current findings show that LMWH is not required for a good perinatal outcome in asymptomatic carriers of a thrombophilic defect.

Abstract in Croatian

UVOD: Habitulani pobačaji pogađaju 1% žena reproduktivne dobi. U više od 50% slučajeva, etiologija habitualnih pobačaja ostaje nepoznata i samim time pristup pacijenticama s takvom anamnezom predstavlja jedan od najvećih izazova današnje ginekologije i opstetricije. Nasljedna trombofilija kao mogući uzrok spontanih pobačaja tema je velikog broja istraživanja posljednjih dva desetljeća. Osnovni je cilj ove studije ustanoviti opravdanost primjene niskomolekularnog heparina u svrhu poboljšanja perinatalnog ishoda kod trudnica s nasljednom trombofilijom i stanjem nakon dva ili više zadržanih pobačaja. Također, istraživanjem se analizirao perinatalni ishod u skupini asimptomatskih nositelja mutacije gena za nasljednu trombofiliju bez primjene niskomolekularnog heparina. MATERIJALI I METODE: Prospektivno istraživanje provedeno je na trudnicama Klinike za ženske bolesti i porođaje Kliničkog bolničkog centra u Zagrebu u razdoblju od 2011. do siječnja 2018. godine. Istraživanje je uključilo tri skupine ispitanica. Prva skupina (NMH+) obuhvaćala je 133 trudnice s dva ili više uzastopnih reteniranih pobačaja i dijagnozom nasljedne trombofilije kojima je u terapiju uključen niskomolekularni heparin u profilaktičnoj dozi, druga je skupina (NMH-) obuhvaćala je 35 trudnica s nasljednom trombofilijom i dva ili više uzastopnih reteniranih pobačaja kojima u profilaksu nije uveden niskomolekularni heparin, a treća skupina (kontrolna) uključila je 55 zdravih trudnica s nasljednom trombofilijom i urednom osobnom i opstetričkom anamnezom (neopterećenom tromboembolijskim bolestima i patologijom prethodnih trudnoća u obliku insuficijencije posteljice) kojima u profilaksu nije uveden niskomolekularni heparin. Definicija nasljedne trombofilije uključila je FVL, mutaciju protrombinskog gena, deficijenciju antitrombina, proteina C, proteina S, mutaciju MTHFR i PAI-1 gena. U sve tri skupine ispitanica pratio se tijek sadašnje trudnoće, način i tjedan završetka trudnoće i rani neonatalni ishod. REZULTATI: Trudnice s nasljednom trombofilijom i habitualnim pobačajima koje su tijekom trudnoće uzimale profilaksu niskomolekularnim heparinom imale su značajno manji broj ponovnih spontanih pobačaja u odnosu na trudnice s nasljednom trombofilijom i habitualnim pobačajima koje nisu uzimale niskomolekularni heparin (P= 0,001). Kod asimptomatskih trudnica s nasljednom trombofilijom i urednom osobnom i opstetričkom anamnezom (neopterećenom TE bolestima i patologijom prethodnih trudnoća u obliku insuficijencije posteljice), primjena niskomolekularnog heparina nije se pokazala neophodnom za uredan ishod trudnoće. ZAKLJUČAK: Niskomolekularni heparin utječe na uredan ishod trudnoće kod trudnica s nasljednom trombofilijom i habitualnim pobačajima u opstetričkoj anamnezi u smislu prevencije ponovnog spontanog pobačaja. Kod asimptomatskih trudnica s nasljednom trombofilijom i urednom osobnom i opstetričkom anamnezom, primjena niskomolekularnog heparina nije se pokazala neophodnom za uredan ishod trudnoće.

Item Type: Thesis (PhD)
Mentors:
Mentor
Ivanišević, Marina
Departments: Izvan medicinskog fakulteta
Depositing User: Anja Majstorović
University: Sveučilište u Zagrebu
Institution: Medicinski fakultet
Number of Pages: 101
Status: Unpublished
Creators:
CreatorsEmail
Sokol Karadjole, VesnaUNSPECIFIED
Date: 10 December 2018
Date Deposited: 14 Jan 2019 12:45
Last Modified: 14 Jan 2019 12:45
Subjects: /
Related URLs:
    URI: http://medlib.mef.hr/id/eprint/3020

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