Complications of pregnancy in patients with hereditary thrombophilia and the effects of therapy on pregnancy outcomes

[S. Dugalilć]

122 str.

Medicina - Humana reprodukcija, perinatologija i neonatologija / Medicine - Human reproduction, perinatology and neonatology

Uvod: Dat je uvid u trudnoću kao hiperkoagulatno stanje i fiziološke efekte uteroplacentne konekcije, neophodne za uspešan razvoj trudnoće. Pregled literaturnih podataka dosadašnjih istraživanja dokazuje da neadekvatna placentna perfuzija u stanjima koja prevazilaze fiziološki nivo koagulabilnosti, dovodi do formiranja mikrotromboza uteroplacente jedinice. Vaskulopatija, kao bazični uzročnik pogoršanja uteroplacentne i fetoplacentne cirkulacije, dovodi do kompikacija trudnoće. Preventivnim dijagnostičkim i terapijskim procedurama, smanjujemo morbiditet majke, kao i morbiditet i mortalitet fetusa (rani gubici trudnoće, ponovljeni gubitak trudnoće prvog trimestra, gubitak trudnoće drugog i trećeg trimestra, preeklampsija, abrupcija placente, prevremeni porođaj, intrauterina smrt ploda, restrikcija fetalnog rasta, venski tromboembolizam). Klinička i bazična medicinska istraživanja dovode u vezu nasledne trombofilije i negativan ishod trudnoće. Data je analiza studija koja porede komplikacije trudnoće i hereditarne trombofilije, opis hereditarnih trombofilija, podela i klasifikacija. Nedostatak jake i konzistentne baze dokaza za kliničke smernice je doveo do različitih preporuka kliničarima. U odnosu na tromboprofilaksu, preporuke American College of Chest Physicians (ACCP), u poređenju sa preporukama Royal College of Obstetricians and Gynecologists (RCOG), nemaju apsolutni konsenzus. Za žene sa trombofilijama i istorijom negativnih ishoda trudnoće ovo je veoma delikatno i emotivno područje. Zato su klinički lekari u obavezi da aktivno kontrolišu poznate faktore rizika, i pored nedostatka kvalitetnih dokaza koji ovo podržavaju. Metod: Studija je sprovedena u Klinici za ginekologiju i akušerstvo Kliničkog centra Srbije u Beogradu retrospektivno (dve godine) i prospektivno (godinu dana). Ispitivanjem su obuhvaćene sve hospitalizovane trudnice u periodu od januara 2016. do decembra 2018. godine, kod kojih je utvrđena kongenitalna trombofilija. Studija je rađena delom retrospektivno i delom prospektivno zbog činjenice da je primena terapije nije obavezna kod svih vrsta hereditarnih trombofilija po Preporukama za testiranje prisustva urođenih trombofilija i antifosfolipidnog sindroma Klinike za hematologiju Kliničkog centra Srbije od februara 2017. godine. Pacijentkinje sa jednom ili više hereditarnih trombofilija bile su razvrstane u dve grupe, kod kojih nije korišćena antikoagulantna terapija, kod kojih je korišćena. Ispitane su demografske karakteristike, porodična i lična anamneza, zastupljenost komplikacija trudnoće, vrsta i zastupljenost trombofilija, perinatalne ishode prethodnih trudnoća, način porođaja u prethodnim trudnoćama, vrednosti laboratorijskih i sonografskih parametara (proteini, D-dimer, Doppler protok kroz arteriju umbilikalis - RiAu), vreme i način završavanja aktuelne trudnoće, kao i ishod trudnoće sa telesnom masom novorođenčeta i ocenom po Apgar skoru na rođenju, u odnosu na primenu antikoagulantne terapije. Analiza navedenih laboratorijskih i sonograsfkih parametara izvršena je posle kategorizacije po gestacijskoj starosti trudnoće u 3 grupe. Analizirane su komplikacije trudnoće, rani i kasni spontani pobačaji, prevremeni porođaji, intrauterusna restrikcija rasta ploda, intrauterina smrt ploda, preeklampsija, abrupcija posteljice i duboka venska tromboza. Za statističku obradu podataka korišćen je statistički program IBM SPSS 21. U radu su se koristile metode deskriptivne i analitičke statistike. ANOVA za ponovoljena merenja koristila su se za testiranje promene vrednosti kvantitavnih varijabli po ispitivanim grupama. Za identifikaciju faktora koji utiču na pojavu komplikacija trudnoće koristila se univarijantna i multivarijantna logistička regresiona analiza. Rezultati: Studijom je obuhvaćeno 358 trudnica sa dijagnozom trombofilije lečenih na Klinici za ginekologiju i akušerstvo Kliničkog Centra Srbije u periodu od 1.1.2016. godine do 1.8.2018. godine. U okviru aktuelnih trudnoća, primarno su praćena dva terapijska pristupa, sa i bez primenu antikoagulantne terapije...

Introduction: The insight of pregnancy as hypercoagulable state and physilogical effects of uteroplacental connections that are both necessary for successful development of pregnancy. Literature data review of recent investigations proves that inadequate placental perfusion leads to the development of microthrombosis within the uteroplacental unit. Vasculopathy,as the main cause of worsening of the uteroplacental and fetoplacental circulation, leads to the complications of pregnancy. By preventive diagnostical and therapeutical procedures, we lower the morbidity and mortality of mothers, as well as the morbidity and mortality of fetus (early pregnancy losses, recurrent pregnancy loss, placental abruption, preterm delivery, interauterine fetal death, fetal growth restriction, venous thromboembolism). Clinical and basical medical researches suggest the connection between inherited thrombophilias and adverse pregnancy outcomes. The analysis of studies that compare complications of pregnancy and inherited thrombophilias, description of hereditary thrombophilias and their clasification is given. Missing the strong and consistant data base for clinical use has lead to different guidelines for clinical practice. Considering thromboprophylaxis, American College of Chest Physicians (ACCP) and Royal College of Obstetricians and Gynecologists (RCOG) do not have absolute consensus. For women with thrombophilias and positive personal history for adverse pregnancy outcomes, this is very delicate and emotional field. Because of that clinical doctors are obliged to actively control the risk factors, even though that the qualitive proofs that support this are missing. Methods: The study is undertaken in the Clinic for Gynecology and Obstetrics, Clinical Centre of Serbia retrospectively (for two years) and prospectively (for a year). We have encompassed all hospitalised pregnant women wih hereditary thromobophilia in the period from january 2016 till december 2018. The study has been done retrospectively and prospectively becvause of the fact that therapy for thrombophilia is not obliged according to Recommendations for testing hereditary thombophilias and antiphospholipid syndrome of Clinic for Hematology, Clinical Centre of Serbia, from february 2017. Patients with one or more hereditary thrombophilas were devided in two gropus, with and without anticoagulation therapy. We investigated all demographic data, family and personal history, complications of pregancy, types and representations of thrombophilias, perinatal outcomes of past pregnancies, ways of delivery in past pregnancies, laboratory values and ultrasonographic parametres (proteins, D dimer, resistance index of Doppler flow velocitometry in the umbilical artery - RiAu), term of the current pregnancy and way of the delivery, as well as the pregnancy outcome with body weight of newborn and Apgar score comparing to the use of anticoagulation therapy. The analysis was made according to weeks of gestation of the pregnancy in 3 groups. We have analysed complications of pregnancy, early and advanced spontaneous abortions, preeclampsia, placental abruption and deep vein trombosis. For statistical evaluation we used program program IBM SPSS 21. Descriptive and analytical statistical methods were used. ANOVA for repeated measurements were used for testing of the changing of values of qualitative variables in analyzed groups. Results: The study includes 358 patients with hereditary thrombophilia that were hospitalized in the Clinic for Gynecology and Obstetrics, Clinical Centre of Serbia from 1.1.2016. till 1.8.2018. Considering current pregnancies, we have primarily investigated to therapeutical approaches, with and without the use of anticoagulation therapy. As for family history, we have found that in patients with therapy, the frequency of hypertension, thrombosis, CVI, emboly and the diagnosis of thrombophilias in family is higher than in those without therapy...

nepovoljni ishodi trudnoće, hereditarne trombofilije, restrikcija fetalnog rasta, intrauterina smrt ploda, spontani pobačaji, prevremeni porođaj, terapija visoko rizičnih trudnoća, natalitet, gubitak konceptusa, rekurentni gubitak trudnoće, porođaj

adverse pregnancy outcomes, hereditary thrombophilias, fetal growth restriction, intrauterine fetal death, spontaneous abortions, preterm deliveries, therapy of high risk pregnancies, loss of conceptus, recurrent pregnancy lost, delivery

618.3(043.3)

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