Trombofilie v těhotenství

• Název práce v češtině: Trombofilie v těhotenství
• Název v anglickém jazyce: Thrombophilia in pregnancy
• Klíčová slova: trombofilie, těhotenství, Enoxaparin, FXa, Osteoprotegerin, RANKL
• Klíčová slova anglicky: Thrombophilia, Pregnancy, Enoxaparin, FXa, Osteoprotegerin, RANKL
• Akademický rok vypsání: 2011/2012
• Typ práce: disertační práce
• Jazyk práce: čeština
• Ústav: Ústav lékařské biochemie a laboratorní diagnostiky 1. LF UK a VFN (11-00410)
• Vedoucí / školitel: prof. MUDr. Jan Kvasnička, DrSc.
• Řešitel: skrytý - zadáno a potvrzeno stud. odd.
• Datum přihlášení: 03.09.2012
• Datum zadání: 03.09.2012
• Datum potvrzení stud. oddělením: 03.09.2012
• Datum a čas obhajoby: 06.12.2012 11:30
• Místo konání obhajoby: Fyziologický ústav 1. LF
• Datum odevzdání elektronické podoby: 13.09.2012
• Datum proběhlé obhajoby: 06.12.2012
• Předmět: Obhajoba dizertační práce (B90002)
• Oponenti: prof. MUDr. Zdeněk Hájek, DrSc.

Seznam odborné literatury

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Předběžná náplň práce

ABSTRAKT
Úvod:Tromboembolická nemoc je v civilizovaných zemích jedna z nejčastějších příčin nemocnosti a úmrtnosti u těhotných žen. V graviditě se často poprvé projeví vrozená, nebo získaná trombofilie. Pacientky s trombofilií mají i zvýšené riziko těhotenských komplikací. Optimální antikoagulační profylaxe pomáhá těmto komplikacím předcházet.
Metody: Práce je zaměřena na sledování koagulačních parametrů, krevního obrazu a proteinů akutní fáze u gravidních žen (N=68) s trombofilií, léčených v průběhu gravidity enoxaparinem, a na kontrolu účinnosti antikoagulační léčby v těhotenství pomocí anti-FXa aktivity, stanovení závislosti inhibice FXa na hmotnosti, koagulačních parametrech a proteinech akutní fáze. V první a druhé části studie není, z etických důvodů, kontrolní skupina těhotných pacientek se závažnou trombofilií, ale bez antikoagulační léčby. Ve třetí části práce jsme pomocí dotazníků zkoumali nežádoucí účinky enoxaparinu v místě vpichu injekce. A v závěrečné čtvrté části jsme hodnotili vliv enoxaparinu na markery kostní remodelace v porovnání s kontrolní skupinou gravidních žen bez antikoagulační léčby.
Výsledky: U pacientek dochází k četným změnám v parametrech hemostázy, krevního obrazu i proteinů akutní fáze. Koncentrace anti FXa klesala se stoupajícím týdnem gravidity a už v 15. týdnu bylo 10,29 % pacientek pod doporučeným profylaktickým rozmezím. Byla zjištěna statisticky významná negativní korelace mezi BMI, hmotností, fibrinogenem, D-dimery a inhibicí FXa. Nežádoucí účinky v místě vpichu injekce enoxaparinu jsou relativně časté. Žádná pacientka neprodělala závažné krvácení. V markerech kostní přestavby nebyl zjištěn významný rozdíl mezi skupinou těhotných pacientek s léčbou a bez léčby.
Závěr: Těhotenství je hyperkoagulační stav. Účinnost enoxaparinu hodnocená metodou inhibice FXa je v těhotenství ovlivněna mnoha faktory, proto jí doporučujeme pravidelně monitorovat.

Předběžná náplň práce v anglickém jazyce

ABSTRACT
Background: Thromboembolic disease is one of the most common causes of pregnant women morbidity and mortality. The pregnancy period is often the first time, when the apparent congenital or acquired thrombophilia is identified. Patients with thrombophilia have an increased risk of pregnancy complications. The optimal anticoagulant prophylaxis helps to prevent these complications.
Methods: The presented work is focused on monitoring of coagulation parameters, blood counts and acute phase proteins in pregnant women (N = 68) with thrombophilia treated with enoxaparin during pregnancy and it is also concerned with evaluation of effectiveness of anticoagulant therapy during pregnancy using anti FXa activity determination based on inhibition of FXa weight, coagulation parameters and acute phase proteins. In the first and the second part of the study, there is no control group of pregnant patients with severe thrombophilia, but no anticoagulation – this is justified by ethical reasons. In the third part, we examined by questionnaire our patients for enoxaparin adverse reactions at the injection site. Finally, the last part is focused on evaluation of enoxaparin effects on bone remodelling markers, compared with a group of pregnant women without anticoagulation.
Results: During the pregnancy, the patients are undergoing numerous changes in coagulation parameters, blood counts and acute phase proteins. The concentration of FXa was decreasing with the increasing weeks' gestation. As early as in the 15th week there were 10.29% of patients below the recommended prophylactic range. We found statistically significant negative correlation between BMI, weight, fibrinogen, D-dimers and inhibition of anti-FXa. Adverse reactions at the injection of enoxaparin were reported to be relatively frequent. No patient went through severe bleeding. Regarding the markers of bone remodelling, there was not found any significant difference between the groups of treated pregnant patients adn the control untreated group.
Conclusion: Pregnancy is a hypercoagulable state. The efficiency of enoxaparin assessed by inhibition of FXa is influenced by many factors during pregnancy, therefore we recommend regular monitoring.