Prevention and treatment of thromboembolic disease in pregnancy

Abstract

Venska tromboembolija (VTE) je medicinski pojam koji obuhvaća duboku vensku trombozu (DVT) i plućnu emboliju (PE). Poznati čimbenici rizika za VTE su trudnoća i puerperij. Uzrok tome su fiziološke promjene u trudnoći koje rezultiraju hiperkoagulabilnošću, venskom stazom donjih udova i ozljedom endotela. Liječenje i prevencija VTE u trudnoći zahtijevaju prilagođen pristup. ----- U antepartalnom i postpartalnom periodu, pacijentice u kojih postoji visok stupanj sumnje na PE, liječe se antikoagulantnom terapijom prije potvrde dijagnoze. Ukoliko je sumnja umjerena ili niska, potreban je individualan pristup. Pacijenti u kojih postoji sumnja samo na DVT ne primaju antikoagulantnu terapiju prije dijagnostičke evaluacije. Varfarin se u trudnoći ne primjenjuje u terapiji VTE jer prolazi placentu i dokazano je teratogen. Neki drugi antikoagulansi također se ne preporučuju u trudnoći: fondaparinuks iz skupine pentasaharida po strukturi sličan niskomolekularnom heparinu, prelazi placentarnu barijeru i stoga je potencijalno opasan, a o peroralnim direktnim inhibitorima trombina i inhibitorima faktora Xa nema za sada dovoljno podataka o sigurnosti u trudnoći. Zajedničke smjernice većina studija upućuju na primjenu niskomolekularnog heparina (Low Molecular Weight Heparin - LMWH) koji se primijenjuje isključivo subkutano. Za razliku od LMWH-a, nefrakcionirani heparin (Unfractionated Heparin - UFH), može se primjenjivati intravenski i subkutano. Osim u iznimnim slučajevima, prednost u liječenju trudnica treba dati LMW heparinu zbog jednostavnije primjene, bolje učinkovitosti i manje nuspojava. ----- UFH je pak prikladniji u stanjima šoka ili kad postoji visoki rizik krvarenja, bubrežno zatajenje ili ako pretpostavljamo da bi mogla zatrebati brza reverzija antikoagulantnog učinka (npr. raniji porod ili hitna operacija). Terapiju LMWH treba obustaviti bar 24 sata prije poroda, a terapiju UFH 4 do 6 sati prije poroda. Antikoagulantnu terapiju treba nastaviti bar šest tjedana postpartalno. Ukupno, terapija u pacijenata s prolaznim faktorom rizika treba trajati 3 do 6 mjeseci. Žene s trajnim rizikom (npr. protetičke mehaničke srčane valvule) zahtijevaju prilagođen pristup. Pacijentice koje su prije prve trudnoće već preboljele neki tromboembolijski incident ili imaju dokazanu trombofiliju, moraju dobivati profilaktičke, a ponekad i terapijske doze LMWH-a od početka do kraja trudnoće.Venous thromboembolism (VTE) is a medical entity that refers to deep vein thrombosis (DVT) and pulmonary embolism (PE). Two well known risk factors for VTE are pregnancy and puerperium. This is due to physiological changes in pregnancy which result in hypercoagulability, venous stasis of lower extremities and endothelial injury. Treatment and prevention of VTE in pregnant patients require a modified approach. ----- In antepartal and postpartal period, patients who are highly suspected of having PE are treated with anticoagulant therapy before confirming diagnosis. If suspicion is low or moderate, an individual approach is needed. Patients suspected of having DVT alone are not given therapy before diagnostic evaluation. Warfarin is not used in therapy of VTE in pregnant women because it crosses the placenta and is proven to be teratogenic. Most studies advise against synthetic heparin pentsaccharides like fondaparinux, oral direct thrombin inhibitors and factor Xa inhibitors, for the lack of safety data in pregnancy. It is generally recommended and consistent with latest guidelines to administer subcutaneous low molecular weight heparin (SC LMWH). It is preferred over other two options: intravenous unfractionated heparin (IV UFH) and subcutaneous unfractionated heparin (SC UFH). This is due to easier use, apparent higher efficacy and better safety profile of SC LMWH. IV UFH is still an acceptable alternative and even more appropriate in shock, renal failure, high risk of bleeding or when rapid reversal of anticoagulation is required ( eg, an urgent surgery or unexpected delivery). ----- SC LMWH is to be discontinued at least 24 hours prior to delivery, and IV UFH should cease to be administered only 4-6 hours before delivery. Anticoagulant therapy should be continued at least six weeks postpartum. In total, anticoagulant therapy for patients with transient risk factors (e.g. pregnancy) is recommended to last three to six months. Women with persistent risk (e.g. mechanical heart valves) require modified approach. Patients who have a history of VTE before the first pregnancy, proven thrombophilia or otherwise meet the criteria for pharmacologic thromboprophylaxis are treated during the whole pregnancy with prophylactic doses of the same drugs used in treatment of VTE, and sometimes even with therapeutic doses