Dr. ALESSANDRA PISTELLI, Dr. ALESSANDRA IERI, SODc Medical Toxicology and Poison Control Centre, Regional Reference Center for Perinatal Toxicology, AOU Careggi, Florence
During pregnancy, in response to the progressive physiological increase in estrogen levels, there is an increase in coagulation factors and at the same time a reduction in the activity of the coagulation inhibition factors. Consequently, the thromboembolic risk increases during gestation. Deep vein thrombosis and possible pulmonary embolism can be pregnancy-related complications. In women with different types of cardiomyopathy and who take antiplatelet or anticoagulant drugs, there is a risk of maternal or fetal hemorrhages and fetal malformations.
We report here some data and recommendations.
In women who present an increased thrombotic and embolic risk, but who are not already taking anticoagulant drugs, anti-platelet aggregation therapy with acetylsalicylic acid (SO) at low dosage (100 mg/day). The activity of the drug begins quickly after intake and acts for the lifespan of the platelets (7-10 days). Acetylsalicylic acid does not increase the basic malformation risk, a risk present in all women during pregnancy and estimated in our country at around 3-5% of live births for minor and major defects. The drug is generally stopped around the 34tha week of gestation to avoid hemorrhagic complications. In case of intolerance to ASA, the use of ASA is recommended clopidogrel.
Le low molecular weight heparins (LMWH: enoxaparin, dalteparin or nadroparin) constitute a valid therapeutic alternative associated with lower feto-neonatal risks. LMWH is currently preferred to unfractionated heparin (UFH). In any case, for both types the transplacental passage is minimal or absent and consequently they are not associated with an increase in the underlying malformation risk. In case of intolerance or other contraindications to LMWH, therapy based on LMWH can be considered fondaparinux.
In women with mechanical, mitral and/or aortic heart valves, it is necessary to continue taking Vitamin K antagonists, such as warfarin (commercial name Coumadin) to Acenocoumarol (commercial name Sintrom).
Vitamin K antagonists (Warfarin and Acenocoumarol) they are well absorbed after oral intake (“by mouth”). They increase the risk of miscarriage and bleeding complications during and after pregnancy (postpartum hemorrhage and retroplacental bleeding). They can also induce fetal cerebral hemorrhage, fetal death and low birth weight
Il warfarin, taken in the first trimester of pregnancy and especially between the 6th and 12th weeks after conception, a dosage greater than 5 mg/day, increases up to 6-10% of cases treated risk of malformation of the fetus. This risk, however, appears to drop to 0.45-0.9% for daily doses less than 5 mg. When the drug is taken in the second and third trimester the risk of fetal malformations is around 0.7-2% of treated cases.
In women who intend to become pregnant and are carriers of a Cardiomyopathy, and who need to start or continue anticoagulant therapy, with Vitamin K antagonists (warfarin o Acenocoumarol) or with new oral anticoagulants (NAO), factor Xa inhibitors, such as rivaroxaban, apixaban ed Edoxaban or direct thrombin inhibitors such as Dabigatran, is absolutely It is necessary to request advice in reference centers, in order to carefully evaluate the risk and a possible alternative therapy when possible, such as replacement with low molecular weight heparin
This is because, unfortunately, to date, i new oral anticoagulants (NAO), factor Xa inhibitors, such as rivaroxaban, apixaban ed Edoxabano direct thrombin inhibitors such as Dabigatran, they do not constitute a possible therapeutic alternative. The placental passage of these molecules has been documented and their use is correlated with greater ease of bleeding and an increase in the incidence of spontaneous abortion. It is not yet clear what the risk is for the fetus and congenital anomalies. For this reason these drugs they should be avoided during pregnancy.
Il Regional Reference Center for Perinatal Toxicology of the Careggi University Hospital of Florence provides information on the possible adverse effects of drugs on the course of pregnancy and fetal development and answers the number 0557946731 every day from 9am to 19.30pm.
Affiliation: SODc Medical Toxicology and Poison Control Center, Regional Reference Center for Perinatal Toxicology, AOU Careggi, Florence
Biblio:
2018 ESC Guidelines for the management of cardiovascular disease during pregnancy. Eur Heart J 2018: 39, 3165-3241
Andersen AS et al: Venous thromboembolism in pregnancy: prophylaxis and treatment with low molecular weight heparin. Acta Obstet Gynecol Scand 2010; 89, 15-21
Schaefer C et al: Vitamin K antagonists and pregnancy outcome. A multi-centre prospective study. Thromb Haemost 2006; 95:949-957
