1. Introduction 2. Acquired causes of thrombophilia 3. Inherited causes of thrombophilia 4. Rationale for use of aspirin in pregnancy 5. Rationale for use of heparins in pregnancy 6. Direct oral anticoagulants 7. Interventions in GVCs 8. Intervention in assisted reproductive technologies 9. Interventions in pregnancy-related VTE 10. Conclusion 11. Expert opinion Review Aspirin and heparin in pregnancy Elvira Grandone † , Michela Villani & Giovanni L Tiscia Atherosclerosis and Thrombosis Unit, I.R.C.C.S. ‘ Casa Sollievo della Sofferenza’ , S. Giovanni 5 Rotond (FOGGIA), Italy Introduction: A pro-coagulant state during pregnancy can be involved in the occurrence of gestational vascular complications (GVCs) and venous thromboembolism (VTE). Areas covered: Antithrombotic drugs are used to prevent GVCs and VTE. 10 Aspirin is not efficacious to prevent recurrences in women with previous early loss, while it can prevent pre-eclampsia in some groups of women. Heparins are not effective in the prevention of early recurrent loss and there is uncer- tainty about their efficacy in women carrying inherited thrombophilias. They could be efficacious in the prevention of GVCs in carriers of inherited 15 thrombophilias, as GVCs have heterogeneous causes, and future studies have to focus on more homogeneous groups of patients. Not enough data are available regarding prophylaxis with heparins to prevent pregnancy- related VTE, but an accurate risk stratification of women during pregnancy and puerperium is crucial for administering prophylaxis in moderate-/high- 20 risk women. Aspirin does not improve live births after assisted reproductive technologies, while heparins increase the number of clinical pregnancies and live births. Expert opinion: Aspirin is efficacious in the prevention of GVCs in women at risk for pre-eclampsia and in those with antiphospholipid antibodies 25 syndrome. Heparins could give benefit to women at risk for GVCs and/or pregnancy-related VTE. Keywords: aspirin, gestational vascular complications, heparin, venous thromboembolism Expert Opin. Pharmacother. (2015) Early Online:1-11 30 1. Introduction Normal pregnancy is associated with changes in the coagulation and fibrinolytic systems. These include increase in a number of clotting factors (I, II, VII, VIII, IX and XII), a decrease in protein S levels, and inhibition of fibrinolysis. As gesta- tion progresses, there is also a significant drop in the function of activated protein 35 C (APC), an important anticoagulant. Pregnancy progression induces a marked increase in tissue-factor (TF)-dependent thrombin generation in vitro, despite an elevation in the level of TF Pathway Inhibitor (TFPI) [1]. Placental trophoblasts obtained from pregnancies with gestational vascular complications (GVCs) have an impaired balance between TF and TFPI [2]. Physiological changes during preg- 40 nancy may be important for minimizing intra-partum blood loss, but they entail an increased risk of thromboembolism during pregnancy and the post-partum period [3]. Indeed, venous thromboembolism (VTE) is known to be a leading cause of maternal morbidity and mortality during pregnancy in developed countries [4-7]. Globally, the incidence of VTE per pregnancy-year increases about fourfold during 45 pregnancy and by 14- to 84-fold during the first 6 weeks of puerperium [5,8]. Among pregnancy-associated VTE events, about 80% are deep vein thromboses (DVT) and 20 -- 25% pulmonary embolisms (PE) [9]. The pro-coagulant state of pregnancy could also expose a woman to the occurrence of GVCs (recurrent pregnancy loss, foetal growth restriction (FGR), placental abruption, pre-eclampsia), especially in 50 the presence of acquired or inherited thrombophilia [10,11]. GVCs are quite common 10.1517/14656566.2015.1066335 © 2015 Informa UK, Ltd. ISSN 1465-6566, e-ISSN 1744-7666 1 All rights reserved: reproduction in whole or in part not permitted