Abstract

Venous thromboembolism (VTE) in pregnancy increases the risk of foetal loss, foetal growth retardation, pre-eclampsia, and placental abruption; VTE was more frequent and the risk was higher in ante partum RR 2.5, 95% CI 1.2–5.2. range 2.1%–4.2%, and post partum RR 2.9, 95% CI 1.4–6.9. range 7.1%–11.5%. Risk factors for VTE during pregnancy are: age >38 years, obesity, familial or personal history of VTE, abnormalities of blood flow, and vessel wall injury; they lead to venous thrombosis just as comorbility conditions associated to thrombophilia or to a state of hypercoagulability (Factor V Leiden, prothrombin gene mutation G20210A, hyperhomocysteinemia with C677T mutation, deficiencies of PS and/or PC, ATIII, elevated levels of FVIII, dysfibrinogenemia, anticardiolipin antibodies / lupus anticoagulant), or they may be associated to additional risk factors (sepsis, inflammation, recent major surgery, prolonged bed rest, trauma, severe varicose vein); any of these factors approximately tripled the absolute risk of VTE. Antithrombotic agents during pregnancy in patients with a familial history of thrombosis are recommended prior and during pregnancy. The overall prevalence of VTE in these patients is 60% without any therapy; in about 80% of these cases there was an involvement of the left lower limb; the high risk for pulmonary embolism (60% in patients with Factor V Leiden deficiency) justifies the thrombo-prophylaxis throughout pregnancy and puerperium. The complications of pregnancy associated with maternal carriage of Factor V Leiden are: VTE, hypertensive disorder (gestational hypertension, HELLP-syndrome, preeclampsia), late pregnancy loss, intrauterine growth restriction, placental abruption. We have studied a 28 years old patient that showed leg pain, skin tension, swelling, oedema, fever, tenderness, low abdominal pain, and raised WBC, with Factor V Leiden (R506Q) heterozygosis and a familial history and personal history of recurrent VTE. Factor V Leiden is resistant to the action of activated C-protein (ACP) because the mutation G1691A (substitution of a glutamine for arginine residue 506) occurs on ACP cleavage site (there are three major cleavage site for this molecule: R 306, R 506, R 679); the frequency of Factor V Leiden in Caucasian people was between 3–10% (7.2% heterozygotes - 0.8% homozygotes). An exhaustive bilateral comparative color-Doppler ultrasound investigation was performed during and after the end of pregnancy for six months. Current strategy to prevent thrombus formation consists on using unfractioned heparin (UHF), low molecular weight heparin (LMWH) (enoxaparine 40 mg sc daily, or 30 mg sc twice daily; or dalteparin 5000 U s.c. once or twice daily), or consists on danaparoid that do not cross the placenta; heparin may be associated with warfarin, and this regimen can be continued in the post partum for 12 weeks. We used active prophylaxis with enoxaparine 40 mg sc daily with ASA 150 mg during the second and third three months, (plasma heparin levels measured as anti FX activity of 0.2 to 0.6 U/ml), in addition to graduated compression socks; medications used during pregnancy included folic acid and iron supplement (80 mg/daily) without any bleeding event or other clinic problem. The therapeutic approach to VTE includes two potential foetal complication: teratogenesis from coumarin derivates (nasal hypoplasia, stippled epiphyses, optic atrophy, cleft lip), and bleeding; the main maternal complications include bleeding, osteoporosis, heparin induced thrombocytopenia which may occur during both therapy with heparin or LMWH.

Author notes

Disclosure: No relevant conflicts of interest to declare.