127 Proc. West. Pharmacol. Soc. 45: 127-128 (2002) Anti-Xa Activity with Low-Molecular-Weight Heparin, Enoxaparin, During Pregnancy in Women with Mechanical Heart Valves RAÚL IZAGUIRRE*, AURORA DE LA PEÑA, ALVARO RAMÍREZ, EVELYN CORTINA, MARGARITA HUERTA & EDUARDO SALAZAR Instituto Nacional de Cardiología "Ignacio Chávez", Departamento de Hematología, Juan Badiano 1, Tlalpan CP 14080, México, D.F. *e-mail: rizagui@yahoo.com Increased risk of venous thromboembolism has been associated with pregnancy. Physiological adaptation for delivery may include an increase in hypercoagulability. High levels of von Willebrand factor, factor VII, factor X, factor VIII, factor V, and fibrinogen, acquired resistance to activated protein C, reduction of protein S and impaired fibrinolysis have been reported during pregnancy. Venous stasis may also augment the risk of venous thromboem- bolism [1]. Pregnant women with mechanical heart valves are at high risk of thrombosis as all mechanical valves are thrombogenic. Several design modifications have been made in these valves to improve their duration and to reduce throm- bogenicity. Nevertheless, thromboembolism remains the major problem for mechanical prosthetic valves and long- term anticoagulation is mandatory to prevent this complication. Controversy exists regarding the appropriate and safe anticoagulation regimen in pregnant patients with these valve prostheses. Coumarin derivatives are effective in preventing thromboembolic phenomena in these patients. However, these agents cross the placental barrier and should be avoided from the 5 th to 13 th weeks of pregnancy due to their teratogenic effect [2]. Salazar et al. have reported the failure of a regimen of adjusted doses of subcutaneous unfractionated heparin for preventing thrombosis of mechanical valves [3]. Heparin- induced osteoporosis and thrombocytopenia also restrict its use. Low molecular weight heparin (LMWH) consti- tutes a promising alternative for anticoagulation in these cases, as it does not cross the placenta in clinically sig- nificant amounts, and it is not associated with fetal ab- normalities, osteoporosis or thrombocytopenia [4]. LMWHs are derived from unfractionated heparin by depolymerization. The resultant molecules differ not only in molecular weight but also in chemical characteristics and pharmacologic properties [5]. The anticoagulant activity is related to a pentasaccha- ride sequence, which in the presence of antithrombin III, leads to a factor Xa inhibition with an anti-Xa/anti-IIa ratio greater than 1 [6]. However, inhibition of activated factor X is not the only antithrombotic mechanism. LMWHs also increase tissue related plasminogen activa- tor (t-PA) and tissue factor inhibitor (TFPI) [7]. TFPI is now recognized as a major physiological anticoagulant. Its main role is to modulate factor VIIa/tissue factor cata- lytic activity. METHODS: Nine women with mechanical heart valves were treated with enoxaparin (40 mg, sc) every 12 h, from the 5 th to the 13 th weeks of pregnancy. Table 1 shows the different types of mechanical heart valves and the site of implantation. Two of these women also had aor- tic protheses (one bileaflet and one porcine xenograft). The average age of the patients was 32.6 ± 5.6 (range 25 to 42 years). In every case, the protocol was discussed thoroughly with the pa- tient and her husband, and informed consent was obtained. After two days of acenocumarol withdrawal, the patient was admitted to the He- matology service for a pre-dose blood sample. Subsequent blood sam- ples were taken at 2, 4, 6, and 8 h after enoxaparin administration (40 mg; sc). Plasma samples were obtained by centrifugation and frozen until next day. Anti-Xa activity was used as a biological marker of LMWH activ- ity. (Coatest LMW heparin/heparin, Chromogenix). Positive D-D dimer test (Boehring) was considered as an evidence of thrombosis. Treatment with acenocumarol was resumed in all cases after the end of 12 th week to maintain an international normalized ratio of 3.0 to 3.5. Enoxaparin (40 mg, sc twice daily) was resumed during the last two weeks of pregnancy. Prenatal care and delivery were performed at a high-risk obstetric hospital. Information about the post-partum period was obtained from the patients. Table 1. Types of mechanical heart valves implanted Type Number Bileaflet 7 Disc 2 Ball 1 Bioprothesis 1 TOTAL 11 RESULTS: Mean anti-Xa levels were 0.06 ± 0.09, 0.51 ± 0.17, 0.49 ± 0.14, 0.40 ± 0.21 and 0.31 ± 0.19 U/mL re- spectively, at pre-dose, 2, 4, 6 and 8 h after administration of enoxaparin. The anti-Xa activities declined by 6 h after the administration. In two cases, the dose of enoxaparin was increased to 50 mg every 12 h. No thromboembolic accidents were observed and no bleeding episodes oc-