The value and impact of anti-Xa activity monitoring for prophylactic dose adjustment of low-molecular-weight heparin during pregnancy

Abstract

: Low-molecular-weight heparin (LMWH) is the anticoagulant drug class of choice for the prevention of thrombosis during pregnancy and often used for prevention of severe obstetrical complications, yet the optimal dosage is still a matter of debate. Although several studies have evaluated LMWH dose adjustment methods based on anti-Xa levels, no definitive conclusion as yet exists. This extensive retrospective study sought to address the rationale of regular anti-Xa activity monitoring in pregnant patients given LMWH prophylaxis. We evaluated pregnant patients receiving LMWH prophylaxis with three or more anti-Xa measurements. The initial LMWH dose was fixed and adjusted for obesity. The desired anti-Xa activity was 0.2-0.6 IU/ml and LMWH dose was increased for anti-Xa levels less than 0.3 IU/ml. Of the 173 enrolled women, 79% required LMWH dose adjustment (56%: one dose increase; 20%: two; 3%: three). In the vast majority of patients, LMWH dose was increased before substantial body weight gain. The number of dose adjustments positively correlated with BMI, though not with body weight gain. Based on our study findings, we recommend conducting LMWH dose adjustments based on anti-Xa levels, monitored regularly during pregnancy to keep the anti-Xa activity within the desired range.

Obstetric venous thromboembolism: a systematic review of dalteparin and pregnancy

“…Most reports support increasing LMWH dose as pregnancy progresses, and adjustments in LMWH dosing during pregnancy are recommended (Bates et al 2012; Swedish Society of Obstetrics and Gynecology (SFOG) and Working Group on Hemostatic Disorders (Hem-ARG) 2012; Royal College of Obstetricians and Gynaecologists 2015). Most requirements for dose adjustments are reported where the anticoagulant effect of LMWH is monitored by analyses of anti-FXa (Wahlberg and Kher 1994;Hunt et al 1997;Blomb€ ack et al 1998;Pettil€ a et al 1999;Schambeck et al 2001;Antovic et al 2002;Ulander et al 2002;Jacobsen et al 2003;Barbour et al 2004;Bauersachs et al 2007;Voke et al 2007;Lindqvist et al 2011;Schoenbeck et al 2011;Bj€ orgvinsdottir et al 2013;Revelj et al 2015;Boban et al 2017).…”

Do Anti-Factor Xa Levels have any Impact on Pregnancy Outcome in Women with Previous Adverse Outcomes?

“…Also, the cost-effectiveness of monitoring all pregnant women taking LMWH should be considered after taking into account the potential complications and their expense. In previous studies investigating anti-FXa levels in pregnant women under LMWH prophylaxis, anti-FXa levels were not at the desired levels in a high percentage of patients [3,6]. In a recent study by Boban et al [3], 77 % of pregnant women under prophylactic LMWH treatment needed a dose increase.…”

“…In previous studies investigating anti-FXa levels in pregnant women under LMWH prophylaxis, anti-FXa levels were not at the desired levels in a high percentage of patients [3,6]. In a recent study by Boban et al [3], 77 % of pregnant women under prophylactic LMWH treatment needed a dose increase. Fox et al [6] reported that only 56 % of anti-FXa levels of pregnant women were in prophylactic range, whereas 29 % were sub-prophylactic.…”

“…Anticoagulant therapy with low-molecular-weight heparin (LMWH) is widely used in pregnant women with thrombophilia, a history of venous thromboembolism, and a history of poor pregnancy outcomes [1,2]. Dose adjustment of LMWH therapy is usually based on body weight and can be monitored with anti-factor Xa (anti-FXa) levels [3,4]. The mean targeted level of anti-FXa activity for the effective dose of LMWH is 0.2-0.6 IU/ml, although these references change according to assays and laboratories [3].…”

“…Dose adjustment of LMWH therapy is usually based on body weight and can be monitored with anti-factor Xa (anti-FXa) levels [3,4]. The mean targeted level of anti-FXa activity for the effective dose of LMWH is 0.2-0.6 IU/ml, although these references change according to assays and laboratories [3]. Because important physiological changes and sustained weight gain occurs in pregnancy, it is difficult to make the optimal dose adjustment at a single check-up [5].…”