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Thromboprophylaxis in pregnant women: For whom and which LMWH dosage? Reply

We are very encouraged that our study has provoked such a thoughtful and considered response; its authors are to be congratulated that they are carrying out the first randomized clinical exploring optimal low‐ molecular‐weight heparin (LMWH) dosing for prevention of preg‐ nancy‐associated venous thromboembolism (VTE) in women consid‐ ered to have a personal history of high‐risk VTE.1 As they state, women with personal history of VTE been excluded from studies of LMWH dosing, and we agree that there is a knowledge gap relating to the ef‐ ficacy of different doses of LMWH in this clinical setting. However, arguably there is a more fundamental knowledge gap that should be addressed first. Data compiled from studies of pregnancy‐associated venous thromboembolism suggest that around one in 10 women with a personal history of VTE are at risk of recurrent VTE during pregnancy and in the postpartum,2 but despite this, to date, there is no large ran‐ domized clinical study published that establishes the safety and effi‐ cacy of thromboprophylaxis compared with clinical observation alone. The risk of pregnancy‐associated VTE is highest in women who have had previous VTE associated with hormonal risk factors (i.e., the com‐ bined oral contraceptive pill or pregnancy or who have had unprovoked events). Clinicians continue to follow recommendations2 that are based on low‐level evidence, albeit carefully considered, which leads to pre‐ scription of thromboprophylaxis to large numbers of women during pregnancy and in the postpartum who are perceived to be at highest risk. Although there is no safety concern regarding an adverse fetal effect of LMWH because the drug does not cross the placenta, clearly the use of any anticoagulant could introduce an increased risk of bleed‐ ing complications. The lack of data from a clinical trial that addresses this critical knowledge gap leaves clinicians practicing in the field open to the criticism that thromboprophylaxis is overused.3 We share the authors’ frustrations at the difficulty at carrying out clinical trials in the setting of pregnancy and the pragmatic reasons that led to the decision investigators in the HighLow study1 should be able to use different preparations of LMWH. However, as we out‐ lined in our paper, even the “low‐dose” LMWH regimens are weight‐ adjusted, and we are simply concerned that such a range of doses introduces a degree of complexity that may make it difficult to inter‐ pret the study outcomes and translate findings into clinical practice.