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• W1604196400 abstract "We would like to address a recently published article entitled ‘Thrombin generation assay identifies individual variability in responses to low molecular weight heparin in pregnancy: implications for anticoagulant monitoring’ (Chowdary et al, 2015). In this retrospective study, the authors concluded that some patients with ‘safe’ anti-Xa levels may potentially be under anticoagulated in pregnancy. We agree with the authors that anti-Xa activity is not the ideal tool for monitoring low molecular weight heparin (LMWH). However, we would be cautious in accepting their conclusion based on the large variation in timing of blood sampling for peak anti-Xa level (up to 6 h) post-LMWH administration reported by Chowdary et al (2015). Peak anti-Xa activity occurs 3- to 4-h post-LMWH administration, depending on the type of LMWH used (Hirsh et al, 2001). We have prospectively performed 24-h anti-Xa profiling in patients receiving LMWH (Tinzaparin) thromboprophylaxis post-caesarean section (Ismail et al, 2012). Levels of anti-Xa in our pregnant population peaked sharply at 4 h post-injection (Fig 1). In addition, our study showed that, anti-Xa levels do not show the full anticoagulant profile of LMWH in women post-caesarean section. Thrombin production (as reflected by thrombin antithrombin complex) is effectively reduced even when anti-Xa levels are negligible, reflecting a significant anticoagulation effect up to 24 h post-LMWH (Fig 1). Chowdary et al (2015) found significant variation in thrombin generation between individuals in the study, stating that a substantial proportion of pregnant patients show poorly suppressed thrombin generation despite an ‘acceptable’ anti-Xa level. The variation in timing of blood sampling reported may have contributed to the heterogeneity of the results observed. Ismail et al (2012) Furthermore, the population studied by Chowdary et al (2015) was heterogeneous in terms of thrombosis risk; over a third of patients were of parity 3 or more, which is a risk factor for thrombotic events on its own. Twenty-two per cent of the cohort had three or more miscarriages, although it is not clear whether or not these were recurrent miscarriages. Hence, the significant variation in thrombin generation in this cohort would be in keeping with the heterogeneous group of pregnant women included. The weight or body mass index distribution of the women could also play a role in the variation of thrombin generation observed. In a study of morbidly obese pregnant women, we found a significant increase of endogenous thrombin potential (ETP) compared to normal weight pregnant women (Ismail et al, 2014). We also found that thrombin generation levels (ETP) had a significant negative correlation with anti-Xa levels at weight-adjusted dose of 75 iu/kg tinzaparin (r = 0·570) (P < 0·05) but not at fixed dose of 4500 iu tinzaparin (r = −0·309) (P = 0·282). In our study, there was minimal variation within each homogenous group. We agree that thrombin generation assays may be useful in the optimisation of dosing in pregnant women at risk of thrombosis. However, future studies in this area should place emphasis on appropriate timing of samples and a more homogenous group of pregnant women. SKI, LN and JRH all analysed the data and wrote this manuscript." @default.
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• W1604196400 date "2015-06-17" @default.
• W1604196400 modified "2023-10-01" @default.
• W1604196400 title "Thrombin generation assays for optimizing low molecular weight heparin dosing in pregnant women at risk of thrombosis" @default.
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• W1604196400 doi "https://doi.org/10.1111/bjh.13521" @default.
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