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I read with much interest the article of Derksenet al in the January issue of theAnnals of the Rheumatic Diseases.1 The authors gave a detailed introduction to the difficult field of treatment of pregnant patients with antiphospholipid syndrome (APS). Despite the presence of only a limited amount of data from controlled studies the authors gave helpful recommendations for the daily management of these patients.
However, there is a major concern with which I would like to deal. As we know the success of treatment of APS with oral anticoagulants very much depends on the strictness with which the dose is adjusted to the international normalised ratio. The authors rightly suggest changing from oral anticoagulants to subcutaneous low molecular weight heparin in pregnant patients with APS. However, I believe that the dose of low molecular weight heparin has to be adjusted in individual patients.
The measurement of anti-factor Xa activity in plasma enables us to calculate the dose of low molecular weight heparin which is needed to achieve optimal inhibition of the coagulation cascade. Values of 0.6–1.0 U/ml are believed to give maximum protection against thromboembolic events.
From my experience the optimal dose of low molecular weight heparin may be different in different patients. Moreover, a dose given once daily rarely guarantees the desired value of anti-factor Xa activity and often a second injection has to be applied to achieve optimal effect. Therefore, as long as controlled data are missing I would suggest that the measurement of anti-factor Xa activity in pregnant patients with APS should be used to adjust the dose of low molecular weight heparin. This may result in better protection of mother and fetus in this disease.
We thank Dr Fiehn for his interest and comments on our recent leader in the Annals.1-1 At present, there are insufficient data from randomised trials to give evidence based guidelines for optimal (prophylactic) treatment of many of the clinical manifestations of the antiphospholipid syndrome (APS). This not only holds for prevention of pregnancy related complications, the topic of our leader, but also for treatment of thrombosis related to antiphospholipid antibodies.1-2
The major issue raised by Dr Fiehn is that he believes that in patients with APS one should use adjusted, not fixed, doses of low molecular weight heparin (LMWH). It is well known that anti-Xa activity relates to antithrombotic effects of LMWHs, and that the amount of LMWH needed to achieve and maintain a certain range of anti-Xa activity increases during the course of pregnancy. In most patients dose adjustment is needed in the second trimester and, in some, in the third trimester (mean (SD) 20.5 (8.2) weeks), but individual patients vary widely in the time when the dose of LMWH needs to be adjusted from once to twice daily.1-3 Despite this, there is so far no clinical proof that for thromboprophylaxis in pregnancy or prevention of poor pregnancy outcome an adjusted dose LMWH (with cumbersome and costly monthly monitoring of pre- and/or post-injection anti-Xa activity) is better than a fixed dose based on body weight.1-4 1-5Therefore, we do not share Dr Fiehn's view that one should advise adjusted doses of LMWH in all pregnant patients with APS.