We appreciate the important points made by Sagedal in her Letter. In our article we indeed failed to provide vital information on the use of oral anticoagulants [1]. Actually, none of our HD patients was treated with either warfarin or acenocoumarol. Inspired by Sagedal's final comment that enoxaparin may not be superior to dalteparin for blood anticoagulation during HD, we attentively compared the two reports [1,2]. Detailed analysis of the graphically presented data in the elegant Norwegian study (figure 1, middle) indicates that plasma PF1+2 levels in six warfarin-free patients remained stable until 180 min of dalteparin-anticoagulated HD, and then increased by a mean of 17% at 240 min compared with baseline [2]. In our study employing enoxaparin in a comparable bolus dose of 70 anti-factor Xa IU/kg in 25 oral anticoagulant-free HD subjects, PF1+2 levels were measured pre-dialysis, at 10 and at 180 min of HD, and were found to be stable as well [1]. However, as we did not perform the PF1+2 measurements at 240 min of the HD session, the potential increase in the activated coagulation marker occurring over the last hour of the procedure could have been missed. Therefore, our previous suggestion that enoxaparin provides a better over-dialytic anticoagulant effect than dalteparin is not corroborated enough [1]. This, however, does not affect the main finding of our study that enoxaparin is superior to unfractionated heparin (UFH) in this clinical setting [1].
Nowadays, low-molecular-weight heparins have become the anticoagulants of choice for intermittent HD therapy. We think that future studies of their effects on HD-related haemostasis should consider the fact that even these heparins compose a very heterogeneous group. They differ by molecular weight, glycosaminoglycan content, pharmacokinetics, affinity to factor Xa, thrombin (factor IIa), plasma proteins and endothelium, ability to release tissue factor pathway inhibitor [3], and likely by their dialysability and interactions with different filter membranes. The common clinical practice of pre-rinsing of dialyser with UFH-containing saline (utilized in our study [1] but not mentioned by Sagedal and colleagues [2]) may also influence the results. We are also of the opinion that the aspect of heparin used during HD deserves much more attention. This simple anticoagulant seems to be a truly pleiotropic agent that may affect vital body functions and the course of critical diseases due to its recently recognized effects on some pluripotent growth factors [4,5]. The issue is of special importance in mainte-nance HD patients who are exposed to heparin over years and often a lifetime.
Conflict of interest statement. None declared.
Department of Nephrology and Internal Medicine Medical Academy Bialystok Poland Email: bnaumnik{at}poczta.onet.pl
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