Heparin‐induced thrombocytopenia: pathogenesis and management – Response to Rasheed Saad

Dr Saad correctly states that the activated partial thromboplastin time (aPTT) does not measure the anticoagulant effect of lepirudin as accurately as the ecarin clotting time (ECT). However, this advantage of ECT over aPTT is known to be relevant only in situations of very high lepirudin dosing, such as surgery requiring cardiopulmonary bypass (Warkentin & Greinacher, 2003). This is because the dose–response curve of the aPTT to increasing lepirudin concentrations flattens at high lepirudin concentrations (Greinacher, 2001). However, for most clinical situations, such as prophylaxis against or the treatment of thrombosis in acute heparin-induced thrombocytopenia (HIT), use of aPTT is believed to provide acceptable monitoring. Indeed, the pivotal clinical trials of lepirudin for the treatment of thrombosis complicating HIT used aPTT monitoring, with a target aPTT of 1.5–2.5 × baseline for most aPTT reagents (Greinacher et al, 2000). Laboratories should assess their aPTT responsiveness of assay to increasing concentrations of plasma lepirudin: if the curve begins to flatten during the high therapeutic lepirudin concentrations (about 750–1000 ng/ml), then the physician should either aim at the low end of the aPTT target range (to avoid the potential for significant overdosing that might not be apparent if the aPTT lies within the high-therapeutic aPTT range) or utilize the ECT, if available. Whether the ECT might generally provide superior anticoagulation (i.e. greater therapeutic efficacy with less bleeding) than the aPTT in non-cardiac surgery situations is unknown. This hypothesis would need testing in clinical trials comparing monitoring by aPTT versus ECT. However, even if the ECT was shown to be better, the aPTT might still remain the preferred monitoring method. Indeed, this is the current status for the monitoring of unfractionated heparin therapy in many clinical situations, although heparin levels can be measured more accurately by protamine neutralization assay or anti-factor Xa assay (Hirsh et al, 2001).

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