Clinical Utility of the Less Commonly Employed Assays for Lupus Anticoagulant Detection: the Evidence

Review Article

Clinical Utility of the Less Commonly Employed Assays for Lupus Anticoagulant Detection: the Evidence

W Gary Moore
Affiliation: Centre for Haemostasis and Thrombosis, GSTS Pathology, St Thomas’ Hospital, London, UK


ABSTRACT

Accurate detection of persistent antiphospholipid antibodies (aPA) is crucial to the diagnosis of the antiphospholipid syndrome. Lupus anticoagulants (LA) are aPA that are detected by their behavior in coagulation assays, a process that is complicated by marked antibody heterogeneity and significant variation between reagents, analytical techniques, and result interpretation strategies. The accepted mainstay of LA detection is the pairing of activated partial thromboplastin time (aPTT) and dilute Russell’s viper venom time (DRVVT) screening assays complemented by appropriate confirmatory procedures. Despite being proven to detect the majority of clinically significant antibodies, this reagent coupling does not constitute a gold standard, and evidence is accumulating that less commonly employed assays are able to identify LA that manifest in aPTT and/or DRVVT, but also some that do not. The dilute prothrombin time (DPT) and activated seven lupus anticoagulant (ASLA) assay are extrinsic pathway‐based assays that detect many aPTT/DRVVT‐reactive LA and also a subpopulation of aPTT/DRVVT‐unreactive antibodies in symptomatic patients. Textarin, Taipan, and Ecarin snake venom fractions contain prothrombin activators capable of activating prothrombin in orally anticoagulated patients. Ecarin does not require phospholipid as a cofactor and can be used as a confirmatory test for Textarin or Taipan screening tests in patients in whom other assays are compromised by the oral anticoagulant effect. LA unreactive in aPTT/DRVVT have been detected in these alternative snake venom‐based assays. Modifications of aPTT and DRVVT themselves have also been described. Recent updates to the international guidelines for LA detection recommend the use of aPTT and DRVVT for LA detection, yet dismiss other assays because of technical considerations or insufficient evidence and familiarity. The present review assesses the available evidence for the clinical utility of the less commonly employed LA assays.

Keywords: lupus anticoagulant, activated partial thromboplastin time, dilute Russell’s viper venom time, dilute prothrombin time, activated seven lupus anticoagulant assay, Textarin/Ecarin ratio, Taipan snake venom time
Correspondence: Gary W Moore, Centre for Haemostasis and Thrombosis, First Floor North Wing, St Thomas’ Hospital, Westminster Bridge Road, London SE1 7EH, UK. Tel: (44)‐(0)20‐7188‐0814; Fax: (44)‐(0)20‐7188‐2726; e‐mail: gary.moore@gsts.com