Laboratory Testing for Lupus Anticoagulants: A Review of Issues Affecting Results

Tripodi, Armando

doi:10.1373/clinchem.2007.089524

Cited by 66 publications

(87 citation statements)

References 46 publications

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“…In contrast, the activated partial thromboplastin time (aPTT), the kaolin clotting time (KCT), and the silica clotting time (SCT) assays activate the contact activation and common coagulation pathways. 11 The International Society of Haemostasis and Thrombosis (ISTH), 12 the British Committee for Standards in Haematology (BCSH), 13 and the Clinical and Laboratory Standards Institute (CLSI) 14 recognize that a single assay that can detect all individuals who are truly positive for LAC does not currently exist, so in their respective guidelines, they recommend that 2 different assays with distinct performance principles be undertaken to detect LAC. 15 A recent survey in Australia found that most hematology laboratories perform the dRVVT and aPTT LAC assays and 1/3 also use the KCT method.…”

Section: Lac Assaysmentioning

confidence: 99%

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Laboratory methods to detect antiphospholipid antibodies

Krilis

Giannakopoulos

2014

Hematology

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This chapter reviews several important themes pertaining to the antiphospholipid syndrome (APS), including a description of the clinical features, a discussion of the main autoantigen, beta 2-glycoprotein I (␤ 2 GPI), and insights into the characteristics of the pathogenic anti-␤ 2 GPI autoantibodies. Evidence-based considerations for when to test for APS are explored, along with the clinical significance of patients testing positive on multiple APS assays, so-called triple positivity. A detailed review of recently published laboratory guidelines for the detection of lupus anticoagulant and the solid-phase anticardiolipin and anti-␤ 2 GPI ELISAs is undertaken. Finally, a brief review of nonclassification criteria laboratory assays with potential future diagnostic utility is presented. Learning Objectives• To understand that the term antiphospholipid is a misnomer: the major autoantigen in APS is ␤ 2 GPI • To understand that aCL, anti-␤ 2 GPI, and LAC triple positivity does not predict thrombotic risk

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Section: Lac Assaysmentioning

confidence: 99%

“…This procedure may cause loss of VWF and consequently factor VIII, leading to artificial prolongation of coagulation tests responsive to factor VIII, namely aPTT. 11 For this reason, plasma filtration is no longer recommended.…”

Section: Lac Assays Preanalytic Considerationsmentioning

confidence: 99%

Laboratory methods to detect antiphospholipid antibodies

Krilis

Giannakopoulos

2014

Hematology

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“…37 The mixing studies involve combining the patient's plasma with normal plasma (1:1) and assessing the influence of this procedure on clotting time, the theoretical underpinning being that if prolongation of clotting time is the result of a coagulation factor deficiency, it will correct to normal, whereas with LA, correction requires larger volumes of normal plasma. 33 A number of methods have been proposed by which this step can be interpreted, 36 the most robust being the calculation of the index of circulating anticoagulant, initially proposed by Rosner et al 38 To determine whether the inhibitor is phospholipid-dependent, the platelet-neutralization procedure, which uses either washed platelets activated with calcium ionophore or platelets lysed by repeated freeze-thawing (leading to the exposure of anionic phospholipid surfaces), is commonly used. 33 Correction of the clotting time will occur in the presence of LA.…”

Section: Overview Of the Assays Lupus Anticoagulantmentioning

confidence: 99%

“…35 One of the screening tests undertaken should use activation of the intrinsic pathway of coagulation (eg, aPTT or kaolin clotting time) and the other the direct activation of factor X (eg, dRVVT). 36 Local reference ranges should be established for each LA method used and for each coagulometer. 37 The mixing studies involve combining the patient's plasma with normal plasma (1:1) and assessing the influence of this procedure on clotting time, the theoretical underpinning being that if prolongation of clotting time is the result of a coagulation factor deficiency, it will correct to normal, whereas with LA, correction requires larger volumes of normal plasma.…”

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How we diagnose the antiphospholipid syndrome

Giannakopoulos

Passam

Ioannou

et al. 2009

Blood

163

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IntroductionThe antiphospholipid syndrome (APS) is an important cause of acquired thrombophilia and recurrent miscarriages. This narrativestyle review discusses the key laboratory and clinical aspects of APS. Particular focus is given to antibodies against beta 2-glycoprotein I (␤ 2 GPI), in view of their recent inclusion in the APS laboratory classification criteria 1 (Figure 1). The evidence for assessing antiprothrombin and antiphosphatidylethanolamine antibodies to diagnose APS is also examined.The utility of the ␤ 2 GPI enzyme-linked immunosorbent assay (ELISA), when used in conjunction with the cardiolipin (CL) ELISA and the lupus anticoagulant (LA) assays, in risk-stratifying APS patients is explored. Work undertaken by many groups over the years, ours included, in delineating the key characteristics of anti-␤ 2 GPI antibodies that associate with APS is presented.Miscarriages are a major feature of APS. The relative importance of the LA assays, the CL-ELISA, and the ␤ 2 GPI-ELISA in diagnosing APS in the context of early and late gestation miscarriages is assessed. The value of recent epidemiologic and basic science insights in refining our understanding of obstetric APS pathophysiology is examined, particularly with regards to considering the possibility that distinct mechanisms may be responsible for early and late miscarriages. The clinical implications arising from these observations are discussed. Clarification of the nomenclatureAntiphospholipid antibodies is a term applied to antibodies detected traditionally by 2 types of assays, the CL-ELISA, which stems from the earlier work of Harris et al, 2 and the LA assays. 3 The first report of a cofactor requirement for antibodies to bind cardiolipin (an anionic phospholipid) from patients with APS was by McNeil et al in 1989. 4 This was subsequently confirmed by Galli et al 5 and Matsuura et al 6 in 1990. Purification and sequencing of the cofactor as ␤ 2 GPI was reported by McNeil et al in 1990. 7 It was noted that anionic phospholipid is not an absolute requirement for antibodies to bind ␤ 2 GPI, 8 negating the notion that ␤ 2 GPI is a "cofactor" for antibody binding. Antibodies from these patients can bind to ␤ 2 GPI immobilized on an irradiated plate in the absence of anionic phospholipids. 9 A negatively charged surface serves a 2-fold role. It enables ␤ 2 GPI clustering, allowing divalent binding by the low affinity antibodies. 10,11 It also enables the ␤ 2 GPI molecule to undergo a conformational change, 9 exposing a cryptic epitope on the first domain. 12 Positivity on the CL-ELISA is not directed against ␤ 2 GPI in the context of a number of infections. 13 However, this is not true for all types of infections, as elevated anti-␤ 2 GPI antibodies in patients with leishmaniasis, leptospirosis, 14 and leprosy 15 have been noted. A key distinguishing feature between anti-␤ 2 GPI antibodies occurring in the context of leprosy and those that strongly associate with thrombosis is that in the former instance they are directed against an epitope on dom...

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