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However&#44; is LA always associated with SLE&#63; Does it inhibit coagulation&#63; Is it an antibody&#63; First&#44; the majority of the patients who are positive for LA do not have SLE&#46; In the absence of concomitant thrombocytopenia or a deficiency of coagulation factors or inhibitors of coagulation factors&#44; with certain exceptions&#44; LA is related to processes of hypercoagulability and arterial and venous thrombosis&#44; but is not&#44; <span class="elsevierStyleItalic">per se</span>&#44; a risk factor for bleeding or hemorrhage&#46; With the currently available scientific evidence&#44; it can be said the LA is constituted by a group of antibodies that have yet to be characterized&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Lupus anticoagulant is detected using functional assays that demonstrate a PL-dependent prolongation of the clotting time&#44; due to the <span class="elsevierStyleItalic">in vitro</span> interference of antibodies with PL-dependent function&#44; as with certain essential cofactors in the coagulation cascade &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41; that result in the prolongation of the activated partial thromboplastin time&#46; The International Society on Thrombosis and Haemostasis &#40;ISTH&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">7</span></a> a society that has unsuccessfully attempted to change the name&#44; established the following criteria to confirm the presence of LA&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0020" class="elsevierStylePara elsevierViewall">Phospholipid-dependent prolonged coagulation tests&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0025" class="elsevierStylePara elsevierViewall">Demonstration of the coagulation inhibitor utilizing mixed plasma&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#46;</span><p id="par0030" class="elsevierStylePara elsevierViewall">Demonstration of the PL dependence of the inhibitor&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4&#46;</span><p id="par0035" class="elsevierStylePara elsevierViewall">Ruling out other coagulation disorders&#44; particularly due to deficiency of coagulation factors&#46;</p></li></ul></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Lupus anticoagulant can be detected in patients with SLE&#44; and with other autoimmune diseases&#44; infections like human immunodeficiency virus&#44; hepatitis and malaria&#44; neoplastic disease or those taking certain drugs &#40;procainamide and chlorpromazine&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">6&#44;8</span></a> A prevalence of 5&#37; has been reported in the general adult population and up to 9&#46;5&#37; in women of reproductive age&#46; Although the pathogenic mechanism has not been defined&#44; the presence of LA has been related to stroke&#44; transitory ischemic attack&#44; acquired thrombophilia and obstetric events&#44; like early and&#47;or recurrent pregnancy loss&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">7</span></a> Although it is certain that&#44; in general&#44; antiphospholipid antibodies have been associated with the clinical manifestations of APS&#44; this association seems to be more evident with LA both in thrombosis and in the morbidity related to pregnancy&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">8&#44;9</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Studies dealing with the relationship between the processes of coagulation and inflammation would establish the clinical relevance of the detection of LA alone&#44; as well as the emergent association of LA to C-reactive protein and mortality&#46; The therapeutic management of asymptomatic carriers of LA could require prophylactic treatment given the presence of cardiovascular risk factors or autoimmune disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">5&#44;8</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In view of the potential thrombotic risk in patients who are positive for LA&#44; it is essential to develop an accurate method for performing its assessment in terms of the diagnosis and follow-up of these patients and the decision on the anticoagulant therapy they should receive&#46; Unfortunately&#44; since we lack a technique to serve as a reference for the detection of LA&#44; laboratories utilize heterogeneous and non-quantitative assays&#44; impeding the characterization of positive results in terms of low or elevated titers&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">10&#44;11</span></a> This requires that the validation of the results be performed only by expert staff&#46; In turn&#44; it impedes their being standardized&#44; the establishment of a consensus and the automation of this determination&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">6&#44;11</span></a> A study published by Devreese et al&#46; points out the need to analyze other additional procoagulant markers&#44; like P-selectin &#40;a marker of platelet activation&#41; and coagulation factor <span class="elsevierStyleSmallCaps">vii</span> in patients with weak LA&#44; in order to optimize its clinical utility&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">12&#44;13</span></a> It is evident that both overrating and underrating LA would expose our patients to long-term anticoagulation or to an increase in the risk of recurrent thrombosis&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">13</span></a> Likewise&#44; it should be possible to report LA quantitatively to enable the identification of low titers or those near the reference value&#46; There is an unquestionable need to perform prospective studies&#44; that examine the relevance of these laboratory tests&#46; This&#44; together with possible new prognostic laboratory parameters&#44; would help in the stratification of the patients in accordance with the risk groups and in making therapeutic decisions&#46;</p></span>"
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        "texto" => "<p id="par0055" class="elsevierStylePara elsevierViewall">The authors wish to thank Dr&#46; Nora Butta &#40;Laboratory for Research on Coagulopathies and Hemostatic Disorders&#44; Hematology Unit&#44; Hospital Universitario La Paz-IDIPaz&#44; Madrid&#44; Spain&#41; for her critical reading and the corrections she made in this manuscript&#46;</p>"
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Letter to the Editor
A Reflection on How We Define, Determine and Interpret the Finding of Lupus Anticoagulant
Una reflexión sobre el anticoagulante lúpico: cómo lo definimos, determinamos e interpretamos
Lara Valora,b,
Corresponding author
lvalor.hgugm@salud.madrid.org

Corresponding author.
, Diana Hernández-Flóreza,b, Julia Martínez-Barrioa,b, Francisco Javier López Longoa,b
a Servicio de Reumatología, Hospital General Universitario Gregorio Marañón, Madrid, Spain
b Instituto de Investigación Biomédica, Hospital Gregorio Marañón, Madrid, Spain
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However&#44; is LA always associated with SLE&#63; Does it inhibit coagulation&#63; Is it an antibody&#63; First&#44; the majority of the patients who are positive for LA do not have SLE&#46; In the absence of concomitant thrombocytopenia or a deficiency of coagulation factors or inhibitors of coagulation factors&#44; with certain exceptions&#44; LA is related to processes of hypercoagulability and arterial and venous thrombosis&#44; but is not&#44; <span class="elsevierStyleItalic">per se</span>&#44; a risk factor for bleeding or hemorrhage&#46; With the currently available scientific evidence&#44; it can be said the LA is constituted by a group of antibodies that have yet to be characterized&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Lupus anticoagulant is detected using functional assays that demonstrate a PL-dependent prolongation of the clotting time&#44; due to the <span class="elsevierStyleItalic">in vitro</span> interference of antibodies with PL-dependent function&#44; as with certain essential cofactors in the coagulation cascade &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41; that result in the prolongation of the activated partial thromboplastin time&#46; The International Society on Thrombosis and Haemostasis &#40;ISTH&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">7</span></a> a society that has unsuccessfully attempted to change the name&#44; established the following criteria to confirm the presence of LA&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0020" class="elsevierStylePara elsevierViewall">Phospholipid-dependent prolonged coagulation tests&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0025" class="elsevierStylePara elsevierViewall">Demonstration of the coagulation inhibitor utilizing mixed plasma&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#46;</span><p id="par0030" class="elsevierStylePara elsevierViewall">Demonstration of the PL dependence of the inhibitor&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">4&#46;</span><p id="par0035" class="elsevierStylePara elsevierViewall">Ruling out other coagulation disorders&#44; particularly due to deficiency of coagulation factors&#46;</p></li></ul></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Lupus anticoagulant can be detected in patients with SLE&#44; and with other autoimmune diseases&#44; infections like human immunodeficiency virus&#44; hepatitis and malaria&#44; neoplastic disease or those taking certain drugs &#40;procainamide and chlorpromazine&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">6&#44;8</span></a> A prevalence of 5&#37; has been reported in the general adult population and up to 9&#46;5&#37; in women of reproductive age&#46; Although the pathogenic mechanism has not been defined&#44; the presence of LA has been related to stroke&#44; transitory ischemic attack&#44; acquired thrombophilia and obstetric events&#44; like early and&#47;or recurrent pregnancy loss&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">7</span></a> Although it is certain that&#44; in general&#44; antiphospholipid antibodies have been associated with the clinical manifestations of APS&#44; this association seems to be more evident with LA both in thrombosis and in the morbidity related to pregnancy&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">8&#44;9</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Studies dealing with the relationship between the processes of coagulation and inflammation would establish the clinical relevance of the detection of LA alone&#44; as well as the emergent association of LA to C-reactive protein and mortality&#46; The therapeutic management of asymptomatic carriers of LA could require prophylactic treatment given the presence of cardiovascular risk factors or autoimmune disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">5&#44;8</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In view of the potential thrombotic risk in patients who are positive for LA&#44; it is essential to develop an accurate method for performing its assessment in terms of the diagnosis and follow-up of these patients and the decision on the anticoagulant therapy they should receive&#46; Unfortunately&#44; since we lack a technique to serve as a reference for the detection of LA&#44; laboratories utilize heterogeneous and non-quantitative assays&#44; impeding the characterization of positive results in terms of low or elevated titers&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">10&#44;11</span></a> This requires that the validation of the results be performed only by expert staff&#46; In turn&#44; it impedes their being standardized&#44; the establishment of a consensus and the automation of this determination&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">6&#44;11</span></a> A study published by Devreese et al&#46; points out the need to analyze other additional procoagulant markers&#44; like P-selectin &#40;a marker of platelet activation&#41; and coagulation factor <span class="elsevierStyleSmallCaps">vii</span> in patients with weak LA&#44; in order to optimize its clinical utility&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">12&#44;13</span></a> It is evident that both overrating and underrating LA would expose our patients to long-term anticoagulation or to an increase in the risk of recurrent thrombosis&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">13</span></a> Likewise&#44; it should be possible to report LA quantitatively to enable the identification of low titers or those near the reference value&#46; There is an unquestionable need to perform prospective studies&#44; that examine the relevance of these laboratory tests&#46; This&#44; together with possible new prognostic laboratory parameters&#44; would help in the stratification of the patients in accordance with the risk groups and in making therapeutic decisions&#46;</p></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Detection&#44; interpretation and possible clinical consequences of a positive result in lupus anticoagulant testing&#46; aCL&#44; anti-cardiolipin&#59; anti-&#946;2GPI&#44; anti-&#946;2-glycoprotein <span class="elsevierStyleSmallCaps">i</span>&#59; aPTT&#44; activated partial thromboplastin time&#59; dRVVT&#44; dilute Russell&#39;s viper venom time&#59; Ig&#44; immunoglobulin&#59; LA&#44; lupus anticoagulant&#59; PL&#44; phospholipid&#46;</p>"
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        "texto" => "<p id="par0055" class="elsevierStylePara elsevierViewall">The authors wish to thank Dr&#46; Nora Butta &#40;Laboratory for Research on Coagulopathies and Hemostatic Disorders&#44; Hematology Unit&#44; Hospital Universitario La Paz-IDIPaz&#44; Madrid&#44; Spain&#41; for her critical reading and the corrections she made in this manuscript&#46;</p>"
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Article information
ISSN: 21735743
Original language: English
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2023 January 155 22 177
2022 December 172 55 227
2022 November 186 51 237
2022 October 166 51 217
2022 September 162 53 215
2022 August 165 51 216
2022 July 167 60 227
2022 June 202 50 252
2022 May 216 58 274
2022 April 214 56 270
2022 March 218 66 284
2022 February 217 48 265
2022 January 270 63 333
2021 December 194 56 250
2021 November 157 70 227
2021 October 155 70 225
2021 September 141 58 199
2021 August 158 52 210
2021 July 132 36 168
2021 June 191 34 225
2021 May 171 61 232
2021 April 346 100 446
2021 March 167 48 215
2021 February 118 32 150
2021 January 116 33 149
2020 December 118 24 142
2020 November 74 35 109
2020 October 51 13 64
2020 September 51 28 79
2020 August 32 15 47
2020 July 12 12 24
2020 June 43 23 66
2020 May 31 11 42
2020 April 34 15 49
2020 March 16 9 25
2020 February 2 0 2
2018 November 0 1 1
2018 October 0 1 1
2018 April 0 1 1
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