Advertisement

La ricerca del lupus anticoagulant: raccomandazioni del gruppo di studio sulla coagulazione di SIPMeL

  • Cristina Legnani
  • Giuliana Martini
  • Michele Bertini
  • Pierfrancesco Agostini
  • Francesco Bondanini
  • Maria Rita Cozzi
  • Marta Sofia Angela Demicheli
  • Giovina Di Felice
  • Cristina Novembrino
  • Oriana Paoletti
  • Simona Pedrini
  • Lucia Ruocco
  • Agostino Steffan
  • Lucia Terzuoli
  • Sophie Testa
Raccomandazioni e Linee Guida
  • 176 Downloads

Riassunto

Per porre diagnosi di sindrome da anticorpi antifosfolipidi (APS) è necessario che siano presenti almeno un criterio clinico (trombosi venosa/arteriosa o complicanza della gravidanza) e persistente positività degli anticorpi antifosfolipidi (confermata a distanza di almeno 12 settimane). I criteri di laboratorio per definire la presenza di anticorpi antifosfolipidi sono: presenza di LAC e/o aumento degli anticorpi anticardiolipina (IgG o IgM) e/o anti ß2 glicoproteina I (IgG o IgM). Le variabili che possono influenzare il risultato dei test utilizzati per la diagnostica del LAC sono numerose; la standardizzazione dei test per questa diagnostica è scarsa ed è stata riportata un’ampia variabilità inter-laboratorio in termini di sensibilità e specificità. La probabilità di errori diagnostici in senso negativo (false negatività) e positivo (false positività) è quindi piuttosto elevata. Allo scopo di migliorare l’accuratezza diagnostica di questi test, nel 2009 lo specifico sottocomitato per la standardizzazione dei metodi dell’International Society on Thrombosis and Haemostasis (ISTH) ha aggiornato le linee guida già pubblicate in precedenza. Il Gruppo di Studio in Coagulazione della SIPMeL ha voluto riassumere in questo articolo le linee guida raccomandate dall’ISTH. Successivamente, è stata pubblicata una diversa linea guida da parte del Clinical & Laboratory Standard Institute (CLSI) che per alcuni aspetti si pone su posizioni diverse o contrastanti. Poiché le raccomandazioni indicate dal CLSI vengono seguite da molti Laboratori, si è cercato di rivedere in modo critico queste diverse posizioni. Il Gruppo di Studio SIPMeL ritiene necessario ribadire che per porre diagnosi di APS i test per la diagnostica del LAC devono essere eseguiti seguendo le linee guida ISTH.

Parole chiave

Lupus Anticoagulant LAC Sindrome da anticorpi antifosfolipidi Anticorpi antifosfolipidi Linee guida 

Italian Society of Clinical Pathology and Laboratory Medicine (SIPMeL)—guidelines for laboratory detection of Lupus Anticoagulant (LA)

Summary

To diagnose antiphospholipid syndrome (APS) it is necessary the presence of at least one clinical criterion (venous/arterial thrombosis or pregnancy complications) and persistent positivity of antiphospholipid antibodies (confirmed at least 12 weeks apart). The laboratory criteria to define the presence of antiphospholipid antibodies are: LA presence and/or increase of anticardiolipin and/or anti ß2 Glycoprotein I antibodies (IgG or IgM). Several variables can influence the result of the tests used for LA diagnosis, standardization of tests is poor and a wide inter-laboratory variability has been reported in terms of sensitivity and specificity. The probability of diagnostic errors (false negativity or false positivity) is therefore quite high. In order to improve the diagnostic accuracy of LA tests in 2009 the specific subcommittee for standardization of the methods of the International Society on Thrombosis and Haemostasis (ISTH) has updated the guidelines previously published. The Study Group on Coagulation of the Italian Society of Clinical Pathology and Laboratory Medicine (SIPMeL) summarizes in this article the ISTH guidelines. Subsequently, the Clinical & Laboratory Standard Institute (CLSI) has published its guideline which shows, in some respects, different or conflicting positions. Since the recommendations indicated by the CLSI are followed by many Laboratories, we tried to critically review these different positions. The Study Group of SIPMeL deems necessary to reiterate that for APS diagnosis the LA tests must be performed according to the ISTH guidelines.

Keywords

Lupus Anticoagulant LA Antiphospholipid syndrome Antiphospholipid antibodies Guidelines 

Notes

Conflitti di interesse

Nessuno.

Studi condotti su esseri umani o animali

L’articolo non contiene studi eseguiti su esseri umani e su animali da parte degli autori.

Consenso informato

Non applicabile.

Bibliografia

  1. 1.
    Cervera R (2017) Antiphospholipid syndrome. Thromb Res 151(Suppl 1):S43–S47 CrossRefGoogle Scholar
  2. 2.
    Giannakopoulos B, Krilis SA (2013) The pathogenesis of the antiphospholipid syndrome. N Engl J Med 368:1033–1044 CrossRefGoogle Scholar
  3. 3.
    Pengo V, Biasiolo A, Pegoraro C et al. (2005) Antibody profiles for the diagnosis of anti phospholipid syndrome. Thromb Haemost 93:1147–1152 CrossRefGoogle Scholar
  4. 4.
    Pengo V, Ruffatti A, Tonello M et al. (2015) Antiphospholipid syndrome: antibodies to Domain 1 of beta2-glycoprotein 1 correctly classify patients at risk. J Thromb Haemost 13:782–787 CrossRefGoogle Scholar
  5. 5.
    De Craemer AS, Devreese KM (2016) Role of anti-domain 1-ß2 glycoprotein I antibodies in the diagnosis and risk stratification of antiphospholipid syndrome: reply. J Thromb Haemost 14:2078–2080 CrossRefGoogle Scholar
  6. 6.
    Ruiz-Irastorza G, Cuadrado MJ, Ruiz-Arruza I et al. (2011) Evidence-based recommendations for the prevention and long-term management of thrombosis in antiphospholipid antibody-positive patients: report of a task force at the 13th International Congress on antiphospholipid antibodies. Lupus 20:206–218 CrossRefGoogle Scholar
  7. 7.
    Pengo V, Denas G, Padayattil SJ et al. (2015) Diagnosis and therapy of antiphospholipid syndrome. Pol Arch Med Wewn 125:672–677 Google Scholar
  8. 8.
    Bates SM, Greer IA, Middeldorp S et al. (2012) VTE, thrombophilia, antithrombotic therapy, and pregnancy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 141(Suppl 2):e691S–e736S CrossRefGoogle Scholar
  9. 9.
    Miyakis S, Lockshin MD, Atsumi T et al. (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4:295–306 CrossRefGoogle Scholar
  10. 10.
    Jennings I, Kitchen S, Woods TA et al. (1997) Potentially clinically important inaccuracies in testing for the lupus anticoagulant: an analysis of results from three surveys of the UK national external quality assessment scheme (NEQAS) for blood coagulation. Thromb Haemost 77:934–937 CrossRefGoogle Scholar
  11. 11.
    Arnout J, Meijer P, Vermylen J (1999) Lupus anticoagulant testing in Europe: an analysis of results from the first European concerted action on thrombophilia (ECAT) survey using plasmas spiked with monoclonal antibodies against human beta(2)-glycoprotein I. Thromb Haemost 81:929–934 CrossRefGoogle Scholar
  12. 12.
    Tripodi A, Biasiolo A, Chantarangkul V et al. (2003) Lupus anticoagulant (LA) testing: performance of clinical laboratories assessed by a national survey using lyophilized affinity-purified immunoglobulin with LA activity. Clin Chem 49:1608–1614 CrossRefGoogle Scholar
  13. 13.
    Favaloro EJ, Bonar R, Sioufi J et al. (2005) Multilaboratory testing of thrombophilia: current and past practice in Australasia as assessed through the Royal College of Pathologists of Australasia Quality Assurance Program for Hematology. Semin Thromb Hemost 31:49–58 CrossRefGoogle Scholar
  14. 14.
    Pengo V, Biasiolo A, Gresele P et al. (2007) Survey of lupus anticoagulant diagnosis by central evaluation of positive plasma samples. J Thromb Haemost 5:925–930 CrossRefGoogle Scholar
  15. 15.
    Pengo V, Tripodi A, Reber G et al. (2009) Update of the guidelines for lupus anticoagulant detection. Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost 7:1737–1740 CrossRefGoogle Scholar
  16. 16.
    Brandt JT, Triplett DA, Alving B et al. (1995) Criteria for the diagnosis of lupus anticoagulants: an update. On behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH. Thromb Haemost 74:1185–1190 CrossRefGoogle Scholar
  17. 17.
    CLSI (2014) Laboratory testing for the Lupus Anticoagulant; approved guideline. CLSI document H60-A. Wayne, PA, USA:CLSI Google Scholar
  18. 18.
    Keeling D, Mackie I, Moore GW et al. (2012) Guidelines on the investigation and management of antiphospholipid syndrome. Br J Haematol 157:47–58 CrossRefGoogle Scholar
  19. 19.
    Schouwers SM, Delanghe JR, Devreese KM (2010) Lupus Anticoagulant (LAC) testing in patients with inflammatory status: does C-reactive protein interfere with LAC test results? Thromb Res 125:102–104 CrossRefGoogle Scholar
  20. 20.
    Devreese KM (2014) Antiphospholipid antibody testing and standardization. Int J Lab Hematol 36:352–363 CrossRefGoogle Scholar
  21. 21.
    Hoxha A, Banzato A, Ruffatti A et al. (2017) Detection of lupus anticoagulant in the era of direct oral anticoagulants. Autoimmun Rev 16:173–178 CrossRefGoogle Scholar
  22. 22.
    CLSI (2010) Defining, establishing, and verifying reference intervals in the clinical laboratory; approved guideline—third edition. CLSI document EP28-A3c. Wayne, PA, USA:CLSI Google Scholar
  23. 23.
    Favaloro EJ (2007) Preanalytical variables in coagulation testing. Blood Coagul Fibrinolysis 18:86–89 CrossRefGoogle Scholar
  24. 24.
    Galli M, Finazzi G, Bevers EM et al. (1995) Kaolin clotting time and dilute russell’s viper venom time distinguish between prothrombin-dependent and beta 2-glycoprotein i-dependent antiphospholipid antibodies. Blood 86:617–623 Google Scholar
  25. 25.
    Urbanus RT, Derksen RH, de Groot PG (2008) Current insight into diagnostics and pathophysiology of the antiphospolipid syndrome. Blood Rev 22:93–105 CrossRefGoogle Scholar
  26. 26.
    Kershaw G, Favaloro EJ (2012) Laboratory identification of factor inhibitors: an update. Pathology 44:293–302 CrossRefGoogle Scholar
  27. 27.
    Kumano O, Ieko M, Naito S et al. (2012) APTT reagent with ellagic acid as activator shows adequate lupus anticoagulant sensitivity in comparison to silica-based reagent. J Thromb Haemost 10:2338–2343 CrossRefGoogle Scholar
  28. 28.
    Tripodi A, Pengo V (2011) More on: laboratory investigation of lupus anticoagulants: mixing studies are sometimes required. J Thromb Haemost 9:2126–2127 CrossRefGoogle Scholar
  29. 29.
    Pengo V (2012) ISTH guidelines on Lupus Anticoagulant testing. Thromb Res 130(Suppl 1):S76–S77 CrossRefGoogle Scholar
  30. 30.
    Tripodi A (2012) To mix or not to mix in Lupus anticoagulant testing? That is the question. Semin Thromb Hemost 38:385–389 CrossRefGoogle Scholar
  31. 31.
    Rosner E, Pauzner R, Lusky A et al. (1987) Detection and quantitative evaluation of lupus circulating anticoagulant activity. Thromb Haemost 57:144–147 Google Scholar
  32. 32.
    Tripodi A, Chantarangkul V, Clerici M et al. (2002) Laboratory diagnosis of lupus anticoagulants for patients on oral anticoagulant treatment. Performance of dilute Russell viper venom test and silica clotting time in comparison with Staclot LA. Thromb Haemost 88:583–586 CrossRefGoogle Scholar
  33. 33.
    Jacobsen EM, Barna-Cler L, Taylor JM et al. (2000) The Lupus Ratio test—an interlaboratory study on the detection of lupus anticoagulants by an APTT-based, integrated, and semi-quantitative test. Fifth International Survey of Lupus Anticoagulants—ISLA 5. Thromb Haemost 83:704–708 CrossRefGoogle Scholar
  34. 34.
    Tripodi A, Chantarangkul V, Cini M et al. (2017) Variability of cut-off values for the detection of lupus anticoagulants: results of an international multicenter multiplatform study. J Thromb Haemost 15:1180–1190 CrossRefGoogle Scholar
  35. 35.
    Pengo V, Ruffatti A, Legnani C et al. (2010) Clinical course of high-risk patients diagnosed with antiphospholipid syndrome. J Thromb Haemost 8:237–242 CrossRefGoogle Scholar
  36. 36.
    Pengo V, Ruffatti A, Legnani C et al. (2011) Incidence of a first thromboembolic event in asymptomatic carriers of high-risk antiphospholipid antibody profile: a multicenter prospective study. Blood 118:4714–4718 CrossRefGoogle Scholar
  37. 37.
    Pengo V, Ruffatti A, Del Ross T et al. (2013) Confirmation of initial antiphospholipid antibody positivity depends on the antiphospholipid antibody profile. J Thromb Haemost 11:1527–1531 CrossRefGoogle Scholar
  38. 38.
    Pengo V, Biasiolo A, Gresele P et al. (2007) A comparison of lupus anticoagulant-positive patients with clinical picture of antiphospholipid syndrome and those without. Arterioscler Thromb Vasc Biol 27:e309–e310 CrossRefGoogle Scholar

Copyright information

© Società Italiana di Patologia Clinica e Medicina di Laboratorio 2018

Authors and Affiliations

  • Cristina Legnani
    • 1
  • Giuliana Martini
    • 2
  • Michele Bertini
    • 3
  • Pierfrancesco Agostini
    • 4
  • Francesco Bondanini
    • 5
  • Maria Rita Cozzi
    • 6
  • Marta Sofia Angela Demicheli
    • 7
  • Giovina Di Felice
    • 8
  • Cristina Novembrino
    • 9
  • Oriana Paoletti
    • 10
  • Simona Pedrini
    • 11
  • Lucia Ruocco
    • 12
  • Agostino Steffan
    • 6
  • Lucia Terzuoli
    • 13
  • Sophie Testa
    • 10
  1. 1.UO Angiologia e Malattie della Coagulazione, Azienda Ospedaliera di BolognaPoliclinico S. Orsola-MalpighiBolognaItalia
  2. 2.Centro Emostasi, LaboratorioSpedali CiviliBresciaItalia
  3. 3.UOC di Patologia Clinica e Ambulatorio per lo studio della Trombofilia, Ospedale S. Filippo NeriASL Roma1RomaItalia
  4. 4.UOC Patologia Clinica, PO San PaoloAsl BariBariItalia
  5. 5.UOC Biochimica Clinica, Ospedale Sandro PertiniASL Roma2RomaItalia
  6. 6.Immunopatologia e Biomarcatori OncologiciIRCCS Centro di Riferimento OncologicoAvianoItalia
  7. 7.Laboratorio Malattie Emorragiche e Trombotiche, Laboratorio AnalisiAzienda Ospedaliera SS. Antonio e Biagio e C. ArrigoAlessandriaItalia
  8. 8.Laboratorio Analisi RomaIRCCS Ospedale Bambino GesùRomaItalia
  9. 9.Centro Emofilia e Trombosi Angelo Bianchi Bonomi, e Laboratorio Centrale Analisi Chimico Cliniche e MicrobiologiaFondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilanoItalia
  10. 10.Centro Emostasi e Trombosi, Dipartimento di Medicina di LaboratorioASST CremonaCremonaItalia
  11. 11.Servizio di Medicina di Laboratorio, Istituto OspedalieroFondazione PoliambulanzaBresciaItalia
  12. 12.Ambulatorio Antitrombosi, UO Laboratorio Analisi ClinicheAzienda Ospedaliero Universitaria PisanaPisaItalia
  13. 13.Dipartimento Biotecnologie MedicheUniversità degli Studi di SienaSienaItalia

Personalised recommendations