Laboratory detection of lupus anticoagulant
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Published:
Dec 24, 2019
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Abstract
บทนำ
การตรวจ lupus anticoagulants (LA) ในพลาสมาของผู้ป่วยเป็นการตรวจที่สำคัญสำหรับการวินิจฉัยภาวะ antiphospholipid syndrome (APS) ซึ่งเป็นปัจจัยเสี่ยงที่สำคัญต่อการเกิดภาวะหลอดเลือดอุดตัน (thrombosis) ทั้งในหลอดเลือดดำและหลอดเลือดแดง รวมถึงหลอดเลือดที่ไปเลี้ยงรกในขณะตั้งครรภ์ เป็นสาเหตุที่ทำให้เกิดการแท้งซ้ำ ๆ ในผู้ป่วย1−2 LA เป็นสาเหตุหนึ่งที่ทำให้ค่าการทดสอบการแข็งตัวของเลือดยาวผิดปกติ (prolonged clotting time) โดยเฉพาะในการตรวจ activated partial thromboplastin time (APTT) และไม่สามารถแก้ไขให้กลับมาสั้นลง (correct) ด้วยการผสมกับพลาสมาของคนปกติในการตรวจ mixing test ได้3−5 ปัจจุบันการตรวจ LA ใช้หลักการวัดการแข็งตัวของเลือด (clotting based assays) โดยอาศัยการยับยั้ง phospholipids ที่มีอยู่ในน้ำยาทดสอบและวัดผลโดยการวัด clotting time ซึ่งหากในพลาสมามี LA อยู่จะให้ผล prolonged clotting time6−7 อย่างไรก็ตามการตรวจหา LA นั้นมีขั้นตอนที่ยุ่งยากและซับซ้อน อีกทั้ง LA เป็นกลุ่มของ antibodies ที่มีความหลากหลายสูงและให้ผลบวกที่ไม่จำเพาะต่อการตรวจชนิดใดชนิดหนึ่ง8 ดังนั้นจนถึงปัจจุบันจึงยังไม่มีวิธีการตรวจใดที่มีความไว (sensitivity) และความจำเพาะ (specificity) สูงพอที่จะใช้ในการตรวจหา LA ได้เพียงวิธีเดียวและยังไม่มีวิธีใดที่เป็นวิธีมาตรฐาน (gold standard) แต่อาศัยการตรวจ clotting time อย่างน้อย 2 การทดสอบซึ่งวัดปฏิกิริยาใน coagulation pathway ที่แตกต่างกัน ซึ่งทำให้เกิดความหลากหลายของการตรวจและการแปลผลในแต่ละห้องปฏิบัติการ อีกทั้งแนวทางปฏิบัติ (guideline) ในการตรวจ LA ในปัจจุบันมีหลาย guideline การเลือกใช้ guideline ใด ๆ จะส่งผลต่อทั้ง sensitivity และ specificity ในการตรวจและการแปลผล LA ที่แตกต่างกัน ในบทความนี้จะกล่าวในแง่ของการตรวจทางห้องปฏิบัติการ ตั้งแต่การเตรียมตัวอย่าง หลักการและขั้นตอนที่ใช้ในการตรวจ guideline ในการตรวจ หลักการในการแปลผล ตลอดจนปัจจัยรบกวนการทดสอบในการตรวจหา LA
Article Details
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บทความฟื้นวิชา (Subject Review)
References
1. Gomez-Puerta JA, Cervera R. Diagnosis and classification of the antiphospholipid syndrome. J Autoimmun. 2014; 48–49:20–5.
2. Limper M, Scirè CA, Talarico R, Amoura Z, Avcin T, Basile T. Antiphospholipid syndrome: state of the art on clinical practice guidelines. RMD Open. 2018 (Suppl 1);0:e000785.
3. Antovic A, Sennström M, Bremme K, Svenungsson E. Obstetric antiphospholipid syndrome. Lupus Sci Med. 2018(Suppl 1);5:e000197.
4. Tcherniantchouk O, Laposata M, Marques MB. The isolated prolonged PTT. Am J Hematol. 2013;88(1):82–85.
5. Ames PRJ, Graf M, Archer J, Scarpato N, Iannaccone L. Prolonged activated partial thromboplastin time: Difficulties in discriminating coexistent factor VIII inhibitor and lupus anticoagulant. Clin Appl Thromb Hemost. 2015;21(2):149–54.
6. Chng WJ, Sum C, Kuperan P. Causes of isolated prolonged activated partial thromboplastin time in an acute care general hospital. Singapore Med J. 2005;46(9): 450–6.
7. Ortel TL. Antiphospholipid syndrome laboratory testing and dagnostic strategies. Am J Hematol. 2012;87(Suppl 1):S75–S81.
8. Vermylen J, Arnout J. Influence of the lupus anticoagulant on clotting tests. Clin Rheumatol. 1990;9(1 Suppl 1):45-8.
9. Kandiah DA, Krilis SA. Heterogeneity of lupus anticoagulant (LA) antibodies: LA activity in dilute Russell's Viper Venom Time and dilute Kaolin Clotting Time detect different populations of antibodies in patients with the "antiphospholipid" syndrome. Thromb Haemost. 1998;80(2):250–7.
10. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4(2):295–306.
11. Gardiner C, Hills J, Machin SJ, Cohen H. Diagnosis of antiphospholipid syndrome in routine clinical practice. Lupus. 2013;22(1):18–25.
12. Proven A, Bartlett RP, Moder KG, Miller AC, Cardel LK, Heit JA. Clinical importance of positive test results for lupus anticoagulant and anticardiolipin antibodies. Mayo Clin Proc. 2004;79(4):467–75.
13. Saraiva SS, Mazetto BM, Tobaldine LQ, Colella PM, Paula EVD, Bizzachi JA. The impact of antibody profile in thrombosis associated with primary antiphospholipid syndrome. Am J Hematol. 2017;92(11):1163–9.
14. Akkawat B. Laboratory diagnosis of lupus anticoagulant: from guidelines 1995 to 2009. J Hematol Transfus Med. 2011;21(1):41−6.
15. Aryurachai K, Rachakom B, Angchaisuksiri P, Atichartakarn V. Laboratory identification of lupus anticoagulants. J Hematol Transfus Med. 2002;12(3):209−18.
16. Aryurachai K, Archararit N, Rachakom B, Angchaisuksiri P, Atichartakarn V, Rattanasiri S. Comparison of diluted Russell’s viper venom time by a conversional method with an automated kit assay for the detection of lupus anticoagulants. J Hematol Transfus Med. 2005;15(3):155−63.
17. Pengo V, Bison E, Banzato A, Zoppellaro G, Jose SP, Denas G. Lupus anticoagulant testing: Diluted Russell viper venom time (dRVVT). Methods Mol Biol. 2017;1646:169–176.
18. Swadzba J, Iwaniec T, Pulka M, De Laat B, De Groot PG, Musial J. Lupus anticoagulant: performance of the tests as recommended by the latest ISTH guidelines. J Thromb Haemost. 2011; 9(9):1776–83.
19. Kumano O, Ieko M, Naito S, Yoshida M, Takahashi N. APTT reagent with ellagic acid as activator shows adequate lupus anticoagulant sensitivity in comparison to silica-based reagent. J Thromb Haemost. 2012;10(11):2338−43.
20. Aryurachai K, Angchaisuksiri P, Siriputtanapong K. Evaluation of kaolin clotting time for the diagnosis of lupus anticoagulants by using different calculation methods. J Hematol Transfus Med. 2014;24(4):379−88.
21. Pengo V, Biasiolo A, Rampazzo P, Brocco T. dRVVT is more sensitive than KCT or TTI for detecting lupus anticoagulant activity of anti-beta2-glycoprotein I autoantibodies. Thromb Haemost. 1999;81(2):256−8.
22. Galli M, Finazzi G, Bevers EM, Barbui T. Kaolin Clotting Time and Dilute Russell’s Viper Venom Time distinguish between prothrombin-dependent and B2-Glycoprotein I-dependent antiphospholipid antibodies. Blood. 1995;86(2):617−23.
23. Lee HR, Kim JE, Ha SH, Kim HK, Park S, Cho HI. Usefulness of silica clotting time for detection of lupus anticoagulants. Korean J Lab Med. 2009;29(6):497−504.
24. Liu HW, Wong KL, Lin CK, Wong WS, Tse PW, Chan GT. The reappraisal of dilute tissue thromboplastin inhibition test in the diagnosis of lupus anticoagulant. Br J Haematol. 1989;72(2):229−34.
25. Moore GW, Maloney JC, de Jager N, Dunsmore CL, Gorman DK, Polgrean RF, et al. Applications of different lupus anticoagulant diagnostic algorithms to the same assay data leads to interpretive discrepancies in some samples. Res Pract Thromb Haemost. 2017;1(1):62−8.
26. Kumano O, Moore GW. Lupus anticoagulant mixing tests for multiple reagents are more sensitive if interpreted with a mixing test-specific cut-off than index of circulating anticoagulant. Res Pract Thromb Haemost. 2018;2(1):105−13.
27. Moore GW. Commonalities and contrasts in recent guidelines for lupus anticoagulant detection. Int Jnl Lab Hem. 2014;36(3):364−73.
28. Pengo V, Tripodi A, Reber G, Rand JH, Ortel TL, Galli M, et al; Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. 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. 2009;7(10):1737-40.
29. Moore GW. Recent guidelines and recommendations for laboratory detection of lupus anticoagulants. Semin Thromb Hemost. 2014;40(2):163−71.
30. Moore GW. Current Controversies in lupus anticoagulant detection. Antibodies. 2016;5(22):e10.3390.
31. Olteanu H, Downes KA, Patel J, Praprotnik D, Sarode R. Warfarin does not interfere with lupus anticoagulant detection by dilute Russell’s viper venom time. Clin Lab. 2009;55(3-4):138−42.
32. Sangle NA, Rodgers GM, Smock KJ. Prevalence of heparin in samples submitted for lupus anticoagulant testing. Lab Hematol. 2011;17(1):6−11.
33. Gosselin RC, King JH, Janatpur KA, Dager WH, Larkin EC, Owings JT. Effects of pentasaccharide (Fondaparinux) and direct thrombin inhibitors on coagulation testing. Arch Pathol Lab Med. 2004;128(10):1142−5.
34. Murer LM, Pirruccello SJ, Koepsell SA. Rivaroxaban therapy, false-positive lupus anticoagulant screening results, and confirmatory assay results. Lab Medicine. 2016;47(4);275–8.
35. Hoxha A, Banzato A, Ruffatti A, Pengo V. Detection of lupus anticoagulant in the era of direct oral anticoagulants. Autoimmun Rev. 2017;16(2):173–8.
36. Kovacs MR, Lazo-Langner A, Louzada ML, Kovacs MJ. Lupus anticoagulant testing in patients receiving Rivaroxaban or Apixaban for the treatment of venous thromboembolism. Blood. 2016;128(22):5017.
2. Limper M, Scirè CA, Talarico R, Amoura Z, Avcin T, Basile T. Antiphospholipid syndrome: state of the art on clinical practice guidelines. RMD Open. 2018 (Suppl 1);0:e000785.
3. Antovic A, Sennström M, Bremme K, Svenungsson E. Obstetric antiphospholipid syndrome. Lupus Sci Med. 2018(Suppl 1);5:e000197.
4. Tcherniantchouk O, Laposata M, Marques MB. The isolated prolonged PTT. Am J Hematol. 2013;88(1):82–85.
5. Ames PRJ, Graf M, Archer J, Scarpato N, Iannaccone L. Prolonged activated partial thromboplastin time: Difficulties in discriminating coexistent factor VIII inhibitor and lupus anticoagulant. Clin Appl Thromb Hemost. 2015;21(2):149–54.
6. Chng WJ, Sum C, Kuperan P. Causes of isolated prolonged activated partial thromboplastin time in an acute care general hospital. Singapore Med J. 2005;46(9): 450–6.
7. Ortel TL. Antiphospholipid syndrome laboratory testing and dagnostic strategies. Am J Hematol. 2012;87(Suppl 1):S75–S81.
8. Vermylen J, Arnout J. Influence of the lupus anticoagulant on clotting tests. Clin Rheumatol. 1990;9(1 Suppl 1):45-8.
9. Kandiah DA, Krilis SA. Heterogeneity of lupus anticoagulant (LA) antibodies: LA activity in dilute Russell's Viper Venom Time and dilute Kaolin Clotting Time detect different populations of antibodies in patients with the "antiphospholipid" syndrome. Thromb Haemost. 1998;80(2):250–7.
10. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4(2):295–306.
11. Gardiner C, Hills J, Machin SJ, Cohen H. Diagnosis of antiphospholipid syndrome in routine clinical practice. Lupus. 2013;22(1):18–25.
12. Proven A, Bartlett RP, Moder KG, Miller AC, Cardel LK, Heit JA. Clinical importance of positive test results for lupus anticoagulant and anticardiolipin antibodies. Mayo Clin Proc. 2004;79(4):467–75.
13. Saraiva SS, Mazetto BM, Tobaldine LQ, Colella PM, Paula EVD, Bizzachi JA. The impact of antibody profile in thrombosis associated with primary antiphospholipid syndrome. Am J Hematol. 2017;92(11):1163–9.
14. Akkawat B. Laboratory diagnosis of lupus anticoagulant: from guidelines 1995 to 2009. J Hematol Transfus Med. 2011;21(1):41−6.
15. Aryurachai K, Rachakom B, Angchaisuksiri P, Atichartakarn V. Laboratory identification of lupus anticoagulants. J Hematol Transfus Med. 2002;12(3):209−18.
16. Aryurachai K, Archararit N, Rachakom B, Angchaisuksiri P, Atichartakarn V, Rattanasiri S. Comparison of diluted Russell’s viper venom time by a conversional method with an automated kit assay for the detection of lupus anticoagulants. J Hematol Transfus Med. 2005;15(3):155−63.
17. Pengo V, Bison E, Banzato A, Zoppellaro G, Jose SP, Denas G. Lupus anticoagulant testing: Diluted Russell viper venom time (dRVVT). Methods Mol Biol. 2017;1646:169–176.
18. Swadzba J, Iwaniec T, Pulka M, De Laat B, De Groot PG, Musial J. Lupus anticoagulant: performance of the tests as recommended by the latest ISTH guidelines. J Thromb Haemost. 2011; 9(9):1776–83.
19. Kumano O, Ieko M, Naito S, Yoshida M, Takahashi N. APTT reagent with ellagic acid as activator shows adequate lupus anticoagulant sensitivity in comparison to silica-based reagent. J Thromb Haemost. 2012;10(11):2338−43.
20. Aryurachai K, Angchaisuksiri P, Siriputtanapong K. Evaluation of kaolin clotting time for the diagnosis of lupus anticoagulants by using different calculation methods. J Hematol Transfus Med. 2014;24(4):379−88.
21. Pengo V, Biasiolo A, Rampazzo P, Brocco T. dRVVT is more sensitive than KCT or TTI for detecting lupus anticoagulant activity of anti-beta2-glycoprotein I autoantibodies. Thromb Haemost. 1999;81(2):256−8.
22. Galli M, Finazzi G, Bevers EM, Barbui T. Kaolin Clotting Time and Dilute Russell’s Viper Venom Time distinguish between prothrombin-dependent and B2-Glycoprotein I-dependent antiphospholipid antibodies. Blood. 1995;86(2):617−23.
23. Lee HR, Kim JE, Ha SH, Kim HK, Park S, Cho HI. Usefulness of silica clotting time for detection of lupus anticoagulants. Korean J Lab Med. 2009;29(6):497−504.
24. Liu HW, Wong KL, Lin CK, Wong WS, Tse PW, Chan GT. The reappraisal of dilute tissue thromboplastin inhibition test in the diagnosis of lupus anticoagulant. Br J Haematol. 1989;72(2):229−34.
25. Moore GW, Maloney JC, de Jager N, Dunsmore CL, Gorman DK, Polgrean RF, et al. Applications of different lupus anticoagulant diagnostic algorithms to the same assay data leads to interpretive discrepancies in some samples. Res Pract Thromb Haemost. 2017;1(1):62−8.
26. Kumano O, Moore GW. Lupus anticoagulant mixing tests for multiple reagents are more sensitive if interpreted with a mixing test-specific cut-off than index of circulating anticoagulant. Res Pract Thromb Haemost. 2018;2(1):105−13.
27. Moore GW. Commonalities and contrasts in recent guidelines for lupus anticoagulant detection. Int Jnl Lab Hem. 2014;36(3):364−73.
28. Pengo V, Tripodi A, Reber G, Rand JH, Ortel TL, Galli M, et al; Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. 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. 2009;7(10):1737-40.
29. Moore GW. Recent guidelines and recommendations for laboratory detection of lupus anticoagulants. Semin Thromb Hemost. 2014;40(2):163−71.
30. Moore GW. Current Controversies in lupus anticoagulant detection. Antibodies. 2016;5(22):e10.3390.
31. Olteanu H, Downes KA, Patel J, Praprotnik D, Sarode R. Warfarin does not interfere with lupus anticoagulant detection by dilute Russell’s viper venom time. Clin Lab. 2009;55(3-4):138−42.
32. Sangle NA, Rodgers GM, Smock KJ. Prevalence of heparin in samples submitted for lupus anticoagulant testing. Lab Hematol. 2011;17(1):6−11.
33. Gosselin RC, King JH, Janatpur KA, Dager WH, Larkin EC, Owings JT. Effects of pentasaccharide (Fondaparinux) and direct thrombin inhibitors on coagulation testing. Arch Pathol Lab Med. 2004;128(10):1142−5.
34. Murer LM, Pirruccello SJ, Koepsell SA. Rivaroxaban therapy, false-positive lupus anticoagulant screening results, and confirmatory assay results. Lab Medicine. 2016;47(4);275–8.
35. Hoxha A, Banzato A, Ruffatti A, Pengo V. Detection of lupus anticoagulant in the era of direct oral anticoagulants. Autoimmun Rev. 2017;16(2):173–8.
36. Kovacs MR, Lazo-Langner A, Louzada ML, Kovacs MJ. Lupus anticoagulant testing in patients receiving Rivaroxaban or Apixaban for the treatment of venous thromboembolism. Blood. 2016;128(22):5017.