1. bookVolume 29 (2021): Issue 3 (July 2021)
Journal Details
License
Format
Journal
First Published
08 Aug 2013
Publication timeframe
4 times per year
Languages
English
access type Open Access

Lupus anticoagulant in children – a confounding factor in diagnosis and targeted therapy

Published Online: 31 Jul 2021
Page range: 287 - 298
Received: 19 Mar 2021
Accepted: 21 Jun 2021
Journal Details
License
Format
Journal
First Published
08 Aug 2013
Publication timeframe
4 times per year
Languages
English
Abstract

Introduction: Lupus anticoagulant (LAC) belongs to a heterogeneous group of antibodies directed against negatively charged phospholipid-binding proteins, inhibiting phospholipid-dependent reactions. We assessed the frequency, etiological background, clinical and biological expression as well as the appropriate management and outcome of LAC in a pediatric population.

Patients and methods: We included 19 pediatric patients diagnosed with a positive LAC test during a period of 1 year. LAC detection was carried out according to the ISTH/SCC guidelines 2012. Coagulometric assays were performed in order to check for coagulation factor activities. The presence of specific inhibitors has been tested by the Bethesda assay.

Results: LAC was positive in 0.4% of the patients monitored for increased activated partial thromboplastin time (aPTT) during the study period of 1 year. In contrast to the asymptomatic clinical image presented by the majority of our patients, the biological picture was dominated by an elevated aPTT (79 %), the aPTT ratio correlating significantly with the strength of LAC. In 58 % of the patients LAC became negative within 12 weeks, in another 4 (21%) patients within 20 weeks, whereas in 4 (21%) patients LAC remained positive throughout the follow-up.

Conclusion: Albeit usually innocent in asymptomatic patients, LAC needs to be seriously taken into consideration from the diagnostic point of view in order to avoid dangerous therapeutic attitudes..

Keywords

1. Vivaldi P, Rossetti G, Galli M, Finazzi G. Severe bleeeding due to acquired hypoprothrombinemia-lupus anticoagulant syndrome. Case report and review of literature. Haematologica. 1997;82:345-7. Search in Google Scholar

2. Pengo V. ISTH guidelines on Lupus Anticoagulant testing. Throm Res. 2012;130:S76-7. DOI: 10.1016/j.thromres.2012.08.283 Search in Google Scholar

3. Male C, Lechner K, Eichinger S, Kyrle PA, Kapiotis S, Wank H, et al. Clinical significance of lupus anticoagulants in children. J Pediatrics. 1999;134:199-205. DOI: 10.1016/S0022-3476(99)70416-6 Search in Google Scholar

4. Knobe K, Tedgård U, Ek T, Sandström PE, Hillarp A. Lupus anticoagulants in two children-bleeding due to nonphospholipid-dependent antiprothrombin antibodies. Eur J Pediatr. 2012 Sep;171(9):1383-7. DOI: 10.1007/s00431-012-1737-1 Search in Google Scholar

5. Gómez-Puerta JA, Cervera R. Diagnosis and classification of the antiphospholipid syndrome. J Auto-immun. Feb-Mar 2014;48-49:20-5. DOI: 10.1016/j.jaut.2014.01.006 Search in Google Scholar

6. Desposito F, Arkel Y. Inhibitors of coagulation in children. Crit Rev Oncol Hematol. 1987;7(1):53-69. DOI: 10.1016/S1040-8428(87)80014-8 Search in Google Scholar

7. Moore GW. Current Controversies in Lupus Anticoagulant Detection. Antibodies (Basel). 2016 Dec 2;5(4):22. DOI: 10.3390/antib5040022 Search in Google Scholar

8. 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 Mar;21(2):149-54. DOI: 10.1177/1076029614541516 Search in Google Scholar

9. Kallanagowdar C, Chauhan A, Puertolas MV, Warrier R. Prevalence and Resolution of Lupus Anticoagulant in Children. Ochsner J. 2016;16(2):172-5. Search in Google Scholar

10. 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 Sep;9(9):1776-83. DOI: 10.1111/j.1538-7836.2011.04420.x Search in Google Scholar

11. Ames PRJ, Montero D, Archer J. Co-existent Acquired Haemophilia and Lupus Anticoagulant. A Thorny Issue. Indian J Hematol Blood Transfus. 2016 Jun; 32(Suppl 1): 248. DOI: 10.1007/s12288-015-0572-8 Search in Google Scholar

12. Penmetsa GK, Rodgers GM, Smock KJ. Avoiding errors in the laboratory evaluation of potent lupus anticoagulants. Am J Hematol. 2010 Apr;85(4):272-4. DOI: 10.1002/ajh.21666 Search in Google Scholar

13. Wincup C, Ioannou Y. The differences between childhood and adult onset antiphospholipid syndrome. Front Pediatr. 2018 Nov 27;6:362. DOI: 10.3389/fped.2018.00362 Search in Google Scholar

14. Malbora B, Bilaloglu E. Lupus anticoagulant positivity in pediatric patients with prolonged activated partial thromboplastin time: A single-center experience and review of literature. Pediatr Hematol Oncol. 2015;32(7):495-504. DOI: 10.3109/08880018.2015.1065302 Search in Google Scholar

15. Aguiar CL, Soybilgic A, Avcin T, Myones BL. Pediatric Antiphospholipid Syndrome. Curr Rheum Rep. 2015;17. DOI: 10.1007/s11926-015-0504-5 Search in Google Scholar

16. Tagariello G, Radossi P, Salviato R, Zardo M, de Valentin L, Basso M, et al. Clinical relevance of isolated prolongation of the activated partial thromboplastin time in a cohort of adults undergoing surgical procedures. Blood Transf. 2017;15:557-61. Search in Google Scholar

17. Li R, Swaelens C, Vandermijnsbrugge F, Cantinieaux B. Applying a direct aPTT ratio (PlatelinLS/ActinFS) permits to identify rapidly and reliably a bleeding-related factor deficiency or a lupus anticoagulant sequential to an isolated prolongation of aPTT in paediatric pre-operative screening. Euro J Haematol. 2016;96:578-85. DOI: 10.1111/ejh.12634 Search in Google Scholar

18. Devreese KMJ, Ortel TL, Pengo V, de Laat B. Laboratory criteria for antiphospholipid syndrome: communication from the SSC of the ISTH. J Thromb Haemost. 2018;16:809-13. DOI: 10.1111/jth.13976 Search in Google Scholar

19. Dreisbach JD, Dreisbach LP, Young DE, Dreisbach PB. Acquired factor VIII inhibitor and lupus anticoagulant presenting with prolonged aPTT: a case report. Grand Rounds. 2010;10:19-24. Search in Google Scholar

20. Brings HA, Waas JK, McCrae KR, Baele HR, Goldstone J. Successful management of life-threatening hemorrhage in a patient with synchronous lupus anticoagulant and factor VIII inhibitor. J Vasc Surg. 2002 Oct;36(4):853-5. DOI: 10.1067/mva.2002.127336 Search in Google Scholar

21. Agostini V, Biasoli C, Biguzzi R, Santarelli R, Leoni P. Case Report: Coexistence of Factor VIII Inhibitor and Lupus Anticoagulant. Blood. 2007;110:3948. DOI: 10.1182/blood.V110.11.3948.3948 Search in Google Scholar

22. Ballard HS, Nyamuswa G. Life-threatening haemorrhage in a patient with rheumatoid arthritis and a lupus anticoagulant coexisting with acquired auto-antibodies against factor VIII. Br J Rheumatol. 1993 Jun;32(6):515-7. DOI: 10.1093/rheumatology/32.6.515 Search in Google Scholar

23. Seethala S, Collins NP, Comerci G. An Unusual Etiology for Elevation of Activated Partial Thromboplastin Time (aPTT) in SLE: Acquired Hemophilia and Lupus Anticoagulant. Case Rep Hematol 2013;2013:1-3. DOI: 10.1155/2013/521785 Search in Google Scholar

24. Taher A, Abiad R, Uthman I. Coexistence of lupus anticoagulant and acquired haemophilia in a patient with monoclonal gammopathy of unknown significance. Lupus. 2003;12:854-6. DOI: 10.1191/0961203303lu463cr Search in Google Scholar

25. Tiede A, Werwitzke S, Scharf RE. Laboratory Diagnosis of Acquired Hemophilia A: Limitations, Consequences, and Challenges. Semin Thromb Hemost. 2014 Oct;40(7):803-11. DOI: 10.1055/s-0034-1390004 Search in Google Scholar

26. Mustonen P, Lehtonen KV, Javela K, Puurunen M. Persistent antiphospholipid antibody (aPL) in asymptomatic carriers as a risk factor for future thrombotic events: a nationwide prospective study. Lupus. 2014 Dec;23(14):1468-76. DOI: 10.1177/0961203314545410 Search in Google Scholar

27. Sciascia S, Baldovino S, Schreiber K, Solfietti L, Radin M, Cuadrado MJ, et al. Thrombotic risk assessment in antiphospholipid syndrome: The role of new antibody specificities and thrombin generation assay. Clin Mol Allergy. 2016; 14:6. DOI: 10.1186/s12948-016-0043-2 Search in Google Scholar

28. Radin M, Schreiber K, Costanzo P, Cecchi I, Roccatello D, Baldovino S, et al. The adjusted Global Antiphos-Pholipid Syndrome Score (aGAPSS) for risk stratification in young APS patients with acute myocardial infarction. Int J Cardiol. 2017 Aug 1;240:72-77. DOI: 10.1016/j.ijcard.2017.02.155 Search in Google Scholar

Recommended articles from Trend MD

Plan your remote conference with Sciendo