Utility of Lupus Anticoagulant Assays (APTT-LA, KCT, DPT and DRVVT) in Detection of Antiphospholipid Syndrome (APS) in High Risk Pregnancy Cases

  • Ankur Ahuja
  • Seema TyagiEmail author
  • Hara Prasad Pati
  • Renu Saxena
  • Venkatesan Somasundaram
  • Prabhu Manivannan
  • Preeti Tripathi
  • Dinesh Chandra
Original Article


Routine investigation for recurrent pregnancy loss includes measurement of antiphospholipid antibodies. The lupus anticoagulant has long been associated with increased risks for thrombosis and adverse obstetric outcomes. But there are some disadvantages with lupus anticoagulant (LAC) tests which includes varied sensitivity of different clot based assays. ISTH recommends only 2 assays (preferably DRVVT and APTT-LA) for the identification of lupus anticoagulant but there are some studies which don’t support this contention. Our study analyzed 526 samples from high risk pregnancy cases for APLA by all four LAC tests from tertiary centre of northern India. Among all the cases studies 65 cases were positive for lupus anticoagulant 25 of this became negative after 12 weeks. Among the 40 repeated positive assays, dRVVT could able to diagnose 36 cases followed by APTT-LA which could able to diagnose 28 cases, while KCT could able to diagnose 23 cases and dPT could able to diagnose only 14 cases. There were 12 cases in whom all lupus assays were positive. Our study thus concluded that DRVVT was the most sensitive followed by APPT-LA, KCT, dPT. The combination of dRVVT with APTT-LA or KCT appeared to be superior to other combinations. No individual test per se is 100% sensitive for the diagnosis of APLA in high risk pregnancy cases. Further results confirmed that repeated LAC result is required even in a high-risk setting. Positive LAC assay in majority were not associated with exclusively recurrent pregnancy loss but were associated with sporadic stillbirth and thrombosis.


Antiphospholipid syndrome Lupus anticoagulant DRVVT dPT KCT APTT-LA High risk pregnancy Recurrent abortions 



We acknowledge the support of our patients and technical staff, as with their support the study had been feasible.

Author contributions

RS, HPT, AA and ST were involved in conceptualization, designing, writing and critical review of the manuscript and were responsible for overall supervision. PM, AA, DC, PT and VS were involved in literature search, writing and manuscript editing. ST is the overall guarantor of the article.


This study was funded by Haematology Research Society (Grant Number 01) and we are very grateful to them for helping us in research process.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interests.

Ethical Approval

The present study is in compliance with ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Lubbe WF, Liggins GC (1985) Lupus anticoagulant and pregnancy. Am J Obstet Gynecol 153:322–327CrossRefGoogle Scholar
  2. 2.
    Branch DW, Scott JR, Kochenour NK, Hershgold E (1985) Obstetric complications associated with the lupus anticoagulant. N Engl J Med 313:1322–1326CrossRefGoogle Scholar
  3. 3.
    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 7:1737–1740CrossRefGoogle Scholar
  4. 4.
    Wilson WA, Gharavi AE, Koike T, Lockshin MD, Branch DW, Piette JC et al (1999) International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthr Rheum 42:1309–1311CrossRefGoogle Scholar
  5. 5.
    Galli M, Reber G, de Moerloose P, de Groot PG (2008) Invitation to a debate on the serological criteria that define the antiphospholipid syndrome. J Thromb Haemost 6:399–401CrossRefGoogle Scholar
  6. 6.
    Galli M, Finazzi G, Bevers EM, Barbui T (1995) Kaolin clotting time and dilute Russell’s viper venom time distinguish between prothrombin-dependent and beta 2-glycoprotein I-dependent antiphospholipid antibodies. Blood 86:617–623Google Scholar
  7. 7.
    Keeling D, Mackie I, Moore GW, Greer IA, Greaves M (2012) British committee for standards in haematology. Br J Haematol 157:47–58CrossRefGoogle Scholar
  8. 8.
    Pengo V, Biasiolo A, Gresele P et al (2007) Participating centres of Italian Federation of Thrombosis Centres (FCSA). Survey of lupus anticoagulant diagnosis by central evaluation of positive plasma samples. J Thromb Haemost 5:925–930CrossRefGoogle Scholar
  9. 9.
    Jennings I, Mackie I, Arnout J, Preston FE (2004) UK national external quality assessment scheme for blood coagulation. Lupus anticoagulant testing using plasma spiked with monoclonal antibodies: performance in the UK NEQAS proficiency testing programme. J Thromb Haemost 2:2178–2184CrossRefGoogle Scholar
  10. 10.
    Arnout J, Vanrusselt M, Huybrechts E, Vermylen J (1994) Optimization of the dilute prothrombin time for the detection of the lupus anticoagulant by use of a recombinant tissue thromboplastin. Br J Haematol 87:94–99CrossRefGoogle Scholar
  11. 11.
    Bowie EJ, Thompson JH Jr, Pascuzzi CA, Owen CA Jr (1963) Thrombosis in systemic lupus erythematosus despite circulating anticoagulants. J Lab Clin Med 62:416–430Google Scholar
  12. 12.
    Mueh JR, Herbst KD, Rapaport SI (1980) Thrombosis in patients with the lupus anticoagulant. Ann Intern Med 92:156–159CrossRefGoogle Scholar
  13. 13.
    Clarke CA, Davidovits J, Spitzer KA, Laskin CA (2013) Lupus anticoagulant: results from 2257 patient attending a high risk pregnancy clinic. Blood 18(122):341–347CrossRefGoogle Scholar
  14. 14.
    Vora S, Shetty S, Salvi V, Satoskar P, Ghosh K (2008) Thrombophilia and unexplained pregnancy loss in Indian patients. Natl Med J India 21:116–119Google Scholar
  15. 15.
    Swadzba J, Iwaniec T, Pulka M, De Laat B, De Groot PG, Musial J (2011) Lupus anticoagulant: performance of the tests as recommended by the latest ISTH guidelines. J Thromb Haemost 9:1776–1783CrossRefGoogle Scholar
  16. 16.
    Helgadóttir LB, Turowski G, Skjeldestad FE, Jacobsen AF, Sandset PM, Roald B et al (2013) Classification of stillbirths and risk factors by cause of death—a case–control study. Acta Obstet Gynecol Scand 92:325–333CrossRefGoogle Scholar
  17. 17.
    Duley L (2009) The global impact of pre-eclampsia and eclampsia. Semin Perinatol 33:130–137CrossRefGoogle Scholar
  18. 18.
    Miyakis S, Lockshin MD, Atsumi D, Branch DW, Brey RL, Cervera R et al (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4:295–306CrossRefGoogle Scholar
  19. 19.
    Alijotas-Reig J, Ferrer-Oliveras R, Ruffatti A, Tincani A, Lefkou E, Bertero MT et al (2015) The European Registry on Obstetric Antiphospholipid Syndrome (EUROAPS): a survey of 247 consecutive cases. Autoimmun Rev 14:387–395CrossRefGoogle Scholar
  20. 20.
    Bouvier S, Cochery-Nouvellon E, Lavigne-Lissalde G, Mercier E, Marchetti T, Balducchi JP et al (2014) Comparative incidence of pregnancy outcomes in treated obstetric antiphospholipid syndrome: the NOH-APS observational study. Blood 16(123):404–413CrossRefGoogle Scholar
  21. 21.
    Fischer-Betz R, Specker C, Brinks R, Schneider M (2012) Pregnancy outcome in patients with antiphospholipid syndrome after cerebral ischaemic events: an observational study. Lupus 21:1183–1189CrossRefGoogle Scholar
  22. 22.
    Barbour LA (2001) ACOG committee on practice bulletins-obstetrics. Int J Gynaecol Obstet 75(2):203–212CrossRefGoogle Scholar
  23. 23.
    Branch DW, Silver RM, Porter TF (2010) Obstetric in antiphospholipid syndrome: current uncertainties should guide our way. Lupus 19:446–452CrossRefGoogle Scholar
  24. 24.
    Skrzypczak J, Rajewski M, Wirstlein P, Goździewicz T, Zimmer M, Wołczyński S et al (2011) Frequency of antiphospholipid syndrome in women with pregnancy loss in multicenter study in Poland. Ginekol Pol 82:749–754Google Scholar
  25. 25.
    Martinuzzo ME, Cerrato GS, Varela ML, Adamczuk YP, Forastiero RR (2012) New guidelines for lupus anticoagulant: sensitivity and specificity of cut-off values calculated with plasmas from healthy controls in mixing and confirmatory tests. Int J Lab Hematol 34:208–213CrossRefGoogle Scholar
  26. 26.
    Exner T, Rickard KA, Kronenberg H (1978) A sensitive test demonstrating lupus anticoagulant and its behavioural patterns. Br J Haematol 40:143–151CrossRefGoogle Scholar
  27. 27.
    Pengo V, Biasiolo A, Rampazzo P, Brocco T (1999) dRVVT is more sensitive than KCT or TTI for detecting lupus anticoagulant activity of anti-beta2-glycoprotein I autoantibodies. Thromb Haemost 81:256–258CrossRefGoogle Scholar
  28. 28.
    Urbanus RT, de Groot PG (2011) Antiphospholipid antibodies—we are not quite there yet. Blood Rev 25:97–106CrossRefGoogle Scholar

Copyright information

© Indian Society of Hematology and Blood Transfusion 2019

Authors and Affiliations

  1. 1.Department of Lab Sciences and Molecular MedicineArmy Hospital (Research and Referral)New DelhiIndia
  2. 2.Department of HaematologyAll India Institute of Medical SciencesNew DelhiIndia
  3. 3.Department of PathologyArmed Forces Medical CollegePuneIndia
  4. 4.Department of HaematologySGPGILucknowIndia

Personalised recommendations