Lupus anticoagulant testing using two parallel methods detects additional cases and predicts persistent positivity
-
Daimon P. Simmons
, Adrianna Z. Herskovits , Elisabeth M. Battinelli , Peter H. Schur , Susan J. Lemire and David M. Dorfman
Abstract
Background:
Antiphospholipid antibody syndrome (APS) is characterized by laboratory evidence of antiphospholipid antibodies (aPL) [e.g. lupus anticoagulant (LA), anticardiolipin (ACL), and/or antiβ2-glycoprotein I (aB2GPI)] in a clinical setting of thrombosis or pregnancy morbidity. The International Society on Thrombosis and Haemostasis recommends two different testing modalities to detect LA. To evaluate these recommendations in a clinical setting, our hospital, a tertiary care center with a specialized coagulation laboratory, added the dilute Russell’s viper venom time to be performed in parallel with the PTT-lupus anticoagulant to detect LA.
Methods:
Results of aPL testing were collected on all patients who had LA testing for one year. Chart review was performed to correlate LA results with ACL, aB2GPI, and clinical history.
Results:
Patients who were initially LA positive by both PTT-lupus anticoagulant and dilute Russell’s viper venom time were more likely to be persistently positive. Patients who were positive for ACL and aB2GPI were likely to be positive by both LA methodologies. No single method was absolutely sensitive, as cases of APS were detected by PTTLA only, DRVVT only, and both methods.
Conclusions:
The addition of a second testing method for LA provides additional diagnostic information and may be helpful in stratifying risk of thrombosis.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Wilson WA, Gharavi AE, Koike T, Lockshin MD, Branch DW, Piette JC, et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 1999;42:1309–11.10.1002/1529-0131(199907)42:7<1309::AID-ANR1>3.0.CO;2-FSearch in Google Scholar
2. 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;4:295–306.10.1111/j.1538-7836.2006.01753.xSearch in Google Scholar
3. Pengo V, Tripodi A, Reber G, Rand JH, Ortel TL, Galli M, et al. 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;7:1737–40.10.1111/j.1538-7836.2009.03555.xSearch in Google Scholar
4. Moore GW. Recent guidelines and recommendations for laboratory detection of lupus anticoagulants. Semin Thromb Hemost 2014;40:163–71.10.1055/s-0033-1364185Search in Google Scholar
5. Bertolaccini ML, Amengual O, Andreoli L, Atsumi T, Chighizola CB, Forastiero R, et al. 14th international congress on antiphospholipid antibodies task force. Report on antiphospholipid syndrome laboratory diagnostics and trends. Autoimmun Rev 2014;13:917–30.10.1016/j.autrev.2014.05.001Search in Google Scholar
6. Pengo V, Biasiolo A, Gresele P, Marongiu F, Erba N, Veschi F, et al. Survey of lupus anticoagulant diagnosis by central evaluation of positive plasma samples. J Thromb Haemost 2007;5: 925–30.10.1111/j.1538-7836.2007.02454.xSearch in Google Scholar
7. Martinuzzo ME, Cerrato GS, Varela ML, Adamczuk YP, Forastiero RR. 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 2012;34:208–13.10.1111/j.1751-553X.2011.01376.xSearch in Google Scholar
8. 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: 1776–83.10.1111/j.1538-7836.2011.04420.xSearch in Google Scholar
9. Pengo V, Biasiolo A, Pegoraro C, Cucchini U, Noventa F, Iliceto S. Antibody profiles for the diagnosis of antiphospholipid syndrome. Thromb Haemost 2005;93:1147–52.10.1160/TH04-12-0839Search in Google Scholar
10. Pengo V, Ruffatti A, Del Ross T, Tonello M, Cuffaro S, Hoxha A, et al. Confirmation of initial antiphospholipid antibody positivity depends on the antiphospholipid antibody profile. J Thromb Haemost 2013;11:1527–31.10.1111/jth.12264Search in Google Scholar
11. Petri M, Golbus M, Anderson R, Whiting-O’Keefe Q, Corash L, Hellmann D. Antinuclear antibody, lupus anticoagulant, and anticardiolipin antibody in women with idiopathic habitual abortion. A controlled, prospective study of forty-four women. Arthritis Rheum 1987;30:601–6.10.1002/art.1780300601Search in Google Scholar
12. Clifford K, Rai R, Watson H, Regan L. An informative protocol for the investigation of recurrent miscarriage: preliminary experience of 500 consecutive cases. Hum Reprod 1994;9:1328–32.10.1093/oxfordjournals.humrep.a138703Search in Google Scholar
13. Yetman DL, Kutteh WH. Antiphospholipid antibody panels and recurrent pregnancy loss: prevalence of anticardiolipin antibodies compared with other antiphospholipid antibodies. Fertil Steril 1996;66:540–6.10.1016/S0015-0282(16)58565-3Search in Google Scholar
14. Reznikoff-Etievant MF, Cayol V, Zou GM, Abuaf N, Robert A, Johanet C, et al. Habitual abortions in 678 healthy patients: investigation and prevention. Hum Reprod 1999;14:2106–9.10.1093/humrep/14.8.2106Search in Google Scholar PubMed
15. Clark CA, Davidovits J, Spitzer KA, Laskin CA. The lupus anticoagulant: results from 2257 patients attending a high-risk pregnancy clinic. Blood 2013;122:341–7.10.1182/blood-2013-02-485839Search in Google Scholar PubMed
16. Branch DW, Silver RM, Porter TF. Obstetric antiphospholipid syndrome: current uncertainties should guide our way. Lupus 2010;19:446–52.10.1177/0961203310361490Search in Google Scholar PubMed
17. Froom P, Saffuri-Elias E, Rozenberg O, Barak M. The association of serum antiphospholipid antibodies and dilute Russell’s viper venom times. J Clin Pathol 2014;67:441–4.10.1136/jclinpath-2013-201830Search in Google Scholar PubMed
18. Heikal N, Jaskowski TD, Malmberg E, Lakos G, Branch DW, Tebo AE. Laboratory evaluation of antiphospholipid syndrome: a preliminary prospective study of phosphatidylserine/prothrombin antibodies in an at-risk patient cohort. Clin Exp Immunol 2014;180:218–26.10.1111/cei.12573Search in Google Scholar PubMed PubMed Central
19. Khogeer H, Alfattani A, Al Kaff M, Al Shehri T, Khojah O, Owaidah T. Antiphosphatidylserine antibodies as diagnostic indicators of antiphospholipid syndrome. Lupus 2015;24:186–90.10.1177/0961203314552462Search in Google Scholar PubMed
20. Reynaud Q, Lega JC, Mismetti P, Chapelle C, Wahl D, Cathebras P, et al. Risk of venous and arterial thrombosis according to type of antiphospholipid antibodies in adults without systemic lupus erythematosus: a systematic review and meta-analysis. Autoimmun Rev 2014;13:595–608.10.1016/j.autrev.2013.11.004Search in Google Scholar PubMed
21. Rodriguez-Garcia V, Ioannou Y, Fernandez-Nebro A, Isenberg DA, Giles IP. Examining the prevalence of non-criteria anti-phospholipid antibodies in patients with anti-phospholipid syndrome: a systematic review. Rheumatology (Oxford) 2015; 54:2042–50.10.1093/rheumatology/kev226Search in Google Scholar
22. Ruffatti A, Tonello M, Del Ross T, Cavazzana A, Grava C, Noventa F, et al. Antibody profile and clinical course in primary antiphospholipid syndrome with pregnancy morbidity. Thromb Haemost 2006;96:337–41.10.1160/TH06-05-0287Search in Google Scholar
23. Pengo V, Ruffatti A, Legnani C, Gresele P, Barcellona D, Erba N, et al. Clinical course of high-risk patients diagnosed with antiphospholipid syndrome. J Thromb Haemost 2010;8: 237–42.10.1111/j.1538-7836.2009.03674.xSearch in Google Scholar
24. Pengo V, Banzato A, Bison E, Bracco A, Denas G, Ruffatti A. What have we learned about antiphospholipid syndrome from patients and antiphospholipid carrier cohorts? Semin Thromb Hemost 2012;38:322–7.10.1055/s-0032-1304719Search in Google Scholar
25. Pengo V, Ruffatti A, Legnani C, Testa S, Fierro T, Marongiu F, et al. Incidence of a first thromboembolic event in asymptomatic carriers of high-risk antiphospholipid antibody profile: a multicenter prospective study. Blood 2011;118:4714–8.10.1182/blood-2011-03-340232Search in Google Scholar
26. Sletnes, Kari. Gravem, Karl. Wisloff F. Preparation of plasma for the detection of lupus anticoagulants and antiphospholipid antibodies. Thromb Res 1992;66:43–53.10.1016/0049-3848(92)90154-3Search in Google Scholar
27. Derksen RH, De Groot PG. Tests for lupus anticoagulant revisited. Thromb Res 2004;114:521–6.10.1016/j.thromres.2004.06.009Search in Google Scholar PubMed
28. Froom P, Barak M. Lupus anticoagulant testing: analyzing fresh samples after a single centrifugation and after a 68 h delay. Clin Chem Lab Med 2012;50:367–70.10.1515/cclm.2011.768Search in Google Scholar
29. De Groot PG, Lutters B, Derksen RH, Lisman T, Meijers JC, Rosendaal FR. Lupus anticoagulants and the risk of a first episode of deep venous thrombosis. J Thromb Haemost 2005;3:1993–7.10.1111/j.1538-7836.2005.01485.xSearch in Google Scholar PubMed
30. Pennings MT, De Groot PG, Meijers JC, Huisman A, Derksen RH, Urbanus RT. Optimisation of lupus anticoagulant tests: should test samples always be mixed with normal plasma? Thromb Haemost. 2014;112:736–42.10.1160/TH14-02-0122Search in Google Scholar PubMed
©2018 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Editorials
- Procalcitonin for diagnosing and monitoring bacterial infections: for or against?
- Is it time to abandon the Nobel Prize?
- In Memoriam
- Norbert Tietz, 13th November 1926–23rd May 2018
- Reviews
- Procalcitonin guidance in patients with lower respiratory tract infections: a systematic review and meta-analysis
- Telomere biology and age-related diseases
- Opinion Paper
- Procalcitonin-guided antibiotic therapy: an expert consensus
- Genetics and Molecular Diagnostics
- mRNA expression profile in peripheral blood mononuclear cells based on ADRB1 Ser49Gly and Arg389Gly polymorphisms in essential hypertension — a case-control pilot investigation in South Indian population
- General Clinical Chemistry and Laboratory Medicine
- External quality assessment schemes for glucose measurements in Germany: factors for successful participation, analytical performance and medical impact
- Long-term stability of glucose: glycolysis inhibitor vs. gel barrier tubes
- Observational studies on macroprolactin in a routine clinical laboratory
- Anti-streptavidin IgG antibody interference in anti-cyclic citrullinated peptide (CCP) IgG antibody assays is a rare but important cause of false-positive anti-CCP results
- Point-of-care creatinine testing for kidney function measurement prior to contrast-enhanced diagnostic imaging: evaluation of the performance of three systems for clinical utility
- Hematology and Coagulation
- Analytical performance of an automated volumetric flow cytometer for quantitation of T, B and natural killer lymphocytes
- Lupus anticoagulant testing using two parallel methods detects additional cases and predicts persistent positivity
- Reference Values and Biological Variations
- Within-subject biological variation of activated partial thromboplastin time, prothrombin time, fibrinogen, factor VIII and von Willebrand factor in pregnant women
- Within-subject and between-subject biological variation estimates of 21 hematological parameters in 30 healthy subjects
- Immunoglobulin G (IgG) and IgG subclass reference intervals in children, using Optilite® reagents
- Cancer Diagnostics
- Serum carbohydrate sulfotransferase 7 in lung cancer and non-malignant pulmonary inflammations
- Cardiovascular Diseases
- Clinical performance of a new point-of-care cardiac troponin I test
- Diabetes
- Testing for HbA1c, in addition to the oral glucose tolerance test, in screening for abnormal glucose regulation helps to reveal patients with early β-cell function impairment
- Effects of common hemoglobin variants on HbA1c measurements in China: results for α- and β-globin variants measured by six methods
- Infectious Diseases
- Serum procalcitonin concentration within 2 days postoperatively accurately predicts outcome after liver resection
- Predictive value of serum gelsolin and Gc globulin in sepsis – a pilot study
- Cerebrospinal fluid free light chains as diagnostic biomarker in neuroborreliosis
- Letter to the Editor
- Glucose and total protein: unacceptable interference on Jaffe creatinine assays in patients
- Interference of glucose and total protein on Jaffe-based creatinine methods: mind the covolume
- Interference of glucose and total protein on Jaffe based creatinine methods: mind the covolume – reply
- Measuring procalcitonin to overcome heterophilic-antibody-induced spurious hypercalcitoninemia
- Paraprotein interference in the diagnosis of hepatitis C infection
- Timeo apis mellifera and dona ferens: bee sting-induced Kounis syndrome
- Bacterial contamination of reusable venipuncture tourniquets in tertiary-care hospital
- Detection of EDTA-induced pseudo-leukopenia using automated hematology analyzer with VCS technology
- Early adjustment of antimicrobial therapy after PCR/electrospray ionization mass spectrometry-based pathogen detection in critically ill patients with suspected sepsis
- Thromboelastometry reveals similar hemostatic properties of purified fibrinogen and a mixture of purified cryoprecipitate protein components
- Bicarbonate interference on cobas 6000 c501 chloride ion-selective electrodes
Articles in the same Issue
- Frontmatter
- Editorials
- Procalcitonin for diagnosing and monitoring bacterial infections: for or against?
- Is it time to abandon the Nobel Prize?
- In Memoriam
- Norbert Tietz, 13th November 1926–23rd May 2018
- Reviews
- Procalcitonin guidance in patients with lower respiratory tract infections: a systematic review and meta-analysis
- Telomere biology and age-related diseases
- Opinion Paper
- Procalcitonin-guided antibiotic therapy: an expert consensus
- Genetics and Molecular Diagnostics
- mRNA expression profile in peripheral blood mononuclear cells based on ADRB1 Ser49Gly and Arg389Gly polymorphisms in essential hypertension — a case-control pilot investigation in South Indian population
- General Clinical Chemistry and Laboratory Medicine
- External quality assessment schemes for glucose measurements in Germany: factors for successful participation, analytical performance and medical impact
- Long-term stability of glucose: glycolysis inhibitor vs. gel barrier tubes
- Observational studies on macroprolactin in a routine clinical laboratory
- Anti-streptavidin IgG antibody interference in anti-cyclic citrullinated peptide (CCP) IgG antibody assays is a rare but important cause of false-positive anti-CCP results
- Point-of-care creatinine testing for kidney function measurement prior to contrast-enhanced diagnostic imaging: evaluation of the performance of three systems for clinical utility
- Hematology and Coagulation
- Analytical performance of an automated volumetric flow cytometer for quantitation of T, B and natural killer lymphocytes
- Lupus anticoagulant testing using two parallel methods detects additional cases and predicts persistent positivity
- Reference Values and Biological Variations
- Within-subject biological variation of activated partial thromboplastin time, prothrombin time, fibrinogen, factor VIII and von Willebrand factor in pregnant women
- Within-subject and between-subject biological variation estimates of 21 hematological parameters in 30 healthy subjects
- Immunoglobulin G (IgG) and IgG subclass reference intervals in children, using Optilite® reagents
- Cancer Diagnostics
- Serum carbohydrate sulfotransferase 7 in lung cancer and non-malignant pulmonary inflammations
- Cardiovascular Diseases
- Clinical performance of a new point-of-care cardiac troponin I test
- Diabetes
- Testing for HbA1c, in addition to the oral glucose tolerance test, in screening for abnormal glucose regulation helps to reveal patients with early β-cell function impairment
- Effects of common hemoglobin variants on HbA1c measurements in China: results for α- and β-globin variants measured by six methods
- Infectious Diseases
- Serum procalcitonin concentration within 2 days postoperatively accurately predicts outcome after liver resection
- Predictive value of serum gelsolin and Gc globulin in sepsis – a pilot study
- Cerebrospinal fluid free light chains as diagnostic biomarker in neuroborreliosis
- Letter to the Editor
- Glucose and total protein: unacceptable interference on Jaffe creatinine assays in patients
- Interference of glucose and total protein on Jaffe-based creatinine methods: mind the covolume
- Interference of glucose and total protein on Jaffe based creatinine methods: mind the covolume – reply
- Measuring procalcitonin to overcome heterophilic-antibody-induced spurious hypercalcitoninemia
- Paraprotein interference in the diagnosis of hepatitis C infection
- Timeo apis mellifera and dona ferens: bee sting-induced Kounis syndrome
- Bacterial contamination of reusable venipuncture tourniquets in tertiary-care hospital
- Detection of EDTA-induced pseudo-leukopenia using automated hematology analyzer with VCS technology
- Early adjustment of antimicrobial therapy after PCR/electrospray ionization mass spectrometry-based pathogen detection in critically ill patients with suspected sepsis
- Thromboelastometry reveals similar hemostatic properties of purified fibrinogen and a mixture of purified cryoprecipitate protein components
- Bicarbonate interference on cobas 6000 c501 chloride ion-selective electrodes