Skip to main content

Main menu

  • Home
  • Content
    • Current
    • Ahead of print
    • Archive
  • Info for
    • Authors
    • Reviewers
  • About Us
    • About the Ochsner Journal
    • Editorial Board
  • More
    • Alerts
    • Feedback
  • Other Publications
    • Ochsner Journal Blog

User menu

  • My alerts
  • Log in

Search

  • Advanced search
Ochsner Journal
  • Other Publications
    • Ochsner Journal Blog
  • My alerts
  • Log in
Ochsner Journal

Advanced Search

  • Home
  • Content
    • Current
    • Ahead of print
    • Archive
  • Info for
    • Authors
    • Reviewers
  • About Us
    • About the Ochsner Journal
    • Editorial Board
  • More
    • Alerts
    • Feedback
Research ArticleOriginal Research

Prevalence and Resolution of Lupus Anticoagulant in Children

Chandra Kallanagowdar, Aman Chauhan, Mora V. Puertolas and Rajasekharan Warrier
Ochsner Journal June 2016, 16 (2) 172-175;
Chandra Kallanagowdar
1Department of Hematology/Oncology, Louisiana State University Health Sciences Center/Children's Hospital, New Orleans, LA
MD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Aman Chauhan
2Department of Pediatrics, Louisiana State University Health Services Center/Children's Hospital, New Orleans, LA
MBBS
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mora V. Puertolas
3The University of Queensland School of Medicine, Ochsner Clinical School, New Orleans, LA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rajasekharan Warrier
3The University of Queensland School of Medicine, Ochsner Clinical School, New Orleans, LA
4Department of Pediatric Hematology/Oncology, Ochsner Clinic Foundation, New Orleans, LA
MD, FAAP, FIAP
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • References
  • Info & Metrics
  • PDF
Loading

Abstract

Background: Lupus anticoagulant (LA) is an autoantibody that inhibits phospholipid-dependent reactions. Studies on the incidence and prevalence of LA in the pediatric population are lacking. The objective of our study was to determine the incidence and potential risk of complications of LA in children presenting with abnormal partial thromboplastin time (PTT). Our secondary objective was to identify signs, symptoms, and medical history associated with the presence of LA as documented in the literature. We focused on the correlation between signs of LA in the form of laboratory values consistent with bleeding abnormalities and the presence of clinical symptoms of bleeding.

Methods: We conducted a record-based retrospective analysis of 112 children and adolescents referred to the Department of Hematology/Oncology at Children's Hospital of New Orleans for abnormal coagulation profiles and/or history of mucocutaneous bleeding. Participants were followed up until PTT values normalized.

Results: In our study population with suspected bleeding disorder, the preliminary incidence of LA was 21%. We found that resolution of LA correlated with correction of PTT in 90% of patients.

Conclusion: To minimize extensive and expensive blood workup, we recommend that screening for LA be included in the evaluation of children with prolonged PTT, even if they have a negative history of bleeding problems.

Keywords
  • Antibodies–anticardiolipin
  • lupus coagulation inhibitor
  • lupus erythematosus–systemic
  • pediatrics

INTRODUCTION

Lupus anticoagulant (LA) is a misnomer because it is an acquired immunoglobulin G or immunoglobulin M antibody that inhibits phospholipid-dependent reactions. LA is usually associated with certain autoimmune conditions, drugs, infections, pregnancy loss, bleeding disorders, and malignancies.1 The prevalence of LA is believed to be approximately 5% in adults, with a predominance among females of reproductive age.2

The aim of our study was to determine the incidence and potential risk of complications of LA in children presenting with abnormal partial thromboplastin time (PTT). Our secondary objective was to identify signs, symptoms, and medical history associated with the presence of LA as documented in the literature.

METHODS

We conducted a retrospective longitudinal analysis of the medical records of 112 patients who were referred to the Department of Hematology/Oncology for abnormal coagulation profiles and/or a history of mucocutaneous bleeding. The abnormal coagulation profiles were incidental findings during preoperative evaluation. Patients were included in the trial if they had an abnormally elevated PTT in the absence of a known bleeding disorder or systemic illness associated with a bleeding disorder, such as systemic lupus erythematosus (SLE). The study was conducted using the records of patients treated at Children's Hospital of New Orleans during a period of 3 years. Age, sex, clinical features, family history of symptomatic bleeding, and coagulation profiles (mixing study defined as normal if PTT does not normalize with the addition of normal pooled plasma, prothrombin time with the reference range defined as 11-13.5 seconds, PTT with the reference range defined as 25-35 seconds, dilute Russell viper venom time [dRVVT] with the reference range defined as 29-42 seconds, and factor levels when indicated by history) of the patients were analyzed. Every patient was followed up for PTT and LA every 12 weeks until all laboratory values returned to reference range. Appropriate ethical committee clearance was obtained from the institutional review board at Children's Hospital prior to commencing the study.

RESULTS

Of the 112 children and adolescents who were referred for abnormal hematologic parameters following preoperative evaluation for a variety of minor surgical procedures, 84 (75%) were found to have prolonged PTT when a coagulation profile was repeated in our Department of Hematology/Oncology. These 84 patients underwent mixing studies, platelet neutralization procedure, dRVVT, factor levels, and evaluation for antiphospholipid antibody. Twenty-one percent (n=18) of the prolonged PTT population were LA positive. The Figure depicts the initial and follow-up PTT values in the 18 LA-positive patients. Sixty-seven percent (n=12) of these LA-positive patients were female, and the mean age was 6.05 years.

Figure.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure.

Value of partial thromboplastin time (PTT) at initial presentation and follow-up in 18 patients positive for lupus anticoagulant.

Eighty-nine percent (n=16) of LA-positive patients were clinically asymptomatic. The two who were symptomatic had epistaxis; one required cauterization, and the other had concomitant thrombocytopenia. Only 2 of the 18 LA-positive patients had a family history of bleeding disorders; none of these family members was symptomatic for these disorders at the time the study was conducted. None of the LA-positive patients had concomitant factor VIII or factor IX deficiency. No thrombotic or major hemorrhagic events were documented in the LA-positive study population.

Ten of 18 LA-positive patients later became negative for LA. PTT normalized in 9 of these 10 patients. The mean time for normalization of PTT was 3.3 months (range, 3 weeks to 9 months). Eight patients of the 18 initially LA-positive patients remained positive for LA throughout the follow-up period. We observed normalization of PTT values in 5 of these 8 patients. Two of the 8 LA-positive patients had persistently elevated PTT. One of the 18 initially LA-positive patients was lost to follow-up.

DISCUSSION

The search for LA began in 1948 when Conley and Hartmann3 discovered that some of their patients with SLE had prolonged activated PTT that did not correct after mixing normal plasma with the patient's blood. The unknown compound was named LA, and it was hypothesized to act against negatively charged phospholipids present on the surface of activated platelets. These phospholipids are an integral part of the vitamin K–dependent clotting factor homeostatic cascade. LA belongs to the group of antiphospholipid antibodies that also includes the anticardiolipin antibody and the anti-beta-2 glycoprotein I antibody.

For many years, LA was considered insignificant because patients who tested positive for LA were clinically asymptomatic despite their prolonged activated PTT. Attitudes among clinicians regarding the ramifications of having a positive LA have changed since 1963 when Bowie et al4 reported thrombotic events in LA-positive patients with prolonged activated PTT. Today, the presence of LA is no longer taken to imply that the patient will have a lifelong history of thrombotic events. In fact, the effect of LA may only manifest as a transient elevation in PTT without clinical symptoms as demonstrated in our study. We found LA positivity to be a transient finding in most of our study population. Diagnosis of LA is based on the recommendations of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis.5

No specific tests are available to conclusively diagnose LA, so the diagnosis is made indirectly. Phospholipid-dependent tests such as activated PTT and dRVVT are used as screening tests. The patient's plasma is mixed with normal plasma (mixing study), and normalization of clotting time indicates that confirmatory testing should be done. Today, phospholipids are added to the patient's plasma, and if this addition brings the patient's clotting time into the reference range, the patient is said to be positive for LA.

Once a patient's blood is established as positive for LA, repeat confirmatory tests that may include correction/neutralization are done after a 12-week gap. Confounding factors in the detection of LA are prior treatment with heparin and freezing of the sample, factors that can have more of an effect on the results when LA levels are low and lead to an increase in the number of false-negatives. Delaying testing for LA is advisable during or immediately after a thrombotic event or if the patient is taking anticoagulants.5-9

Patients who are positive for LA are generally asymptomatic but can present with a thromboembolic event.10 Bleeding is uncommon in LA-positive patients and is usually associated with an accompanying factor or platelet deficiency.11,12

LA is an acquired immunoglobulin G or immunoglobin M antibody that inhibits in vitro phospholipid-dependent reactions. LA assays do not measure antibody titers but are nonetheless functional tests. Although 1 positive test is sufficient for LA positivity, 2 or more tests with different assays are recommended because no single test is 100% sensitive for LA.13

Continued long-term follow-up and further evaluation are needed for patients who have persistently prolonged PTT. It may also be advisable to postpone any planned elective surgery until the LA has disappeared. In a child with elevated PTT because of LA, emergency surgery can be carried out with appropriate precautions such as the availability of plasma factors. Careful hematologic follow-up to avoid thrombotic complications is indicated if surgery is unavoidable. In future work, we hope to address the long-term effects of LA in children and adolescents with both resolved and unresolved prolongation of PTT as they transition into adulthood.

This condition has principally been studied in the adult population in whom the prevalence is approximately 5%; scarce literature is available regarding LA in the pediatric age group.14 Most physicians agree that LA is a benign condition often with a transient course lacking significant clinical issues.15,16 Rare reports exist of thrombosis and bleeding episodes associated with LA. Patients with such complications are usually not just positive for LA but also have coexisting conditions such as factor deficiency, SLE, and antiphospholipid antibody syndrome.17 Studies report an association between LA and autoimmune conditions such as SLE, rheumatoid arthritis, malignancies, urticaria, vasculitis, and lymphoproliferative disorders.18 Patients with antiphospholipid syndrome associated with autoimmune disease are more likely to be older and have a higher frequency of venous thrombotic events with hematologic and skin manifestations compared to patients with primary antiphospholipid syndrome who are more likely to be younger and have arterial thrombotic events.19 These differences suggest that the manifestations of LA can be distinguished based on its association with autoimmune disease or infection. Drugs such as chlorpromazine; antibiotics such as amoxicillin; hydralazine; and some viral, bacterial, and protozoal infections are also associated with LA.20,21

One limitation of our study is that it is retrospective. Another limitation is that participants were only followed until their PTT values normalized. Future work could focus on the longitudinal effects of LA positivity with or without the resolution of prolonged PTT, especially in asymptomatic participants. Long-term effects of LA positivity may be expected, particularly in females, as anticardiolipin antibodies are associated with an increased risk of miscarriage.22 This risk is relevant in our study population, considering that LA was more common in females than males. An additional limitation is the lack of a control group. Future studies could include a group of participants with prolonged PTT who are not positive for LA to elucidate how prolonged PTT in the context of LA positivity differs from prolonged PTT because of other hematologic anomalies.

CONCLUSION

Based on our study results, we conclude that LA is common in children and adolescents with abnormal hematologic parameters and is associated with asymptomatic presentation notable for prolonged PTT that may come to medical attention in the context of preoperative evaluation or other unrelated workup. In our study population with suspected bleeding disorders, the preliminary incidence of LA positivity was 21%. We found that the resolution of LA correlated with correction of PTT in 90% of our patients. To minimize extensive and expensive blood workup, we recommend that screening for LA be included in the evaluation of children with prolonged PTT, even if they have a negative history of bleeding problems.

This article meets the Accreditation Council for Graduate Medical Education and the American Board of Medical Specialties Maintenance of Certification competencies for Patient Care, Medical Knowledge, and Practice-Based Learning and Improvement.

ACKNOWLEDGMENTS

The authors have no financial or proprietary interest in the subject matter of this article.

  • © Academic Division of Ochsner Clinic Foundation

REFERENCES

  1. ↵
    1. Ciaudo M,
    2. Horellou MH,
    3. Audouin J,
    4. De Carbonnieres C,
    5. Conard J,
    6. Samama M
    Lupus anticoagulant associated with primary malignant lymphoplasmacytic lymphoma of the spleen: a report of four patients. Am J Hematol. 1991 12; 38 4: 271- 276. pmid:1746535
    OpenUrlPubMed
  2. ↵
    1. Shi W,
    2. Krilis SA,
    3. Chong BH,
    4. Gordon S,
    5. Chesterman CN
    Prevalence of lupus anticoagulant and anticardiolipin antibodies in a healthy population. Aust N Z J Med. 1990 6; 20 3: 231- 236. pmid:2115326
    OpenUrlCrossRefPubMed
  3. ↵
    1. Conley CL,
    2. Hartmann RC
    A hemorrhagic disorder caused by circulating anticoagulant in patients with disseminated lupus erythematosus. J Clin Invest. 1952; 31: 621- 622.
    OpenUrl
  4. ↵
    1. Bowie EJ,
    2. Thompson JH Jr.,
    3. Pascuzzi CA,
    4. Owen CA Jr.
    Thrombosis in systemic lupus erythematosus despite circulating anticoagulants. J Lab Clin Med. 1963 9; 62: 416- 430. pmid:14061973
    OpenUrlPubMed
  5. ↵
    1. Brandt JT,
    2. Triplett DA,
    3. Alving B,
    4. Scharrer I
    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. 1995 10; 74 4: 1185- 1190. pmid:8560433
    OpenUrlPubMed
    1. Greaves M,
    2. Cohen H,
    3. MacHin SJ,
    4. Mackie I
    Guidelines on the investigation and management of the antiphospholipid syndrome. Br J Haematol. 2000 6; 109 4: 704- 715. pmid:10929019
    OpenUrlCrossRefPubMed
    1. Exner T,
    2. Triplett DA,
    3. Taberner D,
    4. Machin SJ
    Guidelines for testing and revised criteria for lupus anticoagulants. SSC Subcommittee for the Standardization of Lupus Anticoagulants. Thromb Haemost. 1991 3 4; 65 3: 320- 322. pmid:1904657
    OpenUrlPubMed
  6. Guidelines on testing for the lupus anticoagulant. Lupus Anticoagulant Working Party on behalf of the BCSH Haemostasis and Thrombosis Task Force. J Clin Pathol. 1991 11; 44 11: 885- 889.
    OpenUrlFREE Full Text
  7. ↵
    1. Tripodi A
    Testing for lupus anticoagulants: all that a clinician should know. Lupus. 2009 4; 18 4: 291- 298. pmid:19276296
    OpenUrlCrossRefPubMed
  8. ↵
    1. Cuadrado MJ,
    2. Hughes GR
    Hughes (antiphospholipid) syndrome. Clinical features. Rheum Dis Clin North Am. 2001 8; 27 3: 507- 524, v. pmid:11534257
    OpenUrlCrossRefPubMed
  9. ↵
    1. Vivaldi P,
    2. Rossetti G,
    3. Galli M,
    4. Finazzi G
    Severe bleeding due to acquired hypoprothrombinemia-lupus anticoagulant syndrome. Case report and review of literature. Haematologica. 1997 May-Jun; 82 3: 345- 347. pmid:9234588
    OpenUrlAbstract/FREE Full Text
  10. ↵
    1. Bernini JC,
    2. Buchanan GR,
    3. Ashcraft J
    Hypoprothrombinemia and severe hemorrhage associated with a lupus anticoagulant. J Pediatr. 1993 12; 123 6: 937- 939. pmid:8229526
    OpenUrlCrossRefPubMed
  11. ↵
    1. Mikayis S,
    2. Lockshin MD,
    3. Atsumi T,
    4. et al.
    International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006 2; 4 2: 295- 306. pmid:16420554
    OpenUrlCrossRefPubMed
  12. ↵
    1. Singh AK,
    2. Rao KP,
    3. Kizer J,
    4. Lazarchick J
    Lupus anticoagulants in children. Ann Clin Lab Sci. 1988 Sep-Oct; 18 5: 384- 387. pmid:3140708
    OpenUrlAbstract/FREE Full Text
  13. ↵
    1. Male C,
    2. Lechner K,
    3. Eichinger S,
    4. et al.
    Clinical significance of lupus anticoagulants in children. J Pediatr. 1999 2; 134 2: 199- 205. pmid:9931530
    OpenUrlCrossRefPubMed
  14. ↵
    1. Casais P,
    2. Meschengieser SS,
    3. Gennari LC,
    4. et al.
    Morbidity of lupus anticoagulants in children: a single institution experience. Thromb Res. 2004; 114 4: 245- 249. pmid:15381387
    OpenUrlCrossRefPubMed
  15. ↵
    1. Manco-Johnson MJ,
    2. Nuss R
    Lupus anticoagulant in children with thrombosis. Am J Hematol. 1995 4; 48 4: 240- 243. pmid:7717372
    OpenUrlPubMed
  16. ↵
    1. Giordano P,
    2. Tesse R,
    3. Lassandro G,
    4. et al.
    Clinical and laboratory characteristics of children positive for antiphospholipid antibodies. Blood Transfus. 2012 7; 10 3: 296- 301. pmid:22244004
    OpenUrlPubMed
  17. ↵
    1. Avcin T,
    2. Cimaz R,
    3. Silverman ED,
    4. et al.
    Pediatric antiphopholipid syndrome: clinical and immunologic features of 121 patients in an international registry. Pediatrics. 2008 11; 122 5: e1100- e1107. pmid:18955411
    OpenUrlAbstract/FREE Full Text
  18. ↵
    1. Follea G,
    2. Coiffier B,
    3. Viale JP,
    4. Dechavanne M
    Antiprothrombinase and factor II deficiency in a non SLE patient. Thromb Haemost. 1981 10; 46 3: 670. pmid:7314062
    OpenUrlPubMed
  19. ↵
    1. Bajaj SP,
    2. Rapaport SI,
    3. Fierer DS,
    4. Herbst KD,
    5. Schwartz DB
    A mechanism for the hypoprothrombinemia of the acquired hypothrombinemia-lupus anticoagulant syndrome. Blood. 1983 4; 61 4: 684- 692. pmid:6403077
    OpenUrlAbstract/FREE Full Text
  20. ↵
    1. Jameil NA,
    2. Tyagi P,
    3. Shenefy AA
    Incidence of anticardiolipin antibodies and lupus anticoagulant factor among women experiencing unexplained recurrent abortion and intrauterine fetal death. Int J Clin Exp Pathol. 2015 3 1; 8 3: 3204- 3209. pmid:26045841
    OpenUrlPubMed
PreviousNext
Back to top

In this issue

Ochsner Journal
Vol. 16, Issue 2
Jun 2016
  • Table of Contents
  • Index by author
Print
Download PDF
Email Article

Thank you for your interest in spreading the word on Ochsner Journal.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Prevalence and Resolution of Lupus Anticoagulant in Children
(Your Name) has sent you a message from Ochsner Journal
(Your Name) thought you would like to see the Ochsner Journal web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Prevalence and Resolution of Lupus Anticoagulant in Children
Chandra Kallanagowdar, Aman Chauhan, Mora V. Puertolas, Rajasekharan Warrier
Ochsner Journal Jun 2016, 16 (2) 172-175;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Prevalence and Resolution of Lupus Anticoagulant in Children
Chandra Kallanagowdar, Aman Chauhan, Mora V. Puertolas, Rajasekharan Warrier
Ochsner Journal Jun 2016, 16 (2) 172-175;
del.icio.us logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • INTRODUCTION
    • METHODS
    • RESULTS
    • DISCUSSION
    • CONCLUSION
    • ACKNOWLEDGMENTS
    • REFERENCES
  • Figures & Data
  • References
  • Info & Metrics
  • PDF

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • 3D-Printed Patient-Specific Models of the Aortic Arch for Advanced Visualization of Complex Neurointerventional Cases
  • Accuracy of Perfusion Index and Perfusion Index Ratio as a Predictor of a Successful Low Interscalene Brachial Plexus Block: A Prospective Observational Study
  • HEART Score Agreement Between Attending and Resident Emergency Medicine Physicians for Patients With Potential Acute Coronary Syndrome
Show more ORIGINAL RESEARCH

Similar Articles

Keywords

  • Antibodies–anticardiolipin
  • lupus coagulation inhibitor
  • lupus erythematosus–systemic
  • Pediatrics

Ochsner Journal Blog

Current Post

Be Careful Where You Publish

Our Content

  • Home
  • Current Issue
  • Ahead of Print
  • Archive
  • Featured Contributors
  • Ochsner Journal Blog
  • Archive at PubMed Central

Information & Forms

  • Instructions for Authors
  • Instructions for Reviewers
  • Submission Checklist
  • FAQ
  • License for Publishing-Author Attestation
  • Patient Consent Form
  • Submit a Manuscript

Services & Contacts

  • Permissions
  • Sign up for our electronic table of contents
  • Feedback Form
  • Contact Us

About Us

  • Editorial Board
  • About the Ochsner Journal
  • Ochsner Health
  • University of Queensland-Ochsner Clinical School
  • Alliance of Independent Academic Medical Centers

© 2025 Ochsner Clinic Foundation

Powered by HighWire