Data Registry of Auto Immune Hemolytic Anemia

NCT04024202 | Unknown

• 1 other identifier: PPOC 15-27
• Study Type: observational
• Target: 720
• Locations: 1 country
• Sites: 2

Brief Summary

In autoimmune hemolytic anemia (AIHA) auto-antibodies directed against red blood cells (RBCs) lead to increased RBC clearance (hemolysis). This can result in a potentially life-threatening anemia. AIHA is a rare disease with an incidence of 1-3 per 100,000 individuals. An unsolved difficulty in diagnosis of AIHA is the laboratory test accuracy. The current 'golden standard' for AIHA is the direct antiglobulin test (DAT). The DAT detects autoantibody- and/or complement-opsonized RBCs. The DAT has insufficient test characteristics since it remains falsely negative in approximate 5-10% of patients with AIHA, whereas a falsely positive DAT can be found in 8% of hospitalized individuals. Also apparently healthy blood donors can have a positive DAT. The consequences of DAT positivity are not well known and may point to early, asymptomatic disease, or to another disease associated with formation of RBC autoantibodies, such as a malignancy or (systemic) autoimmune disease. Currently, there are no guidelines to follow-up DAT positive donors. A second unsolved difficulty is the choice of treatment in AIHA. Hemolysis can be stopped or at least attenuated with corticosteroids, aiming to inhibit autoantibody production and/or RBC destruction. Many patients do not respond adequately to corticosteroid treatment or develop severe side effects. Currently, it is advised to avoid RBC transfusions since these may lead to aggravation of hemolysis and RBC alloantibody formation. But in case symptomatic anemia occurs, RBC transfusions need to be given. An evidence-based transfusion strategy for AIHA patients is needed to warrant safe transfusion in this complex patient group. To design optimal diagnostic testing and (supportive) treatment algorithms, the investigators will study a group well-characterized patients with AIHA and blood donors without AIHA, via a prospective centralized clinical data collection and evaluation of new laboratory tests. With this data the knowledge of the AIHA pathophysiology and to evaluate diagnostic testing in correlation with clinical features and treatment outcome can be improved.

Conditions

Autoimmune Hemolytic Anemia

Outcome Measures

Primary Outcomes (2)

• Immunological characteristics of autoantibodies in autoimmune hemolytic anemia (AIHA) patients - laboratory tests.

  Documentation of characteristics of autoantibodies (e.g. isotype, subtype, titer, thermal amplitude).

  12-18 months

• Assessment of hemolysis before and after therapy, reported per class of auto-immune hemolytic anemia. - laboratory tests

  Documentation of hemolysis parameters (hemoglobin level (g/dL), reticulocytes (%), haptoglobin (mg/dL), bilirubin (μmol/L) and LDH(U/L)) before and after each type of therapy. AIHA classification as IgG/IgA only, IgG/IgA with complement activation or complement activation only.

  12-18 months

Secondary Outcomes (8)

• Incidence of underlying disease that causes or is associated with AIHA.

  12-18 months

• Type of treatment prescribed as first-line, second-line or further-line treatment for AIHA.

  12-18 months

• Hematological response after each treatment line (CR, CR-u, PR and NR)

  12-18 months

• Relapse-free survival, defined as the time since the achievement of complete or partial remission until relapse of AIHA or dead from any cause.

  12-18 month

• Documentation of adverse events during the treatment of AIHA.

  12-18 month

Study Arms (2)

Patients

1. Patients with a positive DAT, a positive eluate and signs of hemolysis 2. Patients with a positive DAT with complement only, negative eluate, but with hemolysis

Blood donors

Blood donors with a positive direct antiglobulin test and a positive eluate and/or clinically relevant cold auto-antibodies

Eligibility Criteria

• Age: 3 Months+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients, from the age of 3 months, with a positive DAT a positive eluate and signs of hemolysis and patients with a positive DAT for complement only with a negative eluate but with signs of hemolysis, and blood donors with a positive DAT and a positive eluate and/or clinically relevant cold autoantibodies.

You may qualify if:

• Sufficient comprehension of the Dutch language
• Signed informed consent by patient and/or parent/caretaker or donor
• Patients older than 3 months
• Patients with a positive DAT, a positive eluate and signs of hemolysis\*
• Patients with a positive DAT with complement only, negative eluate, but with signs of hemolysis
• Donors with a (repeatedly) positive DAT and a positive eluate and/or clinically relevant cold auto-antibodies

Sponsors & Collaborators

• Sanquin Research & Blood Bank Divisions: lead
• Leiden University Medical Center: collaborator
• Radboud University Medical Center: collaborator
• UMC Utrecht: collaborator
• Maastricht University Medical Center: collaborator
• Erasmus Medical Center: collaborator
• Haga Hospital: collaborator
• Isala: collaborator
• Jeroen Bosch Ziekenhuis: collaborator
• St. Antonius Hospital: collaborator
• Onze Lieve Vrouwe Gasthuis: collaborator
• Spaarne Gasthuis: collaborator
• Amsterdam University Medical Center: collaborator
• Prothya Biosolutions: collaborator

Study Sites (2)

AMC

Amsterdam-Zuidoost, Netherlands

NOT YET RECRUITING

UMC Radboud

Nijmegen, Netherlands

RECRUITING

Related Publications (9)

• Garratty G. Immune hemolytic anemia associated with negative routine serology. Semin Hematol. 2005 Jul;42(3):156-64. doi: 10.1053/j.seminhematol.2005.04.005.

  PMID: 16041665 BACKGROUND

• Freedman J. False-positive antiglobulin tests in healthy subjects and in hospital patients. J Clin Pathol. 1979 Oct;32(10):1014-8. doi: 10.1136/jcp.32.10.1014.

  PMID: 521494 BACKGROUND

• Barcellini W, Fattizzo B, Zaninoni A, Radice T, Nichele I, Di Bona E, Lunghi M, Tassinari C, Alfinito F, Ferrari A, Leporace AP, Niscola P, Carpenedo M, Boschetti C, Revelli N, Villa MA, Consonni D, Scaramucci L, De Fabritiis P, Tagariello G, Gaidano G, Rodeghiero F, Cortelezzi A, Zanella A. Clinical heterogeneity and predictors of outcome in primary autoimmune hemolytic anemia: a GIMEMA study of 308 patients. Blood. 2014 Nov 6;124(19):2930-6. doi: 10.1182/blood-2014-06-583021. Epub 2014 Sep 16.

  PMID: 25232059 BACKGROUND

• Rottenberg Y, Yahalom V, Shinar E, Barchana M, Adler B, Paltiel O. Blood donors with positive direct antiglobulin tests are at increased risk for cancer. Transfusion. 2009 May;49(5):838-42. doi: 10.1111/j.1537-2995.2008.02054.x. Epub 2009 Jan 2.

  PMID: 19170992 BACKGROUND

• Meulenbroek EM, de Haas M, Brouwer C, Folman C, Zeerleder SS, Wouters D. Complement deposition in autoimmune hemolytic anemia is a footprint for difficult-to-detect IgM autoantibodies. Haematologica. 2015 Nov;100(11):1407-14. doi: 10.3324/haematol.2015.128991. Epub 2015 Sep 9.

  PMID: 26354757 BACKGROUND

• Zanella A, Barcellini W. Treatment of autoimmune hemolytic anemias. Haematologica. 2014 Oct;99(10):1547-54. doi: 10.3324/haematol.2014.114561.

  PMID: 25271314 BACKGROUND

• Reynaud Q, Durieu I, Dutertre M, Ledochowski S, Durupt S, Michallet AS, Vital-Durand D, Lega JC. Efficacy and safety of rituximab in auto-immune hemolytic anemia: A meta-analysis of 21 studies. Autoimmun Rev. 2015 Apr;14(4):304-13. doi: 10.1016/j.autrev.2014.11.014. Epub 2014 Dec 9.

  PMID: 25497766 BACKGROUND

• Shi J, Rose EL, Singh A, Hussain S, Stagliano NE, Parry GC, Panicker S. TNT003, an inhibitor of the serine protease C1s, prevents complement activation induced by cold agglutinins. Blood. 2014 Jun 26;123(26):4015-22. doi: 10.1182/blood-2014-02-556027. Epub 2014 Apr 2.

  PMID: 24695853 BACKGROUND

• Wouters D, Stephan F, Strengers P, de Haas M, Brouwer C, Hagenbeek A, van Oers MH, Zeerleder S. C1-esterase inhibitor concentrate rescues erythrocytes from complement-mediated destruction in autoimmune hemolytic anemia. Blood. 2013 Feb 14;121(7):1242-4. doi: 10.1182/blood-2012-11-467209. No abstract available.

  PMID: 23411737 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples from patients (older than 16 years) and blood donors (older than 18 years) and urine samples from the first 20 included patients in each of the participating hospitals, will be collected for experimental diagnostic testing at inclusion (T0) and after 1-1,5 year (T1) of follow-up.

MeSH Terms

Conditions

Anemia, Hemolytic, Autoimmune

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• M. De Haas, Prof. MD PhD

  Center for Clinical Transfusion Research (CCTR), Sanquin, The Netherlands

  PRINCIPAL INVESTIGATOR

• S.S Zeerleder, Prof. MD PhD

  University Hospital, University of Bern, Switzerland and Department for BioMedical Research, University of Bern, Switzerland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

M. Jalink, MD

CONTACT

+31205123373; m.jalink@sanquin.nl

Masja De Haas, Prof. MD PhD

CONTACT

+31205123373; m.dehaas@sanquin.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2019
• First Posted: July 18, 2019
• Study Start: July 12, 2019
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: July 19, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2)