Autoimmune Hemolytic Anemia
Conditions
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.
Interventions
None listed
Sponsors
Leiden University Medical Center
Radboud University Medical Center
UMC Utrecht
Maastricht University Medical Center
Erasmus Medical Center
Haga Hospital
Isala
Jeroen Bosch Ziekenhuis
St. Antonius Hospital
Onze Lieve Vrouwe Gasthuis
Spaarne Gasthuis
Amsterdam University Medical Center
Prothya Biosolutions
Sanquin Research & Blood Bank Divisions
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
3 Months to No maximum
Healthy volunteers
Yes
Inclusion criteria
* 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
Exclusion criteria
* Prior inclusion in the DRAIHA study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immunological characteristics of autoantibodies in autoimmune hemolytic anemia (AIHA) patients - laboratory tests. | 12-18 months | Documentation of characteristics of autoantibodies (e.g. isotype, subtype, titer, thermal amplitude). |
| Assessment of hemolysis before and after therapy, reported per class of auto-immune hemolytic anemia. - laboratory tests | 12-18 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hematological response after each treatment line (CR, CR-u, PR and NR) | 12-18 months | Percentage of patients with CR, CR-u, PR and NR after each treatment line. Hematological response will be classified as CR (complete remission), CR-u (CR- undetermined), PR (partial response) and NR (no response). CR: normal hemoglobin, no signs of hemolysis (normal haptoglobin, normal amount of reticulocytes, bilirubin, LDH), no treatment and transfusion independence during the last 4 weeks. CR-u: as CR, but hemoglobin, reticulocytes, LDH and/or bilirubin are deviating through another reason (e.g. underlying malignant disease). PR: 1. Hemoglobin \> 10g/dL, no signs of hemolysis, transfusion independent, but a continuous treatment with low dose prednisone (\< 10 mg/day) or other immunosuppressive therapy is necessary. 2. Compensated hemolytic anemia with an stable hemoglobin \>10g/dL, transfusion independent, maximal dose of prednisone \< 10mg/day or other continuous immunosuppressive therapy or EPO. NR: no PR reached |
| Change in the incidence of auto- and alloantibodies after red blood cell transfusion. | 12-18 months | Compare the incidence of auto- and alloantibodies before and after red blood cell transfusion. |
| 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 | Relapse-free survival will be calculated as the time since the achievement of complete or partial remission until relapse of AIHA or dead from any cause. Median RFS and 95% CI will be calculated. |
| Incidence of underlying disease that causes or is associated with AIHA. | 12-18 months | Documentation of physician-reported underlying disease that caused AIHA (e.g. autoimmune and/or lymphoproliferative disease, infection, medication). |
| Assessment of hemolysis parameters after red blood cell transfusion. | 1 and 7 days after transfusion | Documentation of hemolysis parameters (hemoglobin level (g/dL), reticulocytes (%), haptoglobin (mg/dL), bilirubin (μmol/L) and LDH (U/L)) before red blood cell transfusion. |
| Characteristics of autoantibodies of DAT positive blood donors. | 12-18 months | Documentation of characteristics of autoantibodies (e.g. isotype, subtype, titer, thermal amplitude) of DAT positive blood donors. |
| Documentation of adverse events during the treatment of AIHA. | 12-18 month | Documentation of adverse events during the treatment of AIHA indicated according to the Common Terminology Criteria for Adverse Events v4.0 (CTCAE) Publish Date: May 28, 2009 |
| Type of treatment prescribed as first-line, second-line or further-line treatment for AIHA. | 12-18 months | The percentage of patients receiving first, second or further-line treatment for AIHA will be calculated. |
Countries
Netherlands
Contacts
Primary ContactM. Jalink, MD
Backup ContactMasja De Haas, Prof. MD PhD
Outcome results
None listed