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.
Study Type
OBSERVATIONAL
Enrollment
720
AMC
Amsterdam-Zuidoost, Netherlands
NOT_YET_RECRUITINGUMC Radboud
Nijmegen, Netherlands
RECRUITINGImmunological characteristics of autoantibodies in autoimmune hemolytic anemia (AIHA) patients - laboratory tests.
Documentation of characteristics of autoantibodies (e.g. isotype, subtype, titer, thermal amplitude).
Time frame: 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.
Time frame: 12-18 months
Incidence of underlying disease that causes or is associated with AIHA.
Documentation of physician-reported underlying disease that caused AIHA (e.g. autoimmune and/or lymphoproliferative disease, infection, medication).
Time frame: 12-18 months
Type of treatment prescribed as first-line, second-line or further-line treatment for AIHA.
The percentage of patients receiving first, second or further-line treatment for AIHA will be calculated.
Time frame: 12-18 months
Hematological response after each treatment line (CR, CR-u, PR and NR)
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
Time frame: 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.
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.
Time frame: 12-18 month
Documentation of adverse events during the treatment of AIHA.
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
Time frame: 12-18 month
Assessment of hemolysis parameters after red blood cell 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.
Time frame: 1 and 7 days after transfusion
Change in the incidence of auto- and alloantibodies after red blood cell transfusion.
Compare the incidence of auto- and alloantibodies before and after red blood cell transfusion.
Time frame: 12-18 months
Characteristics of autoantibodies of DAT positive blood donors.
Documentation of characteristics of autoantibodies (e.g. isotype, subtype, titer, thermal amplitude) of DAT positive blood donors.
Time frame: 12-18 months
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