DRAIHA Study

Background

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.
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, we aim to 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 we want to improve the knowledge of the AIHA pathophysiology and to evaluate diagnostic testing in correlation with clinical features and treatment outcome.

Objectives

Primary objective
1. The primary study endpoint is to determine diagnostic predictors for the course of AIHA. 

Secondary objectives
1. Determine diagnostic predictors for safe and efficient blood transfusion in AIHA patients.
2. Determine the clinical consequences of DAT-positivity in blood donors to develop a clinical guideline for follow up and counseling.

 

Study design: An observational cohort study.

Study population: Patients, from the age of 3 months, and blood donors with a positive DAT and a positive eluate and patients with a positive DAT with a negative eluate but with hemolysis.

Intervention: Patients, from the age of 16 years, and donors with a positive DAT and a positive eluate; and patients with a positive DAT with a negative eluate but with hemolysis, will be informed about the DRAIHA study and requested to participate by their (donor) physician. Around diagnosis and concomitantly with a standard blood test performed in the hospital or at Sanquin, 20 ml of blood and an urine sample will be additionally collected for experimental diagnostic testing. No extra venipuncture has to be done. Physician, patient and blood donor need to fill in a questionnaire about their history, health, medication and diagnostic test results.
After 1-1,5 year the participant will be requested to once again donate an additional amount of 20 ml of blood at time of a standard blood test and an urine sample to perform the same experimental diagnostic tests. At that time point clinical data will also be collected by a structured report form for patient/donor and their physician.
In patients, aged 3 months until 16 years old, if appropriate, both patient and parent/caretaker are informed about the DRAIHA study and requested to participate by their physician. No extra blood or an urine sample will be collected. This patients will only be registered in the databank and experimental diagnostic testing will be performed on residual blood obtained from routine diagnostic testing.

Main study parameters/endpoints:
This study will yield a registry and databank that is unique for AIHA. With this data we want to improve our knowledge of the pathophysiology and to improve diagnostic testing. We want to identify diagnostic predictors of AIHA treatment outcome and safe and efficient transfusion in the individual AIHA patient.
Since the databank will contain samples from DAT-positive individuals with and without clinical signs of hemolysis (AIHA patients and blood donors, respectively), it has the additional valuable feature that it allows studies in prediction of disease and hence also optimization of assays for predictive power.

Research Staff

Prof. Masja de Haas, MD PhD
Prof. Sacha Zeerleder, MD PhD
Marit Jalink, MD