Week 11 - Drug-Induced Immune Haemolytic Anaemias

Question 1

Drug-Induced Immune Haemolytic Anaemia (DIIHA)

Answer 1

Administration of drug → antibody production → immune-mediated RBC destruction
Haemolysis may be intravascular or extravascular
Patients with history of treatment with same drug may present with severe haemolysis
Treatment is simple - stop administration of the drug

Question 2

Mechanisms of Antibody Formation - Unifying Theory

Answer 2

Antibodies can form against any one of three epitopes:
1. Antibody to membrane
2. Antibody to drug and membrane
3. Antibody to drug

Question 3

Mechanisms of Antibody Formation - Non-Immunologic Protein Adsorption (NIPA)

Answer 3

Drug binds to, and modifies, the RBC membrane
Change in the membrane results in binding of plasma components (i.e. IgG, albumin, complement proteins) in a non-immunologic manner
DAT +ve w/o antibody production
No haemolysis

Question 4

Most Commonly Implicated Drugs

Answer 4

Piperacillin - semi-synthetic penicillin
Ceftriaxone - 3rd generation cephalosporin
Cefotetan - 2nd generation cephalosporin

Question 5

Drugs used in NIPA

Answer 5

Cephalothin – 1st generation cephalosporin
β-lactamase inhibitors
- Clavulanic acid, Sulbactam, Tazobactam
Cisplatin, carboplatin, oxalipatin - anti-cancer

Question 6

Presentation of Drug-Induced Immune Haemolytic Anaemia

Answer 6

Haemolytic anaemia
Temporal association with drug administration
Full drug history important
- prescription
- over the counter
- alternative/Herbal
- timing and dosage of current medication
- historical treatments

Question 7

Serological Findings

Answer 7

Panagglutinin
Positive auto control
Positive DAT
- relatively strong (2+ or greater)
- most cases are positive with both anti-IgG and anti-C3 monospecific reagents
Eluate is negative
- may be +ve, but is weaker than the DAT
Antibody may be IgG or IgM

Question 8

DIIHA vs Warm AIHA

Answer 8

Eluate
- DIIHA - neg
- WAIHA - pos
Panagglutinin
- DIIHA - disappears after drug cessation
- WAIHA - continues after drug cessation

Question 9

Drug-Dependent Antibody

Answer 9

Reason as to why you see panagglutination before administration of drug
Drug may be present in patient’s plasma (without you adding it)
Need to remove it to demonstrate drug dependence
Perform dialysis on sample

Question 10

Drug-Independent Antibody

Answer 10

Doesn’t require presence of drug to bind RBCs, so it will bind even after the drug has cleared

Question 11

Two Categories of Drug Dependent Antibodies

Answer 11

Those reacting with drug-treated RBCs
- RBCs are treated with drug BEFORE testing with serum
- e.g. penicillin, ampicillin, many cephalosporins
Those reacting in the presence of drug
- RBCs are reacted with serum AND drug in solution
- e.g. piperacillin, ceftriaxone, NSAID’s, quinine

Question 12

Serologic Classification of Drug Independent Antibody

Answer 12

Do not require drug in the test system to be detected
- Methyldopa
- Fludarabine
Eluate is positive