Other Haemolytic Diseases Flashcards
What is Allo-immune haemolytic anaemia?
Allo-IHA is caused by alloantibodies which are found in the patient’s plasma, bind on RBCs to form an Ag-Ab complex and activate ‘c. This leads to RBC destruction and HTR’s or HDFN.
What is Auto-immune haemolytic anaemia?
Auto-IHA is caused by autoantibodies which are formed against a patient’s own RBC antigens. Can be idiopathic, secondary to infections or autoimmune disease, or drug induced.
What are the types of Autoantibodies?
Warm Autoantibodies: reactive at 37°C
Cold Autoantibodies: reactive at 2-22°C
Discuss warm autoantibodies.
- Makes up 70-80% of AIHA’s
- Optimum reactivity at 37°C
- IgG (Rh, ABO, Kell, M-N)
- More severe than C.AIHA because of continuous RBC destruction due to fragmentation and erythrophagocytosis
- Directed at any tissue or cell, irrespective of its phenotype
- Causes: Idiopathic (drugs-rare), Secondarily (lymphomas, infections, SLE)
- Testing: DAT +, IAT +, anti-c3 and anti-c4 is + in 40-50% of cases
Discuss cold autoantibodies.
- Mostly benign, occasionally cause haemolytic episodes
- Mostly IgM
- Reactive at 2-22°C
- Activate ‘c after Abs bind to RBC Ag and cause RBC lysis
- In vivo RBC destruction due to Ag-Ab complexing at low temperatures
- Causes CHAD and PCH
- DAT +
-Causes: Idiopathic (CHAD), Secondarily (Influenza, Infectious mononucleosis, Mycoplasma pneumonia, lymphomas)
Discuss Cold Haemagglutinin Disease.
- Mild haemolytic episodes when exposed to cold temperatures
- Purely IgM, anti-I
- Regions of low body temperature will stimulate an Ag-Ab complex formation between the autoantibodies and RBC Ag
- In regions of normal body temperature, the Ag-Ab complex dissociates
- If ‘c is bound to the Ag-Ab complex, haemolysis will follow
Discuss Paroxysmal Cold Haemoglobinuria.
- More severe haemolytic episodes when exposed to cold temperatures
- Caused by Donath Landsteiner antibody (anti-P specificity, commonly seen in children)
- IgG antibody, anti-P
- After infections (Chicken pox, measles, mumps, and advanced syphilis)
- Biphasic IgG Ab:
1. Binds Ag on RBCs in cold temperatures
2. Activates ‘c at 37°C, haemolysis - Cause: Idiopathic or Secondary to infections
- Diagnosed: DL Test
What is drug-induced immune haemolytic anaemia?
Immunological reaction that occurs due to administration of drugs.
Classify drug-induced IHA.
- Drug-dependent Immune: Abs bind to both the drug and RBC membrane
- Drug-independent Immune: Abs bind to the RBC membrane in the absence of drugs
- Drug-induced Autoimmune: Testing for Abs, the drug must be present in the reaction to demonstrate the Ab
What are the mechanisms involved in drug-induced immune haemolytic anaemia?
- Ab directed at drug coating RBC
- anti-Penicillin - Drug modifies the RBC membrane so that the proteins become non-specifically bound
- Cephalosporin - RBC autoantibody stimulation (not directed at, but capable of RBC destruction)
- Aldomet - Immune complex formation (drug + Ab = ‘c activation and RBC destruction)
- Streptomycin
What is the method of investigation and protocol for investigating possible immune haemolytic anaemias?
- Methods of investigation
1. Determine the temperature of reactivity of the Ab present by doing a panel titer starting at 37°C, then at 32°C, then at 22°C, and lastly at 4°C
2. Determine the auto-Ab specificity in very specific labs
3. Collect, transport, and separate the sample at 37°C
4. Separate serum immediately - Protocols for investigating possible IHA’s
1. DAT with poly-specific antiserum is done to test for pt. RBCs coated by Abs
2. If DAT is + - Test if it is ‘c binding Ab by using monospecific antiserum
- Prepare an eluate to determine Ab specificity
- Investigation protocol
1. Test pt. for ABO, Rh, and Kell blood groups
2. Ab screening test
3. Test temperature of reactivity of identified Abs by doing Ab temperature amplitude (warm/cold auto-Abs)
4. Is the pt. on any drug?
5. Are there any other serological abn.? - Do protein electrophoresis, test for SLE, test for Mycoplasma, ‘c tests.
