Haemolytic Anaemia Flashcards
What are biochemical findings suggestive of intravascular haemolysis?
Evidence of RBC breakdown
- ↑ bilirubin, LDH
- ↓ haptoglobin (clean up the free Hb from haemolysis)
- ↑ Urinary haemosiderin (takes ≥48 hours from onset before you see it)
- ↑ Urinary / faecal urobilinogen
Evidence of compensatory erythropoiesis
- Reticulocytosis
- Polychromasia (↑ immature RBCs in the blood)
Evidence of RBC damage
- Spherocytosis
- Fragmented RBCs
What is the initial work up for Haemolysis?
- Bilirubin: conjugated/unconjugated
- Haptoglobin
- LDH
- Reticulocyte count
- Blood film
- Urinary haemosiderin
- DAT
- Others: B12, folate, iron studies
What are the major causes of haemolytic anaemia? (categories)
Think ADAM-TS
Autoimmune (warm/cold)
Drug-induced
Acquired Membrane abnormalities (cirrhosis, uraemia, PNH)
Mechanical (DIC, valvular HD, TTP, vasculitis)
Thalassaemia and other congenital conditions (HS, G6PD…etc)
Sepsis, including Malaria
Which drugs cause warm AIHA? (3)
- Methyldopa (maybe DAT + but only minority develop haemolysis)
- Penicillin
- Quinidine
Blood film shows schistocytes (schizocyte) – DDx (4)?
- DIC
- TTP/HUS
- Drug induced TMA
- Mechanical heart valves
What clinical/biochemical findings would be consistent with TTP (thrombotic thrombocytopaenic purpura) or HUS (5)?
FAT RN
- Fever
- Anaemia (microangiopathic haemolytic)
- Thrombocytopaenia
- Renal failure
- Neurological abnormalities
Differentials for +ve DAT? (3)
- Warm AIHA
- Cold AIHA
- Drugs (methyldopa, quinine, penicillin)
What is the difference in the test results (DAT) between the warm and cold agglutinin disease?
- Warm AIHA: IgG +
- Cold AIHA: IgG –ve, C3b+, IgM +
Causes of warm and cold agglutinin disease?
Warm
Lymphoma, CLL, solid tumours
Connective tissue disease (especially SLE)
Drugs
Cold
Mycoplasma
Hep C
EBV (glandular fever)
Lymphoma
If patient gets haemoglobinuria at night, pancytopaenic and DVT– what’s the diagnosis? – how would you investigate?
Dx = Paroxysmal nocturnal haemoglobinuria (PNH)
Inv = Flow cytometry for CD59 and CD55
- CD55 = DAF = decay-accelerating factors
- CD59 = membrane inhibitor of reactive lysis
Mechanisms
- There are proteins bound to RBC surface by anchor proteins called GPI
- In PNH these are lost/faulty in myeloid stem cells → all will have a defect
- When you sleep → breathing shallow → ↑CO2 → acidosis activates compliment → complement-mediated lysis (usually anchor protein protects RBCs but in PNH these are defective) → intravascular haemolysis
PNH Management options? Acute and Chronic.
Acute thrombotic episodes → anticoagulation with Heparin (warfarin) and start anti-C5 (Eculizumab)
Chronic disease
- Eculizumab
- Allogeneic HCT
Management of warm AIHA (2; including options for resistant disease – 3)?
- Steroids – 1mg/kg/day → once Hb recovers, slow taper
- Replace folate (as they are required for production)
- Discontinue the drugs if drug-induced
•For those who do not respond to steroids consider…
- Splenectomy
- Immunosuppressive: AZA, Cyclophosphamide
- IVIG
- Rituximab (off label)
Would you transfuse a patient with warm AIHA?
- Not unless Hb <80
- It may exacerbate haemolysis because antibody in immune-mediated haemolysis will likely to react with donor RBCs
- Laboratory testing – cross match - in such cases most often reveals a ‘pan agglutining’ autoantibody.
- Occasionally the autoantibody has Rh antigen specificity and donor red cells lacking the antigen can be safely transfused under close observation.
Management of cold AIHA? (5)
Treat underlying condition
Maintain warm environment
Transfusion – through warmer
Plasmaparesis
Anti-B cell therapy for those with clonal production
- Treat underlying malignancy
- Rituximab + chemo (bendamustine) in those without underlying malignancy
- Consider Bortezomib in those with MGUS
- Eclulizumab under investigation
TTP – pathophysiological mechanism?
An enzyme called ADAMS-TS13 is either deficient or inhibited by autoimmune Abs.
The enzyme is responsible for cleavage of vWF multimers into monomers. Thus, vWF remain as a large multimer, which causes excess platelet aggregation to it (recall that Gp Ib of platelet binds to vWF), leads to overconsumption of platelets.
This leads to MAHA, because platelet microthrombi forms in small blood vessels which shears or lyses RBCs when they go through it.
Comment on the following blood test result.
Blood film: moderate anisocytosis, numerous spherocytes, prominent polychromasia; nucleated red
cells, neutrophilia and band forms.
What test would you ask for?
There is normocytic anaemia.
Markedly elevated Reticulocyte, high bilirubin in absence of abnormal LFTs, raised LDH and low Haptoglobin suggest haemolytic anaemia.
Blood film shows prominent polychromasia & nucleated cells indicating marrow erythroid activity.
Numerous spherocytes suggests hereditary spherocytosis or immune haemolysis. Lack of fragmented cells indicate that mechanical haemolysis or MAHA is less likely.
I would ask for DAT (Coombs’ test) to distinguish between AIHA from HS.
