0327 - Red Cell Disorders II Flashcards
What is Aplastic Anaemia? What are the most common causes?
A rare syndrome of reduced or absent haematopoiesis due to marrow failure. 70-80% cases immune, also genetic, or insults (drug, chemical, radiation).
What are the characteristics of immune-mediated aplastic anaemia?
No identifiable drug, infections, environmental, or toxic causes.
HLA-DR2 is over-represented.
In animals, its induced by CD8+ (cytotoxic)
Responds to immunosuppression against T-cells.
What are the clinical features of IAA?
Too few cells - Red, White, or Platelets, at any age.
Anaemia - tiredness, lethargy, dyspnoea etc
Neutropenia - Cutaneous or deep-seated infections, opportunistic infections.
Thrombocytopenia - Bleeding or bruising.
(No symptomatic difference between IAA and MDS, but MDS is mailny elderly).
What are the initial tests of suspected IAA?
Discuss with haemotologist. FBC and reticulocytes Blood film HbF (in children) Bone marrow biopsy.
What is myelodysplastic syndrome (MDS)?
Group of clonal stem cell disorders that are characterised by ineffective haematopoiesis and a higher risk of transformation to AML. Qualitative and quantitative defects in various cells, and predominantly a disease of the elderly.
What is the cause and pathophysiology of MDS?
Caused by stem cell damage (prior chemo/radiotherapy, complication of IAA, leukaemia etc.)
Multiple defects in multi-potent stem cells lead to disordered (dysplastic) differentiation in all three lineages - erythroid, myeloid, and megakaryocytic. Existing genome damage gives a higher chance of mutation to AML, with epigenetic methylation playing a role as well.
What are the clinical features of MDS?
Too few, or poor-quality cells - Red, White, or Platelets, mostly in the elderly.
Anaemia - tiredness, lethargy, dyspnoea etc
Neutropenia - Cutaneous or deep-seated infections, opportunistic infections.
Thrombocytopenia - Bleeding or bruising.
No symptomatic difference between MDS and IAA, except that MDS is mostly in elderly.
What are the lab findings characteristic of MDS that can differentiate it from IAA?
Basophilic stippling - remnants of mRNA inside RBC
RBC dimorphism - both concave and convex
Nucleated RBCs
Pelger-huet anomaly - Neutrophils with less than 3 nucleic lobes
Hypogranular neutrophils and blasts in peripheral blood.
What is paroxysmal nocturnal haematuria (PNH)?
A clonal disorder of haematopoietic stem cells, leaving them more vulnerable to complement-mediated lysis. Can be primary or secondary (associated with AA)
What are the clinical features of PNH?
Features of: Iron deficiency haemolytic anaemia Thrombosis at atypical sites >40yo
