Red cell disease Flashcards
What is the meaning of HCT, MCV, MCH, MCHC, RDW respectively?
HCT (haematocrit): proportion of red cells after centrifugation
MCV (mean corpuscular volume)
MCH (Mean corpuscular Hb)
MCHC (Mean corpuscular Hb conc.)
RDW (Red cell distribution width)
RR for MCV
80~100 fL
Which disease leads to elevated MCHC?
hereditary spherocytosis
DDx for nucleated RBCs
BM stress / damage
DDx for pencil cell
IDA
DDx for target cells (4)
(Increase membrane to cell volume ratio)
1. IDA
2. Thalassaemia
3. Sickle cell disease, HbC, HbE
4. Liver disease
DDx for spherocytes (2)
- Hereditary spherocytosis
- Warm AIHA
DDx for elliptocyte
Hereditary elliptocytosis
DDx for bite cells
G6PD deficiency
DDx for schistocytes
MAHA
DDx for golf ball cells
HbH disease
DDx for red cell agglutination
cold AIHA
DDx for rouleaux formation
multiple myeloma
DDx for basophilic stippling (3)
(Aggregates of ribosomes or fragments of ribosomal RNA)
- Lead poisoning
- Megaloblastic anaemia
- Thalassaemia
DDx for Howell-Jolly bodies (4)
- Megaloblastic anaemia
- Thalassaemia
- Sickle cell disease
- Splenectomy / Hyposplenism
Which red cell disease causes koilonychia?
IDA
Which red cell disease causes leg ulcers?
Sickle cell disease
Microcytic hypochromic anaemia DDx
- IDA
- Anaemia of chronic disease
- Sideroblastic anaemia
- Thalassaemia
Normochromic normocytic anaemia DDx (6)
- ACD
- Renal failure
- Aplastic anaemia
- Acute blood loss
- Haemolytic anaemia
- Mixed deficiencies
Congenital syndrome for pure red cell dysplasia
Diamond-blackfan syndrome
Microcytic hypochromic red cells on blood film
size < nucleus of lymphocytes
central pallor >1/2 of red cell diameter
Iron profile and ferritin for IDA, ACD, sideroblastic anaemia, and thalassaemia respectively
(Serum Fe, TIBC, TSAT, Ferritin)
IDA: ↓ , ↑ , ↓ , ↓
ACD: ↓ , ↓ / N, ↓ , ↑ / N
sideroblastic anaemia: ↑ , N , N / ↑ , N / ↑
thalassaemia: ↑ , N , ↑ , ↑
Effect of hepcidin
↓ ferroportin –> ↓ Fe absorption & release
DDx of iron deficiency anaemia
- chronic blood loss (GI, uterine)
- ↑ demands (pregnancy, EPO therapy)
- malabsorption
- Plummer-Vinson syndrome
DDx and pathogenesis of sideroblastic anaemia
Congenital (ALA-S mutation)
–> defective protoporphyrin –> ⨉ haem
Acquired (lead poisoning)
–> inhibit haem & globin synthesis
Treatment for sideroblastic anaemia caused by ALA-S mutation
pyridoxine
Pathogenesis of megaloblastic anaemia
defective DNA synthesis –> nuclear-cytoplasmic maturation asynchrony
DDx of vitamin B12 deficiency
(1) Nutritional: strict vegetarian
(2) Malabsorption
a. Stomach: pernicious anaemia, gastrectomy
b. Pancreas
c. Small intestine: blind loops, Crohn’s disease, ileal resection / bypass
(3) Drugs: N2O anaethesia, metformin, PPI, H2 antagonists
Diagnosis of pernicious anaemia
anti-IF Ab
DDx for folate deficiency
- Nutritional
- Malabsorption: coliac disease
- Excess utilisation: pregnancy, haemolytic anaemia, CA
- Drugs: valproate, phenytoin, methotrexate
Which neurological syndrome is irreversible after B12 deficiency?
Subacute combined degeneration of spinal cord
Supplement for B12 and folate deficiency (caution)
B12: Hydroxocobalamin
(S/E: hypoK ; monitor K after treatment)
Folate: Folic acid
(not given alone unless r/o B12 deficiency)
Pathogenesis of hereditary spherocytosis
defected protein –> loss of vertical interaction between cytoskeleton and lipid bilayer –> loss of biconcave shape ==> spherocytes –> ↑ fragility –> ↓ lifespan
Diagnosis of hereditary spherocytes (2)
- Flow cytometry for EMA binding to RBC
- direct Coombs’ test
Pathogenesis of G6PD deficiency
↓ reduction of NADP into NADPH –> ↓ GSH –> ↑ RBC susceptibility against oxidative stress
Diagnosis of G6PD deficiency
G6PD assay
Aetiology (4) and pathogenesis of warm AIHA
Aetiology:
- Idiopathic
- Autoimmune disease
- Lymphoproliferative diseases
- Drugs: methyldopa
[37 °C] IgG coats RBC –> recognised by macrophages –> RBC becomes spherical –> extravascular haemolysis
Diagnosis and treatment (6) of warm AIHA
Dx: DCT anti-IgG +ve
Tx:
- treat underlying cause
- prednisolone
- rituximab
- splenectomy
- folate
- blood transfusion
Aetiology (4) and pathogenesis of cold AIHA
Aetiology:
- idiopathic
- infection (Mycoplasma pneumoniae)
- lymphoproliferative diseases
- Paroxysmal cold haemoglobinuria
Pathogenesis: [4°C] IgM binds on I antigen on RBC –> fix complement quickly –> intravascular haemolysis
Diagnosis (2) and treatment (4) of cold AIHA
Dx:
- red cell agglutination in cold
- DCT: anti-C3d +ve
Tx:
- keep warm
- treat underlying cause
- rituximab
- chemotherapy
DDx of red cell fragmentation syndrome
- cardiac haemolysis
- AVM
- Microangiopathic haemolytic anaemia
When does the main switch from HbF to HbA occur after birth?
3~6 months
Molecular pathogenesis of α thalassaemia
1. which is MC in HK?
2. which produce elongated but unstable chains?
3. which are associated with mental retardation?
- SEA deletion
- Hb Constant Spring, Hb Quong Sze
- ATR-16, ATR-X
Investigations for HbH disease
PBS: target cells, >1 golf ball cells in new methylene blue stain
Hb electrophoresis: HbH
Pathogenesis of β thalassaemia
point mutation –> reduced production / inactivation of β chains –> precipitation of excess α chains in BM –> ineffective erythropoiesis
Which disease shows hair-on-end appearance on X-ray?
β thalassaemia
Investigations for β thalassaemia (3)
PBS: target cells, Howell-Jolly bodies, basophilic stippling
Hb electrophoresis: ⨉ HbA, major HbF
DNA analysis
Management of β thalassaemia (4)
regular transfusion
allogeneic SCT
folic acid
vitamin D, bisphosphonates
Pathogenesis of sickle cell disease
sickle gene: [position 6 of β chain] glutamic acid => valine
low oxygen level –> sickle Hb polymerise into long fibres –> RBCs sickle –> block microcirculations –> organ infarct
3 types of crisis in sickle cell anaemia
vaso-occlusive crisis
aplastic crisis
haemolytic crisis
Investigations of sickle cell disease (3)
PBS: sickle cells, target cells, Howell-Jolly bodies
Screening test for sickling (test with deoxygenation)
Hb electrophoresis: HbS peak, ↑ HbF, ⨉ HbA
Management for sickle cell disease
!! Transfusion is contraindicated (↓ O2 —> sickling)
Prophylaxis
[crisis] rest, warmth, rehydration
Hydroxyurea (↑ HbF)
Which haemoglobinopathy combined with β trait will give thalassaemia major?
HbE
PBS findings of megaloblastic anaemia
oval macrocytes, Howell-Jolly bodies
hypersegmented neutrophils
basophilic stippling
Diagnosis of β-thalassaemia trait
HbA2 > 3.5%
