Inherited Haemolytic anaemias Flashcards
Define haemolytic anaemias
4 features in the blood of all haemolytic anemais
4 featres of Intravascular causes
1 feature of extravascular cause
Breakdown of RBC before normal life span <120 days
All haemolytic anemias:
- Increased Br - unconjugated
- increased urobilinogen
- increased LDH
- reticulocytosis - increased MCV & polychromasia
- pigmented gall stones
Intravascular:
- Decreased Haptoglobin -binds free Hb
- Increased Free Hb
- Hburia - dark red urine
- methaemalbuminuria - Heme + albumin
Extravascular - Splenomegaly
Erythroid hyperplasia states (such as that which results from haemolytic anemias) can cause susceptiblity to certain conditions - name 3
- Iron overload
- Osteoporosis
- Susceptible to B19 > aplastic anemia
Causes of acquired haemolytic anaemis: immune (2), non immune (3)
Immune
- autoimmune - warm or cold
- alloimmune - haemolytic transfusion reactions
Non-immune
- mechanical e.g. metal valves, trauma
- PNH, MAHA
- infections e.g. malaria
Causes of inherited haemolytic anaemis: membrane defect (2), enzyme defect (2), Hbpathies (2)
Membrane defect
- hereditary spherocytosis
- hereditary elliptocytosis
Enzyme defect
- G6PD def
- Pyruvate kinase Def
Hbpathies
- SCD
- Thalassemias
Hereditary spherocytosis
- Cause?
- Dx (2)
- Rx (2)
Hereditary elliptocytosis is also AD with spectrin mutations
AD - use FH to aid dx
- Spectrin or ankyrin def (membrane proteins)
- susceptiblity to B19 & develop gallstones
- Extravascular haemolysis leads to splenomegaly
Dx - Spherocytes & increased osm fragility (lysis in hypotonic solution)
Rx - splenectomy + folic acid
G6PD deficiency: definition, features (6), Ix (2), management (1)
D - X-linked def in G6PD enzyme. Mediterranean/middle east
F - precipitated by Oxidants (G6PD helps RBCs make glutathione which protectes against oxidative damage) flava beans, drugs e.g. nitrofurantoin, aspirin, quinines, fever malaise, increased free plasma Hb, decreased haptoglobins heinz bodies (denatured Hb inclusions), Dark urine
Ix - RBC G6PD acitivity
M - avoid precipitants
Pyruvate kinase def triad
AR condtion
severe neonatal jaundice + splenomegaly +haemolytic anaemia
Sickle cell disease: cause, types (4), pathogenesis
C - mutation in codon 6 of b-globin gene - GAG>GTG so AA changes from glutamine > valine - reduces charge on Hb (glutamine -ve and valine neutral) (resulting in HbS instead of HbA)
T: HbSS - majority of Hb is HbS
HbSC - HbC is due to another mutation on B-globin gene (no normal B globin > so no HbA)
Sickle ß thalassemia - no HbA (HbS from 1 parent & ß-thalaessmia trait from another)
Sickle Trait - asymp carriers HbAS - 1 HbS & 1 normal ß-globin > 40% of Hb is S.
Pathogenesis: HbS polymerizes > Sickling of RBCs > microcirculation trapping > vaso-occlussion. Ischaemia worsens if cold, dehydrated, low pO2 (presents 3-6 months as HbF finishes)
SCD complications - SICKLED
- Stroke
- Infections (hyposplenism > increased suscep to encapsulated organisms)
- Crises (splenic, sequestration, chest)
- Kidnee - nephrotic syndrome
- liver - gallstones
- Eye - retinopathy
- Dactilitis - impaired growth
- Also Priapism
SCD dx (3), Rx (3)
sickle cells, target cells, sickle solubility test, hb electrophoresis
Prophylactic daily oral penicillin (protects against pneumococcal) + Folic acid for increased haemolysis
Acute crises: analgesia + good hydration + O2 + exchange transfusion
chronic problems (recurrent crises): Hydroxyurea - increases HbF, BMT
ß-Thalassaemias: Types (3), features (6), Ix (3), Rx (3)
With thalassemias have unbalanced Hb synth > unmatched globins precipitate > haemolysis & ineffective erythopoeisis
T: Major - no HbA, Intermedia - Some HbA + lots of HbF, Trait - asymp - raised HbA2 & HbF
F - severe anaemia, FTT, pallor, jaundice, bossing of skull & maxiallry growth (rare in developed countries due to transfusions), hepatosplenomegaly. Compliactions of iron overload from transfusions - cariomyopathy, DM, cirrhosis
Ix - microcytic hypochromic anaemia (often misdiagnosed as IDA), to differentiate - will see high HbA2 & normal ferritin (low in IDA) Hb electrophoreisis
M - Lifelong monthly transfusions, Desferrioxamine (iron chelation), BMT
a-Thalassaemia: 3 types & 2 features for each
Hb Barts/ major - all 4 alpha genes deleted - no HbA (or A2) > fetal hydrops - death inutero or few hours post natal
HbH - 3 alpha globin genes deleted - mild-moderate anaemia, sometimes transfusion dependent
a-thalassemia trait - asymp, anaemia mild or absent, may have hypochromic microcytic RBCs
