Haemolytic anaemia

Question 1

What?

Answer 1

Premature breakdown of RBCs -> anaemia

Can be intravascular or extravascular

Question 2

An approach - 4 questions

Answer 2

1) Is there increased RBC breakdown?
Anaemia with normal or increased MCV
Increased bilirubin, unconjugated (pre-hepatic jaundice)
Increased urinary urobilinogen
Increased serum LDH (released from RBCs)
2) Is there increased RBC production?
Increased reticulocytes -> increased MCV and polychromasia
3) Is it mainly extra or intravascular
Extra: splenic hypertrophy + splenomegaly
Intra: increased free plasma hb; methaemalbuminaemia; reduced plasma haptoglobin; haemoglobinurea (red-brown urine, no rbcs; haemosiderinurea (Prussian blue staining 1 week after onset)
4) Why is there haemolysis - see causes

Question 3

History

Answer 3

FH
Race
Jaundice
Dark urine
Drugs
Previous anaemia
Travel

Question 4

Examination

Answer 4

Jaundice
Hepatosplenomegaly
Gallstones (pigmented)
Leg ulcers (poor blood flow)

Question 5

Investigations

Answer 5

FBC, reticulocytes, bilirubin, LDH, haptoglobin, urinary urobilinogen, thick and thin blood films (malaria) if recent travel
Blood film:
Polychromasia and macrocytosis due to increased reticulocytes
Hypochromic microcytic anaemia (thalassaemia)
Sickle cells (sickle cell)
Schistocytes (microangiopathic HA)
Abnormal cells (haem malignancy)
Spherocytes (hereditary spherocytosis or AIHA)
Elliptocyes (hereditary elliptocytosis)
Heinz bodies, ‘bite’ cells (G6PD deficiency)
Direct antiglobulin (Coomb’s) test (DAT): immune cause

Question 6

Classification of causes

Answer 6

1) Acquired
Further divided into immune and non-immune
a) Immune, DAT +ve
i) Drug induced - penicillin, quinine
ii) AIHA - separate deck of cards
iii) Paroxysmal cold haemoglobinuria - viruses/syphilis; isoimmune - acute transfusion reaction, haemolytic disease of the newborn
b) DAT -ve AIHA - <2% of AIHA - autoimmune hepatitis, HBV, HCV, post-vaccinations, drugs (piperacillin, rituximab)
c) Microangiopathic haemolytic anaemia (MAHA): mechanical distruption -> intravascular haemolysis + schistocytes - HUS, TTP, DIC, pre-eclampsia
d) Infection - malaria

2) Hereditory - defect in rbc enzymes, membrane or Hb
a) enzyme defects: G6PD deficiency; pyruvate kinase deficiency
b) membrane defects: DAT -ve: hereditary spherocytosis; elliptocytosis; ovalocytosis; stomatocytosis
c) Haemoglobulinopathy: Sickle cell; Thalassaemia

Question 7

G6PD deficiency

Answer 7

Mainly males
Mediterranean, Africa, Middle/Far East
Mostly asymptomatic, but get oxidative crises due to decreased glutathione production
Triggers: Drugs (primaquine, sulphonamide, aspirin); broad beans/favism; illness; henna
Attacks: rapid anaemia and jaundice
Blood film: bite and blister cells, Heinz bodies
Inv: enzyme assay >8wks after crisis
Rx: Avoid precipitants, transfuse if severe

Question 8

Hereditary spherocytosis

Answer 8

Less deformable spherical RBCs -> trapped in spleen -> extravascular haemolysis
Splenomegaly, jaundice, increased bilirubin
Mild if Hb >11 and reticulocytes <10% of film
Rx: Folate supplementation and splenectomy