On hemolytic anemia (sorry the spelling of hemolytic is wrong everywhere), its classification, and esp in the inherited forms where there is defect in membrane cytoskeleton

2. CLASSIFICATION
GENERAL PATHOPHYSIOLOGY
GENERAL CLINICAL AND LABORARTORY FEATURES
HEREDITARY SPHEROCYTOSIS
HEREDITARY ELLIPTOCYTOSIS
ENZYME DEFECTS – G6PD DEFICIENCY

3. HAEMOLYTIC ANAEMIA
INHERITED ACQUIRED
OR
INTRA-
CORPUSCULAR
EXTRA-
CORPUSCULAR
DEFECTS IN MEMBRANE-
CYTOSKELETON COMPLEX :
HEREDITARY SPHEROCYTOSIS,
HEREDITARY ELLIPTOCYTOSIS
HAEMOGLOBIN DEFECTS :
THALASSEMIA, SICKLE CELL
ANAEMIA,
Hb-H, Hb-C, Hb-H-D, Hb-E
ENZYME DEFECTS: G6PD
DEFICIENCY, PRUVATE KINASE
DEFICIENCY
IMMUNE - MEDIATED
Autoimmune haemolytic anaemia
Allo-immune haemolytic anaemia
NON – IMMUNE MEDIATED
Mechanical, Chemicals, Biological
Infections, Heat, Burns, Osmotic.

4. NORMALLY….
1) In the bone marrow – HSC give rise to erythroblasts, which undergoes a sequence of events with
gradual accumulation of haemoglobin and loss of cellular organelles, and biosynthetic abilities.
2) This leaves behind (in a mature RBC ) –
a) membrane-cytoskeleton complex
b) Haemoglobin
c) metabolic machinery
3) Because of which, if any protein deteriorates - it cannot be replaced .
4) With age, red cells undergoes “degenerative” changes such as –
a) Decline in enzyme activity
b) Clustering of membrane protein which bind to C3 - get opsonized by RE system. (esp. spleen)

5.  About 10% undergoes intravascular haemolysis….
1) In haemolytic disorder – shortened
RBC life span.
2) If Destruction >> Formation, the
disorder manifests as – Haemolytic
anaemia.
3) Anaemia  Hypoxia  EPO 
Erythroid hyperplasia and marrow
expansion  reticulocyte and
nucleated RBCs rise in circulation.
4) Consequences of haemolytic anaemia –
a) GALLSTONES
b) HYPERSPLEENISM  thrombocytopenia
and neutropenia
c) 2⁰ HAEMACHROMATOSIS
d) HAEMOGLOBINURIA  IRON LOSS
5) COMPENSATED VS.
UNCOMPENSATED HAEMOLYSIS.
a) No Anaemia – If compensated
b) Decompensation under precipitating
factors such as –
infection,
drugs
renal failure
pregnancy
folate or Vitamin B12 deficiency

6.  ONSET – ACUTE or CHRONIC
 PALLOR
 JAUNDICE
 DARK URINE
 SPLENOMEGALY +/- HEPATOMEGALY
 LEG ULCERS
 SKELETAL DEFECTS
 MEGALOBLASTIC CRISIS OR APLASTIC CRISIS
Haemolytic facies ( Chipmunk facies )
LABORATORY FEATURES
INCREASED
DESTRUCTION
 Hb/ Hct
 BILIRUBIN
 Urobilinogen increased.
 Reduced haptoglobulin
 Reduced hemopexin
 Hemoglobinemia
 Hemoglobinuria.
 LDH and AST
 Red cell survival studies-
Cr – labelled RBCs
ERYTHROPOEITIC
RESPONSE
 RETICULOCYTOSIS
 POLYCHROMASIA
 RED BLOOD INDICES –
raised MCV, MCH and
MCHC
 BONE MARROW –
ERYTHROID
HYPERPLASIA.

7. MINKOWSKI–CHAUFFARD SYNDROME It is a genetically determined haemolytic disease secondary to a defect in the structural protein
(spectrin) of red cell membrane.
 It is a genetically heterogeneous condition resulting in a broad clinical spectrum of varying severity.

9. 1) WIDE CLINICAL SPECTRUM – ASYMPTOMATIC TO SEVERE ANAEMIA
2) ONSET – at infancy (as severe anaemia with neonatal jaundice), in childhood or in adulthood.
3) ICTERUS
4) SPLENOMEGALY
5) APLASTIC CRISIS – PARVOVIRUS B 19
6) HAEMOLYTIC CRISIS- intercurrent infection such as Infectious mononucleosis.
7) GALLSTONES – highly suggestive if it occurs at young age.
8) FAMILY HISTORY – May be negative.

10.  HAEMOGLOBIN
 RETICULOCYTE COUNT
 RED BLOOD INDICES – MCH and MCHC raised
 BILIRUBIN
 PERIPHERAL SMEAR -
 RED CELL OSMOTIC FRAGILITY
 RED CELL SURVIVAL STUDY –
Using radiolabelled chromium
 AUTOHAEMOLYSIS TEST – Auto-
haemolysis increased and decreases upon
addition of glucose

11.  SPLENECTOMY – a) ONLY after 5 years of age.
b) Avoid in mild cases.
b) Anti-pneumococcal vaccine before splenectomy
c) Post – splenectomy penicillin prophylaxis (??)
 Before 5 years of age – Folic acid supplementation
 In case of neonatal jaundice – exchange transfusion
 In case of aplastic crisis – Blood transfusion.
 Cholecystectomy – if clinically indicated.

12.  Genetically determined haemolytic anaemia characterized by spectrin deficiency and elliptocytes
on peripheral smear.
 Autosomal dominant mode of inheritance.
 Clinical picture can range from mild or asymptomatic haemolytic disorder to severe haemolysis.
 Other clinical feature same as hereditary spherocytosis.
 A rare but severe form of hereditary elliptocytosis – called Hereditary pyropoikilocytosis.
 Treatment – SPLENECTOMY (for severe cases)

13. HEREDITARY STOMATOCYTOSIS
HEREDITARY
ACANTHOCYTOSIS

14. I. Glucose – 6 – phosphate dehydrogenase is an enzyme responsible for catalysing redox
reactions in all aerobic cells and red cells.
II. It is the only source of NADPH in red cells unlike other cells of the body.
GENETICS
I. It is an X- linked disorder characterized by mutations resulting in reduced stability of the
enzyme or , less commonly, decreased production.
II. Genetic mosaicism is seen in females because of lyonization resulting in varying clinical
severity seen in female populace.

15. I. Commonly see in tropical and sub
tropical countries.
II. Different variants of G6PD is
across the globe.
These are – G6PD mediterreanean
G6PD A (Africa,
Southeast
Europe)
G6PD canton (China)
G6PD mahidol and
G6PD
vianchan in S-E Asia
G6PD union
(worldwide).
III. Confers relative resistance against
Plasmodium falciparum.

16.  Many remain asymptomatic.
 However, they are at an increased for developing neonatal jaundice and Acute Haemolytic
Anaemia (AHA) when exposed to oxidative stress.
 AHA is triggered by 3 factors viz. INFECTIONS, DRUGS and FAVA BEANS
 Signs and Symptoms of AHA –
a) Malaise, abdominal or lumbar pain
b) within hours to 2-3 days – pallor, dark urine and icterus develops
c) ARF
 Chronic non - spherocytic haemolytic anaemia (CNSHA)- subset of G6PD deficiency characterized
by anaemia, jaundice, splenomegaly and gallstones. Above triggers can precipitate haemolytic
anaemia.

18.  Hb/Hct decreased
 Reticulocytosis
 MCV increased
 Peripheral smear -
 BILIRUBIN
 LDH
 G6PD Enzyme assay
 Hemoglobenemia, hemoglobinuria.
 Reduced haptoglobulin levels.

19.  STOP THE OFFENDING DRUG.
 MAINTAIN HIGH URINE OUTPUT, if required HAEMODIALYSIS.
 In case of severe anaemia – Blood transfusion.
 In case of CNSHA – FA supplementation.
 In case of severe neonatal jaundice, phototherapy or exchange transfusion