The destruction of red cells
Clinical signs & symptoms of haemolysis
Classification of Haemolytic anaemias
G6PD deficiency
Thalassaemias
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3. Aged red cell-
*Changes on the surface membrane
*Decrease in enzyme activity
• Signals it’s incapacity to the RE system
• Macrophages of the RE system remove it
(bone marrow, liver ,spleen)
• 1% of the red cells are destroyed &
replaced by new cells each daywww.usmlemcq.com
4. Breakdown of normal red cells
Haemoglobin
Haem Globin
Iron Protoporphyrin Amino acids
Transferrin CO Bilirubin (free)
Erythroblast conjugation (liver)
secreted in bile
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5. Haemolytic Anaemia-
Those anaemias which result from an
increase in the rate of red cell destruction
*Haemolytic state can exist without anaemia
(compensated haemolytic disease)
*normal adult marrow can produce 6-8 times
the normal rate.
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6. 1.Erythroid hyperplasia-
Increase in the proportion of cells
committed to erythropoeisis in the marrow
(brings out immature cells-reticulocytes)
2.Expansion of the volume of active marrow
When the haemolysis exceeds the
compensatory capacity of the marrow
Haemolytic anaemia
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7. Haemolytic anaemias
1.Extra vascular-
breakdown of red cells in the RE system
(commoner than 2.)
2.Intra vascular-
breakdown of red cells within the
circulatory system
(liberation of haemoglobin)
Causes of IV haemolysis
•Oxidant stress (G6PD)
•Cold auto immune
•Red cell fragmentation synromes
MAHA
•Drug induced
•Infections
•ABO,Rh incompatibility
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8. Haemolytic anaemias
1.Intra corpuscular
breakdown of red cells due to a defect
in the cell.
(almost all are Congenital. except-PNH)
2.Extra corpuscular-
breakdown of red cells due to an external
cause.
(Acquired)
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9. Anaemic patient
Haemolytic?
Extravascular or
Intravascular?
Cause?
Clinical history
Examination
Investigations
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10. Clinical signs & symptoms of
haemolysis
Anaemia
Jaundice
Dark urine (urobilinogen/haemoglobinuria)
Abdominal pain
Leg ulcers
Precipitating factors- drugs,infections,warm,cold
Family history
Hepatosplenomegaly
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13. 2.Increased red cell production
*Reticulocytosis (if severe, normoblasts also +)
*Erythroid hyperplasia in bone marrow
3.Abnormal red cells in blood picture
*Spherocytes
*Sickle cells
*Fragmented cells
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16. 14 year old boy
C/O - fever, yellow discolouration
of eyes and abdominal pain – 2 weeks
O/E – Pale ++ , Icteric +, Spleen – 1cm
What are the first line investigations?
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17. Hereditary spherocytosis
Commonest hereditary haemolytic anaemia
Auto. Dominant
Defect in structural protein – Spectrin
Red cells lose membrane as they circulate
through the spleen & RE system – spherocytes
Die prematurely as they circulate through
spleen
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18. H.S cont.
Anaemia may present from infancy to old age.
may suddenly increase- Aplastic crisis
Jaundice is typically fluctuating
Splenomegaly + in most cases
Pigment gallstones are frequent
Reticulocytosis +
Microspherocytes in the blood picture
i
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20. H.S cont.
Special tests
*Coombs test negative (D/D autoimmune
haemolysis)
*Osmotic fragility increased +
*autohaemolysis increased, corrected by
glucose
Treatment
*Splenectomy treatment of choice
(avoided in early childhood-
pneumococcal infection)
i
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22. G6PD deficiency
Deficiency or functional inadequacy of glucose 6
phosphate dehydrogenase enzyme.
Sex linked recessive
GSH GSSG
Glucose
G6P 6PG
NADP NADPH
G6PD
Oxidant
stress
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23. G6PD cont.
Oxidant stress- primaquin, sulphonamides,
infections fava beans.
Rapid intravascular haemolysis with
Hburia.Usually self limiting within 7 days.
May present as neonatal jaundice
High frequency in Mediterranean countries and
in South east Asia
Blister and bite cells in the blood picture with
reticulocytosis
Heinz bodies – 2nd to 10 th day
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25. G6PD cont.
Brewer test
Nitrite oxidizes Hb to methHb, methylene blue
reduces it to oxyHb if HMP is intact
Enzyme assay
Treatment
*Avoid precipitating factors
*Symptomatic – blood transfusions
*Good hydration
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26. Pyruvate kinase deficiency
Auto. Recessive
Red cells are rigid due to reduced ATP formation
Prickle cells in blood film
Auto haemolysis increased but not corrected
with glucose
Enzyme assay to diagnose
Splenectomy may alleviate the anaemia but
does not cure it
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27. Thalassaemias
Reduced synthesis of normal globin chains
Adult blood has-
*HbA (2 alpha ,2 beta globin chains)
*HbA2 (2 alpha ,2 delta)
*HbF (2 alpha ,2 gamma)
Alpha globins are coded by 4 genes (2 genes for each
globin chain)
alpha alpha alpha - (Thal)www.usmlemcq.com
28. Thal cont.
Beta globins are coded by 2 genes
beta beta beta - - -
normal Thal minor Thal major
Thal inter.
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29. Thal cont.
Reduction of alpha chains – alpha thal
Haemolysis, Hb H (beta 4), Hb Barts (gamma 4)
Reduction in beta chains – beta thal
Precipitation of alpha chains – ineffective
erythropoeisis.
Excess alpha chains are mopped up by producing
more gamma chains.Therefore increase in HbF
(Thal major)
increase in HbA2 (Thal minor)
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31. Thal cont.
Reduction of alpha chains – alpha thal
Haemolysis, Hb H (beta 4), Hb Barts (gamma 4)
Reduction in beta chains – beta thal
Precipitation of alpha chains – ineffective
erythropoeisis.
Excess alpha chains are mopped up by producing
more gamma chains.Therefore increase in HbF
(Thal major)
increase in HbA2 (Thal minor)
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32. Thal major
Clinical features
*severe anaemia at 3- 6 months after birth
*hepatosplenomegaly due to red cell destruction
and extra medullary haematopoeisis
*expansion of bones –skull
*Iron overload –liver, pancreas, myocardium,
thyroid, parathyroid, skin
*susceptibility to infection
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34. Thal major cont.
Investigations
*blood film- hypochromic microcytic
red cells, target cells, reticulocytes,
normoblasts
*haemoglobin electrophoresis – almost
complete absence of HbA, over 90% HbF.
*serum ferritin increased
*skull x-ray – hair on end
appearance
i
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36. Thal major cont.
Treatment
*Splenectomy may be required to reduce
blood transfusions but delayed until 6 years
of age
*Bone marrow transplant
*Gene therapy
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37. Sickle cell anaemia
Synthesis of an abnormal Hb, HbS
(alpha 2, betas 2)
Substitution of valine for glutamic acid at
position 6 on the beta chain
Hb forms insoluble crystals at low oxygen tens.
Red cells sickle and block the microcirculation
causing infarcts in various organs
Homozygous disease-severe haemolytic anaemia
punctuated by crises
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38. Sickle cell anaemia cont.
Clinical features
*Painful crises- frequent, due to ischaemia.
Precipitated by infections, acidosis,
dehydration.
Infarcts of bones, lungs, spleen(small spleen),
brain
*Haemolytic crises- fall in Hb, rise in retic count
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40. Sickle cell anaemia cont.
Clinical features
*Aplastic crises- fall in Hb, fall in retic count
(parvo virus or folate def)
*Visceral sequestration- severe chest syndrome,
commonest cause of death
*leg ulcers
*pigment gall stones
*priapism www.usmlemcq.com
41. Sickle cell anaemia cont.
Investigations
*Hb 6-9g/dl.low in comparisson to symptoms
of anaemia as HbS shifts the dissociation
curve to the right.
*Sikcle cells & targets in the blood film
*positive sickling test
*HbS band on elecrophoresis
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42. Sickle cell anaemia cont.
Investigations
*Hb 6-9g/dl.low in comparisson to symptoms
of anaemia as HbS shifts the dissociation
curve to the right.
*Sikcle cells & targets in the blood film
*positive sickling test
*HbS band on elecrophoresis
i
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44. Haemoglobin E
Commonest Hb variant in South east asia
Alpha 2, beta26glu—lys 2.
Microcytic hypochromic anaemia with targets.
HbE band on electrophoresis
May remain undetected
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46. Warm autoimmune haemolytic anaemia cont.
Pathogenesis
IgG antibodies are present on the red cells,
some of them also bind complement(C3)
Red cells are destroyed mainly in the RE
system (preferentially spleen)
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47. Warm autoimmune haemolytic anaemia cont.
Clinical features
Haemolytic anaemia
Jaundice
Splenomegaly
Investigations
Reticulocytosis
Spherocytes
Increased serum bilirubin
Positive direct coomb test
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49. Cold autoimmune haemolytic anaemia
Auto antibodies (IgM) that react best at
temp. <370 (0-40)
Causes
*Idiopathic (CHAD)
*secondary
Mycoplasma
Infectious mononucleosis
Lymphoma
SLE
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50. Cold autoimmune haemolytic anaemia cont.
Clinical features
Some have acute IV haemolysis & Hburia
in cold weather but maintain a normal Hb
in warm weather
Others have a compensated chronic
haemolysis with a mild to moderate
reduction of Hb.
Acrocyanosis, Raynauds phenomenon due
to agglutinates.
Spleen may not be enlarged
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51. Cold autoimmune haemolytic anaemia cont.
Investigations
Anaemia with red cell agglutinates
Macrocytosis
Reticulocytosis
Positive direct coomb test
Features of IV haemolysis
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52. Cold autoimmune haemolytic anaemia cont.
Treatment
Avoid cold
May need blood transfusions
Plasmapheresis has been used
Corticosteroids and splenectomy are rarely
of any benefit
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53. ABO & Rh incompatibilty
Haemolytic transfusion reactions may be
immediate or delayed.
Immediate life threatening reactions
associated with massive IV haemolysis is
seen with complement activating antibodies
of IgM & IgG classes(ABO antibodies)
Severity of the reaction depends on the
recipient’s titre of antibody
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54. ABO & Rh incompatibilty cont.
Extra vascular haemolytic transfusion
reactions are seen with the immune
antibodies( IgG, unable to bind complement).
The only feature may be unexplained
anaemia with jaundice
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55. 14 year old boy
C/O - fever, yellow discolouration
of eyes and abdominal pain – 2 weeks
O/E – Pale ++ , Icteric +, Spleen – 1cm
What are the first line investigations?
Hb- 9g/dl, Retic count- 6%,
S.Bilirubin – 2.5mg/dl
Urine urobilinogen – normal
Coombs test – Negative
What is the D/D, What further investigations to
Confirm the diagnosis?www.usmlemcq.com
56. Mechanical haemolytic anaemia
Red cells may be injured by excess physical
trauma as they circulate through the vascular
system.
Cardiac – Occasional complication of open
heart surgical procedures eg. valve
prostheses.In severe cases marked anaemia
with intravascular haemolysis.
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57. Mechanical haemolytic anaemia
March haemoglobinuria – Hbnaemia & Hburia
following strenuous exercise in healthy young
adult males.
soldiers,athletes,karatekas.
Traumatic effect on the blood within vessels
of sole.
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58. Microangiopathic haemolytic anaemia
Mechanical haemolytic anaemia in which the
red cell fragmentation is due to contact
between red cells & abnormal intima of partly
thrombosed, narrowed, or necrotic small
vessels.
1.Disseminated intravascular coagulation
2.Haemolytic uraemic syndrome
3.Thrombotic thrombocytopaenic purpura
Associated thrombocytopaenia
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59. DIC
Due to widespread intra vascular coagulation
induced by pro coagulants that overcome the
natural anti coagulant mechanisms with
formation of thrombin.
These pro coagulants may be produced in
the blood or introduced from out side the
circulatory system.
This results in-
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62. HUS-TTP
Initially described as two distinct entities but
now thought to be two points in the same
spectrum
Formation of platelet thrombi (hyaline
thrombi) in terminal arterioles & capillaries.
Microangiopathic haemolytic anaemia with
Thrombocytopaenia
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63. HUS-TTP
Pathogenesis
Presence of abnormal vwf (platelet adhesion)
Deficiency of vwf cleaving proteases
Increase in vwf activity, platelet aggregation
Microthrombi formation
Clinical features
Fever
Neurological symptoms
Renal failure
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64. HUS-TTP
Investigations
Red cell fragmentation
Low platelets
Increase in indirect bilirubin
Increase in LDH
No alteration of clotting profile
Causes
E.Coli o157 toxin
Shigella dysenteriae
Drugs- Quinine, Cyclosporine Awww.usmlemcq.com
66. Infections
Malaria – anaemia is often only mild
*can be severe esp.with falciparum infections
*Blackwater fever rare but serious complication,
seen in endemic areas & in those who have
repeated attacks. Pptd by antimalarial drugs.
*Diagnosis by demonstrating the parasite
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67. Infections
Clostridium welchii – due to direct action of
toxin
*mostly post abortal or puerperal infections
*Intra vascular spherocytic anaemia, retic count
not very high
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68. Drugs
Due to direct toxic effects in normal subjects
*Sulphasalazine
Haemolysis in subjects with metabolic
abnormality G6PD def
*primaquine, nitrofurantoin
Due to a immune mechanism
*Quinine, Penicillin, Sulphonamides
Toxins – Snake bite
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