Treatment, Diagnosis, Prevention and Basics of Anemia.

1. Anaemia

2. Normocytic anaemia
Presented by :-
Dr.Tahira Zainab

3. Normocytic anaemia:-
Normocytes
Normal sized cell
Normal MCV (80-
96fL)
Acute blood loss
anaemia of chronic
disease
Renal failure
Autoimmune
rheumatic fever
Marrow
infilteration/fibrosis
Endocrine disease
Haemolytic anmia

4. Haemolytic anaemia:-
• anaemia caused by increased destruction of
red blood cells.
• Life span of RBC’s decreased from 120 to
fewer days.
• Break down occurs in macrophages of bone
marrow,liver and spleen.

5. Sites of haemolysis:-
• Extravascular haemolysis
• Most common; spleen and liver macrophages are sites
of destruction.
• Intravascular haemolysis
• Hemoglobin is liberated and binds to hepatolobulins
• Deposited as hemosiderin
• Hemosiderin excreted in urine
• Free Hb oxidized to methaemoglobulin 
spectrophotometry of plasma forms bands;schumm’s
test.

6. Evidence of haemolysis
• Radioisotop labled red cells  51c labelled red
cells
• Raised plasma Hb levels
• Haemosiderinuria
• Low haptoglobins
• Schumm’s test
• Compensated haemolytic anaemia  erythroid
hyperplasia
• Reticulocytes increased in peripheral blood film.
Consequences:-

7. Causes:-
Inherited Acquired
Red cell membrane defect Immune
Hereditary spherocytosis Autoimmune, warm
Hereditary eliptocytosis Cold
Haemoglobinopathies Alloimmune
Thalassaemia Haemolytic transfusion reaction
Sickle cell disease Haemolytic disease of newborn
Metabolic defects Allogenic bone marrow transplantation
G6PD deficiency Drug induced
Pyruvate kinase deficiency Non immune
Pyrimidine kinase deficiency Acquired membrane defects paroxysmal
nocturnal haemoglobinuriaMiscllaneous
MechanicalInfections e.g. malaria
Drugs Renal and liver disease

8. Inherited:-
• Red cell membrane defects
– Hereditary spherocytosis
– Hereditary eliptocytosis

9. Hereditary spherocytosis:-
• Most common hereditary hemolytic anaemia
• Due to deficiency of structural protein Ankyrin
commonly and spectrin.
• Fragile and spherical cells destructed in spleen

10. Clinical Features:-
• Jaundice may be present
at birth or delayed for
years or asymptomatic
throughout life.
• Symptomatic patients
develop
anaemia,spleenomegaly
and ulcers on legs.
• Haemolysis pigmented
gallstones

11. Investigation:-
• Mild anaemia
• Blood film shows spherocytes
• Serum birlirubin and urinary urobilinogen will
be raised
• Osmotic fragility
• Direct antiglobulin (coomb’s test) Is negetive

12. Treament:-
• Raised bilirubin,gallstones present 
splenectomy
• Postponed in until after childhood
• Preceded by immunization and lifelong
penicillin
• Spherocytes persist but Hb normal
• Prophylactic folate supplements

13. Hereditary eliptocytosis:-
• Milder than spherocytosis
• Deficiency of protein spectrin/actin 4.1
complex leading to weakness of horizontal
protein interaction
• Requires spleenctomy in severe cases

14. Hereditary stomatocytosis:-
• Red cells in which pale central area appears
slit like
• Rare condition, alcohol is one of causes
• Spleenectomy contraindicated as it may leade
to severe thromboembolic events.

15. Haemoglobinopathies:-
– Thalassaemia
– Sickle cell anaemia
• Already discussed

16. Metabolic defects:-
– G6PD deficiency
– Pyruvate kinase deficiency
– Pyrimidine 5’ nucleotidase deficiency

17. Normal metabolism:-
• ATP required for membrane integrity,shape
maintanace and other works is obtained via
• Glycolytic pathway 90%
• HMP shunt 10%
• In addition to provide ATP;HMP shut provides
reducing power in form of NADPH (enzyme
required G6PD)
– Maintains reduced glutathion to combate oxidative
stress
• Combates oxidative stress and prevents Hb oxidation to
• methaemoglobin;that precipitates as heinz bodies

18. G6PD deficiency:-
• Required to convert NADP to NADPH;
• Common condition presenting as hemolytic anaemia
• Gene involved is on X chromosome;that’s why more
common in males
• Over 400 structural types
• On severity of haemolysis and enzyme deficiency WHO
classified variants;common are…
• African or milder type A ;haemolysis only in older
cells,self limiting haemolysis b/c new cells have
sufficient enzyme
• Mediterranean or B type; severe deficinecy

19. Clinical syndromes:-
• Acute drug induced haemolysis
• Chronic haemolytic anaemia
• Neonatal jaundice
• Precipitated by infection
• In all conditions presents as anaemia,jaundice
and haemoglobinuria

20. Investigation:-
• Blood counts normal
between attacks
• During attacks;
– Blood film shows;
bite cells,blister
cells,heinz bodies
– reticulocytosis
• Evident haemolysis
• Enzyme assay

21. Treatment:-
• Offending drug
should be stopped
• Infections treated
• Blood transfusion
may be life-saving
• Splenectomy not
usualy required

22. Pyruvate kinase deficiency:-
• Common after G6PD deficiency
• Presents as anaemia and blood film
disorders,pyruvate kinase activity low
• Treated by blood transfusion
• Splenectomy in severe cases

23. Pyrimidine 5’ nucleotidase deficiency:-
• Enzyme required for RNA degradation in
reticulocytes to remove residues of RNA
• Deficiency causes basophilic stipling of RBC’s
• Enzyme also inhibited by lead
• Causes haemolytic anaemia

24. Acquired hemolytic anaemias:-
– Immune
– Non immune

25. Immune:-
– Autoimmune
• Warm and cold
– Alloimmune
• HDN (haemolytic disease of newborn)
– Drud induced

26. Immune:-
• Autoimmune Haemolytic anaemia (AIHA):-
– Increased cell destruction because of red cell
autoantibodies
– Antibodies detected on cell surface (coomb’s test)
– Depending on if antibodies attaches to cell at 37
Oc or at lower temperature AIHA divided into cold
and warm types
– Destruction may be complement mediated (by
lysis complex) or phagocytesed by macrophages.

27. Warm autoantibodies:-
• IGg predominantly
• Direct antiglobin test positive with IGg
alone,IGg and compliment ,or complement
alone

28. Clinical features:-
• Middle aged female common but can occur in
both sexes at any age
• Short episodes of anemia
• Remintting and relapsing jaundice
• Intermittent chronic pattern
• Spleen palpable
• May be associated with WBC’s malignancy
Rheumatoid arthritis,SLE or drugs

29. Investigations:-
• Evidence of haemolysis
• Spherocytes present
• Coomb’s test positive
• Autoimmune thrombocytopenia may be
present

30. Treatment:-
• Corticosteroids; e.g. prednisolone 1mg/kg
daily effective 80%
– Reduced antibody formation
– Reduced RBC destruction
• Splenectomy in no response to steroids
• Immunosupperssive e.g. azathioprine
• Blood transfustion

31. Cold autoantibodies:-
• Agglutinins reacting at 40C
• Harmless usualy. At low temperature presents
just like warm antibodies present as.

32. Drug induced haemolytic anaemia:-
• Interaction between drug and cell
membrane,three types of intraction
– Antiboies to drug only;quinidine,rifampicin:-
resolves when drug withdrawn
– Antibodies to cell membrane only;methyldopa
– Antibodies to both; e.g. penicillin

33. Alloimmune haemolytic anaemia:-
• Antibodies produced in one individual react
with the red cells of another. Occurs in;
• Haemolytic disease of newborn
• Transfusion reactions
• Allogenic transplants of bone
marrow,liver,heart,kidney.

34. Haemolytic disease of newborn
(HDN):-
• HDN due to fetomaternal incompatibility for
red cell antigens.
• Maternal antibodies only IGg cross placenta
and destroy fetal red cells.
• Common types
• ABO type common but milder;mother is O and fetus A
• RhD incompatibility less common b/c of anti-D
prophylaxis

35. Note:-
• Fetal blood cells that enter maternal
circulation at time of delivery caus maternal
immune activation against antigens and
antibody formation
• Thus chances of HDN for the next babies
increase
• 1st is baby usually spared.

36. Clinical features:-
• May Presents as
• Mild anaemia to
• Intrauterine death from 18 weeks;hydrops fetalis
(hepatosplenomegaly,oedema and cardiac failure)
• Kernicterus owing to severe jaundice,unconjugated
billirubin exceeding 250 µmol/L,bile deposition in basal
ganglia
• Permanent brain damage,spacticity
• May present as deafness

37. Investigation:-
• Routine antenatal serology;
• ABO and RhD group determined of all mothers and
repeated at 28 weeks

38. Postnatal care:-
• Mild cases  phototherapy
• Severe case; exchange transfusion indication
• Note:- blood used should be ABO compatible
with mother and fetus and should lack antigen
against which mother antibody is directed.

39. Prevention of RhD incompatibility
HDN:-
• Anti-D should be given to mother after delivery
when all of following present;
– Mother is RhD negative
– Father is RhD positive
– Mother immune system not yet activated against
antigen
• Dose is 500 i.u of IGg anti-D intramuscularly
within 72 hours of delivery.

40. Non immune:-
– Acquired membrane defects
• Paroxysmal nocturnal haemoglobinuria
– Mechanical
– Systemic disease

41. Paroxysmal nocturnal
haemoglobinuria:-
• Urine voided at night and morning is dark
colored, cause of this timing not known
• Is caused by defective gene of proteins
required for complement degradation 
continued complement degradation of RBC’s

43. Clinical feature:-
• Major clinical signs intravascular haemolysis ,
venous thrombosis, haemoglobinuria
• In severs cases all urine samples dark
• Iron deficiency
• Budd-chiari syndrome  venous thrombosis
in liver
• Thrombosis at other sites like GI,brain

44. Investigation:-
• Intravenous haemolysis evident
– Radioisotop labled red cells  51c labelled red cells
– Raised plasma Hb levels
– Haemosiderinuria
– Low haptoglobins
– Schumm’s test
• Flow cytometric analysis of red cells with anti-
CD55 and anti-CD59
• Bone marrow hypoplastic (exhuastion)

45. Treatment:-
• Chronic disorder requires supportive measures
– Leukocyte depleted blood transfusion
– Eculiczumab (prevent c5 cleavage)
• Long term
– Anticoagulants (venous thrombosis)
• Bone marrow aplasia cases
– Immunosuppression with antilymphocyte globulin or
bone marrow transplant ; survival 10-15 years
• Note:- may lead to acute leukemia

46. Thank you all…