descriptive study

1. CH.VYSHNAVI
MSC MLT
1st YEAR

2.  DEFINITION
 CLASSIFICATION

3.  Haemolytic anaemia is a condition in which red
blood cells are destroyed and removed from the
bloodstream before their normal lifespan is over.
 Haemolytic anaemia are the anaemia's that result
due to increase in the rate of red cell
destruction.
 About 1%blood is destructed ever day in normal
adult

4.  RBC’s normally survive 120 days .
 Bone marrow has the capacity to increase
erythropoiesis 6 - 8 times than normal.
 Therefore Hemolytic Anemia may not be seen until
the red cell lifespan is less than 30 days.
 Anemia is the result of premature destruction of red
cells exceeding the erythropoietic capacity of the
bone marrow

5.  When blood cells die, the body's bone marrow makes
more blood cells to replace them. However, in
haemolytic anaemia, the bone marrow can't make
red blood cells fast enough to meet the body's needs.
 An increase in destruction and production of
erythrocytes can result in a compensated haemolytic
state without anaemia being present so a called
compensated haemolytic disease

6. Red cell destruction
Extravascular Intravascular
RES
Haem
Globin
Plasma
iron pool
Plasma
protein pool
Protoporphyrin
Expired CO Unconjugated
bilirubin
Liver
Conjugated
bilirubin
GI tract
Urobilinogen
Faeces
Urine
Free plasma Hb
Hb- Hpt
complex
Liver
Hpt and
Hpx
Haemopexin-
methem complx
Excess Hb
Kidney
Haemosiderin
uria
Haem+globin
Hb
methem
Hemogl
obinuria

7.  Hemolytic anemias are classified in a variety of
ways
1. Location of hemolysis
 INTRA VASCULAR (vascular space)
 EXTRA VASCULAR(reticuloendothelial
system)

8. 2) Source of defect causing hemolysis:
 Intra corpuscular defect
 Extra corpuscular defect
3) Mode of onset:
 Hereditary
 Acquired

9. Hereditary Acquired
a) Red cell Membrane defect
spherocytosis
elliptocytosis
a) Red cell Enzyme deficiency
G-6-PD deficiency
PK deficiency
a) Hemoglobin abnormalities
 Deficient globin synthesis
Thalassemias
 Structurally abnormal globins
[hemoglobinopathies]
sickle cell anemia
Unstable haemoglobins
a) Paroxysmal
nocturnal
hemoglobinuria
a) Infections

10. Immune haemolytic anaemia(antibody-mediated
destruction)
 Autoimmune haemolytic anaemia
Warm antibody auto immune haemolytic anaemia
Cold antibody auto immune haemolytic anaemia
Paroxysmal cold haemoglobinuria
 Alloimmune haemolytic anaemia
Haemolytic disease of the newborn
Haemolytic transfusion reactions : mismatched blood
transfusion

11. Microangiopathic haemolytic anaemia
 Disseminated intra vascular coagulation(DIC)
 Hemolytic uremic syndrome
 Thrombotic thrombocytopenic purpura
Sequestration(hyperspleenism & Spleenomegaly)
Drugs and chemicals

12. Physical/chemical trauma
 Thermal injury/burns
 March haemoglobinuria
Infections and infectious agents
 Malaria
 Clostridium infections
 Bartenellosis
 Cholera
 Animal venoms

13. Symtoms of Hemolysis
Paleness of skin
Fatigue
Fever
Confusion
Lightheadedness
Dizziness

14. Lab findings of Hemolytic Anemia
Hemoglobinuria & hemoglbinemia
Reticulocytosis
Peripheral smear- anisocytosis , poikilocytosis
Haptoglobin &hemopexin -decreased
Indirectbilirubin - increased.

15.  Increased serum and stored iron.
 Increased activity of bone marrow
(erythroid hyperplasia)
 Urine & feacal urobilinogen - elevated

16. Red cell Membrane defect

17. • The most common defect of red cell membrane due to
deficiency of cytoskeleton protein
- SPECTRIN
- ANKYRIN
- BAND 3
• Deficient of membrane protein causes change of shape
(round, no central pallor)
• Hereditary spherocytosis is caused by a genetic defect.

18.  RBCs: abnormally small, round without center
pallor.

19.  Osmotic fragility is increased there is shift of
curve to right

20.  Red cell membrane defect.
 Abnormality in the skeltal protien

21. Causes :
1. Defective spectrin chain
2. Abnormality in the integral protiens
3. Deficiency or defect in ‘band 4.1’
4. Abnormally permeable to Na
 Cells become elliptical due to the stress after
entering the microcirculation.
 Normal cells remains without any change.

22. RED CELL ENZYME DEFICIENCIES

23.  G-6-PD catalyses the conversion of g-6-phosphate
into ribulose 5 phosphate
 A deficiency of this enzyme reduces the ability of
RBCs to with strand the effect of various oxidising
drugs/agents, resulting in haemolytic anaemia
 Fava beans
 High fevers
 Severe infections
 Anti malarials-primaquine /quinine and choloroquine

25. Heinz bodies

26.  Pyruvate kinase deficiency is an autosomal recessive
disorder which causes congenital chronic hemolytic
anemia
 In pyruvate kinase deficiency ATP is not formed
 ATP is required for maintaining cell permeability.
 Potassium is lossed result in dehydration and
hemolysis.
 The peripheral blood film shows normocytic
normochromic anemia and increased reticulocytes

28. Hemoglobin abnormalities

29.  Substitution of valine in place
of glutamic acid at the 6th
position of β chain
 Mutant Hb is the Hb-S
 Hb-S : minimum solubility in
deoxygenated state.
 Deoxy Hb is formed and
polymerize
 RBC become stiff and sickle
shape
 Extravascular hemolysis

31.  Hb electrophoresis
 Sickling test
 HPLC: high –performance liquid chromatography is
useful for confirmation of diagnosis

32.  The thalassemia syndrome is a heterogeneous group
of inherited disorder in which one or more globin
chain synthesis is either absent or reduced.
 Thalassemia syndrome results in microcytic
hypochromic anemia due to decreased production of
hemoglobin with erythroid hyperplasia of the bone
marrow.
 The imbalance of globin synthesis causes an excess
of the normally produced globin chain. This results
in damage to red blood cells or their precursors and
hemolysis

33. Thalassemia syndrome is mainly of two types,
1. Alpha thalassemia
2. Beta thalassemia
β-THALASSEMIA
-Thalassemia major(homozygous)
-Thalassemia minor(trait)
-Thalassemia intermedia
α-THALASSEMIA
-Hydrops foetalis
-Hb-H disease
-α-thalassemia trait

34. THALASSEMIA ASOCIATED WITH OTHER
HAEMOGLOBINOPATHIES
-Hb-S thalassemia
-Hb-E thalassemia
-Hb-D thalassemia
-HPFH(Hereditary Persistence of Foetal Hb)

36.  Paroxysmal nocturnal hemoglobinuria is a rare ,
acquired , potentially life-threatening disease.
 Characterized by complement-induced intra vascular
hemolytic anemia(anemia due to destruction of red
blood cells in the blood stream),red urine(due to the
appearance of hemoglobin in the urine)
 It is the only hemolytic anemia caused by an intrinsic
defect in the cell
 It may develop on its own or in the context of other
bone marrow disorders such as aplastic anemia

38.  The gold standard is flow cytometry for CD55
and CD59 on red blood cells. Based on the levels
of these cell proteins, erythrocytes may be classified
as type I, II, or III PNH cells. Type I cells have
normal levels of CD55 and CD59; type II have
reduced levels; and type III have absent levels.The
fluorescein-labeled proaerolysin (FLAER) test is
being used more frequently to diagnose PNH on
WBCs (neutrophil and monocyte).

39. Immune haemolytic anaemia
 Immune haemolytic anaemia is a group of anaemia's in
which premature red cell destruction is mediated by
antibodies that bind to red cells.
 The antibodies may be either allo or auto antibodies
 The haemolysis is caused by extracorpuscular mechanism
 The site of haemolysis may be extravascular or
intravascular

40.  Alloimmune hemolytic anemia
 Hemolytic disease of new born
 Hemolytic transfusion reaction
 Autoimmune hemolytic anemia
 Warm antibody type (IgG antibodies active at 37Oc)
 Primary(idiopathic)
 Secondary
• Autoimmune disorders(systemic lupus
erythematosus

41.  In alloimmune hemolytic anemia allo-antibodies are
present either in serum or bound to red cells
Hemolytic disease of the new born(HDN)
 This is an immune hemolytic anemia which affects
the fetus and newborn baby

42.  It is due to maternal foetal blood group
incompatibility.
 HDN develops when mother lacks an antigen that
expressed by the foetal red cells
 HDN may be due to incompatibility of Rh type or
ABO group.

44.  Autoimmune hemolytic anemia(AIHA)are a group
of disorders in which antibodies against self-
antigens on the RBC membrane cause premature
destruction of RBCs.
 Interaction of the autoantibody with the red cell
antigen is dependent on the temperature, i.e. warm
or cold type.

45. Warm antibody type
 Warm antibody type is the most common type(50to
70%) of immunohemolytic anaemia
 This can be further divided into idiopathic
(primary)or secondary to drug exposure or
predisposing diseases.
 The antibodies are mainly of IgG type.
 The antibodies combine with red cell antigen at 34°c
(warm antibody).

46.  There IgG bound RBCs bind to Fc receptors on
phagocytes (macrophages)
 This remove part of red cell membrane with attached
antibody and hence known as “partial” phagocytosis.
 Progressive loss of membrane converts the red cells to
spherocytes.
 As in hereditary spherocytosis , the spleen is the
major site of removal and destruction of these
spherocytes , resulting in moderate splenomegaly..

47.  Antibodies bind to red cell antigens at low
temperature(4-18oc).
 The antibodies are of IgM type.
 It fixes complement and result in intra vascular
hemolysis

48. Clinical features
 Skin color turn white and then blue
 On rewarming it becomes red
 Numbness, tingling and pain
 Hemoglobinuria

49.  The autoantibodies are of IgG type and bind to red
cells at low temperatures and fix the complement.
 Massive, intermittent , acute haemolysis and
hemoglobinuria after cold exposure.
 Caused by biphasic IgG antibody (Donath-
Landsteiner antibody).
 It often follows viral infections and patient recover
within a month.

50.  Shear damage to red cells as the result of
endothelial cell activation/damage.
 Hallmark is presence of schistocytes on
the peripheral smear.

52. Causes :
- DIC=(DISSEMINATED INTRA VASCULAR
COAGULATION)
- TTP=(THROMBOTIC THROMBOCYTOPENIC
PURPURA)
- HUS=(HAEMOLYTIC UREMIC SYNDROME)

53.  HAEMOLYTIC UREMIC SYNDROME
 Damage to renal glomerular capillaries resulting in
agglutination of cells and thrombi formation
 THROMBOTIC THROMBOCYTOPENIC
PURPURA
 Haemolysis is due to the deposition of thrombi in
microcirculation
 DISSEMINATED INTRA VASCULAR
COAGULATION
 Activation of coagulation mechanism invivo by
thromboplastic substances resulting in the
deposition of fibrin in the microvasculature.
 RBC fragmentation due to stress produced by fibrin.

54.  Wintrobe’s haematology and clinical pathology
 Essentials in Hematology & Clinical pathology-
ramdas nayak ,sharada rai , astha gupta
 Practiacal pathology- Dr.k. uma chaturvedi, Dr
tejinder singh
 Text book of haematology by Mckenzie
 PARTICAL HEMATOLOGY-dacie and lewis