Classification on hereditary and acquired basis as well as Intra and extra vascular Hemolysis by solomon suasb mphil student uhs Lahore Pakistan

1. Overview of Hemolytic
Anemia.
i-e Intra & Extravascular
Hemolysis
Usman Ali Shams
MLS M-Phil HaematoTechnology
University of Health Sciences Lahore

2. Learning Outcomes
• In the end of the session students will be able to.
• Describe Normal RBC Destruction
• Briefly elaborate the Hemolytic Anemias.
• Classify the hemolytic Anemias.
• Describe Intra and Extra Vascular Hemolysis

3. Contents
• Normal RBC Destruction
• Introduction to Hemolytic Anemia.
• Classification of Hemolytic Anemia.
• Acquired and Hereditary Hemolytic Anemia.
• Intra and Extra Vascular Hemolysis.
• Classification of Intra and Extravascular Hemolysis.

4. Introduction to RBC Normal Destruction
• Red cell destruction usually occurs after a mean lifespan of 120 days when the cells
are removed extravascularly by the macrophages of the reticuloendothelial (RE)
system.
• The main sites of normal RBC destruction are mainly in marrow but also in the liver
and spleen.
• As we know that RBC has no command center i-e Nucleus, so the RBC metabolism
become progressively Worse as enzyme are degraded and finally the cell has no
capability of survival.

5. Normal RBC Destruction
• The breakdown of Haem from hemoglobin liberates iron for recirculation via plasma
transferrin mainly to marrow erythroblasts.
• Protoporphyrin, which is broken down to bilirubin. Bilirubin circulates to the liver
where it is conjugated to glucuronides, which are excreted into the gut via bile and
converted to stercobilinogen and stercobilin(excreted in feaces)
• Stercobilinogen and stercobilin are partly reabsorbed and excreted in urine as
urobilinogen and urobilin.
• Globin chains are broken down to amino acids which are reutilized for general
protein synthesis in the body.

6. Normal RBC Destruction
Haem
Globin
Iron
Protopho-
rphryin
Amino
Acid
Protein
Synthesis
Marrow
Erythroblas
t
Via Transferrin
Unconjugate
d Bilirubin
Conjugat
ed
Bilirubin
RBC
Liver
Exreted
through
Gut via
Bile
Bilirubin
Gluconari
des
Stercobilin
Stercobilin
ogen
urobilinog
en &
urobilin
Re-Absorbed
In kidey

8. Introduction to hemolytic anemias
• Hemolytic anemias are defined as anemias that result from an increase in the rate of
immature red cell destruction.
• Because of erythropoietic hyperplasia and anatomical extension of bone marrow, red
cell destruction may be increased several‐fold before the patient becomes anemic.
• The normal adult marrow, after full expansion, is able to produce red cells at 6–8
times the normal rate provided.
• Therefore, anemia due to hemolysis may not be seen until the red cell lifespan is less
than 30 days.

9. Clinical features of Hemolytic Anemia
• Pallor of the mucous membranes
• Mild fluctuating jaundice and splenomegaly
• There is no bilirubin in urine, but this may turn dark on standing because of
excess urobilinogen.
• Pigment (bilirubin) gallstones may complicate the condition
• Some patients (particularly with sickle cell disease) develop ulcers around
the ankle.
• Aplastic crises may occur, usually precipitated by infection with parvovirus
which ‘switches off’ erythropoiesis and are characterized by a sudden
increase in anemia and drop in reticulocyte count.

10. Laboratory findings
Can be divided into three categories.
1) Features of increased red cell breakdown:
(a) serum bilirubin raised, unconjugated and bound to albumin;
(b) urine urinobilinogen increased;
(c) serum haptoglobins absent because the haptoglobins become
saturated with hemoglobin and the complex is removed by RE cells.

11. 2) Features of increased red cell production:
(a) Reticulocytosis;
(b) Bone marrow erythroid hyperplasia; the normal marrow myeloid:erythoid
ratio of 2 :1 to 12 :1 is reduced to 1:1 or reversed.
Laboratory findings CONT….

12. Laboratory findings CONT….
3) Damaged red cells:
(a) morphology (e.g., micro spherocytes, elliptocytes, fragments);
(b) osmotic fragility;
(c) specific enzyme, protein or DNA tests.

13. Laboratory Finding CONT……..

14. Classification of Hemolytic anemia
Hemolytic
anemia
Hereditary
Hemolytic
anemia
‘intrinsic’ red
cell defects
Acquired
Hemolytic
Anemia
‘extra
corpuscular’ or
‘environmental’

15. Classification
based on
Hereditary
&
Acquired
Causes

17. Hereditary Hemolytic Anemia
Hereditary Hemolytic
Anemia
Membranopathies
Hereditary Spherocytosis
Hereditary Elliptocytosis
Stomatocytosis
South East Asian ovalocytosis
Enzymopathies
G6PD Deficiency,
Pyruvate Kinase Defiance
Hemoglobinopathies
Quantitative Defect:
Thalassemia
Qualitative Defect:
HbS, HbE, HbD, HbC

18. Acquired Hemolytic Anemia
AcquiredHemolytic
Anemia
Immune
Mediated
Auto-Immune
Allo-Immune
Non-Immune
Mediated
Red cell Fragmentation
Syndrome
Infection i-e
Malaria, Clostridia
March Hemoglobinuria
Chemical & Physical Agents ,Drugs,
Industrial, Domestic Substance,
Burns
Secondary disease i-e
Liver and Renal Disease
Paroxysmal nocturnal
hemoglobinuria PNH

19. ImmuneMediated
Auto-Immune
Warm antibody type
Idiopathic Secondary SLE
CLL, Lymphomas, Drugs
(MethylDopa)
Cold antibody type
Idiopathic Secondary
Infection Mycoplasma Pneumonia,
Infectious Mononucleosis,
Lymphomas
Paroxysmal Cold Hemoglobinuria
Allo-Immune
Induced by Red Cell
Antigen
Hemolytic Transfusion
Reaction HTR
HDN & Post Stem Cell grafts
Drug Induced
Drug Red cell membrane
Complex
Immune Complex

20. ExtraVascular Hemolysis
• Extravascular hemolysis occurs when RBCs are phagocytized by macrophages in the
spleen, liver and bone marrow.
• During the normal aging of red blood cells in the circulation, effete RBCs are destroyed
by macrophages, i.e. extravascular hemolysis is always occurring to some degree in our
body when RBCs have finished living.

21. • With extravascular hemolysis, the erythrocytes are degraded within
macrophages.
• Hemoglobin is not released free into the cytoplasm. Thus, we do not see
hemoglobinemia or hemoglobinuria with extravascular hemolysis alone,
unless it is accompanied by intravascular hemolysis.
ExtraVascular Hemolysis

22. ExtraVascular Hemolysis CAUSES
• Immune-mediated hemolytic anemia.
Attachment of IgG or IgM causes fixation of complement (to C3b) on red cell
membranes.
• Erythroparasites.
• Mycoplasma haemofelis (feline infectious anemia)
• Oxidant injury.
Oxidant injury (e.g. acetaminophen toxicity in cats) can result in extravascular
hemolysis.
• Histiocytic disorders.
Normal RBC being Destructed by macrophages being stimulated by cytokines.
• Inherited red blood cell defects,
Inherited defects of RBC enzymes (e.g. pyruvate kinase deficiency

23. Intravascular Hemolysis
• Intravascular hemolysis results from the rupture or lysis of RBC within the
circulation, i.e. the RBC are lysing in vivo.
• In Intravascular haemolysis, free haemoglobin is released which rapidly
saturates plasma haptoglobins and the excess free haemoglobin is
filtered by the glomerulus.
• If the rate of haemolysis saturates the renal tubular reabsorptive capacity,
free haemoglobin enters urine.
• Iron released from haemoglobin in the renal tubules is seen as
haemosiderin in a urinary deposit.

24. IntraVascular Hemolysis CONT…..
Laboratory Features of Intravascular Hemolysis are.
1 Haemoglobinaemia and haemoglobinuria.
2 Haemosiderinuria.
3 Methaemalbuminaemia (detected spectrophotometrically).

25. • Mismatched blood transfusion (usually ABO)
• G6PD deficiency with oxidant stress
• Red cell fragmentation syndromes
• Some severe autoimmune haemolytic anaemias
• Some drug‐ and infection‐induced haemolytic anaemias
• Paroxysmal nocturnal haemoglobinuria
• March haemoglobinuria
• Unstable haemoglobin
IntraVascular Hemolysis CAUSES

27. Classification
Based on
Intra and Extra
Vascular Hemolysis

28. Hemolysis on basis of Intra and Extravascular
Hemolysis
Extravascular
(Spleen & RES Mediated)
Hemolysis
Intrinsic to RBC
Extrinsic to RBC
Intravascular
(Hemolysis within
Circulation)
Infections
Complement Mediated
Mechanical Shearing

29. Extravascular Hemolysis CONT…..
Extrinsic to
RBC
Immune
Mediated
Warm Auto-
Immune
Hemolytic Anemia
Cold Auto-
Immune
Hemolytic Anemia
Allo-immune
Delayed HTR
Drug-Induced
HTR

30. Extravascular Hemolysis CONT…..
Intrinsic to RBC
Abnormal HGb and HGb
Defect
Thalassemia
Sickle cell
Membrane Defect
Hereditary Spherocytosis
Elliptocytosis
Southeast Asian
ovalocytosis
RBC Enzyme Defect
G6PD Deficiency
PK Deficiency

31. Intravascular Hemolysis
Intravascular
Hemolysis
Infections
Malaria
Babesiosis
C. Perfringes
Complement
Mediated
Cold AIHA
Paroxysmal Cold hemoglobinuria PCH
Paroxysmal nocturnal hemoglobinuria
PNH
Drug Induced Immune Complex
hemolytic anemia
Acute HTR
Mechanical
Shearing
MAHA (TTP, DIC, HUS)
Prosthetic Heart Valves
Arteriovenous Malformations