Hematology Lecture

1. HEMOLYTIC ANEMIA
6th
Approach for Hemolysis
Pathophysiology and Classification
PNH, HS
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2. Learning objectives
• ✓To define hemolysis
• ✓To classify hemolytic anemia
• ✓To differentiate between intravascular and extravascular
hemolysis
• ✓To list the clinical & laboratory features of hemolytic
anemia
• ✓To recognize PNH and hereditary spherocytosis
• ✓To identify splenectomy measures
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3. Approach to hemolytic diseases
HEMOLYTIC ANEMIA
results from an increasing red cell destruction
(decreased red cell lifespan)
RBCs are destroyed faster than the bone marrow
can produce them.
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4. Hemolytic anemia
•Manifestation
•Features of Increased Red Cell Destruction &
•Features of Increased Red Cell Production .
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6. Pathophysiology
1. Increased RBC destruction -anemia
2. Release of RBC contents- breakdown of Hb. –
catabolism to bile pigment- mild jaundice
3. Unconjugated is water insoluble (indirect
hyperbiliurbinemia) - not cross GFR-
acholuric jaundice
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7. Pathophysiology
4. Increase conjugation in liver –multiple
pigmented stones
5. Increase marrow erythroid activity-
reticulocytosis.
6. Marrow expansion &hyperplasia- bone
&skeletal changes
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8. Classification
• On etiology
• Inherited disorders
I. Genetic defect of hemoglobin
• Abnormal structure :SCD, Unstable Hb.
• Deficiency :Thalassemia .
II. RBC membrane abnormality (spherocytosis
elliptocytosis)
III. RBC metabolism abnormality (G6PDdeficiency,
pyruvate kinase deficiency)
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9. Classification
• Acquired disorders
I. Immune HA
I. Autoantibodies: (AIHA, warm and cold)
II. Alloantibodies: (incompatibility, HDN)
II. Non Immune HA
I. Mechanical:
• Traumatic &microangiopathic hemolysis
(MAHA):HUS,TTP,DIC
• prosthetic valves ,march hemoglobinuria
II. Infection: malaria, clostridial
III. Chemical/physical: copper, drugs, venoms, burn,drowning
IV. Acquired membrane abnormality: PNH .
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10. Classification
•On clinical presentation;
•Acute (favism)
•Chronic (spherocytosis)
•On site of hemolysis;
•Intravascular :(incompatibility, PNH, favism)
•Extravascular: (HS, thalassemia,immune)
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11. Intravascular hemolysis
•is the minor pathway
•Anemia
•Jaundice
•Hemoglobinemia
•Hemoglobinuria
•Hemosiderinuria
•splenomegaly is not
found
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12. Extravascular hemolysis
•It is the major pathogenesis mechanism
•Anemia
•Jaundice
•Splenomegaly:
•No evidence of hemoglobinemia and
hemoglobinuria
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13. Extravascular haemolysis
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14. Clinical features of HA
1. Anemia; chronic congenital- mild ,moderate.
Acute attack – severe
2. Jaundice; mild: risk in neonates-kerinkterus.
No bilirubin in urine.
3. Splenomegaly: extravascular destruction.
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15. Clinical features of HA
4. Cholethiasis: Biliary colic ,cholangitis or
Asymptomatic
5. Aplstic crisis;
chronic congenital hemolysis.
Transient arrest in RBC production due to
parvo virus B19 infection
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16. Clinical features of HA
6. Leg ulcers; chronic
congenital
hemolysis,
sluggish flow in
capillaries.
HS&SCD.
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17. Clinical features of HA
7. Skeletal changes;
skull bossing,
zygomatic
prominence,
maxillary ,dental
abnormalities.
Enlarging
metacarpals bones
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18. Laboratory features
1. Excess RBC destruction
1. Increase S.bilirubin (indirect) <5mg/dl
2. Increase S.LDH
3. Low or absent S. haptoglobin.
4. Increase urobilinogen in urine,
5. no bilirubin in urine.
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19. Laboratory features
2. Intravascular hemolysis
1. Hemoglobinemia;red color plasma
2. Hemoglobinuria; pink –dark color urine
( no microscopic RBC)
3. Haemosiderinuria; proximal tubules iron re
absorption
4. Met-hemalbuminemia; coffee brown plasma
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20. Laboratory features
3. Accelerated erythropoiesis
1. Reticulocytosis.
2. Polychromasia,macrocytosis, nucleated
RBC,LEP.
3. Thrombocytosis,leucocytosis.
4. BM erythroid hyperplasia
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21. Laboratory features
4. Radiological features
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22. Erythrocyte membrane defect
Disturbances (quantities
or function);
Extravascular RBC
destruction –hemolysis
or loss of part of
membrane
•Classification according
to shape; (spherocyte ,
elleptocyte, stomatocyte)
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23. Hereditary spherocytosis
•most common hereditary membrane defect
•Deficiency in β spectrin or anykrin
•Autosomal dominant.
•75%,+ve FH
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24. Clinical Presentation
1. At childhood, commonly manifested: chronic mild –
moderate HA
Anemia, jaundice, gall stone, splenomegaly, bone
changes
2. At neonatal ,prolonged neonatal jaundice (1st wk)
3. Delayed presentation at adulthood (6th decade)
4. Asymptomatic until-----------pregnancy
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25. Clinical Presentation
•It is chronic mild compensated hemolysis, may
exacerbated by attack of
•haemolytic crisis: acute severe (infection,
vaccination).
•Aplastic crisis
•Megaloblastic crisis
•Leg ulcers
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26. Investigation
•Features of extravascular hemolysis
•CBC; anemia ,spherocytes,
polychromasia, reticulocytosis
•Eosin-5-maleimide (EMA) Binding
Test
•Osmotic fragility test; increased
sensitivity to lysis if incubated in
hypotonic saline. (diagnosis & screen)
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27. Differential diagnosis
1. Immune hemolytic
anemia; +ve Coomb’s
2. HDN (neonatal
jaundice)
Treatment:
1. Folic acid ; 5mg/week. Life
long. Alleviate anemia &
prevent megloblastic anemia
2. Blood transfusion in acute
hemolytic complication.
3. Exchange transfusion in
neonate
4. splenectomy .
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28. Splenectomy
oCorrect anemia, improve RBC survival, relieve
jaundice
• Indications:
1. severe chronic hemolysis
2. recurrent acute hemolytic crisis or acute aplastic
crisis.
3. cholecystitis or biliary colic.
4. Severe disease in other affected family member.
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29. Preparation & complications
oDelayed after 9-10 yrs.
o preoperative vaccine against encapsulated mo
• Streptococcus pneumonia
• Hemophilius influenza -B.
• Neisseria meningitidies-C
• & influenza
 long term prophylaxis : Risk of infection, sepsis, malaria,
 Thrombocytosis ; risk of thrombosis.
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30. Paroxysmal Nocturnal Hemoglobinuria
(PNH)
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31. Paroxysmal Nocturnal Hemoglobinuria
(PNH)
•acquired mutation in stem cells leading to defect in
red cell membrane and other blood cells .
•Deficiency of GPI protein (CD55,CD59) in RBC
membrane
•Susceptible to intravascular lysis by complement
activation.
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32. Paroxysmal Nocturnal Hemoglobinuria
(PNH)
•Rare
•Young adult, both sexes, overlap with AA
•chronic intravascular hemolysis (episodic), dark
urine(coca)
•Chronic anemia
•Jaundice
•Pancytopenia
•Thrombosis.
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33. Paroxysmal nocturnal hemoglobinuria
PNH
• Flow cytometry:
lack of CD 55,CD 59.
• HAM test (acidified serum
lysis test),
• Folate,iron, transfusion,
anticoagulation,
SC transplantation
• Eculizumab: anti C5
• MDS,AML
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