1. Hemolytic anemia
Premature destruction of
circulating RBC

2. Types
 Hereditary-
 Hemoglobinopathy- thalassemia, sickle cell disease
 Defective RBC membrane- hereditary spherocytosis
 Defective RBC metabolism- G-6-PD deficiency
 Acquired-
 Immune mediated- AIHA-warm/cold Ab/drugs, PNH
 Hypersplenism
 Physical trauma- DIC, TTP, prosthetic valve

3. Common features
 Anemia- depends on RBC destruction &
BM compensation
 Spherocytes on PBS
 Reticulocyte count- raised
 Jaundice- raised indirect bilirubin
 Urobilinogen in urine
 LDH elevated, haptoglobin low

4. Further
 Thalassemia
 Sickle cell anemia
 Hereditary spherocytosis
 G-6-PD deficiency
 AIHA
 PNH

5. Thalassemia
 Hereditary disorder- autosomal recessive
 Mutation abolishing one or more globin chain
production- α or β
 Heterozygous- trait, homozygous- disease
 1 or 2 α allele –nt- α-thalassemia trait
 3 α allele –nt- HbH- β4- uncommon
 4 α allele –nt- Hb Barts- γ4- death in-utero- hydrops foetalis
 β heterozygote- trait- asymptomatic
 β homozygote- β-thalassemia

6. Clinical
 Homozygotes have anemia
 RBC- microcytic, hypochromic, target cells
 Dx- Hb electrophoresis- raised HbA2 >4%
(HbA- α2β2, HbA2- α2δ2, HbF- α2γ2)
 Rx- PRBC transfusion, no iron therapyno iron therapy
 Death- transfusion related iron overload &
other complications
 Prevention- genetic counseling &
in-utero fetal blood sampling

7. Sickle cell disease
 Hereditary disorder, autosomal recessive
 Due to mutation at position 6 in β-globin chain
replacing glutaminevaline
 Heterozygote- trait, homozygote- disease
 Characteristic sickle cells, due to
deoxygenated HbS polymers
 Sickling promoted by low O2/pH, fever,
sluggish blood flow, raised s. osmolality

8. Clinical features
 Occlusion of blood vessels by stiff sickled
RBC, causing-
 Vaso-occlusive painful crisis in bones, chest, abdomen, spleen
 Autsplenism due to repeated infarctions & fibrosis- increases
susceptibility to infection with encapsulated bacteria
 CVA
 Proliferative retinopathyretinal detachmentblindness
 Priapism, renal papillary necrosis,
spontaneous painless hematuria
 Aseptic necrosis of femoral head
 Non-healing leg & ankle ulcers

9. continued
 Hemolysis of sickled cell, causing-
 Anemia, jaundice, hepatomegaly,
raised cardiac output, gallstones
 Aplastic crisis- erythroid aplasia,
due to parvovirus B19, lasting 7-10 days
 Increased risk of infection-
 Sepsis, pneumonia, meningitis,
osteomyelitis (Salmonella)

10. Management
 Dx-
 Suspected- PBS showing sickle cells
 Confirmed- HB electrophoresis
 Antenatal- PCR in CVS/amniotic fluid cells
 Rx-
 Vaso-occlusive crisis- hydration, oxygen, opioid analgesics,
look for & treat infection
 Aplastic crisis- PRBC transfusion
 Chronic transfusion programme after CVA
 Hydroxyurea, increases HbF
 Folic acid supplementation
 Supportive treatment
 PBSCT, if successful, is curative

11. Hereditary spherocytosis
 Autosomal dominant
 Quantitative deficiency of spectrin/ankyrin
 RBC become small, spherocytic,
poorly deformable
 C/F- anemia, jaundice, splenomegaly
 Hemolytic or aplastic crisis may occur
 Dx- +ve osmotic fragility test,
-ve Coomb’s test
 Rx- splenectomy

12. G-6-PD deficiency
 G-6-PD- an enzyme of pentose phosphate
pathway
 X-linked recessive, seen in males only
 Prediposes RBC to oxidative stress induced
hemolysis
 Oxidative drugs-
 Sulpha drugs, primaquine, NFT, nitrates, doxorubicin
 Dx- RBC G-6-PD assay
 Rx- avoid drugs mentioned

13. Auto-immune hemolytic anemia
 Hemolysis due to warm antibodies
 Idiopathic or secondary (CLL, NHL, SLE)
 Insidious- anemia, jaundice, s’megaly or
Sudden- profound anemia, abdomen/back
pain, darkened urine-hemoglobinuria
 Dx- +ve direct Coomb’s test
 Rx-
 Steroids
 Splenectomy
 Azathioprine/cyclophosphamide- steroid sparing
 Transfusion, in life-threatening situations

14. PNH
 Paroxysmal nocturnal hemoglobinuria
 An acquired clonal disorder, with
susceptibility of RBC to complement lysis
 Causes chronic hemolytic anemia with
hemosiderinuria leading to iron deficiency
 Causes venous thrombosis- DVT,
hepatic/portal/mesenteric/cerebral vein
 May be associated with aplastic anemia

15. Management
 Dx-
 Sucrose lysis testHam’s acidified serum lysis test
 CD55/59 by flow-cytometry, on RBC/WBC
 Rx-
 Steroids for acute hemolytic crisis
 Eculizumab prevents hemolysis by inhibiting
complement system
 Iron & FA supplementation
 Warfarin to prevent thrombosis