Hemolytic Anemias

Three essential features

Premature destruction of red cells and a
shortened red cell life span
Elevated erythropoietin levels and a
compensatory increase in erythropoiesis
Accumulation of hemoglobin degradation
products

Pathogenesis and classification

Acute and Chronic (clinical classification)
Inherited or Acquired
Sites of red cell destruction
Intravascular
Extravascular (tissue macrophages,mainly spleen)

Nature of defect
Intrinsic /intracorpuscular RBC abnormality
(Usually inherited,exception PNH)
Extrinsic abnormality /extracorpuscular

Etiologic and pathogenetic

classification scheme
Inherited hemolytic disorders
Defects in the erythrocyte membrane (hereditary
spherocytosis,elliptocytosis,stomatocytosis etc)
Hereditary enzyme deficiency (disorders of HMP
shunt,G6PD def, PK deficiency etc)
Inherited disorders of Hb or synthesis (Unstable
Hb disorders,sickle cell,thalassemia syndromes,
other homozygous hemoglobinopathies)

Etiologic and pathogenetic

classification scheme
Acquired Hemolytic anemia (classified on the
basis of extrinsic factor causing hemolysis)
Immune causes
Auto-immune acquired Hemolytic anemia
Hemolytic disease of new born
Incompatible blood transfusion

 Non-immune causes
Mechanical hemolytic anemia
(cardiac,microangiopathic,march hemoglobinuria)
Miscellaneous (infectious agents,physical
agents,chemical agents,hypophosphatemia,liver
disease etc)

Paroxysmal Nocturnal Hemoglobinuria

(acquired hemolytic but intrinsic red cell abn)

porphyrin globin
bilirubin
bilirubin

Enterohepatic
circulation

Conjugated
bilirubin

urobilinogen

stercobilinogen

Urobilinogen
Urinary
elimination
Fecal elimination

Sites of destruction of red

cells:Extravascular and
intravascular
Extravascular : RE system
Red cells become less
deformable or are
identified as Foreign
Spleen is the major assasin

Significant intravascular destruction

PNH
Associated with certain infections
Blackwater fever
Clostridial sepsis

Chemical agents
Thermal injury

Clinical features of congenital

hemolytic anemias

Degree of anemia
Jaundice
Aplastic crisis
Splenomegaly
Cholelithiasis
Leg ulcers
Skeletal abnormalities

Splenomegaly in hereditary spherocytosis

Clinical features of acquired hemolytic

anemias
Onset mainly acute,may also be insidious
After transfusion of incompatible blood or
after exposure to drugs
Aching pain back,abdomen,limbs
Pallour
Jaundice
Trachycardia

Lab features of hemolysis

Signs of increased red cell destruction
Increased indirect s.bilirubin
Increased serum LDH
Decreased serum haptoglobin
Decreased RBC survival
Increased rate of CO production

Signs of intravascular hemolysis

Hemoglobinemia
Hemoglobinuria
Hemosiderinuria
Decreased hemopexin
Methemalbuminemia
Increased serum bilirubin

Signs of accelerated erythropoeisis

Reticulocytosis
Macrocytosis
Polychromatophilia
Basophilic stippling
Erythroblastosis
Abnormal red cell forms,autoagglutination
Bone marrow:erythroid hyperplasia

Morphological abn in hemolytic

anemia
Cell

Description

Disorder

Spherocyte

Spheric

HS,IHA,Burns

Elliptocyte

OVal

HE,Megaloblastic a

Stomatocyte

Uniconcave,slit like pallour

Her
stomatocytosis,alcoholism

Acanthocytes,

irregular spicules

Spur cell anemia

Echinocytes

Regular,even,excess
spicules

Uremia

Sickle cell

crescent

SC Anemia

Target cell

Solid area in central pallor

Thalasemia,HbC,liver
disease

Schistocyte

Triangular,helmet shaped

Microangiopathic
anemia,HUS

Bite cells,ghost cells

G6PD

Specific tests

Osmotic fragility
Coombs test
Heinz Body determination
Hb electrophoresis/HPLC

100

% of hemolysis

75
50
25

80 70 60 50 40

30

% of NaCl

20

10

Anti-Globulin (Coombs) Testing

Direct antiglobulin testing

+
Patients RBCs

Anti-C3d
Anti-IgG

Indirect antiglobulin testing

+
Patients serum RBCs

+
Anti-IgG

 To be differentiated from
Post haemorrhagic anemia
Recovery from nutritional deficiency anemia
Recovery from marrow failure

Look for signs of hemolysis to establish a

diagnosis of hemolytic anemia