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)

globin porphyrin

bilirubin

bilirubin

Conjugated bilirubin

urobilinogen

Urobilinogen Urinary elimination

stercobilinogen Fecal elimination

Enterohepatic circulation

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

80 50 70 60 30 40 20 10

25

100

75

50

% of NaCl

% o

f hem

oly

sis

Anti-Globulin (Coombs) Testing Direct antiglobulin testing

Indirect antiglobulin testing

Patients RBCs

Patients serum

Anti-C3d

Anti-IgG

+

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