Post on 06-Nov-2015
description
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