Classification of Hemolytic anemias Classification of Hemolytic anemias I. Red cell abnormality (Intracorpuscular factors) I. Red cell abnormality (Intracorpuscular factors) A. Hereditary A. Hereditary 1. Membrane defect (spherocytosis, elliptocytosis) 1. Membrane defect (spherocytosis, elliptocytosis) 2. Metabolic defect (Glucoze-6-Phosphate-Dehydrogenaze 2. Metabolic defect (Glucoze-6-Phosphate-Dehydrogenaze (G6PD) (G6PD) deficiency, Pyruvate kinase (PK) deficiency) deficiency, Pyruvate kinase (PK) deficiency) 3. Hemoglobinopathies (unstable hemoglobins, 3. Hemoglobinopathies (unstable hemoglobins, thalassemias, sickle cell anemia ) thalassemias, sickle cell anemia ) B. Acquired B. Acquired 1. Membrane abnormality-paroxysmal nocturnal 1. Membrane abnormality-paroxysmal nocturnal hemoglobinuria (PNH) hemoglobinuria (PNH)
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Classification of Hemolytic anemias I. Red cell abnormality (Intracorpuscular factors) A. Hereditary 1. Membrane defect (spherocytosis, elliptocytosis)
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Classification of Hemolytic anemias Classification of Hemolytic anemias
- red cells destruction occurs in reticuloendothelial system - red cells destruction occurs in reticuloendothelial system - clinical states associated with extravascular hemolysis :- clinical states associated with extravascular hemolysis : autoimmune hemolysis autoimmune hemolysis delayed hemolytic transfusion reactions delayed hemolytic transfusion reactions hemoglobinopathies hemoglobinopathies hereditary spherocytosis hereditary spherocytosis hypersplenism hypersplenism hemolysis with liver disease hemolysis with liver disease- laboratory signs of extravascular hemolysis:- laboratory signs of extravascular hemolysis: indirect hyperbilirubinemia indirect hyperbilirubinemia increased excretion of bilirubin by bile increased excretion of bilirubin by bile erythroid hyperplasia erythroid hyperplasia hemosiderosis hemosiderosis
1. Pathogenesis1. Pathogenesis - an acquired clonal disease, arising from a somatic mutation in a - an acquired clonal disease, arising from a somatic mutation in a
single abnormal stem cell single abnormal stem cell - glycosyl-phosphatidyl- inositol (GPI) anchor abnormality - glycosyl-phosphatidyl- inositol (GPI) anchor abnormality - deficiency of the GPI anchored membrane proteins - deficiency of the GPI anchored membrane proteins (decay-accelerating factor =CD55 and a membrane inhibitor (decay-accelerating factor =CD55 and a membrane inhibitor of reactive lysis =CD59) of reactive lysis =CD59) - red cells are more sensitive to the lytic effect of complement - red cells are more sensitive to the lytic effect of complement - intravascular hemolysis - intravascular hemolysis 2. Symptoms2. Symptoms - passage of dark brown urine in the morning - passage of dark brown urine in the morning
3. PNH –laboratory features:3. PNH –laboratory features: - pancytopenia - pancytopenia - chronic urinary iron loss - chronic urinary iron loss - serum iron concentration decreased - serum iron concentration decreased - hemoglobinuria - hemoglobinuria - hemosiderinuria - hemosiderinuria - positive Ham’s test (acid hemolysis test) - positive Ham’s test (acid hemolysis test) - positive sugar-water test - positive sugar-water test - specific immunophenotype of erytrocytes (CD59, CD55) - specific immunophenotype of erytrocytes (CD59, CD55)
4. Treatment4. Treatment:: - washed RBC transfusion - washed RBC transfusion - iron therapy - iron therapy - allogenic bone marrow transplantation - allogenic bone marrow transplantation
SICKLE CELL ANEMIA
Definition: chronic hemolytic anemia occuring almost exclusively in blacks and characterized by sickle-shaped red cells(RBCs) caused by homozygous inheritance of Hemoglobin S
SICKLE CELL ANEMIA-pathogenesis
- In Hb S, valine is substituted for glutamic acid in
the sixth amino acid of the ß chain.
- Deoxy-Hb S is much less soluble than deoxy Hb A;
it forms a gelatinous network of fibrous polymersthat cause RBCs to
sickle at sites of low pO2.
- Hemolysis-because sickle RBCs are too fragile to withstand the
mechanical trauma of circulation
- Occlusion in microvascular circulation caused by distorted, inflexible
RBCs adhering to vascular endothelium
SICKLE CELL ANEMIA-incidence
- Homozygous - about 0,3% of blacks in the USA
(have sickle cell anemia)
- Hetezygotes-8-13% of blacks, (are not anemic, but the sickling trait=sicklemia can be demonstrated in vitro)
SICKLE CELL ANEMIA-clinical featuresIN HOMOZYGOTES1. Clinical complications due to severe hemolytic anaemia
- slowed growth and development in children - bilirubins stones- aplastic crisis- congestive heart failure from chronic anemias and cardiac
overload compensation2. Consequences of vaso-occlusion of the microcirculations (tissue
ischemia and infarction)- infarction of spleen, brain, marrow, kidney, lung, aseptic
necrosis, central nervous system and ophtalmic vascular lesions
SICKLE CELL ANEMIA-laboratory findinges
1. Anemia-normocytic or slightly macrocytic
2. Leukocytosis(chronic neutrophilia)
3. Thrombocytosis-usually mild<1000G/l
4. Reticulocytosis
5. Peripheral smear: sickle shaped red cells, polychromatophilia, Howell-Jolly bodies
6. Hb -electrophoresis
SICKLE CELL ANEMIA-therapy
Preventive measures:
prevention or remedy of: infections(penicillin prophylaxis and pneumococcal vaccination), fever, dehydratation,acidosis, hypoxemia, cold exposure
Blood transfusions for very severe anemia
New approaches to therapy;
1. Activation of Hb F synthesis -5-azacytidine
2. Antisickling agents acting on hemoglobin or membrane