Hemolytic Anemias
Dr. Akram Al-Hilali 2010
08/05/14
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Definition of Hemolytic Anemia ď Ž Anemia caused basically by significant
shortening of red cell life span. ď Ž There are cases where hemolysis, or shortening of life span is not the basic cause of the anemia. ď Ž There are cases where there is mild hemolysis, not leading to anemia because bone marrow increases production sufficiently to compensate. 08/05/14
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What causes a red cell to lyse? Abnormal red cell structure. Abnormal membrane structure. Abnormal Hb structure that can lead to deformity in shape. Imbalance in peptide synthesis leading to deposition of the excess type. Loss of red cell resistance to complement effect. Abnormal red cell metabolism In the glycolytic pathway In the pentose phosphate shunt. Peripheral factors damaging the red cell. Antibodies Mechanical Involvement in micro clots 08/05/14
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Hemolysis due to abnormal membrane structure Inherited defect in membrane Hereditary
spherocytosis Some cases of hereditary elliptocytosis Hereditary pyropoikilocytosis Hereditary acanthocytosis Stomatocytosis
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Hemolytic anemia due to abnormal structure of hemoglobin Abnormal Hb structure may sometimes
deform the red cell and thus lead to hemolysis Inherited Hb molecule structural abnormality
Sickle anemia
SS disease S-Beta thalassemia SC combination
Hb C disease HbE disease
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Imbalanced Peptide Synthesis (Thalassemia) α thalassemia (α chain suppressed)
β chains will become excess and precipitate within red cells.
β thalassemias (β chain suppressed)
α chain will be in excess and precipitate within red cells.
Spleen removes the excess chains, leading to
deformity of red cells and microcytosis. Many cells will be destroyed in the process. 08/05/14
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Abnormal Sensitivity to Complement This is PNH (paroxysmal Nocturnal
Hemoglobinuria) Red cells normally have on their surfaces molecules that protect them from complement action. These molecules are diminished or absent in PNH. This is due to an acquired mutation in the stem cells. 08/05/14
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Hemolysis due to abnormal metabolism Metabolism produces energy to keep cell membrane
intact. If metabolism fails to give energy to preserve integrity of membrane cells will lyse earlier than normal. Most famous hemolytic anemia in this category is that due to G6PD deficiency and rare related disorders. Abrupt oxidation will make the available G6PD (which is low) unable to cope. This could be on ingestion of oxidizing drug or broad beans. Others include Pyruvate kinase deficiency and related disorders.
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Peripheral Factors Damaging Red Cells ANTIBODIES Auto-immune Allo-immune CHEMICAL FACTORS Oxidizing poisons Oxidizing drugs, in presence of G6PD deficiency MECHANICAL FACTORS Abnormal cardiac valve anatomy. DISSEMINATED THROMBOTIC CONDITIONS. Vasculitis Hemolytic uremic syndrome Thrombotic thrombocytopenic purpura 08/05/14
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Hemolysis by Antibodies Produced by patient’s own immune system
against own red cells (auto-immune hemolytic anemia). Produced by patient’s immune system but against transfused red cells (allo-immune hemolysis) Produced by mother or donor and act against patient’s red cells (allo-immune hemolysis). Hemolysis is extra vascular, unless antibody fixes complement 08/05/14
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Special Features in Immune HA Spherocytes may be seen in
film. Autoagglutination may be seen in film. Direct Coombs test is positive in most. 08/05/14
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Chemical Factors causing Hemolysis In presence of G6PD deficiency. Direct destruction of cells by chemical agent,
usually potent oxidant poison like phenol and phenolic acid, moth balls, etc The red cell has a healing process that can counteract mild poisons but not when in big doses or if they are potent. Hemolysis is intravascular.
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Mechanical Hemolytic Anemias Red cells are damaged while passing, under
pressure through fine apertures. This usually occurs after surgical intervention with distorted cardiac valves (repair) or from distorted, calcified cardiac valves. Red cells are cut into schistocytes, some of which lyse immediately, while others stay in the circulation for a while. No coagulopathy is involved and platelets are not consumed in the process. Hemolysis is intravascular
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Disseminated Thrombotic conditions leading to red cell Hemolysis
Microthrombi could occur due to inflammation of
vessel wall (vasculitis) They could be started by damage to vessel wall by immune process. Emboli of cancer or amniotic fluid can cause thrombi. Thrombi will consume platelets and fibrin threads can cut red cells. Abnormal platelet adhesion to vessel wall can start them (TTP) Schistocytes and thrombocytopenia are the common features. Hemolysis is intravascular
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Features common to all Hemolytic Anemias All Hemolytic Anemias Anemia Reticulocytosis Polychromasia Basophilic stippling Erythroblastosis in severe cases High bilirubin High LDH in serum Low haptoglobins 08/05/14
Specific for intravascular hemolysis Hemoglobinuria Hemosiderinuria Schistocytes in most
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