§ Intrinsic red blood cell abnormalities
definition:
Defects intrinsic to the RBC that can cause hemolysis involve abnormalities of the RBC membrane, cell metabolism, or hemoglobin structure. Abnormalities include hereditary cell membrane disorders, acquired cell membrane disorders), disorders of RBC metabolism). Quantitative and functional abnormalities of certain RBC membrane proteins (alpha- and beta-spectrin, protein 4.1, F-actin, ankyrin) cause hemolytic anemias.
o Sickle cell anemia and other sickling syndromes
Homozygosity for a unique hemoglobin gene mutation (HBB glu6val, GAG —> GTG, sickle hemoglobin, HbS), located on chromosome 11, causes sickle cell anemia (SCA). Upon deoxygenation, HbS molecules polymerize into intracellular fibers, forming a high molecular weight gel and causing the sickle cell deformity. This process initiates an elaborate and incompletely understood pathophysiological cascade that includes injury to the sickle red cell; intravascular and extravascular hemolysis; adhesive interactions among sickle cells, endothelial cells, other blood cells, and plasma factors; reperfusion injury; and inflammation. As a result of this cascade, vital tissues are injured, impairing their function, causing localized pain (ie, the sickle cell vaso-oclusive crisis) and, in many cases, premature death for the affected individual.
Lab tests:
CBC and Automated Differential
Blood Smear with Interpretation
Solubility testing
Hemoglobin electrophoresis
DNA testing (Prenatal diagnosis)
o Thalassemias and related disorders
Thalassemia refers to a group of inherited hemoglobinopathies where there is a quantitative defect in the production of alpha globin or beta globin chains. The resulting imbalance in the ratio of alpha to beta globin chains leads to precipitation of the unpaired chains, which in turn causes destruction of developing red blood cell precursors in the bone marrow that can lead to ineffective erythropoiesis, anemia, and iron overload.
Lab tests:
CBC and Automated Differential
Blood Smear with Interpretation
Iron and TIBC
Hemoglobin electrophoresis
DNA testing (Prenatal diagnosis)
o Pyruvate kinase deficiency (PKD)
Pyruvate kinase (PK) deficiency is an inherited (autosomal recessive) red blood cell (RBC) enzyme disorder that causes chronic hemolysis. It is the second most common RBC enzyme defect but is the commonest cause of hemolytic anemia from an RBC enzyme deficiency.
Lab tests:
CBC and Automated Differential
Blood Smear with Interpretation
Reticulocyte count
Iron and TIBC
LDH
Indirect bilirubin
Haptoglobin
Direct and Indirect antiglobulin (coombs) test
Alanine aminotransferase (ALT)
Other tests can be helpful:
Hemoglobin electrophoresis
RBC enzyme assay
Flow cytometry
Cold agglutinins
Osmotic fragility
o Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Glucose-6-phosphate dehydrogenase (G6PD) deficiency, an X-linked disorder, is the most common enzymatic disorder of red blood cells in humans, affecting more than 400 million people worldwide. The clinical expression of G6PD variants encompasses a spectrum of hemolytic syndromes. Affected patients are most often asymptomatic, but many patients have episodic anemia, while a few have chronic hemolysis. With most G6PD variants, hemolysis is induced in children and adults by the sudden destruction of older, more deficient erythrocytes after exposure to drugs having a high redox potential (including the antimalarial drug primaquine and certain sulfa drugs) or to fava beans, selected infections, or metabolic abnormalities. However, in the neonate with G6PD deficiency, decreased bilirubin elimination may play an important role in the development of jaundice.
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§ Lab tests:
§ CBC and Automated Differential
§ Blood Smear with Interpretation
§ Reticulocyte count
§ Evaluation of G6PD
§ Auto hemolysis test
§ Heinz body stain
§ LDH (lactate dehydrogenase)
§ Indirect and direct bilirubin level
§ Serum Haptoglobin
§ Urinalysis
§ Urinary hemosiderin
o Hereditary Elliptocytosis syndromes:
HE syndromes are a group of inherited erythrocyte disorders defined by elliptical RBC on the peripheral blood smear. The clinical symptoms are extremely variable, from asymptomatic condition to a moderate hemolytic anemia. The HE is occurred by abnormalities of spectrin, Ankyrin, Protein 4.2, Protein 4.1, Band 3 protein and Glycophorin C.
Lab tests:
CBC and Automated Differential
Blood Smear with Interpretation
Iron and Iron Binding Capacity
Serum Ferritin
Reticulocyte count
LDH (lactate dehydrogenase)
Haptoglobin
Direct antiglobulin test (coombs)
Analysis of RBC proteins
Osmotic gradient ektacytometry
o Paroxymal nocturnal hemoglobinuria (PNH)
Paroxymal nocturnal hemoglobinuria (PNH) is a rare acquired disorder characterized by intravascular hemolysis and hemoglobinuria. Leukopenia, thrombocytopenia, arterial and venous thromboses and episodic crises are common. Subsequent investigations have clarified much of the pathogenesis of the disease, including the genetic defect and the mechanism of complement-mediated hemolysis.
Lab tests:
CBC and Automated Differential
Blood Smear with Interpretation
Reticulocyte count
LDH (lactate dehydrogenase)
Coombs test
Indirect and direct bilirubin level
Urinalysis
Flow cytometry test
References:
- van Wijk R, van Solinge WW. The energy-less red blood cell is lost: erythrocyte enzyme abnormalities of glycolysis. Blood 2005; 106:4034.
- Poyart C, Wajcman H. Hemolytic anemias due to hemoglobinopathies. Mol Aspects Med 1996; 17:129.
- Jacobasch G, Rapoport SM. Hemolytic anemias due to erythrocyte enzyme deficiencies. Mol Aspects Med 1996; 17:143.
- Bossi D, Russo M. Hemolytic anemias due to disorders of red cell membrane skeleton. Mol Aspects Med 1996; 17:171.
- Walshe JM. The acute haemolytic syndrome in Wilson’s disease–a review of 22 patients. QJM 2013; 106:1003.
- Kummerfeldt CE, Toma A, Badheka AO, et al. Severe hemolytic anemia and acute kidney injury after percutaneous continuous-flow ventricular assistance. Circ Heart Fail 2011; 4:e20.
