Inherited Red Cell Disorders Flashcards
3 main components of an RBC
Membrane
Hemoglobin
Enzymes
What will you see in hemolytic anemia
Decreased hemoglobin concentration
Increased red cell breakdown (hyperbilirubinemia, cholelithiasis)
Increased bone marrow compensation (reticulocytosis, splenomegaly)
What is the main genetic driving force for red cell disorders?
Malaria
Hereditary spherocytosis
Mutations in “vertical” support components (ankyrin, spectrin, Band 3, protein 4.2)
Spherocytes are rigid and have decreased deformability, easily bursts and causes hemolysis
What is splenic conditioning?
Seen in hereditary spherocytosis
Progressive loss of the membrane during each cycle through the spleen
Hereditary spherocytosis inheritance pattern
75% autosomal dominant
25% autosomal recessive
Symptoms triad of hereditary spherocytosis
Anemia
Jaundice
Splenomegaly
3 ways hereditary spherocytosis is diagnosed
Blood smear
Osmotic fragility test
Flow cytometry
How to manage hereditary spherocytosis
Supportive treatment (folic acid, spleen protection) Splenectomy is a symptomatic cure (but need to give vaccines before)
Beta thalassemia major
Mutation in beta globin
Decreased beta globin production causing imbalance between alpha and beta pairing
Excess alpha chains precipitates damaging red cell membrane
Ineffective erythropoiesis
Severe anemia after 6 months old, marrow expansion, hepatosplenomegaly
Complications from beta thalassemia
Marrow expansion: osteoporosis
Endocrine failure: hypogonadotrophic hypogonadism, hypotheyroidism, ovarian failure
Transfusion hemosiderosis: CHF, liver cirrhosis, liver carcinoma
Transfusion related complications: infections, transfusion reactions
Psychosocial impact
Management of beta thalassemia major
Need to start regular transfusion by 6-12 months
Blood transfusions every 3-4 weeks - high iron deposition
Needs iron chelation meds after 20 transfusions
Good transfusion and chelation and they will be fine
Sickle cell anemia
Single nucleotide change (glu to val)
Hb S polymerizes when deoxygenated
RC becomes stiff and deformed
Sludging in capillaries (leads to recurrent infarctions - tissues can die and get inflammed which causes pain)
Vaso-occlusive crises
In sickle cell anemia
Extreme excruciating pain in long bones, back or abdomen
Treat early, prevent it from happening
Acute chest syndrome
From sickle cell disease Sickling in lungs Vicious cycle Most common cause of death Lung collapses and you become hypoxic Need early transfusions, spirometry, and ventilation
What is the definitive diagnosis for sickle cell anemia
Hb electrophoresis
Management of sickle cell anemia
Comprehensive care program Supportive (hydration, pain control) Prevent and treat infections Drug: hydroxyurea Blood transfusions (but dont over do it!!)
GP6D Deficiency
Unstable enzyme
Sex linked inheritance (more common in boys)
Reduced glutathione in red cells
Oxidation of Hb and oxidative damage of membrane (oxidative hemolysis)
RC damage - bite cells, blister cells - intravascular hemolysis
Diagnose via enzyme assay
Management of GP6D Deficiency
Avoid fava beans, oxidizing drugs
Vigilance during severe infections
Treatment of acute hemolysis (self limiting) - hydration, alkalinization
Pyruvate kinase deficiency
Final rate-controlling step in glycolysis
ATP depletion - decrease membrane ionic pumps = ionic leak and dehydration - hemolysis
Increased intracellular 2.3-DPG - right shift of oxygen dissociation curve - increased oxygen unloading - better tolerance to anemia
What will you see in a pyruvate kinase deficiency
Neonatal jaundice (some elevation of conjugated bilirubin) Life long anemia, but well tolerated Mild jaundice, cholelithiasis Supportive management (splenectomy usually not helpful, transfusion may be needed at times)
