Haemolytic Anaemias Year 4 Paediatrics Notes OmpathStudy

Haemolytic Anaemias Year 4 · Paediatrics Collection: 4TH YEAR ALL NOTES / PAEDS / PAEDS 4.3 / Munge / HAEMATOLOGY -- Slide 1 Haemolytic Anaemia Dr Rose Munge Slide 2 Introduction Hemolysis is defined as the premature destruction of red blood cells (RBCs). Anemia results when the rate of destruction exceeds production of additional RBCs.\n Normal RBC survival time is 110-120 days (halflife: 55-60 days). Slide 3 During hemolysis, RBC survival is shortened, the RBC count falls, erythropoietin is increased, and marrow erythropoietic activity is stimulated,\nLeads to compensatory erythroid hyperplasia with increased RBC production, reflected by an increase in the reticulocyte count.\n The marrow can increase its output 2-3–fold acutely, with a maximum of 6-8–fold in chronic hemolysis. Slide 4 Compensatory erythroid hyperplasia may lead to significant expansion of the medullary spaces at the expense of cortical bone. Seen in severe chronic hemolytic anemia, such as thalassemia.\n These changes may be evident on physical examination or radiography of the skull and long bones.\n In severe cases, there is increased propensity for long-bone fracture. Slide 5 Hemolysis also leads to increased degradation of hemoglobin resulting in indirect hyperbilirubinemia, increased biliary excretion of heme pigment derivatives, and formation of bilirubinate gallstones Slide 6 During hemolysis, heme-binding proteins in the plasma are altered Hemoglobin binds to haptoglobin and hemopexin, both of which are cleared more rapidly as heme-bound complexes.\nOxidized heme binds to albumin to form methemalbumin, which is increased in the plasma during hemolysis.\nWhen the capacity of these heme-binding molecules is exceeded, free haemoglobin appears in the plasma.\nFree hemoglobin in the plasma is considered prima facie evidence of intravascular hemolysis. Slide 7 Free hemoglobin dissociates into dimers and is filtered by the kidneys.\n When the tubular reabsorptive capacity of the kidneys for hemoglobin is exceeded, free hemoglobin appears in the urine.\n Even in the absence of hemoglobinuria, iron loss can result from reabsorbed hemoglobin and the shedding of renal epithelial cells in which the iron from hemoglobin is stored as hemosiderin.\n This iron loss can lead to iron deficiency during chronic intravascular hemolysis. Slide 8 The ongoing presence of circulating free hemoglobin and hemin have been linked to vascular disease, including pulmonary hypertension, thrombosis, inflammation, and impaired renal function. Slide 9 Hemolytic anemia can be classified by whether there is a cellular abnormality of the erythrocyte (intrinsic or intracorpuscular) or an extracellular abnormality of the erythrocyte (extrinsic or extracorpuscular) resulting from antibodies, mechanical factors, or plasma factors.\n Hemolytic anemia can be also classified as inherited or acquired, whether there is immune-mediated (immune ) or nonimmune-mediated (nonimmune ) hemolysis, whether hemolysis is acute or chronic, or whether hemolysis occurs in the vasculature (intravascular ) or in the reticuloendothelial system (extravascular). Slide 10 Most intrinsic defects are inherited, such as hereditary disorders of the erythrocyte membrane, metabolic defects of the erythrocyte, and hemoglobin disorders (though paroxysmal nocturnal hemoglobinuria is acquired).\n Most extrinsic defects are acquired, with examples including immune-mediated mechanisms such as warm and cold agglutinin hemolysis and nonimmune causes such as systemic diseases, drug- or toxin-mediated effects, and mechanical destruction of erythrocytes. Slide 11 Evaluation A detailed history of the current illness with attention to coexisting diagnoses, past medical history, family history, detailed list of medications, or recent exposures.\n A complete blood count with erythrocyte indices, peripheral blood smear examination, reticulocyte count, and a direct antiglobulin test.\n Bilirubin, increased serum lactate dehydrogenase, or serum decreased haptoglobin, indicating the presence of hemolysis, may also be obtained. Slide 12 Hereditary Spherocytosis Hereditary spherocytosis (HS) is a common cause of inherited hemolytic anemia, with a prevalence of approximately 1 in 2,000-5,000 persons.\n It is the most common inherited abnormality of the erythrocyte associated with inherited hemolytic anemia in persons of Northern European origin.\n HS is marked by wide variability in the associated clinical, laboratory, and genetic manifestations.\n Symptomatology ranges from asymptomatic patients with well-compensated anemia to severely affected patients with hemolytic anemia requiring regular blood transfusions. Slide 13 Aetiology The pathophysiology underlying HS is twofold: an intrinsic defect of the erythrocyte membrane and an intact spleen that selectively retains, damages, and removes mutant HS erythrocytes. Qualitative or quantitative defects of key membrane proteins lead to a multistep process of accelerated HS ery