Haemolytic Anaemia 2023 PDF

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Haemolytic anaemia Class Year 1 Course Pathology Lecturer Prof Siobhan Glavey Prof Abdullah Darwish...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Haemolytic anaemia Class Year 1 Course Pathology Lecturer Prof Siobhan Glavey Prof Abdullah Darwish Date 8th October 2023 LEARNING OUTCOMES Describe the classification of haemolytic anaemia including immune and non immune. Describe the pathogenesis of sickle cell anaemia and its complications. Describe the pathology of thalassaemia Describe the clinical effects of haemolysis. Describe the laboratory tests used in the diagnosis of haemolytic anaemia. CAUSES OF ANAEMIA ALREADY COVERED Failure to make red cells: marrow problem Lack of haematinics: iron, B12, Folate e.g. dietary deficiency, malabsorption, loss Increased loss of red blood cells e.g. bleeding Increased destruction of red cells: Haemolysis Chronic Disease HAEMOLYTIC ANAEMIA Condition in which mature red cells are destroyed faster than they can be made HAEMOLYSIS CONSEQUENCES OF HAEMOLYTIC ANAEMIA The release of red cell contents into the blood stream causes high levels of bilirubin and LDH These can be detected in the blood and can be a clue that haemolysis is occurring This condition can be asymptomatic until haemoglobin levels are dangerously low Rapid haemolysis can be life threatening and requires emergency management LETS REVIEW AUTOIMMUNE HAEMOLYTIC ANAEMIA https://www.osmosis.org/learn/Autoimmune_hemolytic_a nemia Some of this video is very detailed, you really only need to look at the first 4 minutes or so HAEMOLYTIC ANAEMIA CAUSES Abnormality intrinsic to red cells 1. Hereditary spherocytosis 2. Sickle cell disease 3. Thalassaemia 4. G-6PD deficiency Abnormality extrinsic to red cells 1. Immune 2. Mechanical AUTOIMMUNE HAEMOLYTIC ANAEMIA Warm antibody AIHA-by an IgG autoantibody – Lymphoma, Cll, collagen vascular ds Cold antibody AIHA-by an IgM autoantibody – Seen in cold agglutinin ds, mycoplasma EB virus Diagnosis – – Reticulocytosis, elevated LDH, and indirect hyperbilirubinaemia. – Peripheral blood smear may show Spherocytes, occasional fragmented RBCs. – Positive DAT (direct Coombs test) – Warm AIHA: IgG+and/or C3+ – Cold AIHA: IgG-andC3+ HISTORY TAKING IN HAEMOLYTIC ANAEMIA Symptoms (same as in other causes of anaemia but shorter course of onset) Infectious symptoms – cough, fevers, ill contacts Recent new drugs – medications or over the counter Recent travel - malaria Family history Previous transfusions – SO SO IMPORTANT!! – May be a distant or unknown history – Check with your lab for previous transfusions CLINICAL EXAM IN HAEMOLYTIC ANAEMIA INHERITED HAEMOGLOBIN DEFECTS Abnormal genetic code in haemoglobin Sickle cell disease mutation Thalassaemia major and minor Globin chains are normal but rate of synthesis is reduced Accumulation of abnormal chain leads to structural defects Sickle cell disease mutation (valine for glutamic acid) causing increased HbS with RBC aggregation at low oxygen tensions SICKLE CELL DISEASE Sickle cell anaemia: coinheritance of HBS and another abnormal β chain variant Sickle cell trait: inheritance of one gene encoding for HBS SICKLE CELL DISEASE INHERITANCE SICKLE CELL DISEASE Chronic haemolytic anaemia HbS in deoxygenated state (50X less soluble than HbA) Insoluble chains crystallise in the red cells with distortion of membrane, cell becomes crescent shaped Sickle RBC last only 10-20days Deformed cells more rigid and cannot pass microcirculation Causes vascular occlusion Structural change and  bld viscosity > venous stasis > local obstruction > tissue hypoxia > more sickling > tissue infarction  Ca s e 8 A b lac k m a le c h ild ag e d 10 yr s h as s uff e r e d f r o m r e c ur r e nt b ut inf r e q ue nt e pis o d e s o f s e ve r e pa in in t h e lim b s f o r s e ve r al y e ar s.Eac h e pis o d e la s t s a f e w d ay s at a t im e. SICKLE CELL DISEASE Sickling can be spontaneous May be precipitated by – Hypoxia – Acidosis – Hypotension – Infection – Dehydration – Hypothermia Look for precipitating features OTHER COMPLICATIONS OF SCD Osteomyelitis (infected bones) – why? Gall stones Renal failure Cardiac failure Chronic leg ulcer Know why these occur! THALASSAEMIA A group of inherited conditions that cause reduced synthesis of either alpha or beta globin genes BETA THALASSAEMIA LABORATORY TESTS FOR HAEMOLYTIC ANAEMIA – Hb reduced – Haptoglobin decreased – why? – LDH increased – Why? – Bilirubin ↑ - Why? – Reticulocytosis in peripheral blood – Erythroid hyperplasia in bone marrow – Coombs test may be positive if immune – Blood film – look for shape of RBC – Electrophoresis and Molecular tests REDUCED HAPTOGLOBIN Haptoglobin “mops” up degenerative fragments of RBC’s and rapidly breaks down →↓ haptoglobin ↑ LDH – released from RBC’s ↑ Bilirubin due to breakdown of haeme MANAGEMENT OF HAEMOLYTIC ANAEMIA Acute haemolytic anaemia can be brisk and life threatening If acute – initiate emergency management, ABC, iv access, blood pressure and urine output monitoring Check FBC, bilirubin, LDH, DAT, haptoglobin Screen for infection – urine, blood cultures, chest Rapid initiation of steroids Avoid transfusion unless Hb