Haemolytic Anaemia 2023.pptx

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...

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. 2. 3. 4. • Hereditary spherocytosis Sickle cell disease Thalassaemia 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 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 <5 – can stimulate further antibody production • Some patients require massive transfusions over several weeks/months MANAGEMENT OF HAEMOLYTIC ANAEMIAS • • Chronic haemolysis is managed differently based on the underlying cause If due to immune haemolysis may require long term immune suppression – Can follow remitting and relapsing course – If underlying cause like bone marrow malignancy then needs to be treated • Sickle cell and thalassemia – Need regular transfusions to sustain growth and life – Will cause iron overload which also needs to be managed with medication or can cause organ damage SUMMARY • Haemolytic anaemias can be caused by several different disease entities • It is very important to establish if this is acute or chronic • If acute – is the patient stable, initiate emergency management • Avoid blood transfusion if possible as may stimulate further haemolysis – ask for help