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Haemolytic Anaemia
SR-General Features and Inherited Disorders (May 13)
| Question | Answer |
|---|---|
| Haemolysis: Haemolytic Anaemia | -anaemia of differing aetiology -abnormal destruction of red cells -reduced life span of red cells |
| 3 main considerations for classifications of haemolytic anaemias: | 1. mode of aquisition 2. location of the abnormality-intrinsic, extrinsic 3. site of red cell destruction: blood stream (intravascular haemolysis) or spleen and liver (extravascular haemolysis). |
| inherited disorders | intrinsic to red cell |
| acquired disorders | extrinsic to red cell |
| inherited disorders | subdivided by site: membrane, haemoglobin, metabolic pathways. |
| acquired disorders | divided depending on whether the aetiology has an immune basis. |
| symptoms of haemolytic anaemias: | particularly increase red cell breakdown. Accelerated catabolism of haemoglobin releases increased amounts of bilirubin into plasma and can cause Jaundice. |
| aetiology | study of causes of a disease |
| Jaundice | Also called icterus. Pathology . yellow discoloration of the skin, whites of the eyes, etc., due to an increase of bile pigments in the blood, often symptomatic of certain diseases, as hepatitis. |
| Inherited disorders | 1. red cell membrane 2. haemoglobin 3. Metabolic pathways |
| acquired disorders | 1. immune 2. isoimmune 3. nonimmune and trauma |
| Inherited: red cell membrane | Hereditary spherocytosis and hereditary elliptocytosis |
| Inherited: haemoglobin | Thalassaemia syndromes and sickling disorders |
| Inherited: metabolic pathways | Glucose-6-phosphate dehydrogenase and pyruvate kinase deficiency. |
| Acquired: immune | warm and cold autoimmune haemolytic anaemia |
| Acquired: isoimmune | Rhesus or ABO incompatibility (e.g. haemolytic disease of newborn, haemolytic transfusion reaction) |
| Acquired: Non-immune and trauma | Valve prostheses, microangiopathy, infection, drugs or chemicals, hypersplenism. |
| spleen as major site of red cell destruction | there may be palpable splenomegaly. |
| prolonged haemolytic anaemia in childhood | can lead to expansion of the marrow cavity and skeletal abnormalities ex. frontal bossing of the skull |
| Initial laboratory investigations of haemolysis | 1-blood count 2.blood film 3. reticulocyte count |
| Haemolysis: blood count | low haemoglobin |
| haemolysis: normochromic normocytic red cell | many cases show this although some are macrocytic |
| macrocytic | caused by increased number of immature red cells (reticulocytes)in the peripheral blood. A compensatory increase of red cells by the bone marrow occurs. |
| Reticulocytes | -characteristic blue tinge with Romanovsky stains -their presence in the film causes "polychromasia" |
| other indicators of haemolysis | raised levels of urine urobilinogen and faecal stercobilinogen. Bilirubin is unconjugated and doesnt appear in urine. |
| haptoglobin | glycoprotein bound to free haemoglobin in the plasma, is depleted in haemolysis. |
| intravascular haemolysis | haemoglobin and haemosiderin can be detected in the urine. |
| examination of the bone marrow in haemolysis | will show an increased number of immature erythroid cells. |
| other demonstrations (not frequent) or reduced red cell survival can be: | 1. tagging of cells with radioactive chromium (Cr) 2. in vivo surface counting of radioactivity to identify the site of red cell destruction |
| Hereditary spherocytosis | -inheritance may be autosomal dominant or recessive. -possible gene mutations: in spectrin, ankyrin, and other membrane proteins. -red cells are spheroidal (spherocytes), reduced diameter, more red -premature destruction in microvasculature of spleen |
| hereditary spherocytosis continued: | -severity is variable -any age -fluctuating levels of jaundice and palpable splenomegaly are common |
| hereditary spherocytosis: aplastic crisis | -severe anemia associated with the transient marrow suppression of a viral infection. -mostly caused by parvovirus -prolonged haemolysis can lead to bilirubin gallstones. |
| spherocytes | -suggests hereditary spherocytosis -BUT spherocytes may also be seen in autoimmune haemolysis. -antiglobin test: negative in hereditary spherocytosis, positive in immune haemolysis |
| osmotic fragility | spherocytes lyse at higher saline concentrations than normal red cells |
| autohaemolysis test | -spherocytes show an increase rate of haemolysis when incubated in their own plasma. |
| serious cases of hereditary spherocytosis | -spleen is removed as this is the main site of destruction of abnormal red cells. |
| Inherited disorders: Hereditary elliptocytosis | -cells are elliptical in shape -milder clinical course than spherocytosis -splenectomy helps in rare severe cases -gene mutations: most common is defective spectrin molecule. |
| inherited disorders: Abnormalities of haemoglobin | -referred collectivelly as "haemoglobinopathies" -Thalassaemia and sickle cell syndromes |
| inherited disorders: Abnormalities of red cell metabolism | -metabolic pathways to generate energy and also to protect it from oxidant stress -loss of key enzymes leads to premature destruction -two common: 1. Glucose-6-phosphate dehydrogenase (G6PD) deficiency 2. pyruvate kinase (PK)deficiency |
| Glucose-6-phosphate dehydrogenase (G6PD) deficiency | -G6DP: necessary enzyme for generation of glutathione which protects the red cell from oxidant stress. -affects males (sex linked) -increased oxidant stress: severe haemolytic anemia w/intravascular destruction of red cells |
| triggers of (G6PD) | -fava beans -drugs (antimalarials, analgesics) -infections |
| G6PD | -present often as jaundice in the neonate -diagnosis requires direct assay-not done during acute haemolysis as reticulocytes have higher enzyme levels than mature red cells (false normal level can result) -treated by stopping offending drug |
| Piruvate Kinase (PK)deficiency | -autosomal recessive disorder -lack of enzyme in Embden -Meyerhof pathway -not adequate ATP and become rigid. Leads to increased intracellular 2,3 DPG levels facilitating release of oxygen by Hb. -splenectomy reduces transfusion requirements |
| Summary: Haemolytic anemia I: general features and inherited disorders | -haemolytic anemias are caused by abnormal destruction of red cells -Most inherited haemolytic disorders have a defect within the red cell whilst most acquired disorders have the defect outside the cell. |
| Summary: Haemolytic anemia I: general features and inherited disorders | -Haemolysis causes characteristic clinical features and laboratory abnormalities. can be intra or extravascular. -hereditary spherocytosis and hereditary elliptocytosis are disorders caused by a deficiency in red cell membrane. |
| Summary: Haemolytic anemia I: general features and inherited disorders | -Glucose-6-phosphate dehydrogenase and pyruvate kinase are key enzymes in red cell metabolism: inherited deficiency leads to haemolysis. |
| Autoimmune Haemolytic anemia (AIHA)is an example of. | -An acquired form of haemolysis with a defect arising outside the cell |
| How is premature destruction of the normal red cells created in the autoimmune haemolytic anemia. | -Premature destruction is caused by the production of aberrant autoanti-body targeted against one or more antigens on the cell membrane. -IgM antibodies cause destruction by agglutination or by direct activation of serum complement |
| IgG Antibodies | -Class antibodies generally mediate destruction by binding to the Fc portion of their cell-bound immuneoblobulin molecule by macrophages in the spleen and liver. |
| Classification of Autoimmune haemolytic anemia. | -Divided into 'warm' and 'cold' -Red blood cells react with 47 C or 4 C. |
| Warm Autoimmune Haemolytic anemia, and how is it caused. | -Most common form. -Red Cells can be coated with IgG alone, IgG and a complement, or a complement alone. -Premature destruction usually takes place in the reticuloendothelial system |
| Causes of Warm AIHA. | -approx half of all causes are idiopathic -other half have apparent underlying cause. The antibody is usually non-specific |
| Splenomegaly (AIHA) | -Severe cause of warm AIHA. -Where refractoriness to steroids develops, splenectomy is usually indicated. |
| DAT | -Positive direct antiglobulin test (DAT), (sometimes referred to as the Coombs' test. -important to stop on offending drug-implicated agents include methyldope and penicillin. |
| The use of Steroids in Haemolytic | -Heamolysis requires prednisiolone40-60 mg daily. -idiopathic AIHA patients respond with significant rise in haemoglobin. -Usually controlled but not cured,and relapses occur. |
| Other immuneosuppressive drug used. | -Azathioprine, Cytotoxic agents, may be helpful in supplementing the immunosupressive effect of prednisolone. |
| Cold autoimmune haemolytic anaemia | -The antibody is generally of IgM with specificity for the I red cell antigen. -Red blood cell attach to peripheral circulation, where the blood temperature is lowered. |
| Monoclonal proliferation and Cold AIHA | -Can occur in monoclonal proliferation of B-lymphocytes, the so-called "idiopathic cold haemagglutinin syndrome" or a variety of lymphomas. -The other major cause is infection. |
| Severity and problems of Cold autoimmune haemolytic amaemia. | -Agglutination (clumping) of red cells may cause circulatory problems such as acrocyanosis, Raynauds's phenomenon and ulceration. -Often worse in the winter. |
| Intravascular destruciton in Cold AIHA | -due to direct lysis -Free haemoglobin is released into the plasma (haemoglobinaemia). -May appear in the urine (haemoglobinuria) giving it a dark color. |
Created by:
Divinita
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