Microcytic | ||||||||||||
Type | Aeitology | Clinical features | Investigations | Management | ||||||||
Blood loss: GI bleeding (peptic ulcer, diverticulitis), Menorrhagia, hookworm (developing countries) Poor Diet Malabsorption | – Brittle hair + nails – Atrophic glossitis – Angular stomatitis – Koilonychia – (Rare: post- cricoid webs) | – Hb ↓, ↓MCV – RBC microcytic, hypocgromic, anisocytosis, poikilocytosis. -Serum ferritin ↓ -Serum Iron ↓ – TIBC ↑ | – Treat underlying cause. – Oral iron – ferrous sulphate (SE = constipation) | |||||||||
Diseases: infection, colloagen vascular disease, rheumatoid arthritis, malignancy, renal failure, chronic inflammatory disease (crohns), TB, endocarditis. ↓ release of iron from bone marrow to developing erythroblasts, inadequate erythropoietin response to the anaemia, ↓RBC survival. | Normochromic, normocytic or microcytic anaemia | – ↓serum iron levels – ↓ serum iron binding capacity – ↑or normal serum ferritin. | – Treat underlying cause – If due to renal failure then anaemia partly due to erythropoeitin deficiency – thus recombinant erythropoietin is useful. | |||||||||
Sideroblastic | – Inherited or – Acquired · 2* to myelodysplasia, · alcohol, · lead or isoniazid poisoning, · idiopathic, · malignancy, · anti- TB drugs, · – malabsorption | There is iron available but the body is unable to synthesize it into the RBCs’ · Dyserythropoiesis (defective developement of eyrocytes) · iron loading bone marrow · haemosiderosis (storage of iron compound – haemosiderin in various places e.g. endocrine, liver, cardiac damage) | Disorder of haem synthesis: · refractory anaemia · hypochromic cells in the peripheral blood · ring sideroblasts in bone marrow. (erythrocytes with granules of iron in their cytoplasm) | – Withdraw causative agents – some response to pyridoxine (Vit B6) – Maybe transfusion dependent and iron overload is a problem. | ||||||||
See haemolytic anaemias | ||||||||||||
Macrocytic – Macrocytosis – presence of abnormally large red blood cells in the blood | ||||||||||||
Type | Aetiology | Clinical Features | Investigations | Management | ||||||||
Megaloblastic | The presence in the bone marrow of developing RBCs with delayed nuclear maturation relative to that of the cytoplasm. – defective DNA synthesis, – ↓WC (leukopenia)- may be hyper-segmented, – ↓ platelets (thrombocytopenia) Causes: – B12/ Folate deficiency – Drugs (hydroxycarbamide/ hydroxyurea) | – Usually asymptomatic as the fall in the levels of Hb in response to the falling levels of B12/ folate occur over a long period of time therefore allowing the body to adjust. | Blood film: – hypersegmented polymorphs (B12 ↓), target cells (liver disease). – ESR – Malignancy – LFTs – T4 – Serum B12 and serum folate/ red cell folate. Bone marrow biopsy if above unsignificant:- Megaloblastic – B12/folate deficiency, cytoxic drugs Normoblastic marrow – liver damage, myoxedema (coarsening of skin due to hypothyroidism) Increased erythropoiesis – e.g. haemolysis Abnormal erythropoiesis – sideroblastic anaemia, leukaemia, aplasia. | |||||||||
Vit B12 Deficiency | Diet: If no animal products are consumed (vegan) Impared absorption: – Pernicious anaemia, – Gastrectomy (no IF from terminal ileum), – illeal disease/resection, coeliac disease. | Peripheral neuropathy – dorsal column degen. (Rarely – dementia) | – Treat cause NB confirm whether B12 or folate deficient as folate will correct Hb in B12 deficiency but will not treat neuropathy | |||||||||
Pernicious anaemia | Autoimmune condition where there is atrophy of the gastric mucosa, with failure of Intrinsic Factor (and acid production)→ B12↓ absorption. – usually older people, – ↑common in women, fair hair blue eyes. – Associated with other autoimmune conditions: e.g. Thyroid, Vitiligo | General: – Glossitis – Angular stomatitis – Mild jaundice – weakness + tiredness – Dysponea – Mild Splenomegaly – Fever Neurological – fits with very low levels of B12 and in Polyneuropathy – weakness, ataxia, paraplegia Optic atrophy – dementia, visual disturbances. | Macrocytic anaemia – MCV > 110 with hypersegmented neutrophil nuclei – in severe cases leucopoenia and thrombocytopenia. – Hb ↓ – WCC + Platelets ↓ – Serum B12 ↓ < 50ng – Red cell folate ↓ – Serum autoantibodies. Parietal cell antibodies 90% , IF antibodies 50%. – Serum Bilirubin ↑ (↑ breakdown of haemoglobin, due to ineffective erythropoiesis in the Bone marrow) – Schilling test (to differenciate PA from small bowel malabsorption) – Bone marrow exam -Hypercellular BM with megaloblastic changes. | – IM Hydroxocobalamin – x2 weekly for 3 weeks to replenish body stores, 3 monthly for life. – watch for hypokalaemia when tx begins – oral K+ may be required | ||||||||
Folate Deficiency | Poor Intake – old age – poverty – alcohol excess – anorexia Sources = green veg, beans, whole grains, some breakfast cereals Malabsorption – coeliac disease – tropical sprue Excess utilization – pregnancy, lacatation, prematurity – chronic haemolytic anaemia, malignant and inflammatory diseases, – dialysis | Anaemia symptoms | – Red cell folate ↓ – Serum folate ↓ – jejunal biopsy to look for small bowel disease. | – Tx of underlying conditon. – Oral folic acid 5mg daily for 4 months, higher doses if due to malabsorption. – Prophylactic folic acid is given to pts with chronic haemolysis and pregnant women. | ||||||||
Normocytic | ||||||||||||
Type | Aeitology | Clinical features | Investigations | Management | ||||||||
Aplastic anaemia | Pancytopenia – deficiency of all cell elements of the blood, Aplasia – hypocellularity of the bone marrow – Congenital – Idiopathic acquired (50%) Chemicals e.g benzenes Drugs e.g. cytotoxics, chemotherapy, chloramphenicol, gold, insecticides, ionising radiation – Infections e.g. viral hepatitis, HIV | Resulting from deficiency of RBCs, WBCs, Platelets. – Anaemia – ↑ likelyhood of infection – Bleeding – Bruising – Bleeding gums – Mouth infections are common | FBC – pancytopenia with low/ abscent reticulocytes. Bone marrow exam –hypocellular marrow with ↑fat spaces. | Tx Cause: – Supportive care – Transfusions of RBC, platelets – Antibiotic tx. Poor prognosis: – peripheral blood neurtophil count < 0.5 x10⁹/L – peripheral blood platelet count < 20×10⁹/L – reticulocyte count of <40×10⁹/L If no recovery: – Bone marrow transplantation – Immunosuppressive tx with antilymphocyte gobulin and ciclosporin (where BMT is not possible due to ↑GVHD risk) | ||||||||
Haemolytic anaemias overview | There is increased destruction of red cells and a reduction of circulating lifespan to which the bone marrow is unable to compensate for the increased loss. This may be: extravascular (within reticuloendothelial system) they are removed from the circulation as they are defective or intravascular (within blood vessels)e.g. due to trauma, complement fixation or other extrinisic factors. Causes: RBC membrane defect: – Hereditary spherocytosis – Hereditary elliptocytosis Haemoglobin abnormlaities: – Thalassaemia – Sickle cell disease RBC metabolic defects: – Glucose-6-phosphate dehydrogenase defieciency -Pyruvate kinase defeicency Immune: – Autoimmune haemolytic anaemia – Haemolytic transfusion reactions -Drug induced Non-Immune: – Paroxysmal noctural haemoglobinuria – Microangiopathic haemolytic anaemia – March haemoglobinuria Other: – Infections (e.g. malaria) – Drugs/chemicals – Hypersplenism – Trauma | Jaundice Hepatospenomegaly Hx: – family history – race -drugs -previous anaemia Is there significant haemolysis:- Is there increased cell breakdown:- – bilirubin↑ (unconjugated), – urinary urobilinogen ↑, – haptoglobin↓. Is there increased red cell production:- e.g. reticulocytosis, -polychromasia, -macrocytosis, -marrow hyperplasia. Is the haemolysis mainly intra/extra vascular:- E: → splenic hypertrophy I: methaemalbuminaemia, – free plasma haemoglobin, – haemoglobinuria, – ↓haptoglobin, – haemosiderinuria. | -FBC, -Reticulocytes, -Bilirubin, -LDH, -Haptoglobin, -Urinary urobilinogen. Blood films:polychromasia, macrocytosis, spherocytes, elliptocytes, fragmented cells or sickle cells. Direct Coombs’ test: identifies RBCs coated with antibody/complement and a positive result ususally indicates an immune cause. Chromium labelling: for RBC lifespan and the major site of breakdown | |||||||||
Thalassaemia | Multiple gene defects → ↓ rate of production of one or more globin chains. The imbalance of globin chain production leads precipitation of globin chains within red cells or precursors. This → cell damage, death of RBC precursors in the bone marrow and haemolysis. – α thalassaemia: reduced α chain synthesis – β thalassaemia: reduced β chain synthesis | – Symptoms may be mild–severe, depending on how many α/β chain genes have been deleted | – FBC – MCV – Film – Iron – HbA2 – HbF – Hb – Electrophoresis | – Transfusion keep Hb >9g/dL – Iron chelators e.g. desferrioxamine. To protect against cardiac disease & DM. – ↑ doses of ascorbic acid (vitamin C) also ↑iron output – Splenectomy , if hypersplenism px. – Folate supplements – BMT | ||||||||
Sickle cell anaemia | Inheritance of the β-globin gene. May have: sickle cell anaemia HbSS sickle cell trait HbAS HbSC – one S haemoglobin and one C haemoglobin group, (the C group causes the red blood cells to develop). | HbAS – there are usually no symptoms unless the patient is exposed to extreme hypoxia HbAC – a milder course of HbSS but there is a ↑likelyhood of thromboses occuring. HbSS – symptoms due to haemolysis and vaso-occlusion. As the sickled cells are fragile and haemolyse and block small vessels. …continued in large box below…. | – ↓ Hb – ↑ Reticulocyte count – Bilirubin may be raised – Blood film shows sickled erythrocytes Dx: Viz electrophoresis showing 80-90% HbSS and absent Hb A. | – Folic acid in patients with severe haemolysis – pneumococal vaccine to ↓ infection risk, daily oral penecillin – Exchange transfusions to ↓ frequency of crises – Hydroxycarbamide (hydroxyurea) raises the conc of fetal Hb – possible BMT | ||||||||
Haemolysis: – mild anaemia (usually no symptoms due to hyperdynamic circulation and a lower O2 affinity of HbS than normal Hb). – jaundice – painful swelling of hands and feet – recurrent sickle cell crises – recurrent haemolysis → formation of pigment gallstones Vaso-occlusion: A vascular necrosis of BM results in the bone marrow pain crisis, may be precipiated by hypoxia, dehydration or infection – usually affects ribs, spine, pelvis in adults – hands and feet (dactylitis) in children – may require addmission to hospital for analgesia Other complications:- – Splenic atrophy resulting in ↑infection risk with Pneumococcus, Salmonella species and Haemophilus – Cerebral infection causing fits and hamiplegia – Retinal ischaemia, may precipitate proliferative sickle retinopathy and visual loss. Other:- – renal papaillary necrosis – leg ulcers – acute chest syndrome (commonest cause of death in adults with sickle cell ) – fever – cough – dysponea – pulmonary infarcts on the CXR Caused by infection, fat emboli from necrotic bone marrow or pulmonary infarction due to sequestration of sickle cells | ||||||||||||
