Haematology: Anaemia Flashcards
At what Hb levels is a pt considered anaemic?
Men - Hb 13 g/dL (130 g/L)
Women - Hb 11.5 g/dL (115 g/L)
What are the generalised symptoms of anaemia?
Lethargy
Fatigue
Shortness of breath
Palpitations
Angina/intermittent claudication
Pallor
Tachycardia
Systolic flow murmur
Cardiac failure
For a patient with suspected anaemia what features of a Hx should be explored?
Occupation = lead exposure (present like iron def), paints, solvents
Dx = chemotherapy, haematinics
Co-morbidities
Diet/bowel habits = steatorrhoea (malabsorption/pancreatitis), vegetarian, weight loss
Blood loss = trauma, surgery, pregnancy, abortions, menorrhagia, malena, PR, haemoptysis
FH = bleeding disorders, abnormal Hb, gallstones, splenectomy (ITP - increased destruction of RBC autoimmune)
For a patient with suspected anaemia what features of an examination should be explored?
GI = malnutrition, cachexia, pallor (assess in sunlight), nail changes - koilonychia (spooning, iron def), brittle nails (iron def)
Palmar erythema (oestrogen level changes), purpura, facial puffiness
Cardiomegaly, hepatosplenomegaly
Liver disease = gynaecomastia, change in testicular size, spider naevi
Neurological = paraesthesia, posterior column defect - defect in position sense, proprioception
PR exam
Outline the morphological approach to differentiating the type of anaemia
Microcytic (MCV <80)
- Most common iron def (bleeding)
- Reduced heme synthesis (LAL need to be converted to heme, by LAL dehydrogenase - inhib by lead)
- Reduced globin prod = thalassaemia
Macrocytic
- Reduced B12, folate
- Liver disease - alcohol (also has toxic effect on bone marrow)
- Hypothyroidism (hashimoto’s)
How can ferritin be used to help Dx anaemia?
Low = diagnostic of iron def
High = acute phase protein in inflam (anaemia of chronic disease)
How should anaemia be investigated?
Microcytic = look for source of bleeding - Lab tests = serum iron, ferritin, transferrin sat, total iron binding capacity
Macrocytic = shillings test for pernicious anaemia (destruction of parietal cells = low intrinsic factor = low absorption of B12 in ileum)
DCT - direct coombs test
PNH - cold autoimmune destruction of RBC
Decreased prod investigations = bone marrow aspiration + biopsy
How should anaemia be treated?
Blood loss = transfusion (short term)
Chronic = EPO injections
Iron supplementation
B12/folate supplements
Autoimmune = steroids, immunosuppressant - azathioprine (need to have serial blood tests to make sure the bone marrow is not suppressed), splenectomy (HS, HE) (give pneumococcal vaccine - capsulated bacteria removed in the spleen)
Bone marrow transplant
Chemotherapy
How can reticulocyte count help differentiate anaemia?
Raised = normal response to anaemia, haemolysis, bleeding, splenic sequestration
Low = bone marrow failure
- microcytic = iron def, thalassemia, AoCD
- normocytic = acute blood loss, AoCD, renal failure, marrow infiltration
- macrocytic = vit B12 def, folate def, liver disease, reticulocytosis
Where is iron absorbed?
Duodenum
What is ferroportin?
Transmembrane protein
Transports iron out of duodenal mucosal cells
What is ferritin?
How iron is stored in duodenal mucosal cells
What is transferrin?
Iron is transported in the blood bound to transferrin
Protein made by the liver
What causes iron supplies to be insufficient?
Decreased intake = malnutrition, poor absorption
Increased loss = bleeding
Increased demand = pregnancy, growth
What are the signs of iron def?
Koilonychia
Angular stomatitis
Atrophic glossitis
How does iron def appear on a blood film?
Microcytic
Hypochromic
Poukilocytosis
Anistocytosis
Pencil cells
Target cells
What investigations should be performed when iron def is suspected?
Blood film
Serum iron = low
Ferritin = low (if inflam cause then it may be high)
Total iron binding capacity = raised
How is iron def treated?
Oral ferrous sulphates 200mg BD
- should raise Hb by 1g/dl/week
SE = epigastric pain, nausea, altered bowel habit and dark stools. If the side effects are intolerable alternative iron salts should be tried.
What are the symptoms and signs of vit B12 and folate def?
General signs and symptoms of anaemia
B12 = peripheral neuropathy, low mood and poor memory
Folate = neural tube defects in utero, and an increased risk of heart disease and stroke
Hoes does vit B12 and folate def appear on a blood film?
Macrocytic
What is pernicious anaemia?
loss of gastric parietal cells and lack of intrinsic factor leading to an inability to absorb vitamin B12
What is the pathophysiology of AoCD?
Depressed production and response to erythropoetin
Ferritin synthesis may also be unregulated by proinflammatory cytokines diverting iron into the reticuloendothelial system
Increased hepcidin reduces the amount of iron being absorbed from the intestines
Up regulation of white cells causes fewer stem cells to differentiate into red blood cells.
What is sickle cell anaemia?
Autosomal recessive pattern which results in a point mutation. This results in a hydrophilic amino acid in the b Hb chain being replaced by a hydrophobic amino acid.
Over time this reduces the elasticity of the RBC and leads to sickling.
Sickle cells have a reduced life span and have difficulty travelling through microcirculations, occluding vessels resulting in infarction
What can bring about a sickle cell crisis?
Dehydration, infection, hypoxia, hypothermia, stress/emotion and surgery.
Signs and symptoms of a crisis include those of anaemia and pain.
What investigations should be performed if sickle cell is suspect?
Blood count = Hb may be 6-8 g/dl during crisis but will usually be higher at other times. Reticulocytes raised
Blood film = sickle cells.
Sickle cell solubility test will be positive but doesn’t differentiate between sickle cell anaemia and sickle cell trait.
Hb electrophoresis is used to confirm a diagnosis and can differentiate between sickle cell anaemia and sickle cell trait. It can also detect other combinations of abnormal haemoglobins which can cause sickle cell disease such as HbSC (HbS and HbC).
How is sickle cell managed?
Patient education = avoiding triggers, early recognition and prompt management of crisis and the importance of vaccinations/prophylactic penicillin.
Packed red cell transfusions or red cell exchange should be given in specialist centres when necessary e.g. for heart failure, splenic sequestration, aplastic crisis.
Hydroxycarbamide may reduce rate of painful crisis and is used as secondary prophylaxis.
How should thalassemia be investigated?
Blood film = microcytic cells and target cells
DNA analysis = mutation
Bone marrow = hypercellular
Hb electrophoresis = presence of an abnormal form of Hb
What are the causes of haemolytic anaemia?
Membrane disorder = hereditary spherocytosis
Hb disorder = sickle cell, thalassaemia
Metabolic disorder = G6PD def
Autoimmune
Prosthetic heart valves
Malaria
Ingestion of drugs or chemicals causing oxidative stress
What are the components of a haemolytic screen?
Blood film
Bilirubin - raised
LDH - raised
Haptoglobin - decreased as it mops up free Hb
Reticulocytes - raised to compensate haemolysis
Direct Coombs test - detect Ab
How is autoimmune haemolytic anaemia treated?
Corticosteroids
Splenectomy
Immunosuppression
How is aplastic anaemia managed?
Immunosuppression - antilymphocyte globulin (ALG) with cyclosporin
Stem cell transplant
Haematopoietic growth factors
