Anaemia Flashcards
what is anaemia
Haemoglobin (Hb) concentration falls below defined level (outside normal range)
Units of Hb are g/L
what is the clinical consequence of anaemia
Clinical consequence: insufficient O2 delivery
what causes anaemia
low Hb content
low Red blood cells (RBCs)
Altered Hb does not carry sufficient O2
synthesis, consumption, bleeding or sequestering
what are the normal ranges of haemoglobin for pregnant women and children
110-160 g/L
Pregnancy - produce more plasma so more abc dilution
what are the normal ranges of haemoglobin for women and men
women 115-165 g/L
men 130-180 g/L
how many RBCs per litre
4x10^12/L
5litres of blood and 50 million, million red cells
make approx 5 million per second
what is the haematocrit
percentage of red cells after centrifugation
40-45%
what are the symptoms of anaemia
Lethargy, fatigue Shortness of breath (At rest vs On exertion?) Palpitations Headache Worse symtoms if acute onset Acute bleed / haemolysis
what are the signs of anaemia
Skin pallor
Pale conjunctivae
Tachypnoea
Tachycardia
Koilonychia
- spoon shaped nails
- iron deficiency
how does inadequate synthesis cause anaemia
Deficiency in necessary components
Iron, B12, folic acid
Bone Marrow Dysfunction / Infiltration
e.g., myelodysplasia or aplastic anaemia
how does blood loss or consumption cause anaemia
Bleeding
Haemolytic
(Increased red cell destruction
Shortened RBC lifespan)
how can anaemia be classified
Size of red cell
Acute or chronic
Underlying aetiology
what is the most common type of anaemia
iron deficiency in uk and globally
what causes iron deficiency
Bleeding (esp. occult)
Nutritional deficiency
Increased requirements
how is iron deficiency confirmed
with iron studies: Ferritin (measure of iron stores) low Serum Fe low Transferrin high Transferrin saturation % low
what is iron deficiency not
a diagnosis in itself and should always prompt other investigations to establish underlying cause
what are the diagnostic tests for iron
serum ferritin
serum iron
serum transferrin
% transferrin saturation
what is serum ferritin
Storage form of iron
Low = iron deficient (high = iron overload or reactive)
what is serum iron
Labile in blood, so reflects recent intake of iron
what is serum transferrin
Carrier molecule for iron from gut to stores
Homeostatically goes up if iron is deficient
Reflects total iron binding capacity (TIBC) of the blood
what is % transferrin saturation
Sensitive measure of iron status
Reflects proportion of transferrin with iron bound
Low TF saturation indicates iron deficiency
how can bleeding cause iron deficiency
Occult gastro-intestinal blood loss: GI Malignancy (never miss this) GI peptic ulceration Menstrual Renal tract
how can inadequate intake cause iron deficiency
Dietary deficiency:
Vegan/vegetarian diet
Malabsorption:
Coeliac and Crohn’s disease
how does increased requirement cause iron deficiency
pregnancy
how is anaemia caused by chronic disease
caused by chronic inflammation and seen in conditions such as connective tissue disease, malignancy, and chronic infection such as TB
how does mean corpuscular volume categorise size of red blood cell
This is the size of red blood cells (mean cell volume)
Normally about 80-100fL
how does mitcrocytic (small) categorise size of red blood cell
Iron deficiency (acquired) - hypo chromic
Inherited disorders of haemoglobin (beta-thalassaemia trait)
a/B imbalance, abnormal Hb electrophoresis but normal ferritin
how does macrocytic (large) categorise size of red blood cell
B12 and folate deficiency (needed for synthesis of nucleotides) - megaloblastic
Myelodysplasia (causes defective erythropoiesis)
how does normocytic anaemia categorise size of red blood cell
Anaemia of chronic disease
Acute haemorrhage
Renal failure (caused by low erythropoietin levels)
why are blood films used
Easy, quick, useful
what can a blood film be used to diagnose
haematinic deficiency (microcytic/macrocytic, hypochromic, anisopoikilocytosis) haemoglobinopathy (sickled cells, haemolysis, polychromasia) other abnormalities (white cells, platelets, leukaemic cells)
what is RBC lifespan
Red cell lifespan:
approx 100 days in the circulation
how is reticulocyte count done
Can be calculated on a blood film using a stain to detect RNA
Usually measured by flow cytometry based on size and colour
Typically ~1% but can be >10% in haemolysis e.g., sickle cell disease
Causes polychromasia on a blood film (large blue-ish red cells)
what does reticulocyte count indicate
Indicates rate of production of RBCs by bone marrow
Low during precursor deficiencies (e.g. iron)
Low if bone marrow is infiltrated
High in chronic bleeding
High in haemolysis
what is reticulocyte count useful for
Reticulocyte count useful to monitor response to treatment
Red cell production driven by erythropoietin from kidney
how do blood cells appear on a blood film in iron deficiency
Hypochromia
Microcytosis
Pencil Cells
Target Cells
what history should be taken in suspected anaemia
Dietary history
Travel History
Ethnic Origin
Family History
what symptoms indicate anaemia in a history
GI Symptoms Dyspepsia / Reflux Change in bowel habit (?melaena) Weight loss? Menstrual History ?menorrhagia Bowel history ?coeliac / Crohn’s disease
how is megaloblastic anaemia (B12 and folate) seen morphologically
Macrocytic red cells (MCV > 100) Hypersegmented neutrophils (more than 4 nuclear lobes)
what is pernicious anaemia
B12 deficiency
what causes pernicious anaemia
Autoimmune – parietal cell loss
Deficiency of intrinsic factor
Cannot absorb B12 in terminal ileum where IF receptors are located
Check for autoantibodies
against intrinsic factor or gastric parietal cells
Treat with B12 injections
load initially with 5 doses alternate days, then every 3 months
what are other causes of pernicious anaemia
Dietary
Strict vegans (B12 found in diary produce)
Supplement with oral B12
Malabsorption:
Coeliac disease and Crohn’s disease
Post gastric / ileal surgery
how is folate deficiency caused
Dietary – common
Malabsorption
Coeliac
Crohn’s disease
Excess Utilisation
Chronic haemolysis
Pregnancy
Alcohol
Drugs
Phenytoin
Methotrexate
what is the most common cause of anaemia in hospitalised patients
anaemia of chronic disease
what are common causes of anaemia of chronic disease
Chronic inflammation
Chronic infection e.g. TB
Auto-immune conditions
e.g. rheumatoid arthritis
Cancer
Renal failure (also causes low EPO level)
how does poor utilisation of iron in the body cause CD anaemia
Iron is stuck in macrophages of the reticuloendothelial system
There is poor mobilisation of the iron from the stores into the erythroblasts
how does dysregulation of iron homeostasis in the body cause CD anaemia
Decreased transferrin
Increased ferritin (acute phase reactant)
Increased hepcidin
how does Impaired proliferation of erythroid progenitors in the body cause CD anaemia
Blunted response to EPO (erythropoietin)
Iron is functionally unavailable
what causes sickle cell disease
Point mutation in the beta globin gene causing HbS (sickle Hb)
leads to Increased turnover of red cells = survival approx 20 days due to haemolysis
Raised reticulocytes >10%
what is sickle cell crisis
Triggered by low blood O2 level
Vaso-occlusive due to sickling in the vessels
Causes ischaemia leading to pain, necrosis and potential organ damage
how is sickle cell disease managed
Analgesics, hydration, transfusion
compensated by 2,3DPG to move oxygen dissociation curve to the right
what characterised sickle cell disease
Genetic, autosomal recessive
Sub-Saharan Africa
Shortened life expectancy (42 for men and 46 for women without good management)
what is the mechanism of sickle cell disease
Increased mechanical fragility resulting in shortened lifespan (6-10 days)
The rigidity of sickle cells results in increased viscosity with occlusion of small blood vessels
Adhesion of sickle cells to endothelium
what is thalassemia
Insufficient production of normal Hb
Imbalance of alpha and beta chains
Inherited autosomal recessive
Either alpha or beta thalassaemia
what are the clinical features of thalassemia
enlarged spleen, liver, and heart
bones may be misshapen (frontal bossing)
what are the two types of thalassemia
Beta-thal major (homozygous) = disease - requires life-long transfusions
Beta-thal minor (heterozygous) = carrier (aka Beta-thal trait) - clinically healthy
where is beta thalassemia found
Family history
Trait vs disease
Distribution as per malaria
how is beta thalassemia diagnosed
characteristic indices Microcytic Hypochromic Hb electrophoresis Blood Film
what are the diseases of bone marrow infiltration
leukaemia
lymphoma
myeloma
what are the symptoms of leukaemia
Non-specific symptoms
Bone marrow failure
what are the symptoms of lymphoma
Lymphadenopathy
Weight loss
what are the symptoms of myeloma
Anaemia
Hypercalcaemia
Renal Failure
Bone lesions
how is bone marrow infiltration diagnosed
Bone marrow sample obtained from iliac crest:
aspirate film for morphology of cells
trephine biopsy for histological section
when does acute anaemia need a transfusion
Acute > chronic
guided by symptoms rather than Hb level
make blood with haematinic therapy?
If not, then transfuse for symptoms (usually if Hb <80g/L)
what are the signs of acute chronic haemorrhage
Haematemesis (vomiting blood)
Melaena (darkened stools)
how is chronic anaemia managed
Treat the underlying cause:
Iron supplementation (oral ferrous sulphate 3 months)
Folic acid (oral folate for 3 months)
B12 (load initially then injections every 3 months)
how is chronic anaemia treated in patients with haemodialysis or kidney failure
Erythropoietin (EPO) weekly sub-cut injections
what are long term causes for transfusion in chronic anaemia
Iron overload (iron deposition in organs) Allo-antibodies (to foreign red cells)
what is the world wide impact of anaemia
increased risk of morbidity in children
impaired physical and cognitive development
poor pregnancy outcome
contributes to 20% of all maternal deaths
reduced work productivity in adults
what is anaemia of chronic disease
Normal-sized cells
Iron trapped inside macrophages
Cancer, inflammation, rheumatoid arthritis
Normal/raised ferritin, normal/low transferrin
Raised hepcidin (and inflammatory proteins)
what is anaemia due to renal failure
Lack of erythropoietin (low serum Epo level)
Red cell hormone produced by kidney
Treat with recombinant Epo (weekly sc injection)
what is bone marrow failure
Not making enough red cells
Reticulocyte count is low
Haematinics are normal
Can be congenital
rare bone marrow failure states
how can bone marrow failure be acquired
three causes:
1) Marrow is empty (aplastic anaemia)
2) Marrow is full (infiltration e.g. leukaemia)
3) Marrow is not working (e.g. dysplasia)
what is the main causes for haemolysis
Inherited:
Membrane problems
Haemoglobin problems
Metabolic problems
Acquired:
Immune (antibodies)
Non-immune (direct damage)
how can inherited red cell issues be membrane problems
Membrane problems
e.g. hereditary spherocytosis or elliptocytosis
Red cells are spherical, not biconcave
Splenectomy can help (may need cholecystectomy for gallstones also)
what is haemoglobinopathy
inherited issues eg sickle cell disease (wrong type of Hb)
e.g. thalassaemia (not enough Hb)
what are metabolic red blood cell issues
e.g. G6PD deficiency
X-linked recessive, males, Afro-Caribbean
Must avoid fava beans, legumes, certain antimalarials and antibiotics
what are acquired red cell problems
Immune i.e. antibody-mediated (spherocytes)
Autoimmune (warm IgG vs. cold IgM)
Alloimmune (red cell transfusion reaction)
Non-immune (red cell fragments)
Heart valves (mechanical)
DIC (very sick patients - sepsis, metastatic cancer)
MAHA (microangiopathic haemolytic anaemia)
how can haemolysis be diagnosed
inherited?
haemolysis screen
Direct anti-globulin test (DAT or Coomb’s test)
Bilirubin level – is patient jaundiced?
Blood film – are there spherocytes? fragments?
LDH level – goes up in haemolysis
Reticulocyte count – goes up in haemolysis
Haptoglobins – levels go down in serum (binds free Hb)
Haemoglobinuria = free Hb in urine (dark colour)
Urine dipstick shows urobilinogen (colourless)
what are the main causes of bleeding
bowel
menstrual
cancer
what is sequestering
Internal bleeding E.g. trauma or vascular rupture Abdomen Thorax Tissues or due to Big spleen (hypersplenism)
what causes HbS
Substitution of valine for glutamic acid at 6th amino acid position (qualitative change)
deoxygenation, HbS forms parallel aggregates
Valine substitution stabilises this conformational change causing sickling (aggregate formation)
Red cell shape is deformed into sickle shape
how is sickle cell disease inherited
Inherit 1 copy of globin gene from each parent
If only 1 HbS gene inherited = sickle cell trait
This is generally asymptomatic
If both parents have sickle trait, then there is a 25% chance of the offspring inheriting both sickle genes
HbC is genetic variant of sickle Hb (6th aa, lysine)
SC disease clinically very similar to SS disease
what are the clinical features of sickle cell in babies
Presentation in infancy (baby protected by HbF)
Anaemia and jaundice
Dactylitis, epiphyseal damage can result in shortening of the digits
Splenic sequestration only in children
Classical vaso-occlusive crises
Pneumococcal septicemia
how can sickle cell anaemia present as clinical complications
Chest syndrome SOB Pleuritic chest pain Patchy shadowing on CXR Progressive hypoxia and fever Brain syndrome Presents as stroke Aplastic crisis Associated with parvovirus infection
how does sickle cell present on a blood film
Sickle cells
Polychromasia
Howell-Jolly bodies
Nucleated RBCs
how is sickle cell anaemia diagnosed
positive sickle cell solubility test (less soluble)
haemoglobin electrophoresis
how can sickle cell be managed
Antenatal screening In high prevalence areas But variable clinical course Prophylaxis against infections Penicillin prophylaxis Vaccination pneumovax / meningovax / haemophilus (HIB) Prevention of crises Avoid infections, hypoxia, dehydration
how can sickle cell crisis be managed
Exclude underlying infection Intravenous fluids Oxygen Analgesia NSAID’s Opiates Avoid pethidine (seizures and addiction) Antibiotics Monitor FBC and reticulocyte count
how can stroke be prevented in sickle cell
Transcranial doppler predictive of stroke
If blood flow >200cm/sec the risk of stroke is significantly increased
Risk reduced by exchange transfusion
Aim to reduce HbS level to below 30%
Hydroxyurea is an alternative if unable to transfuse
how is exchange transfusion done
Manually or with cell separator machine Aim to reduce HbS level to <30% Blood-match ABO/Rhesus/Kell/Sickle neg Indications: Chest syndrome Stroke Major surgery Recurrent severe crises Priapism
what are complications for sickle cell
Sepsis Bone infarcts Avascular necrosis of femoral/humoral heads Gallstones (pigment stones) Proliferative retinopathy Osteomyelitis (Salmonella) Papillary necrosis/renal failure Leg ulcers
what are new treatments for sickle cell disease
Hydroxyurea reduced frequency of crises, chest syndrome and transfusions
what is hydroxyurea
Also known as hydroxycarbamide
Leads to reactivation of gamma globin locus in patients
Results in increased production of fetal Hb (HbF)
Results in reduced sickling of red cells
Also, reduction in WCC and platelets
Reduction in frequency of crises
what is HPFH (hereditary persistence of fatal Hb
HbF levels over 20%
These patients have fewer crises and a milder clinical phenotype
Understanding the biology might allow new therapies to be developed to increase HbF
what is allogeneic SCT
Potentially curative Survival 90-95%, 80-85% cured Patients usually below 16 years History of stroke, recurrent chest syndrome or severe painful crises Infertility likely 5-10% risk of chronic GvHD
