Anaemia Flashcards
What is anaemia defined as?
Low Hb concentration
Hb <135g/L for men OR <115g/L for women
Give the symptoms of anaemia
May be due to the cause or due to the anaemia itself Fatigue Dyspnoea Faintness Palpitations Tinnitus Anorexia Headache
What are some signs of anaemia
May be absent
Pallor - conjunctival pallor although not a reliable sign
Angina if pre-existing coronary artery disease
Hyperdynamic circulation in severe anaemia - ejection systolic murmur heard at the apex and cardiac enlargement
Retinal haemorrhages
Heart failure
In what situation may blood transfusion for anaemia be fatal?
In heart failure
Which blood value is most important to look at when diagnosing anaemia
MCV (mean cell volume)
List some causes of a microcytic anaemia (low MCV)
Iron deficiency Thalassemia Sideroblastic anaemia (very rare)
What happens to iron in thalassemia?
Accumulation so tests show increased iron and ferritin with a low total iron binding capacity
List some causes of normocytic anaemia (normal MCV)
Acute blood loss Anaemia of chronic disease Bone marrow failure Hypothyroidism Renal failure Haemolysis Pregnancy
What should you suspect if there is decreased WCC or decreased platelets in normocytic anaemia?
Bone marrow failure
List some causes of macrocytic anaemia (high MCV)
B12 or folate deficiency Alcohol excess or liver disease Reticulocytosis Cytotoxic - hydroxycarbamide Myelodysplastic syndromes Marrow infiltration Hypothyroidism Antifolate drugs (phenytoin)
What is reticulocytosis?
> 2% of RBCs are reticulocytes or reticulocyte count >100
How may a haemolytic patient present?
Mildly jaundice - pre hepatic unconjugated jaundice
When does a patient require a blood transfusion?
If Hb<70g/L and acute anaemia
What factors must be considered before giving a blood transfusion?
Comorbidities - IHD
Symptoms
Blood group
Religion
Explain how you treat severe anaemia with heart failure
Restore Hb to 60-80g/L
Give blood slowly with 10-40mg furosemide IV/PO with alternate units
What are some signs of worsening overload?
Rising JVP
Basal crackles
When would you suspect haemolytic anaemia?
Reticulocytosis Mild macrocytosis Decreased haptoglobin Increased bilirubin Increased LDH Increased urobilinogen
What are the causes of iron deficiency anaemia
Blood loss - menorrhagia or bleeding (upper and lower GI)
Malabsorption (eg. coeliac) may cause refractory IDA
What are some signs of chronic iron deficiency anaemia
Koilonychia
Angular cheilosis
Atrophic glossitis
Post-cricoid webs (Plummervison syndrome)
Describe the blood test results in iron deficiency anaemia
Blood film - microcytic, hypochromic anaemia witgh anisocytosis and poikilocytosis
Decreased MCV, MCH, MCHC, ferritin
Increased transferrin
What is ferritin also a marker of
Inflammation - infection and malignancy - acute phase protein
What should all non menstruating men and women be referred for if they have iron defiency anaemia and a negative coeliac serology?
Upper and Lower GI endoscopy
How do you treat iron deficiency anaemia?
Ferrous sulphate 200mg/8h PO, continue 3 months after Hb has normalised to replenish the stores
What are some side effects of ferrous sulphate?
Nausea, abdominal discomfort, diarrhoea, constipation, black stools
What is the main reason iron replacement fails?
Patient non-compliance
Consider alternative diagnosis
How should Hb rise in iron deficiency anaemia treated with oral iron replacement?
10g/L/week
Describe how anaemia of chronic disease arises
Poor use of iron in erythropoiesis
Cytokine induced shortening of RBC survival
Production of and response to erythropoietin reduced
Describe the blood test results for anaemia of chronic disease
Normal MCV, low Hb, ferritin normal or increased in mild normocytic/microcytic anaemia
List some causes of anaemia of chronic disease
Malignancy Infection Vasculitis Rheumatoid Renal failure
What other investigations should be done for anaemia of chronic disease?
Blood film B12 Folate TSH Haemolysis tests
How is anaemia of chronic disease managed?
Treat the underlying cause
Erythropoietin
Give the side effects of erythropoietin
Flu like illness
Hypertension
Mild rise in platelet count
Thromboembolism
Which type of anaemia is most likely with an increased red cell distribution width?
Mixed anaemia
Which anaemia must be thought of for a microcytic anaemia not responsive to iron
Sideroblastic anaemia
What causes sideroblastic anaemia
Congenital (rare, x linked)
Idiopathic as a myeloproliferative disorder
Follows chemo and TB medications
Alcohol or lead excess
What is sideroblastic anaemia characterised by?
Ineffective erythropoiesis leading to increased iron absorption, iron loading into the marrow +/- haemosiderosis
What is haemosiderosis?
endocrine, liver and heart damage due to iron deposition
How is sideroblastic anaemia diagnosed?
Increased ferritin
Blood film - hypochromic blood film and sideroblasts in marrow
How is sideroblastic anaemia treated?
Remove cause
Pyridoxine +/- repeated transfusions for severe anaemia
What is ferritin?
Protein which stores iron
What are howell jolly bodies?
DNA nuclear remnants in RBCs, which are normally removed by the spleen
Which conditions are howell jolly bodies seen in?
Post-splenectomy, Hyposplenism (sickle cell, coeliac, IBD, congenital, myeloproliferative disease Dyserythropoietic states (myelodysplasia and megaloblastic anaemia)
When are reticulocytes seen?
Haemolysis
Active haemorrhage
When treatment is given to Iron/B12/folate deficient marrow
What are reticulocytes?
Young, larger RBCs containing RNA
What is a rouleaux formation?
RBCs stack on top of one enough
Which blood result is increased as a result of rouleaux formation?
ESR
When are rouleaux formations seen?
Chronic inflammation
Myeloma
Paraproteinemia
What are target cells?
Also known as mexican hat cells
RBCs with central staining, ring of pallor and an outer rim of staining
Where are target cells seen?
Liver disease
Hyposplenism
Thalassaemia
Give an example of when a macrocytosis is not associated with anaemia
Alcohol excess
What is a megaloblast?
Cell in which nuclear maturation is delayed in comparison with the cytoplasm
What causes a megaloblastic macrocytic anaemia?
B12 and folate deficiency
Cytotoxic drugs
List some causes of non-megaloblastic macrocytosis
Alcohol excess Hypothyroidism Reticulocytosis - haemolysis Liver disease Pregnancy
What cells are seen on blood film in B12 and folate deficiency
Hyper segmented neutrophils
What can maternal folate deficiency cause
Neural tube defects
Where is folate absorbed?
Duodenum
Jejunum
List some causes of folate deficiency
Poor diet
Increased demand - pregnancy, haemolysis, inflammation
Malabsorption - coeliac and tropical sprue
Drugs - antiepileptics (phenytoin and valproate), methotrexate and trimethoprim
What is the advised folate dose for pregnant women?
400mcg/day from conception till 12 weeks to prevent anaemia and spina bifida
How is folate deficiency anaemia treated?
5mg/day folic acid PO for 4 months
Assess underlying cause
How long do folate stores in the body last?
4 months
How long do B12 stores in the body last?
4 years
What is vitamin B12 used for in the body?
Synthesis of DNA
How is B12 absorbed?
Binds to intrinsic factor in the stomach
Absorbed via the terminal ileum
List the causes of Vitamin B12 deficiency
Dietary - vegans
Malabsorption - lack of intrinsic factor or problems with terminal ileum (Crohns, bacterial overgrowth, resection and tapeworm)
Congenital metabolic error
What is pernicious anaemia?
Autoimmune condition in which atrophic gastritis leads to a lack of intrinsic factor secretion from parietal cells of the stomach. Dietary B12 remains unbound and cannot be absorbed in terminal ileum
List the symptoms of B12 deficiency
Symptoms of anaemia - fatigue, dyspnoea, faintness, palpitations, headache, tinnitus, anorexia
Yellow tinge to skin - combination of pallor (anaemia) and jaundice (haemolysis)
Mouth - Glossitis (beefy, red sore tongue), Angular cheilosis
Neuropsychiatric - irritability, depression, psychosis, dementia, subacute combined degeneration of the spinal cord
Describe subacute combined degeneration of the spinal cord
Combination of peripheral sensory neuropathy with both upper (extensor plantars) and lower motor neuron signs (loss of knee and ankle jerk). Pain and temperature still in tact even in severe cases due to spinothalamic tract. This degeneration affects the posterior dorsal column and corticospinal tracts.
What other conditions are associated with pernicious anaemia?
Autoimmune - hypothyroidism, DM, vitiligo, addisons, hypoparathyroidism
Carcinoma of the stomach - low upper GI endoscopy threshold
What investigations could you do for pernicious anaemia
FBC (decreased Hb, Increased MCV), serum B12 (decreased), reticulocytes (decreased), blood film (hyper segmented neutrophils), specific antibodies for IF and Parietal cells
Describe how you treat B12 anaemia
Treat the cause
If malabsorption - give hydroxocobalamin (B12) 1mg IM every 2 weeks and then 1mg IM every 3 months for life
If dietary - Oral after IM course (50-150mcg daily, between meals)
How do you know B12 anaemia is improving?
Marked reticulocytosis - increased MCV after 4-5 weeks
What is haemolysis?
The premature breakdown of RBCs, before their normal lifespan of 120 days
Where does haemolysis occur?
Intravascular - in the circulation
Extravascular - by macrophages in the liver, spleen and bone marrow
How short may the RBC lifecycle be in sickle cell anaemia?
5 days
What is significant in the history for detecting haemolysis?
FH Travel Jaundice Dark urine Race Drugs Previous anaemia
What is significant on clinical examination for detecting haemolysis?
Jaundice
Hepatosplenomegaly
Gallstones - pigmented - bilirubin high
Leg ulcers - poor blood flow
Give the results of a typical picture of haemolysis
Decreased Hb
Normal or high MCV
Increased bilirubin (unconjugated from haem breakdown - pre-hepatic jaundice)
Increased urinary urobilinogen
Increased serum LDH
Increased reticulocytes
Decreased plasma haptoglobin
Polychromasia and macrocytosis on the blood film
Positive direct antiglobulin test (coombs)
Describe drug induced haemolysis
Formation of RBC autoantibodies from binding to RBC membranes (penicillin) or production of immune complexes (quinine)
What is autoimmune haemolytic anaemia
Mediated by autoantibodies causing mainly extravascular haemolysis and spherocytosis
Give the two classifications of autoimmune haemolytic anaemia
Warm
Cold
Describe warm autoimmune haemolytic anaemia
IgG mediated
Bind at body temp 37
How do you treat warm autoimmune haemolytic anaemia
Steroids/immunosuppression +/- splenectomy
Describe cold autoimmune haemolytic anaemia
IgM mediated
Bind at lower temperatures
Activates cell surface complement
Causes a chronic anaemia made worse by the cold, often with raynauds or acrocyanosis
How do you treat cold autoimmune haemolytic anaemia
Keep warm
Chlorambucil may help
What causes cold autoimmune haemolytic anaemia
Infection - mycoplasma or EBV
What causes warm autoimmune haemolytic anaemia?
Lymphoproliferative disease - CLL, lymphoma
Drugs
Autoimmune disease - SLE
What happens in paroxysmal cold haemoglobinuria
Caused by donath-landsteiner antibodies sticking to RBCs in the cold, causing self limiting complement mediated haemolysis on rewarming
What is paroxysmal cold haemoglobinuria associated with?
Syphilis and viral illness
Describe isoimmune haemolytic anaemia
Acute transfusion reaction, haemolysis of the new-born
Which haemolytic anaemias can be considered if DAT is negative?
Autoimmune haemolytic anaemia (2%)
Membrane defects - hereditary spherocytosis, hereditary elliptocytosis and hereditary ovalocytosis and stomatocytosis
What is microangiopathic haemolytic anaemia
Mechanical damage to RBCs in circulation, causing intravascular haemolysis and schistocytes
What causes Microangiopathic haemolytic anaemia?
Haemolytic-uraemic syndrome TTP DIC Pre-eclampsia Eclampsia Prosthetic heart valves
Name the main infection which exacerbates/causes haemolysis
Malaria
Describe paroxysmal nocturnal haemoglobinuria
Rare acquired stem cell disorder with haemolysis especially at nigh, marrow failure and thrombophilia.
Describe glucose-6-phosphate dehydrogenase deficiency (X-linked)
X-linked
Affects male mediteranean, africa, middle east
100 million
Most asymptomatic - may gegt oxidative crises due to decreased glutathione production
Precipitated by drugs - sulphonamides, primaquine and aspirin, exposure to broad beans or illness.
In attacks, rapid jaundice and anaemia
Tests - enzyme assay
Treat with transfusion if severe, otherwise avoid precipitants
Describe pyruvate kinase deficiency
Autosomal recessive
Decreased ATP decreased RBC survival
Homozygotes presents with neonatal jaundice. Jaundice, haemolysis and splenomegaly if present later
Tests - enzyme assay
Treatment - usually none, splenectomy may help some
Name the 3 membrane defects causing haemolytic anaemia
Hereditary spherocytosis (autosomal dominant) Hereditary elliptocytosis (autosomal dominant) Hereditary ovalocytosis and stomatocytosis are rare - refer to haematology
Name two haemoglobinopathies which can cause a haemolytic anaemia
Sickle cell
Thalassemia
What is sickle cell anaemia?
Autosomal recessive disorder in which production of abnormal haemoglobin results in vaso-occlusive crises
Arises from an amino acid substitution in the gene encoding the beta chain (glu-val at position 6)
Leads to production of HbS rather than HbA
What are heterozygotes for the sickle cell gene called?
Sickle cell trait
When might heterozygotes/sickle cell trait experience symptomatic sickling?
In hypoxia - unpressurised aircraft or anaesthesia
Describe the pathogenesis of sickle cell disease
HbS polymerizes when deoxygenated, causing RBCs to deform, producing sickle cells, which are fragile and haemolyse, also block small vessels
How do you test for sickle cell anaemia?
Haemolysis is variable, may have reticulocytosis
Increased bilirubin
Film - sickle cells and target cells
Sickle solubility test - confirms diagnosis but does not distinguish between HbSS and HbAS types
Hb electrophoresis - confirms the diagnosis and type
When should you aim for a sickle cell diagnosis and why?
At birth from cord
Able to give pneumococcal prophylaxis
What are the three types of sickle cell crisis?
Vaso-occlusive “painful” crisis
Aplastic crisis
Sequestration crisis
What triggers a vaso-occlusive crisis?
Cold
Dehydration
Infection
Hypoxia
Describe vaso-occlusive crisis
Microvascular occlusion, often affects the marrow causing severe pain
Mesenteric ischemia
CNS - stroke, seizures and cognitive effects
Hands and feet are affected if <3yo leading to dactylitis
Avascular necrosis (femoral head)
Leg ulcers
Low flow priapism (venous blood not being able to leave the penis)
What causes an aplastic crisis?
Parvovirus B19
Describe aplastic crisis
Sudden reduction in production of RBCs
Usually self limiting but may require transfusion
Describe sequestration crisis
Mainly affects children as in adults the spleen becomes atrophic
Pooling of blood in the spleen and sometimes liver
Organomegaly
Severe anaemia
Shock
Urgent transfusion needed
List the complications of sickle cell crisis?
Splenic infarction - commonly occurs <2yo, leads to increased susceptibility to infection
Poor growth
Chronic renal failure
Gallstones
Retinal disease
Iron overload
Lung damage - hypoxia causes fibrosis and leads to pulmonary hypertension
Describe the management of chronic sickle cell anaemia
Hydroxycarbamide if frequent crises - increases production of fetal Hb
Splenic infarction leads to Hyposplenism and immunocompromise so vaccinations and prophylactic antibiotics
Bone marrow transplant - curative but controversial
How can sickle cell anaemia be prevented?
Parental education - prevents 90% deaths from sequestration crises
Genetic counselling
Prenatal tests
Describe the acute management of a sickle cell crisis
Give prompt, generous analgesia eg. IV opiate
Cross match blood, FBC and reticulocyte count
Do a septic screen - blood cultures, MSU and CXR
Rehydrate with iVI and keep warm
Give O2 by mask if PaO2 decreases or sats<95%
Consider starting empirical antibiotics early if unwell, temp >38 or chest signs
Inform their haematologist and get help early
Measure PCV, reticulocytes, liver and spleen size daily
Give blood transfusion if Hb or reticulocytes fall sharply (aplastic). Match for RH (C,DE) and kell to prevent alloantibody formation
Exchange transfusion for those who are rapidly worsening
Describe the acute chest syndrome and its management
Pulmonary infiltrates (fat embolism from the bone marrow or infection with chlamydia, mycoplasma and viruses) involving complete lung segments, causing pain, fever, tachypnoea, wheeze and cough
O2 Analgesia Empirical antibiotics - cephalosporin and macrolide until cultures known Blood transfusion ITU if PaO2 <9.2
What is beta thalassaemia?
Genetic disease, caused by point mutations in globin genes, of unbalanced Hb synthesis with underproduction/overproduction of one globin chain (beta). Unmatched globin precipitate, damaging RBC membranes, causing their haemolysis which still in the marrow. Common in areas from the Mediterranean and far east
Which chromosome is beta globin found?
11
What investigations do you do for thalassaemia?
FBC MCV Film Iron studies HbA2 HbF Hb electrophoresis MRI when myocardial siderosis suspected
Name the 3 types of beta thalassaemia
Beta thalassaemia minor/trait
Beta thalassaemia intermedia
Beta thalassaemia major
Describe Beta thalassaemia minior/trait
Carrier state and usually asymptomatic
Minor anaemia, well tolerated, may worsen in pregnancy
MCV<75, HbA2 >3.5%, slight increased HbF
Describe beta thalassaemia intermedia
Intermediate state with moderate anaemia not requiring transfusion
Splenomegaly
Variety of causes
Describe beta thalassaemia major
Significant abnormalities in both beta globin genes and presents in 1st year of life with severe anaemia and failure to thrive
Extra-medullary haematopoiesis (RBCs made outside the marrow) occurs in response to anaemia and causes characteristic bossing of the skull.
Osteopenia
Skull X-ray shows hair on end sign due to increased marrow activity
Lifelong blood transfusions needed with resulting iron overload seen >10 years as endocrine failure, cardiac toxicity and liver disease
Film - hypochromic microcytic cells, target cells, nucleated RBCs
Increased HbF and variable HbA2, HbA absent
Describe the treatment for thalassaemia
Promote fitness, healthy diet and folate supplements
Lifelong regular (2-4 weekly) transfusions to keep Hb>90 and suppress extramedullary haematopoiesis
Iron chelators and ascorbic acid to help mitigate iron overload from transfusions
Splenectomy if hypersplenism persists but avoid till >5yo due to increased infection risk
Hormone replacement and endocrine complication treatment
Bone marrow transplant
