Anaemia Flashcards
Anaemia
How is anaemia classified (bloods)?
Hb:
< 12g/dL in females
<13.5g/dL in males
Anaemia
What is the most common cause of anaemia?
iron deficiency anaemia
Anaemia
List the types of microcytic anaemia.
(4)
- iron deficiency
- thalassemias
- sideroblastic
- anaemia of chronic disease
Anaemia
Macrocytic anaemias can be megaloblastic and non-megaloblastic.
Name some causes of megaloblastic anaemia.
(2)
- Vit B12 deficiency
- folate deficiency
Anaemia
Macrocytic anaemias can be megaloblastic and non-megaloblastic.
Name some causes of non-megaloblastic anaemia.
rare
- Chronic alcoholism
- Liver disease
- Hypothyroidism
- Drugs e.g. anti-retroviral for HIV or hydroxyurea
- Myelodysplastic syndrome
Anaemia
List the causes of normocytic anaemia.
(4)
- Increased loss or breakdown of red blood cells (increased reticulocytes)
- Decreased production of red blood cells (normal or decreased reticulocytes)
- Increased plasma volume (normal or decreased reticulocytes)
- Coeliac disease
Anaemia
What circumstances might cause increased a loss or breakdown of red blood cells (increased reticulocytes) causing anaemia?
(2)
Haemolysis
or
Haemorrhage
Anaemia
What are some causes of haemolysis?
grouped into 2 sets
Acquired
- infections (malaria)
- autoimmune disorders
- physical damage (from an artificial heart valve)
- drugs
Hereditary
- G6PD deficiency (X – linked recessive and more common in African/Mediterranean backgrounds)
- sickle – cell anaemia
- hereditary spherocytosis
- paroxysmal nocturnal haemoglobinuria
Anaemia
What circumstances might cause decreased production of red blood cells (normal or decreased reticulocytes) causing anaemia?
(3)
- CKD or EPO deficiency
- Bone marrow suppression* (due to infection/drugs/malignancy)*
- Anaemia of chronic disease
Anaemia
What circumstance might cause **Increased plasma volume ** (normal or decreased reticulocytes) causing anaemia?
(1)
Pregnancy
Anaemia
Why might coeliac disease cause normocytic anaemia?
mixed deficiencies of folate (macrocytic anaemia) and iron (microcytic anaemia) can occur cancelling each other out and causing normocytic anaemia.
Anaemia
Name some symptoms of anaemia.
4
- fatigue / weakenss
- SOB
- pallor
- palpitations
Anaemia
Name some Symptoms of vitamin B12 deficiency.
- Paraesthesia
- Ataxia/reduced sense of vibration/positive Romberg’s test due to degeneration of the posterior column
- Pale skin
- Petechiae
- Glossitis
- Angular cheilitis
- Cognitive impairment
+ Usual symptoms of anaemia
Anaemia
Name some symptoms of folate deficiency.
- Headache
- Weight loss
+ Usual symptoms of anaemia
Anaemia
Name some symptoms of haemolytic anaemia.
- Jaundice
- Splenomegaly may occur with hereditary spherocytosis or non – Hodgkin’s lymphoma
- Hereditary spherocytosis can cause gallstones – right upper quadrant pain
- Dark urine will be seen in intravascular haemolysis e.g. G6PD deficiency or paroxysmal nocturnal haemoglobinuria
+ Typical signs of anaemia
Anaemia
What parameters of MCV classify:
- micro
- macro
- normo
anaemia
- Microcytic anaemia = MCV <80fL
- Macrocytic anaemia = MCV **>100fL **
- Normocytic anaemia = MCV 80-100fL
Anaemia
How might iron studies come back for:
Iron deficiency anaemia
- low serum iron
- low ferritin
- increased total iron-binding capacity
- transferrin <16%
How might iron studies come back for:
Thalassemia
normal
How might iron studies come back for:
Sideroblastic anaemia
- high serum iron
- high ferritin
- low total iron-binding capacity
How might iron studies come back for:
Anaemia of chronic disease
- low serum iron
- high ferritin
- low total iron-binding capacity
- transferrin 5-15%
Anaemia
What might cause Vit B12 deficiency?
- vegan diet
- Crohn’s disease
- gastric bypass
- pernicious anaemia
What might cause folate deficiency?
pregnancy or diet
Anaemia
What might cause iron deficiency anaemia?
- Blood loss
- diet
- Poor iron absorption e.g. coeliac disease, IBD, H. Pylori, GI surgery or TMRPSS6 gene mutation
Anaemia
How do pts with beta-thalassemia trait present?
usually asymptomatic with little anaemia, but marked microcytosis
Anaemia
What is sideroblastic anaemia?
Why might be the cause of this happening? (3)
iron accumulation in red blood cell’s mitochondria prevents the ability to use iron to produce haemoglobin
- Inherited (X – linked recessive, ALAS2 gene)
- Acquired e.g. alcoholism, myelodysplastic syndrome, copper deficiency, B6 deficiency
- Idiopathic
Anaemia
What chronic diseases might cause anaemia of chronic disease?
Autoimmune disease
Cancer
Anaemia
What might reticulocyte count be like in normocytic anaemia?
Hyperproliferative (reticulocyte count >2%) due to haemmorhage/haemolysis and therefore increased erythropoeisis
Hypoproliferative (reticulocyte count <2%) due to disease of decreased erythropoeisis originally
Anaemia
Why might creatinine be raised in a pt with normocytic anaemia?
CKD
Anaemia
What investigation (beyond bloods) might you do for iron deficiency anaemia?
- Test for H. Pylori infection
- Consider faecal occult blood test and endoscopy or colonoscopy in patients with suspected GI bleeding
- Coeliac serology to rule out coeliac disease
Anaemia
What investigation is required to diagnose sideroblastic anaemia?
What will a positive test show?
Bone marrow biopsy and staining of red blood cells
- ringed sideroblasts in mitochondria seen.
Anaemia
What investigation (beyond iron studies) might you do for megaloblastic anaemia?
- Blood smear
- Test vitamin B12 and folate levels
- Plasma homocysteine
- Plasma or serum methylmalonic acid
- Test for anti–Intrinsic factor antibodies
- Endoscopy for patients with suspected Crohn’s disease
Anaemia
How would a blood smear help is to differentiate between megaloblastic and non-megaloblastic anaemia?
Macrocytosis and hypersegmented neutrophils seen on a blood smear for megaloblastic
Anaemia
How do plasma homocysteine and plasma/serum methylmalonic appear in B12 and folate deficiency?
Plasma homocysteine
- increased in B12 deficiency
- increased in folate deficiency
Plasma/serum methylmalonic acid
- increased in B12 deficiency
- normal in folate deficiency
Anaemia
What investigation (beyond bloods) might you do for non-megaloblastic anaemia?
Very complicated, just read thru this one
- Imaging to look for suspected haemorrhage.
- Haemolysis: increased LDH, decreased haptoglobin, increased bilirubin, raised reticulocytes. A peripheral smear will show abnormal red blood cells such as schistocytes, spherocytes, blister cells or tear cells depending on the cause.
- Hereditary spherocytosis (haemolytic anaemia) can cause gallstones which can be seen on x-ray.
- Coombs test used to test for or rule out autoimmune haemolytic anaemia, in which case it will be positive.
- Haemoglobin electrophoresis may be needed to diagnose sickle cell disease.
- G6PD deficiency: Peripheral blood smear will show Heinz bodies and bite cells. (Note that during an acute attack, G6PD levels will not be low).
- Flow cytometry is needed for paroxysmal nocturnal haemoglobinuria diagnosis: >1-3% of anchor-deficient granulocytes.
Anaemia
How do we treat pts with iron deficiency anaemia? (prescribing)
Iron replacement
- Oral
- Consider ascorbic acid alongside iron supplementation if oral iron is not well tolerated.
- IV iron replacement can be used for patients not tolerating oral iron.
- A blood transfusion may also be required.
Anaemia
In what form do pts take oral iron replacement? What is taken alongside it?
- ferrous sulphate
- ferrous gluconate
- ferrous fumarate
- ferric maltol
usually taken alongside vitamin C
Anaemia
How do we treat pts with Vit B12 deficiency, asymptomatic/mild deficiency? (prescribing)
vegan pts or over 65 years old with an inadequate diet
- oral B12 supplementation
- if no response -> cyanocobalamin or hydroxocobalamin for life.
pts with chronic GI condition/reasons cyanocobalamin or hydroxocobalamin should be used.
Anaemia
How do we treat pts with Vit B12 deficiency, symptomatic? (prescribing)
**mild/moderate symptoms **
- lifelong cyanocobalamin or hydroxocobalamin
severe symptoms
- parenteral cyanocobalamin or hydroxocobalamin for life is required.
- refer to specialist to a
Some patients may also require a blood transfusion and folic acid supplementation also.
Anaemia
Who do we give folate supplementation to? (prescribing)
(2)
- All pregnant women
- those at risk of deficiency from other conditions
Anaemia
How do we treat pts with normocytic anaemia caused by chronic renal disease:? (prescribing)
Erythropoiesis stimulating agents
- epoetin alfa can be used
Anaemia
How do we manage sickle cell disease? (prescribing / non-prescribing)
- Long term hydroxycarbamide
- Avoid cold weather, sudden changes in temperature, high altitude or dehydration to prevent a sickle cell crisis.
- Regular blood transfusions with iron chelation therapy may be required.
Anaemia
How do we treat paroxysmal nocturnal haemoglobinuria? (prescribing)
- Eculizumab
- Blood transfusions
Anaemia
How do we treat siderolastic anaemia?
- Treat underlying cause
- Vitamin B6 therapy
- Desferrioxamine subcutaneously or intramuscular used to remove excess iron
Anaemia
How do we manage G6PD deficiency?
- Avoid broad beans or drugs that can cause an attack such as primaquine, aspirin, dapsone or sulphonamides.
- Blood transfusions and folic acid supplementation.
- Splenectomy may be required
Anaemia
What should pt with G6PD deficiency avoid?
broad beans
drugs that can cause an attack:
- primaquine
- aspirin
- dapsone
- sulphonamides
Anaemia
How would these values be in IDA?
____ Hb and haematocrit
____ MCV and ____ MCH
Peripheral blood smear showing ____ and ____
____ Reticulocyte count
____ Serum Iron
____ Total iron-binding capacity (TIBC)
____ Transferrin Saturation
____ Serum Ferritin
< Hb and haematocrit
< MCV and <MCH
Peripheral blood smear showing microcytic, hypochromic cells.
< Reticulocyte count
< Serum Iron
> Total iron-binding capacity (TIBC)
< Transferrin Saturation
< Serum Ferritin
Anaemia
Name some classical signs and symptoms of IDA
10
- Fatigue
- Headaches
- Exercise intolerance
- Weakness
- Pica
- Restless Leg Syndrome
- Exertional Dyspnoea
- Koilonychia
- Cheilosis/Angular Cheilitis
- Atrophic Glossitis
Anaemia
Who is IDA most common in?
2
most common amongst women of childbearing age, children, and those living in middle or low-income countries
Anaemia
IDA can stem from 3 groups of issues:
- Reduced iron intake
- Increased requirements of iron
- Iron loss
Anaemia
Name 4 inherited types of haemolytic anaemias.
- Hereditary spherocytosis
- Glucose-6-phosphate deficiency
- Pyruvate kinase deficiency
- Haemoglobinopathies (sickle cell anaemia and thalassaemia)
Anaemia
What are the 2 mechanisms of destruction of red blood cells in haemolytic anaemia?
intra (occurs within the circulation) and extravascular (a normal physiological process)
Anaemia
What are red blood cell fragments on a blood film called?
Schistocytes
Anaemia
When might you see schistocytes on a blood smear?
found in microangiopathic haemolytic anaemias (e.g. disseminated intravascular coagulation, haemolytic uraemia syndrome, HELLP syndrome) and traumatic processes (e.g. mechanical prosthetic heart valve)
Anaemia
When might you see spherocytes on a blood smear?
found in hereditary spherocytosis and autoimmune haemolytic anaemias
Anaemia
When might you see Blister or bite cells on a blood smear?
found in enzyme deficiencies
(e.g. G6PD deficiency and pyruvate kinase deficiency)
Anaemia
How might we manage autoimmune haemolytic anaemias?
corticosteroids to reduce AB porduction
Anaemia
What might blood count and LFTs show in haemolytic anaemia?
- increased MCHC
- raised serum bilirubin
- raised LDH
Anaemia
What might urinalysis show in haemolytic anaemia?
haemoglobinuria
or haemosiderinuria in intravascular haemolysis
Anaemia
Which test detects the presence of antibodies bound to the red blood cell surface in vivo?
What diagnosis is this test helpful for?
Coombs test
- helpful in the diagnosis of** autoimmune haemolytic anaemia**, haemolytic disease of the newborn and ABO transfusion reactions.
Anaemia
Sideroblastic anaemia is anaemia due to defective ____ synthesis. So if If ____ is deficient, iron stays trapped in mitochondria.
protoporphyrin
Anaemia
Sideroblastic anaemia can be congenital (genetic) or acquired. The most common genetic defect is an X-linked defect in the ____ gene.
ALA synthase
Anaemia
Acquired causes include myelodysplastic syndromes or reversible acquired causes.
Name some reversible acquired causes.
4
- Alcohol is the most common – mitochondrial poison
- Lead poisoning – inhibits ALAD and Ferrochelatase
- Vitamin B6 deficiency – needed cofactor for ALAS. This is most commonly seen as a side effect of isoniazid treatment for tuberculosis but can also be a side effect of linezolid therapy. This is reversible with Vitamin B6 (pyridoxine) administration.
- Copper deficiency
Anaemia
Which stain can we use to visualise ringed sideroblasts in bone marrow in sideroblastic anaemiar?
prussian blue
Anaemia
What may be seen in sideroblastic anaemia on a peripheral blood smear?
- basophilic stippling of RBCs
- Pappenheimer bodies (basophilic granules
- microcytic and hypochromic RBCs
Anaemia
Lab findings of sideroblastic anaemia:
- ferritin
- TIBC
- serum iron
- % saturation
tibc - total iron binding capacity
- increased ferritin
- normal/decreased TIBC
- increased serum iron
- increased % saturation (iron-overloaded state).
Anaemia
Acute management of sideroblastic anaemia (congenital)
1st and 2nd line
1st line: A trial of pyridoxine (50 to 200 mg/day) +/- folic acid
2nd line: Second-line therapy involves packed red blood cell transfusions + iron chelation therapy
Erythropoietin and granulocyte colony-stimulating factor may be trialled in myelodysplasia-associated refractory anaemia with ringed sideroblasts.
Anaemia
Acute management of sideroblastic anaemia (acquired, iatrogenic, drugs)
withdrawing the drug and administering pyridoxine
Anaemia
Management for sideroblastic anaemia (chronic)
- Periodic phlebotomy if iron overloaded.
- Bone marrow transplant if the patient is young and anaemia is refractory to pyridoxine with iron overload and transfusion-dependence.
