Anaemia Tutorial Flashcards
What are the 4 main causes that lead to anaemia?
Reduced production of red cells / haemoglobin in the bone marrow
Reduced survival of red cells in the circulation (haemolysis).
Bleeding / blood loss
Pooling of red cells in a very large spleen
A patients presents with low MCV, low Hb, low RBCs and low MCH
What is the differential diagnosis for this?
Microcytic anaemia (low haemoglobin count)
Issue with RBC production - could be iron deficiency or anaemia of chronic disease
What are the differentials for microcytic anaemia?
Iron deficiency anaemia, thalassaemia, anaemia of chronic disease
What do these test results show?
Low ferritin Low Serum iron High Transferrin Low transferrin saturation No increase HbA2 in Hb electrophoresis
What does this data suggest towards the cause?
Iron deficiency
What further questions would you ask to a patient presenting with iron deficiency anaemia suggestive test results?
Diet - vegetarian or non-vegetarian
GI symptoms e.g. dysphagia, dyspepsia, abdominal pain, change in bowel habit, haematemesis, rectal bleeding, malarna, post-menopausal bleeding
Medications - aspirin, NSAIDs, other steroids
Weight loss
What is haemolysis?
How long does a typical RBC last?
What is anaemia caused by haemolysis?
Destruction of RBCs / shortened life span or RBCs
120 days
Haemolytic anaemia - due to G6PD deficiency
Where is haemolytic anaemia common? And why?
Africa - protects against malaria
What is a common name for a type of haemolytic anaemia?
Who is it more common in and why?
Sickle Cell Anaemia (SCA)
More common in males = recessive disorder
What is the clinical significance between conjugated and unconjugated bilirubin?
UNCONJUGATED = haemolysis
Conjugated = liver disease
Blood count shows:
low Hb
High MCV
High reticulocytes
What does this show?
Reticulocyte = baby RBCs
Bone marrow trying to compensate for anaemia- likely haemolysis due to unconjugated billurubin
What would a blood film for G6PD deficiency show?
Why do we see this?
Ghost cells- shows there’s been intravascular haemolysis
Heinz body- precipitated oxidised Hb
Hemighost
These are all indicators of oxidant damage to the red cells
How can G6PD deficiency be confirmed?
By assay
What advice would be given to a patient with G6DP deficiency?
Avoid oxidant drugs
Avoid broad beans (fava beans)
Avoid naphthalene
Beware haemolysis can result from infection - be mindful getting ill can precipitate a crisis
What are symptoms of SLE with acquired autoimmune haemolytic anaemia?
Fluctuating multi-system disorder: Ploy arthritis Shortness of breath Facial skin rashes Hepatitis Tiredness
Blood tests show:
Low Hb
High Bilirubin
B12 and folate normal
High MCV
What information does this tell us?
Macrocytic anaemia
A patient with haemolytic anaemia has high LDH, why?
Cells are being broken down so intracellular contents are leaking out
What does high unconjugated bilirubin suggest?
Haemolytic anaemia
How can acquired haemolytic anaemia present and what can cause this?
Non-immune: Microangiopathic Haemolytic uraemic syndrome Malaria Snake venom Drugs
Immune mediated:
Auto immune
Allo immune (post blood transfusion)
How is a direct antiglobulin test carried out?
Human antibodies (immunoglobulin) bind to the antigens on saline suspended RBCs
Add to the saline suspended blood cells rabbit antibody, these bind to human immunoglobulin - causes cells to clump giving a positive DAT
When does Autoimmune Haemolytic anaemia occur?
Associated with immune system disorders:
- Systemic auto immune disease
- Underlying lymphoid cancer (lymphoma)
Idiopathic
What is unconjugated bilirubin?
Pre-hepatic bilirubin - has not yet passed through the liver
What would we see on a blood film for hereditary spherocytosis?
Spherocytes - reduced diameter, no central palor = suggests she has something that causes spherocytosis
What is hereditary spherocytosis?
Progressive loss of the RBC membrane - cells get more rigid = rigid spheres
What might we also see on a blood film for hereditary spherocytosis?
Polychromatic macrocytes = reticulocytes
Suggests her bone marrow is producing more RBCs than normal - to replace RBCs that are lost
Haemolysis VS haemolytic anaemia?
Haemolysis = lowered RBC lifespan <120 days
Haemolytic anaemia = cannot compensate for lowered RBC count
How do patients with chronic haemolysis get treated?
Folic acid - need due to increased DNA synthesis
Splenectomy (if severe) to increase red cell life span - spleen takes out the rigid RBCs (spehrocytes) out of the circulation
18 yr patient, previously diagnosed with hereditary spherocytosis, presents with acute upper right abdominal pain and tenderness
Jaundice more marked
High conjugated bilirubin
What is going on?
Gallstones at young age due to increased breakdown of Hb to bilirubin
Stone obstructed bile duct = obstructive jaundice
Liver = still able to conjugate bilirubin but it cannot go anywhere
62F -
Severe tiredness Decreased exercise tolerance Funny feeling on her feet - walking on cotton wool Paler skin and yellowish tinge Depigmentation affecting the face
Blood test shows Low Hb High MCV Low WBC Low platelets High unconjugated bilirubin Low vit B12
What does this information tell you?
Megaloblastic anaemia due to vit B12 deficiency
What does a blood film for megaloblastic anaemia show?
Hypersegmented neutrophils
Very macrocytic RBCs
Poikilocytosis - funny shaped RBCs = tear shapes, ovals, etc.
What are differential for megaloblastic anaemia?
MDS (myelodysplasia)
B12 deficiency
Folate deficiency
Chemotherapy drugs
What are megaloblastic features?
Megaloblasts = large with nucleocytoplasmic dissociation
Impaired DNA synthesis, nuclear maturation and cell division
Adequate cytoplasmic maturation and cell growth
So the maturation of the cytoplasm and nucleus is dyssynchronous (not synchronised) = impaired DNA synthesis
What are B12 and Folic Acid required for?
Vitamin B12 is required for:
- DNA synthesis
- Integrity of the nervous system
Folic acid is required for:
- DNA Synthesis
- Homocysteine metabolism
How can you become B12 or folate deficient?
B12 deficiency: Dietary - malnourishment, veganism Gastric - gastrectomy, autoimmune (pernicious anaemia) Bowel - crohn's disease, ileal resection
Folic acid deficiency:
Reduced availability - poor diet, poverty, alcoholism, malabsorption (coeliac disease, jejunal resection)
Increased demand - pregnancy, lactation, increased cell turnover (haemolysis)
How can B12 and folate deficiencies be treated?
B12 deficiency due to diet = oral supplements
B12 deficiency due to gastric or bowel issues = hydroxocobalamin injections (intramuscular)
Folic acid deficiency = oral supplements
What neurological disorders can present due to Vit B12 and folic acid deficiency?
Vit B12: dementia, SACD (sub-acute combined degeneration) of spinal cord
Folic acid: developmental neural tube defects
Areas of depigmentation suggests?
Vitiligo
What does a medical history of other autoimmune conditions suggest?
Autoimmune - pernicious anaemia
Due to vitiligo which is already an autoimmune condition
Summarise megablastic anaemia and its causes:
Anaemia due to asynchronous nucleocytoplasmic maturation in the bone marrow
Most common causes = Vit B12 and/or folic acid deficiency
Define the terms:
Macrocytic anaemia
Pernicious anaemia
Megaloblastic anaemia
Macrocytic anaemia = anemia with small RBCs
Pernicious anaemia = autoimmune
Megaloblastic anaemia = nucleus and cytoplasm maturation in bone marrow not synchronised; B12 or folic acid deficiency
Case Study:
45M - severe rheumatoid arthritis
Has taken NSAIDs over time and corticosteroids for chronic inflammation
Anaemic - Hb 85
Hb used to be 115 at previous attendance
MCV = 70 = normal Reticulocytes = 54 x 10^9 = lower end of normal Platelets = 550 x 10^9 = high
What does the FBC suggest?
Low reticulocyte for anaemia
High platelet count = due to inflammation
Hb = low
Microcytic anaemia
What are common causes for microcytic anaemia?
Iron deficiency
Patient’s blood test shows:
Hb low MCV low Ferritin high Serum iron low Transferrin low Transferrin saturation normal ESR 79 mm/hr
Which of these results are most important and why?
Ferritin high (can be normal in iron deficiency)
Serum iron low
Transferrin low
Free iron = v. toxic to the body, normally have v.low serum iron
In blood iron is bound to transferrin, in organs iron is bound to ferritin
What does a blood film for anaemia of chronic disease show?
Hypochromic, microcytic, RBCs
Rouleaux (aggregations of RBCs)
What does the high ferritin count suggest?
What does the low transferrin count suggest?
High ferritin = high storage of the iron in the organs
Low transferrin = inappropriately low as it should be raised to allow for iron to be transported around the body where it is required
What is the likely diagnosis?
Anaemia chronic disease - characteristic findings =
Low / normal transferrin when it should be high whilst you’re anaemic
And typically high ferritin
Chronic disease anaemia VS iron deficiency anaemia:
Disease | Anaemia of Chronic Disease | Iron Deficiency Anaemia Hb | low | low MCV | low/normal | low Ferritin | high | low Serum iron | low | low Transferrin | low/normal | high Transferrin saturation | normal | low ESR | high | (may be) high
What is anaemia of chronic disease?
Anaemia in unwell patients with no obvious cause e.g. no bleeding, no haeomlysis, no marrow infiltration, no iron / B12 / folic acid deficiency
Caused by inflammation - e.g. from infections, TB, HIV, autoimmune disorders, rheumatoid arthritis, malignancy etc.
Must treat it which allows anaemia to get better
What is iron haomeostatis?
Excess iron = potentially toxic to organs esp. heart and liver
No physiological mechanism to remove iron from the blood
Therefore, iron absorption is tightly controlled - regulated by hepcidin (hepcidin blocks absorption and release of storage iron)
What happens to hepcidin production when there is increased inflammatory (like in anaemia of chronic disease)?
How does this cause an erythropoeitin production issue eventually leading to anaemia?
Hepcidin production is increased
Hepcidin reduced iron absorption, iron transport and iron availability
This decreases EPO (erythropoeitin) production leading to anaemia
What are the 3 common causes of reduced red cell survival?
Hereditary spherocytosis
Autoimmune haemolytic anaemia
G6DP deficiency
What are the 3 common causes of reduced red cell production?
Iron deficiency anaemia
Anaemia of chronic disease
Megaloblastic anaemia
What is meant by the terms:
Microcytic
Macrocytic
Normocytic
What are each of these normally accompanied by?
Microcytic - RBC smaller than normal, usually also hypochromic
Macrocytic - RBC normal, usually also normochromic
Normocytic - RBC larger than normal, usually also normochromic
Can anaemia be classified on basis of cell size?
Yes
What does microcytic anaemia indicate?
Generally indicates defect in haem synthesis:
- Iron deficiency anaemia
- Anaemia of chronic disease
Or defect in globin synthesis (thalassaemia):
- Defect in alpha chain synthesis (alpha thalassaemia)
- Defect in beta chain synthesis (beta thalassaemia)
How does iron deficiency anaemia and thalassaemia differ in an FBC?
Condition | Iron deficiency anaemia | Thalassaemia trait Hb | low | low MCV | low | low MCH | low | low MCHC | low | preserved RBC | low | high Ferritin | low | normal
How can thalassaemia be distinguised between alpha and beta?
Hb electrophoresis:
Alpha = normal Beta = Hb A2 raised
What does macrocytic anaemia indicate?
Lack of vitamin B12 or folic acid (megaloblastic anaemia)
Use of drugs interfering with DNA synthesis
Liver disease and ethanol toxicity
Haemolytic anaemia (reticulocytes increased)
What can lead to haemolysis?
Reduced erythrocute function due to:
- Loss of integrity of membrane e.g. hereditary spherocytosis, autoimmune haemolytic anaemia
- Change in Hb structure and function e.g. sickle cell anaemia (SCA)
- Change in cellular metabolism e.g. G6PD deficiency
What may cause normocytic anaemia?
- Recent blood loss e.g. GI haemmorrhage, trauma
- Failure of RBC production e.g. early stages of iron deficiency, bone marrow failure or suppression (chemotherapy), bone marrow infiltration (leukaemia)
- Pooling of RBCs in the spleen e.g. hypersplenism (liver cirrhosis), splenic sequestration in SCA (sickle cell anaemia)
What are some clinical signs of iron deficiency anaemia?
Koilonychia
Glossitis Angular stomatitis
What are causes of iron deficiency anemia?
Increased loss (blood loss):
- Commonest cause in adults
- Hookworm commonest cause worldwide
- Menstrual (menorrhagia)
- Gastrointestinal (often occult)
Insufficient iron intake:
- Dietary
- Vegetarians
- Malabsorption
- Coeliac disease (gluten-induced enteropathy)
- H. pylori gastritis
Increased iron requirements:
- Physiological
- Pregnancy
- Infancy
If a patient presents with weight loss, change in bowel habits, rectal bleeding and iron deficiency anaemia, what investigations would you do?
Investigate blood in stool: faecal immunological test
GI investigations: Upper GI endoscopy, duodenal biopsy, colonoscopy
What are symptoms of iron deficiency anaemia?
Tiredness
Lethargy
Breathlessness at rest, worst on exertion
Ankle swelling at end of day
In what 2 conditions are spherocytes seen in?
How can I differentiate between the two?
Hereditary spherocytosis
Acquired autoimmune haemolytic anaemia
Use direct antiglobulin test to differentiate- positive for AAHA
What is laboratory evidence of haemolytic anaemia?
High LDH
Unconjugated hyperbilirubinemia
Reduced haptoglobins
High reticulocytes
