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
Case Study: 58F - presenting with: Tiredness Lethargy Breathlessness at rest, which is worse on exertion ankle swelling at the end of the day
FBC 12 months ago was normal, repeat FBC arranged and it shows:
Hb - 80 g/l MCV - 70 fl MCH - 24.5 pg MCHC - 278 RBC - 3.7 x 10^12 Platelets 550 x 10^9
What do these blood test results show and 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 tests would you conduct next to narrow down the differential diagnosis?
Blood test and blood film
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 does the blood film show?
Microcytic RBCs?
unsure
What further questions could you ask to figure out what is causing the iron deficiency?
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
Case Study:
Healthy man develops jaundice
Unconjugated bilirubin high
What does this say about the cause?
UNCONJUGATED = haemolysis
Conjugated = liver disease
Blood count shows:
Hb 77g/l
MCV = 108 fl
Reticulocytes = 320 x 10^9
What does the high reticulocyte say?
Reticulocyte = baby RBCs
Bone marrow trying to compensate for anaemia
Why is MVC increased?
Because reticulocytes are larger than RBCs (I think)
Why is it likely to be haemolysis?
Due to the high unconjugated bilirubin
What test would you do next to confirm his diagnosis?
Blood film
What does his blood film show?
RBC looks normal - normal central palor, normal size
Some RBCs = hemighosts = irregularly contracted cell (=oxidant stress on RBC) = hyperchromatic + irregular membrane (heinz bodies)
Ghost cell
What is a special test to look for heinz bodies?
Heinz body test - although can be easily seen on a blood film
How can G6PD deficiency be confirmed?
By assay
What advice would be given to the patient to treat this?
Avoid oxidant drugs
Avoid broad beans (fava beans)
Avoid naphthalene
Beware haemolysis can result from infection - be mindful getting ill can precipitate a crisis
Case Study:
38F - afro-caribbean, attends rheumatology clinic
Fluctuating multi-system disorder: Ploy arthritis Shortness of breath Facial skin rashes Hepatitis Tiredness
What would you do next?
Arrange for a blood test
Blood tests show:
RBC - 87 MCV - 104 WBC and platelets - normal Ferritin - 310 Bilirubin - 55 B12 and folate - normal
What information does this tell us?
Macrocytic Low Hb High Bilirubin B12 and folate normal High MCV
She has high LDH, why?
Cells are being broken down so intracellular contents are leaking out
What does a high reticulocyte count indicate?
Modestly high = RBCs are trying to be replaced by the bone marrow
What does high unconjugated bilirubin suggest?
Haemolytic anaemia
How do you work out what type of haemolysis?
Do blood film
How do you know if haemolysis is acquired or inherited?
Inherited = born with
Env = non-immune or immune mediated
What can the different types of haemolysis be caused by and present as?
Non-immune: Microangiopathic Haemolytic uraemic syndrome Malaria Snake venom Drugs
Immune mediated:
Auto immune
Allo immune (post blood transfusion)
What test can be conducted to figure out whether environmental haemolysis is non-immune or immune?
History - she has joint, kidney and history problems = lupus = autoimmune
Suggests immune mediated
Do antibody test = direct antiglobulin test: 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
What are the takeaway points for haemolytic anaemia?
Normocytic anaemia with a raised bilirubin consider haemolysis if also:
Elevated Reticulocytes/LDH/unconjugated Bilirubin Blood film
Clinical history and exam may point to acquired or inherited (eg sickle cell)
In acquired haemolysis, DAT positive confirms immune mechanism:
Systemic auto immune disease
Underlying lymphoid cancer (lymphoma)
Idiopathic
10F - jaundice
Appeared quite well but blood tests were done
No evidence of viral hepatitis but liver function tests and blood count and blood film all abnormal
Liver function test showed increased unconjugated bilirubin, normal liver enzymes
How is unconjugated bilirubin interpreted?
Pre-hepatic bilirubin - has not yet passed through the liver
Her blood count showed Hb98 - slightly low = mild anaemia
What is abnormal on the film?
Spherocytes - reduced diameter, no central palor = suggests she has something that causes spherocytosis
Suggest a differential diagnosis?
Inherited
Haemolytic anaemia
Tests show she has hereditary spherocytosis which is due to an inherited defect in the red cell membrane
Progressive loss of the RBC membrane - cells get more rigid = rigid spheres
Her blood film also shows polychromatic macrocytes, what does this suggest?
Blue macrocytic cells = reticulocytes = increased count of reticulocytes
230 x 10^9
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
Patient, now 18, 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 Hb - 45 (v. v. anaemic) = v. v. low MCV - 128 = high WBC - 3.7 x 10^9 = low Platelets - 140 x 10^9 = low
What does this information tell you?
Issue with bone marrow, all the BCs = low
Unconjugated bilirubin = little high
Reticulocytes = lower part of the normal range
What does this information suggest?
Unconjugated = haemolytic anaemia
Bone marrow is supposed to compensate for anaemia (reticulocytosis) but this is not happening
What does the blood film show?
Hypersegmented neutrophils
Very macrocytic RBCs
Poikilocytosis - funny shaped RBCs = tear shapes, ovals, etc.
What does the blood film suggest for a differential diagnosis?
MDS (myelodysplasia)
B12 deficiency
Folate deficiency
Chemotherapy drugs
Why is a blood test required to diagnose for B12 AND folate?
B12 and folate both present in the exact same way as they are both required for DNA synthesis
The blood test shows low B12
What occurs in bone marrow in megablastic anaemia due to Vitamin B12 deficiency?
Erythroblasts - normal and abnormal erythoid precursors
Megablasts = large with nucleocytoplastmic dissociation
So the maturation of the cytoplasm and nucleus is dyssynchronised (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 =
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
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 the blood film 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)
