🫀🫁Cardio & Resp🫀🫁 - Anaemia Flashcards
What abnormalities can be seen in this blood film?
Spherocytes
Liver function tests show bilirubin of 30μmol/l (normal range <17), and the bilirubin was mainly unconjugated.
What does this tell us?
Pre-hepatic jaundice
High unconjugated bilirubin, and spherocytes on the blood film. What does this tell us?
Hereditary spherocytosis, leading to jaundice due to increased destruction in the spleen
What will also be seen in the blood of someone with increased erythrocyte destruction?
High reticulocyte (immature RBC) count
How are reticulocytes identifiable on a blood film?
Slightly larger with a bluish tinge
What causes the bluish tinge in reticulocytes?
Higher RNA content
How does spherocytosis occur?
Disruption of vertical linkages in membrane
Usually ankyrin/spectrin
What happens due to hereditary spherocytosis?
Haemolysis or haemolytic anaemia
Can result in jaundice
Increase in bone marrow production - leads to young cells found in blood
What is the difference between haemolysis and haemolytic anaemia?
Haemolysis is increased RBC destruction (reduced RBC survival)
Haemolytic anaemia is haemolysis that can’t be compensated for - leads to reduction in Hb
How would someone with haemolytic anaemia by treated?
Folic acid (because of increased erythropoiesis demand)
Splenectomy (if severe) to increased RBC life span
Patient with hereditary spherocytosis diagnosis presents several years later acutely with upper right abdominal pain and tenderness, marked jaundice and high bilirubin, this time conjugated.
What has happened?
Likely gallstones from increased breakdown of haemoglobin to bilirubin
One of the gallstones has obstructed the CBD - obstructive jaundice
Is post hepatic - hence conjugated bilirubin
What is AIHA?
Autoimmune haemolytic anaemia
Usually found in multi-system autoimmune conditions (e.g. SLE)
What would you see in AIHA blood count?
Low Hb (increased RBC destruction)
High MCV (reticulocytes)
Increased reticulocyte count
High bilirubin
LDH - due to tissue damage
What is the DAT?
Direct antiglobulin test
Tests for antibodies that bind to RBCs
What is the mechanism of RBC destruction in AIHA?
Autoantibodies bind to RBCs
Results in destruction in the spleen
Spherocytes are present in which two blood disorders?
Hereditary spherocytosis
AIHA
What test can distinguish between hereditary spherocytosis and AIHA?
DAT
What is the most common enzyme deficiency that results in anaemia?
G6PD deficiency
What does a G6PD deficiency result in for a RBC?
Inhibits the pentose shunt
Key process that protects the RBC from oxidant damage
How does G6PD lead to more oxidative damage being received by a RBC?
G6PD deficiency reduces the ability of red blood cells to regenerate glutathione, a critical antioxidant
What type of jaundice will be exhibited in someone with G6PD deficiency?
Pre-hepatic jaundice
Unconjugated bilirubin
What would you expect to see in the blood count of someone with anaemia caused by G6PD deficiency?
Low Hb
High MCV
High reticulocytes
Classic haemolysis
What will you see in the blood film of someone with G6PD deficiency?
Ghost cells
Heinz body
Hemighosts
(cells with haemoglobin abnormalities due to oxidising damage)
What advice should be given to patients with G6PD?
Avoid oxidant drugs
Don’t eat broad beans (fava beans)
Avoid napthalene
Be aware that haemolysis can result from infection
How can haemolytic anaemia be categorised?
Haemolysis can result from an intrinsic abnormality of the red cells
Haemolysis can result from extrinsic factors acting on normal red cells
ALTERNATIVELY
Inherited haemolytic anaemia can result from abnormalities in the
cell membrane, the haemoglobin or the enzymes in the red cell
Acquired haemolytic anaemia usually results from extrinsic factors
such as micro-organisms, chemicals or drugs that damage the red cell
Extrinsic factors can interact with red cells that have an intrinsic
abnormality
How can haemolytic anaemia be classified in terms of vascularity?
Intravascular haemolysis - occurs when there is acute damage to the RBC
Extravascular haemolysis - defective RBCs removed by the spleen
What general things would you be looking for in haemolytic anaemia?
Otherwise unexplained anaemia, normochromic and either normocytic or macrocytic
Evidence of morphologically abnormal red cells
Evidence of increased red cell breakdown
Evidence of increased bone marrow activity
Give a summary of the inherited haemolytic anaemias
Give a summary of the acquired haemolytic anaemias
Would would you expect to see in the blood count of someone with iron deficiency anaemia?
Low Hb
Low MCV (microcytic anaemia)
Low MCH and MCHC
Low RBC
High platelets
What extra tests would you request if you suspected microcytic anaemia (due to iron deficiency)?
Ferritin
Serum iron
Transferrin
What questions would you ask a patient suspected of having iron deficiency anaemia?
Diet - vegetarian/vegan
GI symptoms
Menstrual history/post-menopausal bleeding
Weight loss
Medications - e.g. aspirin/NSAIDs
What clinical signs might you see in iron deficiency anaemia?
What investigations would you send for in someone suspected of iron deficiency anaemia?
Investigating for blood in stool (faecal immunochemical test, FIT)
GI investigations - endoscopy, duodenal biopsies, colonoscopy
Coeliac antibody testing
What would you expect to see in a blood film of someone with iron deficiency anaemia?
Elliptocytes are the feature you would be looking for, more than target cells
What are the causes of iron deficiency anaemia?
Increased loss (from blood loss)
Insufficient iron intake
Increased iron requirements
In what scenarios would blood loss cause iron deficiency anaemia?
Commonest cause in adults
Hookworm commonest cause worldwide
Menstrual (menorrhagia)
Gastrointestinal (often occult)
How might insufficient iron intake arise?
Dietary - vegetarians/vegans
Malabsorption
-Coeliac disease
-H. pylori gastritis
What can lead to increased iron requirements
Physiological
-Pregnancy
-Infancy
Why is transferrin high in iron deficiency anaemia?
Increase iron absorption capabilities
Compensatory mechanism
Why is there reduced ferritin in iron deficiency anaemia?
Attempt to increase iron supply
Reduced hepcidin production - leads to increased iron absorption in gut and release of storage iron
What is the treatment for iron deficiency anaemia?
Iron replacement therapy
e.g. ferrous sulphate tablets
What type of anaemia would accompany a case of, for example, sever rheumatoid arthritis for many years?
Anaemia of chronic disease
What would you expect to see in the MCV in anaemia of chronic disease?
Decrease
Microcytic anaemia
What would the reticulocyte levels look like in anaemia of chronic disease?
Normal
What profile of results would you expect to see in the blood test of someone with anaemia of chronic disease?
High ferritin
Low serum iron
Low transferrin
Normal transferrin saturation
High ESR
Hypochromic, microcytic red blood cells
Explain the significance of the blood test results of someone with anaemia of chronic disease
High ESR - ongoing inflammatory or chronic disease process, as inflammation increases fibrinogen and other acute-phase proteins
Ferritin is an acute-phase reactant that is elevated in inflammatory states
Low serum iron - reduced availability of iron for erythropoiesis - due to sequestration of iron by macrophages
Transferrin levels reduced in ACD - liver reduces its production in response to inflammation
Transferrin Saturation: Normal - iron and transferrin are lowered in proportion
What is ferritin, and what is it’s significance in ACD?
Storage protein for iron
In ACD, ferritin is elevated due to its role as an acute-phase reactant, even though the body has functionally low iron available for red blood cell production
What is transferrin, and what is it’s significance in ACD?
Protein responsible for transporting iron in the bloodstream
In ACD, transferrin levels are low due to reduced hepatic production during inflammation, limiting iron mobilization
What is ESR, and what is it’s significance in ACD?
ESR measures the rate at which erythrocytes sediment in a test tube over one hour, reflecting inflammation
Elevated ESR indicates a chronic inflammatory or autoimmune process contributing to the anaemia
How would two people with ACD and iron deficiency anaemia’s blood tests compare?
What is the basic mechanism of ACD?
Hepcidin is usually secreted by the liver in response to high iron stores
Hepcidin production is also increased in inflammatory states (ACD results from a prolonged inflammatory state i.e. chronic disease)
This reduces iron supply as hepcidin blocks absorption of iron from the gut and release of storage iron
How is ACD treated?
Underlying cause must be treated
What is pernicious anaemia?
Anaemia caused by a deficiency of vitamin B12
SPECIFICALLY due to autoimmune destruction of intrinsic factor
i.e. vitamin B12 deficiency anaemia
What would you expect to see in the blood tests of someone with B12 deficiency leading to anaemia?
High MCV - macrocytic anaemia
Low WBC - ineffective haematopoiesis
Low platelets - suggest bone marrow involvement - problem lies in haematopoiesis
Normal reticulocytes - bone marrow unable to respond to the anaemia
High LDH - increased cell turnover and haemolysis
Unconjugated bilirubin increased - increased haemolysis
Why might patients with B12 deficiency describe “walking on cotton wool” or other physical sensation disturbances?
Vitamin B12 deficiency can lead to neuropathy - demyelination of peripheral nerves and spinal cord
What would you see in the blood film and bone marrow aspirate of someone with B12 deficiency?
Macrocytosis, poikilocytosis (irregularly shaped RBCs) and hypersegmented neutrophils
Megaloblastic changes (large, immature, nucleated red cell precursors) - suggests impaired DNA synthesis
How would a normal bone marrow aspirate look compared to a bone marrow aspirate taken from someone with megaloblastic anaemia?
What are the causes of megaloblastic change in the bone marrow?
Vitamin B12 and Folate
-Required for DNA synthesis
-Absence leads to severe anaemia which can
be fatal
-Secondary to agents or mutations that impair
DNA synthesis
-Drugs: azathioprine, cytotoxic chemotherapy
-Folate antagonists: methotrexate
-BM cancers: myelodysplastic syndrome
What is vitamin B12 required for?
DNA synthesis
Integrity of the nervous system
What is folic acid required for?
DNA synthesis
Homocysteine metabolism
Outline dietary B12 deficiency
B12 present in animal products
Deficiency can result from poor diet/veganism
Oral supplementation
Outline gastric B12 deficiency
Intrinsic factor required for B12 absorption
Deficiency arise after some bariatric procedures (e.g. gastrectomy), or autoimmune conditions (pernicious anaemia)
Treated with hydroxocobalamin injections (IM)
Outline B12 deficiency based in the bowels
Terminal ileum site of B12 absorption
Crohn’s disease, Ileal resection - things that can effect absorption in the terminal ileum
Treated with hydroxocobalamin injections (IM)
What are the 2 main mechanisms behind folic acid deficiency?
Reduced availability
Increased demand
What are the causes for reduced availability of folic acid?
Dietary
-Poverty
-Alcoholism
Malabsorption
-Coeliac disease
-Jejunal resection
What are the causes for the increased demand of folic acid?
Pregnancy
Lactation
Increased cell turnover - haemolysis
How are all forms of folic acid treated?
Oral supplementation
(Broad review)
What are the 2 primary possible mechanisms of anaemia?
RBC failure of production
OR
RBC excess loss/destruction
(Broad review)
What are some causes of anaemia due to reduced RBC survival (i.e. excess destruction)?
Hereditary spherocytosis, thalassaemias, sickle cell
Autoimmune haemolytic anaemia (AIHA)
G6PD deficiency
(some infections, e.g. malaria)
(hypersplenism)
(Broad review)
What are some of the causes of anaemia due to reduced RBC production?
Iron deficiency anaemia
Anaemia of chronic disease (ACD)
Megaloblastic anaemia (B12/folic acid deficiency)
Bone marrow disorders (myelodysplastic syndromes (MDS), aplastic anaemia, marrow infiltration by malignancy)
(CKD)
(alcohol and drug (e.g. chemotherapy) induced anaemia)
(Broad review)
How can anaemias be classified based on their size?
(Broad review)
What causes microcytic anaemias?
Defect in haem synthesis
-Iron deficiency anaemia
-Anaemia of chronic disease (ACD)
Defect in globin synthesis
-Defect in α chain synthesis (α thalassaemia)
-Defect in β chain synthesis (β thalassaemia)
(Broad review)
Outline the mechanisms and causes of normocytic anaemia
(Broad review)
Outline the common causes of macrocytic anaemia
(Broad review)
What is megaloblastic anaemia?
