1b Anaemia and Transfusion Flashcards
How do we interpret an increase in unconjugated bilirubin?
Unconjugated hyperbilirubinemia is caused byproblems with red blood cell stability and survival or by defects in the bilirubin-conjugating enzyme, UGT.
How do we interpret an increase in conjugated bilirubin?
In contrast, disorders that result in conjugated hyperbilirubinemia are usually caused by intrinsic liver dysfunction
What is seen on a blood film in a patient with raised unconjugated bilirubin?
Round cells that lack central pallor = spherocytes
polychromatic MACROCYTES
high reticulocyte count
What causes hereditary spherocytosis?
Disruption of vertical linkages in the membrane, usually due to ankyrin/spectrin
What causes high reticulocytes?
Reticulocytosis can be a key indicator that the bone marrow is responding to a need for increased red blood cell production. Causes include anaemia,compensated blood loss or hemolysis and hypoxia
How does the bone marrow respond to haemolytic anaemia?
Reticulocytosis - immature red blood cells enter into circulation which then form reticulocytes, and can lead to polychromasia
What is polychromasia?
Polychromasia is thepresentation of multicolored red blood cells in a blood smear test. It’s an indication of red blood cells being released prematurely from bone marrow during formation.
Why is there colour seen on the red blood cells in polychromasia?
ribosomes still left on the immature blood cells, which are not found on mature red blood cells. These cells still contain a nucleus with genetic material as well due to the early release, which is not needed in mature blood cells because their only function is to carry oxygen in the blood.
What is haemolytic anaemia?
Increased destruction with shortened RBC survival and resultant anaemia = haemolysis which leads to a reduction in Hb
What is the treatment for haemolytic anaemia?
Folic Acid (because of the increased need)
Splenectomy (to increase the life span of the red blood cells
Vb12
What is the major consequence of haemolytic anaemia?
Gallstones
What are the symptoms of gallstones which might present in a patient with haemolytic anaemia?
Upper abdominal pain
Tenderness
Jaundice - due to elevated conjugated bilirubin
The gallstones cause obstructive jaundice
Liver is still able to conjugate the bilirubin but it isnt passing from the bile ducts and gall bladder into the duodenum
What type of stones do patients with haemolytic anaemia get?
Pigment stones
What are the two possible causes of anaemia?
RBC failure of production
RBC excess loss / destruction
What are some of the effects of SLE?
Autoimmune
- Polyarthritis
- Renal impairment
- Facial skin rashes
- Hepatitis
- Tiredness
What are some of the changes seen to the blood cells when a patient has SLE?
Low HB = anaemia
High MCV = macrocytic
What is DAT?
Direct anti-globulin test = antibodies that bind to antigens on the erythrocyte membrane in a patient who has developed an auto-antibody
What is DAT used to do?
Confirm the presence of autoimmune haemolytic anaemia
What is AIHA?
Auto-immune haemolytic anaemia
What is AIHA associated with?
Disorders of the immune system = SLE and lymphoma
Outline 4 laboratory evidence of haemolysis?
LDH raised
Unconjugated bilirubin
Reduced haptoglobin
Reticulocytosis
Why is raised LDH a sign of hameolysis?
LDH is present in red cells and hemolysis causes release into the plasma.
Why is reduced haptoglobin a sign of haemolysis?
Haptoglobin is primarily produced in the liver and is functionally important for binding free hemoglobin from lysed red cells in vivo, preventing its toxic effects. Because haptoglobin levelsbecome depleted inthe presence of large amounts of free hemoglobin, decreased haptoglobin is a marker of hemolysis.
What are the 2 categories of haemolytic anaemia?
- Inherited(RBC defect)
- Acquired (RBC environment defect/plasma/vasculature)
Which two conditions are spherocytes present in and what test is used to differentiate between them?
Hereditary spherocytosis
Acquired auto-immune haemolysic anaemia
DAT test = positive in AIHA
What environmental factors can cause non-immune haemolysis?
Microangiopathic
Malaria
Snake venom
Drugs
What pathway provides energy for the cell?
Glycolytic pathway
Which shuttle protects the glycolytic pathway from oxidant damage?
Pentose shunt
What enzyme is key in the pentose shunt?
G6PD
What is G6PD
Glucose-6-phosphate deficiency
What is the HMP shunt tightly coupled to?
The metabolism of glutathione - protects from oxidant damage
Why is G6PD deficiency a problem?
Makes the red cells susceptible to oxidant damage= resulting in haemolysis
What blood cell type shows oxidant damage to the red cell?
Irregularly contacted cells and Heinz Bodies, Ghost cells
What are Heinz Bodies
= precipitated oxidised haemoglobin
What do the prescence of ghost cells show?
intravascular haemolysis
What advice would you give to a patient with G6PD Deficiency?
Avoid oxidant drugs
Dont eat broad beans
Avoid Naphthalene
be aware that haemolysis can arise from infection
A patient is feeling tired, lethargic, breathless at rest which gets worse on exertion, ankle swelling at end of day. Blood count is as follows:
Low Hb
Low MCV- microcytic
Low MCH and MCHC- hypochromic
Thrombocytosis
Low ferritin
high transferrin and TIBC + low transferring sat
How to differentiate between thalassamia and iron deficiency anaemia?
Hb electrophoresis- no high A2 so not thalassaemia
What are the clinical symptoms of iron deficiency anaemia
Koilonychia - spoon nails
Glossitis
Angular Stomatitis
What investigations might be done on a patient who has weight loss but no other symptoms?
Investigate for blood in the stool - FIT
GI Investigations - Upper GI endoscopy - oesophagus, stomach and duodenum
What are the causes of iron deficiency?
Menstrual
Pregnancy
lactation
Vegan
Malnutrition
Vitamin C defiency
What is seen on a blood film with patients who have iron defiency?
Small cells = microcytosis due to low MCV
Pale cells = hypochromia due to low MCHC
Target cells
pencil cells = elliptocytes
What are the differential diagnosis of anaemia associated with a low MCV (microcytic anaemia)?
Iron deficiency anaemia
Thalassaemia
Anaemia of chronic disease
How is iron deficiency of anaemia treated?
Iron deficiency anemia is usually treated in two ways, which involve increasing iron intake and treating any underlying conditions
What is the difference between intravascular and extra-vascular haemolysis?
Intra = acute damage to the RBC
Extra = removed by the spleen
What type of haemolytic anaemia results from a mechanical problem with the entire red blood cell?
Microangiopathic haemolytic anaemia (MAHA)
How is iron deficient anaemia treated?
Iron replacement therapy = ferrous sulphate tablets
What happens when ferritin is low?
reduced hepcidin production
Increases iron supply
What happens to ferritin when transferritin is raised?
Ferritin is low
What happens to iron absorption when hepcidin is lowered?
Absorption of iron from the gut and release of storage iron are increased
What is ferritin and what is the significance of this test?
Ferritin is a universal intracellular protein that stores iron and releases it in a controlled fashion. Produced in liver.
What does a low ferritin indicate?
If a ferritin test reveals that your blood ferritin level is lower than normal, it indicates your body’s iron stores are low and you have iron deficiency.
What is transferrin and what is the significance of this test?
Transferrin is ablood-plasma glycoprotein, which plays a central role in iron metabolism and is responsible for ferric-ion delivery.
What does high and low transferritin indicate?
If it is low, it means a great proportion of it is bound to iron and little free transferrin is available
If it is high, it means a lot of it is unbound to iron⇒ iron deficiency anaemia
What is ESR and what is the significance of this test?
AnESR(erythrocyte sedimentation rate test) is a blood test that helps detect inflammation from autoimmune diseases, infection, cancer, and more.
What does a high ESR indicate?
Anaemia of chronic disease
Describe the pathophysiology of ACD.
Pro inflammatory cytokines reduce EPO production and upregulate hepcidin. This will reduce RBC production (low EPO), and will reduce FE absorption, transport and availability (low hepcidin), which will inhibit cell growth and maturation
Which pro-inflammatory cytokines are activated in ACD?
IL-1
TNF-alpha
IL-6
Which organs is high iron toxic to?
Heart and liver
How is anaemia of Chronic Disease treated?
By treating the underlying disease
What is frequently seen in a blood film with patients who have megaloblastic anaemia?
Hypersegmented neutrophils
Poikilocytosis
megaloblasts
LOW HB
HIGH MCV- MACROCYTIC
LOW PLATELETS, WBC
HIGH LDH + UNCONJUGATED BILIRUBIN (HAEMOLYSIS)
What can cause megaloblastic anaemia?
Vitamin B12 / folate deficiency
What are megaloblasts?
Large cells with nucleocytoplasmic dissociation
Impaired DNA synthesis, nuclear maturation and cell division
Why does folate and B12 deficiency lead to megaloblastic anaemia?
needed for dTTP synthesis which is needed to make thymidine which is needed for DNA synthesis = therefore cannot make DNA, and nuclear maturation cannot occur
deficiency but cells cannot divide but continue to grow = macrocytosis
Which drugs can cause megaloblastic changes?
Aziothioprine
Cytotoxic chemo
Folate antagonists = methotrexate
What is pernicious anaemia?
lack of IF - therefore B12 cannot be absorbed, therefore megaloblastic anaemia
How is folic acid deficiency treated?
oral supplements
What are the common causes of microcytic anaemia?
Defect in haem synthesis and defe5t in globin synthesis
Which two conditions are a result if a defect in haem synthesis?
iron deficiency anaemia and anaemia of chronic disease
What is the only blood test result which is high in iron deficiency anaemia?
Transferrin
What are the mechanisms of normocytic anaemia?
Recent blood loss
failure of production of red cells
Pooling of red blood cells in the spleen
What is a reason the MVC might be raised?
reticulocytosis as younger cells are larger than older cells
What is a megaloblast?
An abnormal erythrocyte in the bone marrow
What are the three characteristic changes seen on a blood film in patients with megaloblastic anaemia?
Tear drop cells
hypersegmented neutrophils
oval macrocytes
How to treat dietary Vitamin B12 deficiency?
Oral supplements
How to treat Intrinsic Factor Deficiencies which leads to Vitamin B12 defiency?
Hydroxocobalamin Injections
What might be some gastric causes of Vitamin B12 deficiency?
Gastrectomy, so less IF can bind
Autoimmune = Pernicious Anaemia (Where you have anti-gastric parietal cells and IF antibodies)
What are some bowel related causes of vitamin B12 defiency?
Crohn’s disease
Ileal Resection
treat with hydroxocobalamin injections (IM)
What are the neurological requirements of folic acid and vitamin B12?
needed for the development of the neural tube, can lead to defects
SACD - Sub-acute combined degenration of the spinal cord
What is the difference between intravascular and extra-vascular haemolysis?
Intra = acute damage to the RBC
Extra = removed by the spleen
What are some of the effects of SLE?
Autoimmune
- Polyarthritis
- Renal impairment
- Facial skin rashes
- Hepatitis
- Tiredness
