Anaemia Flashcards
What causes hereditary spherocytosis?
an inherited defect in the red cell membrane
- disruption of vertical linkages in the membrane, usually ankyrin/spectrin
What is haemolytic anaemia?
increased destruction with shortened RBC survival and resultant anaemia
How would you treat haemolytic anaemia?
- folic acid (increased need)
- splenectomy (if severe, it increase RBC life span)
What can haemolytic anaemia cause?
gallstones, due to increased breakdown of haemoglobin into bilirubin
What is AutoImmune Haemolytic anaemia (DAT positive)?
- Idiopathic
- associated with disorders of the immune system: systemic autoimmune disease (SLE), and underlying lymphoid cancers (lymphoma)
What in bloods can prove haemolysis?
- raised LDH
- unconjugated hyperbilirubinaemia
- reduced haptoglobins
What is the bone marrow response to haemolysis?
- reticulocytosis
When should haemolysis be considered?
- anaemia with raised bilirubin
- elevated reticulocytes, LDH and unconjugated bilirubin
- blood film
What are the possible impacts of inherited RBC defects?
- abnormal RBC membrane
- abnormal haemoglobin
- defect in glycolic pathway
- defect in the enzymes of pentose shunt
What does the pentose shunt do?
protects from oxidant damage
key enzyme: G6PD
What in a blood film suggests oxidant damage?
- irregularly contracted cells
- Hienz bodies
What are Hienz bodies?
precipitated oxidised haemoglobin
What does the presence of ghost cells on a blood film suggest?
intravascular haemolysis
What should be advised during a G6PD deficiency?
- avoid oxidant drugs
- don’t eat broad beans
- avoid naphthalene
- awareness that haemolysis can result from infection
What can be seen on a blood film with a G6PD deficiency?
- irregularly contracted cells
- Hienz bodies
- ghost cells
What can be a symptom of G6PD deficiency?
jaundice
What questions should be asked if iron deficiency anaemia is suspected?
- diet
- GI symptoms (dysphagia, dyspepsia, abdominal pain, change in bowel habits, rectal bleeding)
- menstrual history/post-menopausal bleeding
- weight loss
- medications (NSAIDs)
What are the clinical signs of iron deficiency anaemia?
- Koilonychia
- Glossitis Angular stomatitis
What investigations should be done for suspected iron deficiency anaemia?
- Faecal Immunochemical Test (blood in stool)
- Upper GI endoscopy (oesophagus, stomach and duodenum)
- Duodenal biopsy
- Colonoscopy
- Coeliac antibody testing
What are the possible causes of iron deficiency?
Increased blood loss - hookworm - menstrual (menorrhagia) - GI (occult) Insufficient iron intake - dietary - malabsorption (coeliac, H. pylori) Increased iron requirements - physiological
How is iron deficiency anaemia seen on a blood film?
- microcytosis (low MCV)
- hypochromia (low MCHC)
- occasional target cells
- ellipocytes
How much iron is absorbed daily?
1-2mg per day
What controls iron absorption?
Hepcidin (absorption and release of stores)
What increases hepcidin production?
inflammatory state
What is Koilonychia?
soft nails that looks scooped out (can hold a drop of liquid)
What is Glossitis Angular Stomatitis?
inflamed tongue and sides of mouth
Does a normal ferritin always exclude iron deficiency?
NO - ferritin can be normal with iron deficiency/anaemia of chronic disease
What does hepcidin do?
blocks the absorption and release of storage iron
What are the common causes of anaemia of chronic disease?
- infections (TB, HIV)
- Rheumatoid arthritis and autoimmune disorders
- Malignancy
What is the pathophysiology of anaemia of chronic disease?
- IL-1, TNFa, IL-6 inhibit iron release from macrocytes to erythroids, reducing EPO production
- Hepcidin (triggered by inflammatory proteins) reduced the transport, availability and absorption of iron.
What is megaloblastic anaemia?
anaemia associated with megaloblastic morphological changes in bone marrow due to asynchronous nucleocytoplasmic maturation.
What causes megaloblastic anaemia?
- Vitamin B12 deficiency
- Folic acid deficiency
What can cause a Vitamin B12 deficiency?
- diet
- gastric: structural (gastrectomy) or autoimmune (pernicious anaemia)
- terminal ileum: structural (resection) or inflammation (Crohn’s disease)
What can cause a Folic acid deficiency?
- diet
- proximal jejenum (coeliac disease)
- excess demand
- haemolysis
- pregnancy
How does megaloblastic anaemia present on a blood film?
- macrocytic RBC
- very high MCV
- Impaired DNA synthesis, nuclear maturation and cell division
What are the neurological impacts of a Vitamin B12 deficiency?
- dementia
- SACD (sub-acute combined degeneration) of the spinal cord
What are the neurological impacts of a Folic acid deficiency?
- affects the development of neural tube defects
Where is folic acid absorbed?
- duodenum
- jejunum
Where is Vitamin B12 absorbed?
- ileum
What is microcytic anaemia?
average cell size is decreased
What are the common causes of microcytic anaemia?
- defect in haem synthesis
- defect in globin synthesis
What are the 2 disorders due to defects in globin synthesis?
- alpha thalassaemia: defect in the alpha chain
- beta thalassaemia: defect in the beta chain
What are the 2 difference types of microcytic anaemia?
- anaemia of chronic disease
- iron deficiency anaemia
What are the blood features of anaemia of chronic disease?
Hb - Low MCV - Low/Normal Ferritin - High Serum Iron - Low Transferrin - Low/Normal Transferrin saturation - Normal ESR - High
What are the blood features of iron deficiency anaemia?
Hb - Low MCV - Low Ferritin - Low Serum Iron - Low Transferrin - High Transferrin saturation - Low ESR - High
What is the difference in Hb electrophoresis between iron deficiency anaemia and B thalassaemia trait?
Hb A2 raised in B-thalassaemia trait
What are the mechanisms of normocytic anaemia?
- recent blood loss
- failure of RBC production
- pooling of RBCs in the spleen
What are some causes of normocytic anaemia?
- GI haemorrhage
- trauma
- early stage iron deficiency
- bone marrow failure/supression (chemotherapy)
- bone marrow infiltration (leukaemia)
- hypersplenism (liver cirrhosis)
- splenic sequestration in sickle cell
What are the common causes of macrocytic anaemia?
- lack of VItamin B12 or Folic acid
- drugs that interfere with drug synthesis
- liver disease and ethanol toxicity
- haemolytic anaemia (increased reticulocytes)
What are the causes of haemolytic anaemia?
A defect in:
- integrity of the membrane
- haemoglobin structure and function
- cellular metabolism
What haemolytic anaemias are cause by a defect in the integrity of the membrane?
- hereditary spherocytosis
- autoimmune haemolytic anaemia
What haemolytic anaemias are cause by a defect in the cellular metabolism?
G6PD deficiency
What are the non-immune environmental factors that can damage RBCs?
- Microangiopathic
- Haemolytic uraemic syndrome
- Malaria
- Snake venom
- Drugs
What are the immune mediated (DAT+ive) environmental factors that can damage RBCs?
- autoimmune
- allo-immune (post blood transfusion)
Which two blood disorders both have spherocytes?
- Hereditary spherocytosis
- Acquired auto immune haemolytic anaemia
What test distinguishes between hereditary spherocytosis and acquired autoimmune haemolytic anaemia?
Direct Antiglobulin test (DAT)
What does the Direct Antiglobulin test detect?
whether self-antibodies have formed
What is the treatment for when a gastrectomy or antoimmune pernicious anaemia cause Vitamin B12 deficiency?
Hydroxocobalamin injections (IM)
What is the treatment for Vitamin B12 deficiency caused by Chron’s disease or an Ileal resection?
Hydroxocobalamin injections (IM)
What is the treatment for VItamin B12 deficiency caused by an inadequate diet?
Oral supplementation
How does autoimmune pernicious anaemia cause Vitamin B12 deficiency?
produces anti GPC and IF antibodies
- IF is necessary for Vitamin B12 absorption
What is used to treat folic acid deficiency irrelevant of the cause?
Oral supplementation
