RBC: Acquired Anaemias Flashcards
Factors influencing normal haemoglobin level
- age
- sex
- ethnic origin
- time of day sample taken
- time to analysis
What is the normal haemoglobin level for a male 12-70?
140-180
What is the normal haemoglobin level for a male >70?
116-156
What is the normal haemoglobin level for a female 12-70?
120-160
What is the normal haemoglobin for a female >70?
108-143
What are the clinical features of anaemia?
General features due to reduced oxygen delivery to tissues:
- Tiredness/pallor
- Breathlessness
- Swelling of ankles
- Dizziness
- Chest pain
Depend on age, speed of onset and Hb level
What features of anaemia may relate to the underlying cause?
- Evidence of bleeding
- Menorrhagia
- Dyspepsia, PR bleeding
- Symptoms of malabsorption
- Diarrhoea
- Weight loss
- Jaundice
- Splenomegaly/Lymphadenopathy
Anaemia pathophysiology
- Bone marrow
- Cellularity
- Stroma (environment of the marrow)
- Nutrients
- Red cell
- Membrane
- Enzymes
- Haemoglobin
- Destruction loss
- Blood loss
- Haemolysis
- Hypersplenism
What are red cell indices?
Automated measurement of red cell size and haemoglobin content
MCH
MCV
Mean cell haemoglobin
Mean cell volume (cell size)
What can red indices tell us?
A morphological description of anaemia - and a clue as to cause
Give 3 morphological descriptions of anaemia.
- Hypochromic microcytic (pale and small)
- Normochromic normocytic
- Macrocytic
What investigation should be carried out to establish cause of hypochromic microcytic anaemia?
- Serum ferritin (iron stores - for iron deficiency anaemia)
- Distinguish between thalasaemia carriers and iron deficiency anaemia
What investigation should be carried out to establish cause of normochromic normocytic anaemia?
- Reticulocyte count (immature red blood cells)
- if low then problem with bone marrow.
- if high then due to blood loss or red cell destruction
What investigation should be carried out to establish cause of macrocytic anaemia?
- B12 and folate levels
- Bone marrow
What does low serum ferritin suggest in hypochromic microcytic anaemia?
Iron deficiency
What does normal/increased serum ferritin suggest in hypochromic microcytic anaemia?
- Thalassaemia
- Secondary anaemia
- Sideroblastic anaemia
Iron metabolism
- Total body iron approx 4g
- Dietary intake balanced by loss
- Most of the body’s iron is in Hb and is recycled
- No pathway for excretion of excess iron
What happens to absorbed iron?
- Bound to mucosal ferritin and sloughed off OR
- Transported across the basement membrane by ferroportin
- Then bound to transferrin in the plasma
What happens to the iron absorbed in the duodenum?
- Transported in plasma bound to transferrin
- Stored in cells as ferritin
Which hormone reduces intestinal iron absorption?
- Hepcidin is synthesised in hepatocytes in response to increased iron levles and inflammation so reduces intestinal iron absorption and mobilisation from reticuloendothelial cells
What is the commonest cause of anaemia worldwide?
Iron deficiency anaemia
What is normally in the history of iron deficiency anaemia?
- Dyspepsia, GI bleeding
- Other bleeding, eg menorrhagia
- Diet (NB children and elderly)
- Increased requirement - pregnancy
What can be found on examination of iron deficiency anaemia?
Signs of iron deficiency:
- Koilonychia
- Atrophic tongue
- Angular stomatitis
- Hypochromic microcytic red cells
- Abdominal and rectal examination (bleeding)
Give some examples of causes of iron deficiency.
- GI blood loss
- Menorrhagia
- Malabsorption (can be due to gastrectomy of coeliac disease)
- Diet
How is iron deficiency anaemia managed?
- Correct the deficiency
- Oral iron usually sufficient
- IV iron if intolerant of oral
- Blood transfusion rarely indicated
- Correct the cause
- Diet
- Ulcer therapy
- Gynae interventions
- Surgery
What does increased reticulocyte count suggest in normochromic normocytic?
- Acute blood loss
- Haemolysis
What does a normal or low reticulocyte count suggest in normochromic normocytic anaemia?
- Secondary anaemia
- Hypoplasia
- Marrow infiltrate
Give examples of underlying disease which may cause secondary anaemia
- infection
- inflammation
- malignancy
Blood results for secondary anaemia
- 70% normochromic normocytic
- 30% hypochromic microcytic
- defective iron utilisation
- increased hepcidin in inflammation
- ferritin often elevated
What happens in haemolytic anaemia?
- Accelerated red cell destruction (↓Hb)
- Compensation by bone marrow (↑reticulocytes)
- Level of Hb = balance between red cell production and destruction
What are some congenital causes of haemolytic anaemia?
- Hereditary spherocytosis (HS)
- Enzyme deficiency (G6PD deficiency)
- Haemoglobinopathy (HbSS)
What are some acquired causes of haemolytic anaemia?
- Extravascular
- Auto-immune haemolytic anaemia
- Intravascular
- Mechanical e.g. artificial valve
- Severe infection/DIC
- PET/HUS/TTP
How can acquired haemolytic anaemia be subdivided?
- Immune (mostly extravascular)
- Non-immune (mostly intravascular)
What is a direct antiglobulin test?
A test which detects antibody or complement on red cell membrane
Implies immune basis for haemolysis
What does a positive DAGT suggest in haemolytic anaemia?
Immune mediated
What does a negative DAGT suggest in haemolytic anaemia?
Non-immune mediated
In human haemolysis of haemolytic anaemia, what does a warm-auto-antibody suggest?
- Auto-immune
- Drugs
- CLL
In human haemolysis of haemolytic anaemia, what does a cold auto-antibody suggest?
- CAD (cold agglutinin disease)
- Infections
- Lymphoma
In human haemolysis of haemolytic anaemia, what does an alloantiody suggest?
Transfusion reaction
What can be seen on blood film of immune haemolysis?
- Spherocytes on film
- Agglutination in cold AIHA
What can be seen on blood film of intravascular haemolysis?
Red cell fragments called schistocytes
Tests to show if patient is haemolysing
- FBC, reticulocyte count, blood film
- Serum bilirubin (direct and indirect), LDH
- Serum haptoglobin
How is the mechanism of haemolytic anaemia established?
- History and examination
- Blood film
- Direct Antiglobulin Test (Coombs’ test)
- Urine for haemosiderin/urobilinogen
What is the management for haemolytic anaemia?
- Support marrow function
- Folic acid
- Correct the cause
- Immunosuppression if autoimmune (steroids, treat the trigger)
- Remove site of red cell destruction (splenectomy if severe)
- Treat sepsis, leaky preosthetic valve, malignancy etc. if intravascular
- Consider transfusion
In macrocytic anaemia, what can results of B12 and folate assays, blood films and bone marrow tell us?
Differentiates between megaloblastic and non-megaloblastic anaemia
What can cause megaloblastic macrocytic anaemia?
- B12 deficiency
- Folate deficiency
What can cause non-megaloblastic macrocytic anaemia?
- Myelodysplasia
- Marrow infiltration
- Drugs
How can B12/folate deficiency present?
- Anaemia
- Neurological symptoms (subacute combined degeneration of the cord in B12 deficiency)
What can cause B12 deficiency?
- Pernicious anaemia
- Gastric/ilieal disease
What can cause folate deficiency?
- Dietary
- Increased requirements (haemolysis)
- GI pathology (e.g. coeliac disease)
Why do people have a lemon yellow tinge in megaloblastic anaemia?
- Due the bilirubin and LDH
- Red cells are friable
How is vitamin B12 absorbed?
- Dietary B12 binds to intrinsic factor, secreted by gastric parietal cells
- B12-IF complex attaches to specific IF receptors in distal ileum
- Vitamin B12 bound by transcobalamin II in portal circulation for transport to marrow and other tissues
What is the commonest cause of B12 deficiency?
Pernicious anaemia
What is pernicious anaemia?
- An autoimmune condition where the bodies make antibodies against intrinsic factor (sometimes gastric parietal cells)
- It results in malabsorption of dietary B12
How long does it take for signs and symptoms of pernicious anaemia to develop?
1-2 years due to B12 stores
What is the treatment for megaloblastic anaemia?
- Replace vitamin B12
- B12 intramuscular injection
- Loading dose 3 then 3 monthly maintenance
- Replace folate
- Oral folate replacement
- Ensure B12 normal if neuropathic symptoms
What are ‘other’ causes of macrocytosis?
- Alcohol
- Drugs (Methotrexate, Antiretrovirals, hydroxycarbamide)
- Disordered liver function
- Hypothyroidism
- Myelodysplasia
