Acquired Anaemia Flashcards
Define anaemia
Hb below normal for age and sex
How is normal Hb level worked out?
It is +/- 2 SDs from the mean (this includes 95% of the population)
What factors influence normal Hb levels?
Age Sex (higher in men due to testosterone) Time sample taken (e.g. if fasting sample Hb will be higher, than if diluted) Time to analyse Ethnicity
What is the normal Hb level for woman?
12-70: 120-160
>70: 108-143
What is the normal Hb level for men?
12-70: 140-180
>70: 116-156
What are some general features of anaemia/
Due to reduced O2 delivery to tissues: Tiredness Pallor Dizziness (reduced O2 to brain) Breathlessness Chest pain (myocardial ischaemia) Swelling of ankles
What clues in history may help you identify a cause for anaemia?
Menorrhagia Dyspepsia, PR bleeding Malabsorption (diarrhoea, weight loss) Jaundice (haemolysing --> increased bilirubin) Splenomegaly/lymphadenopathy
What are the main red cell indices to be aware of?
MCV = mean cell volume (size) MCH = mean cell haemoglobin (pigmentation)
How are the red cell indices measured?
Automatic machine that uses a laser
What are the three main types of acquired anaemia?
Hypochromic microcytic (small, pale cells) Normochromic normocytic (normal looking cells, reduced in number) Macrocytic (large cells)
What further tests should you do if you find hypochromic microcytic cells?
Serum ferritin
Most common reason for HM cells = Fe deficient anaemia
What further tests should you do if you find normochromic normocytic cells?
Reticulocyte count
What further tests should you do if you find macrocytic cells?
B12/Folate
Bone marrow
Commonest cause of macrocytic cells = B12/folate deficiency
Hypochromic microcytic cells + low serum ferritin =?
Fe deficient anosmia
Hypochromic microcytic cells + normal/high serum ferritin =?
Thalassaemia
Secondary anaemia (although more commonly get normocytic normochromic cells with this)
A lot more rarely: sideroblastic anaemia
How much iron is in the body?
4g
What is the pathway to get rid of excess iron?
No pathway for this exists
What are the two things that can happen to iron in the gut?
Bound to mucosal ferritin and sloughed off
Transported across basement membrane by ferroportin then bound to transferrin in plasma
Which Fe ion is absorbed more readily in the gut?
Fe2+ (from animals haem form) > Fe3+ (non-haem form)
What form is iron stored as in the body?
Ferritin
What is the role of hepcidin in controlling iron levels in the body?
Hepcidin synthesised by hepatocytes in response to too much iron, liver failure, inflammatory markers (esp. IL6)
Hepcidin blocks ferroportin –> reduced Fe absorption in the gut
What must you do after you get a diagnosis of iron deficient anaemia?
Find a cause
What must you check for in the history?
Dyspepsia, GI bleeding Menorrhagia Diet (e.g. vegan?) Increased requirements? - e.g. pregnant Malabsorption - gastrectomy, coeliac disease, diarrhoea
What are signs of Fe deficient anaemia?
Sore, atrophic tongue
Kolionychia
Angular cheilitis
Management of Fe deficiency
Correct cause (diet, ulcer therapy, gynae interventions, surgery)
Oral iron (IV if intolerant)
Normochromic normocytic anaemia + increased reticulocyte count = ?
Haemolysis
Acute blood loss
(bone marrow working and compensating for loss of blood cells)
Normochromic normocytic anaemia + decreased/normal reticulocyte count = ?
Secondary anaemia
Hypoplasia
Marrow infiltration
what is haemolytic anaemia?
Accelerated RBC destruction –> decreased Hb
With compensation of bone marrow (hence increased retic count)
What are the two types of haemolysis?
Intravascular - RBC destruction in circulation
Extravascular - RBC breakdown in spleen etc.
Where are RBCs normally broken down?
RES (mostly spleen)
What are types of haemolytic anaemia?
Congenital - hereditary spherocytosis, enzyme deficiency, haemoglobinopathy (HbSS)
Extravascular - Auto-immune haemolytic anaemia
Intravascular - mechanical (e.g. heart valve), infection/DIC, PET/HUS/TTP
What is HUS?
Thrombotic microangiopathy in which microthrombi occlude arterioles and capillaries –> thrombocytopenia, haemolytic anaemia, AKI
Acquired haemolytic anaemia is broadly split into two categories - what are these?
Immune - mostly extravascular
Non-immune - mostly intravascular
How do you distinguish between immune and non-immune haemolytic anaemia?
DAT (direct coombs test)
Mix red cells with anti-human globulin, agglutination = positive test (presence of autoantibodies on surface of RBCs)
Normochromic, normocytic cells, high reticulocyte count, positive DAT test, presence of spherocytes on blood film is most likely to indicate what?
Autoimmune haemolytic anaemia
Warm autoantibody is most likely to indicate what?
Autoimmune
Drugs
CLL
Cold autoantibody is most likely to indicate what?
CHAD
Infections
Lymphoma
Alloautoantibody is most likely to indicate what?
Transfusion reactions
Why might you see spherocytes on film in an autoimmune haemolytic anaemia?
Bits of membrane of RBCs tagged with autoantibodies are broken down leading to spherocytes
What kind of cells may you see in intravascular haemolysis?
Schistocytes
smashed up cells
How can you work out if a patient is haemolysing?
FBC, high retic count, blood film (spherocytes/schistocytes) High bilirubin Low serum haptoglobin DAT Urine for haemosiderin/urobilinogen
What is haptoglobin?
Mops up free Hb (so levels of empty haptoglobin are low in haemolytic anaemia)
How do you manage patients with haemolytic anaemia?
Folic acid to support marrow
Correct cause - immunosuppression (steroids)
Treat CLL, lymphoma, stop causative meds Splenectomy (removing site of RBC destruction)
Consider transfusion if struggling
Normochromic, normocytic anaemia + normal/low reticulocyte count mostly commonly = ?
Secondary anaemia
What is the pathophysiology behind secondary anaemia?
Inflammatory markers/renal failure –> increased hepicidin –> blocks ferroportin so there is defective iron absorption
Why do you need to be careful when diagnosing secondary anaemia?
May be initial increase in ferritin
What may cause a secondary anaemia?
Infection, inflammation, malignancy
What are the two types macrocytic anaemia?
Megaloblastic
Non-megaloblastic
What is the cause of megaloblastic anaemia?
B12 and folate deficiency
Aside from anaemia what else is associated with B12/folate deficiency?
Neurological symptoms (due to degeneration of the cord (B12))
What are the two causes of B12 deficiency?
Pernicious anaemia
Gastric/ileal disease
What are the causes of folate deficiency?
Dietary
Increased requirements (e.g. pregnancy, haemolysis)
GI pathology, e.g. coeliac
Why do you get a lemon yellow tinge in megaloblastic anaemia?
Abnormal cells –> increased haemolysis –> increased bilirubin
How is B12 absorbed from the gut?
Binds intrinsic factor (made by parietal cells)
Absorbed in distal ileum
Bound to transcobalamin II in portal circulation for transport to marrow/other tissues
What is the most common cause of B12 deficiency in western world?
Pernicious anaemia
What is the pathophysiology of pernicious anaemia?
Autoantibody against intrinsic factor/parietal cells
Why do the signs/symptoms of B12 deficiency take years to come on after development of IF antibody?
As stores of B12 are so goog
How do you treat megaloblastic anaemia?
B12 replacement (3monthy IM injection) Oral folate
What are other common causes of macrocytosis?
Alcohol Drugs (methotrexate, antiretrovirals, hydroxycarbamide) Disordered liver function Hypothyroidism Myelodysplasia
Macrocytic anaemia that is non-megaloblastic may indicate what?
Myelodysplasia
Marrow infiltration
Drugs