red cells 2 Flashcards
what is anaemia
Hb below normal for age and sex
acquired anaemias are more common
how to determine normal range
subjects w/o disease
normal distribution
mean +/- 2SD
- excludes 5% of ‘normals’
- think about whether the level is normal for your patient
factors influencing reference intervals
age sex ethnic origin time of day sample taken e.g. cortisol levels time to analysis
Hb reference intervals
male 12-70: 140-180
male >70: 116-156
female 12-70: 120-160
female >70: 108-143
drops with age (physiological and increasing co-morbidities)
presentation of anaemia
general features due to reduced oxygen delivery to tissues;
- tiredness
- pallor
- SOB
- ankle swelling
- dizziness (esp on standing)
- chest pain
depends on age, speed of onset and Hb level
clinical features of anaemia related to underlying cause
evidence of bleeding
- menorrhagia
- dyspepsia, PR bleed
symptoms of malabsorption
- diarrhoea
- weight loss
jaundice
splenomegaly/lymphadenopathy
anaemia pathophysiology
red cell indices - what is it
automated measurement of red cell size and Hb content
can give a morphological description of anaemia and a clue to the cause
what is MCH
mean cell Hb
what is MCV
mean cell volume - size
morphological descriptions of anaemia
investigations for anaemia
use of discriminating test to guide further investigations
if lab is given adequate clinical info it will advise on further appropriate investigations
most common cause of hypochromic microcytic anaemia
investigations to check
iron deficiency
- measure serum ferritin
common causes of macrocytic anaemia and investigations to check
B12/folate deficiency
bone marrow disorders also - check if B12/folate are normal
investigation for normochromic normocytic anaemia
reticulocyte count to check red cell production levels
what type of anaemia is this
hypochromic, microcytic anaemia
red cells should be only slightly smaller than the lymphocyte
what is seen here
normal red cells
causes of low serum ferritin in hypochromic microcytic anaemia
iron deficiency
causes of normal/increased serum ferritin in hypochromic microcytic anaemia
- interpret w/ caution in someone who should be iron deficient
thalassaemia - normal iron stores but abnormal red cells
2y anaemia - cannot use iron in inflammatory condition for example
sideroblastic anaemia
- also increases in liver disease and in inflammatory processes but may not have iron bound
iron metabolism
total body iron
how are levels balanced
total body iron ~4g
dietary intake balanced by loss
most of the body’s iron is in Hb and is recycled
no pathway for excretion of XS iron
what happens to absorbed iron
bound to mucosal ferritin and sloughed off
OR
transported across the BM by ferroportin
then bound to transferrin in plasma
stored as ferritin -mainly in liver
role of hepcidin
synthesised in hepatocytes in response to increased iron levels and inflammation
blocks ferroportin so reduces intestinal iron absorption and mobilisation from reticuloendothelial cells
iron absorption in duodenum
Fe2+ > Fe3+
transported from enterocytes and macrophages by ferroportin
transported in plasma bound to transferrin
stored in cells as ferritin
how common is iron deficiency anaemia
commonest cause of anaemia worldwide
iron deficiency anaemia - hx
description not a diagnosis so need to establish cause
hx: dyspepsia, GI bleed other bleeding e.g. menorrhagia diet, NB children and elderly increased requirement - pregnancy
iron deficiency anaemia - signs on exam
signs of iron deficiency:
koilonychia
atrophic tongue
angular cheilitis
abdo and rectal
causes of iron deficiency anaemia
GI blood loss
menorrhagia
malabsorption - gastrectomy, coeliac
management of iron deficiency
correct deficiency:
- oral iron usually sufficient
- IV iron if intolerant or oral
- blood transfusion rarely indicated
correct the cause:
- diet
- ulcer therapy
- gynae
- surgery
causes of increased reticulocyte count in normochromic normocytic anaemia
acute blood loss
haemolysis
causes of normal/low reticulocyte count in normochromic normocytic anaemia
2y anaemia
hypoplasia
marrow infiltration
what is 2y anaemia
‘anaemia of chronic disease’
70% normochromic normocytic
30% hypochromic microcytic
what causes 2y anaemia
what should you look for
defective iron utilisation
- increased hepcidin in inflammation
- ferritin normal/elevated (acute phase reactant)
identifiable underlying disease
- infection, inflammation, malignancy, renal impairment
haemolytic anaemia
- what happens
accelerated red cell destruction (reduced Hb)
compensation by bone marrow (increased retics)
level of Hb - balance between red cell production and destruction
often have normochromic picture
where can haemolysis occur
can be extra or intravascular
causes of haemolytic anaemia
congenital:
- hereditary spherocytosis
- G6PD deficiency
- haemoglobinopathy (HbSS)
acquired:
- extravascular: AI haemolytic anaemia
- intravascular: mechanical (e.g. artificial valve), severe infection/DIC, PET/HUS,TTP
causes of acquired haemolytic anaemia
immune - mostly extravascular
non-immune - mostly intravascular
what is a direct antiglobulin test
implies immune basis for haemolysis
detects antibody/complement on red cell membrane
reagent contains either: anti-human IgG, anti-complement
reagent binds to Ab/complement on red cell surface and causes agglutination in vitro
what will be on the surface of the red cells if the patient has immune haemolysis
antibodies
results of DAT test
+ve - immune mediated
-ve - non-immune mediated
tests for immune haemolysis
warm auto-antibody -AI, drugs, CLL
cold auto-antibody - CHAD, infections, lymphoma
alloantibody - transfusion reaction
DAT will be +ve in all these circumstances
what is seen here
immune haemolysis - mostly extravascular
spherocytes on film
agglutination in cold
AIHA
what is seen here
red cell fragments - schistocytes
seen in intravascular haemolysis
diagnosis of haemolytic anaemia
is pt haemolysing?
- FBC - anaemic, increased reticulocyte count, blood film
- high serum bilirubin (unconjugated/indirect), high lactate dehydrogenase
- low serum haptoglobin
how to determine the mechanism of haemolytic anaemia
hx and exam
blood film
DAT
urine for haemosiderin/urobilinogen
management of haemolytic anaemia
support marrow function - folic acid for all
correct cause:
- immunosuppression if AI: steroids, treat trigger e.g. CLL, lymphoma
- remove site of cell destruction: splenectomy
- treat sepsis, leaky prosthetic valve, malignancy etc if intravascular
consider transfusion
different types/causes of macrocytic anaemia
what causes megaloblastic anaemia
B12/folate synthesis
- can also affect other organs: neurological symptoms (subacute combined degeneration of the cord in B12 deficiency)
causes of B12 deficiency
pernicious anaemia
gastric/ileal disease - absorption problem
causes of folate deficiency
dietary
increased requirements - haemolysis
GI pathology e.g. coeliac disease
vitamin B12 absorption
dietary B12 binds to intrinsic factor
B12-IF complex attaches to specific IF receptors in distal ileum
vit B12 bound by transcobalamin II in portal circulation for transport to marrow and other tissues
where is intrinsic factor secreted
gastric parietal cells
where is intrinsic factor secreted
gastric parietal cells
skin appearance of megaloblastic anaemia
lemon yellow tinge
- bilirubin, LDH
- red cells friable
what class of anaemia is seen here
megaloblastic appearance
- oval macrocytes
- neutrophil hypersegmentation
what is pernicious anaemia
commonest cause of B12 deficiency in western pops
AI disease
antibodies against:
- intrinsic factor (diagnostic)
- gastric parietal cells (less specific)
malabsorption of dietary B12
why does pernicious anaemia take 1-2yrs to develop
stores last a long time so you use these up before symptoms develop
treatment of megaloblastic anaemia
replace vitamin
B12:
- IM injection
- loading dose then 3mthly maintenance
folate:
- oral replacement
- ensure B12 normal if neuropathic symptoms
other causes of macrocytosis that don’t necessarily cause anaemia
alcohol
drugs - methotrexate, antiretrovirals, hydroxycarbamide
disordered liver function
hypothyroidism
myelodysplasia
