W04 - HAEM: Blood; Transfusion; Blood Cells Flashcards
Name the cells of the blood, describe their main functions and understand how they
are derived from stem cells
RBC
* erythroblast => reticulocyte -=> RBC dt EPO (kidney)
WBC (Buffy coat)
lymphocyte SC => lymphocyte
granulpcyte progenitor cell => other white cells
PLT. (Buffy coat) = prevention of leaks
* megakaryocyte
COAG. FACTORS (Plasma) = prevention of leaks, clots
ALBUMIN (Plasma)
ANTIBODIES (Plasma)
- oxygen and co2 transported via rbcs
Know which hormones controlling blood cell production can be used therapeutically.
- EPO
- G-CSF
- Thrombopoietin agonist
Know the constituents of the ‘full blood count’.
Hb
RBC
Platelets
WBC
Neutrophils
Lymph
- monocyte
- eosinophils
- basophils
Describe the main functions of plasma. Understand the main haematological tests.
*plasma transports nutrients, waste, messages
- coag
- albumin
- antibodiies
- Clotting time = clotting factors and platelets
- platelet and leucocyte function tests
- Iron = ferritin
- B12
- Folate
- Marrow aspirate, rephine biopsy
- LN biopsy
Know the function of the spleen and causes of splenomegaly.
The spleen controls the level of white blood cells, red blood cells and platelets (small cells that form blood clots). It screens the blood and removes any old or damaged red blood cells.
*red cell breakdown dt dysfunction = splenomegaly
* pigment gallstones dt chronic hemolysis and increased bilirubin
CHICAGO
C – Cancer
H – Haematological malignancies – anaemia, leukaemia, lymphoma,
I – Infection (CMV, HEP, HIV, TB, parasitic (malaria)). EBV is the most common community acquired
Inflammation – sarcoid, amyloid
C – Congestion; portal hypertension
A – Autoimmune(RA, SLE)
G – Glycogen storage disorders
O – Other – amyloidosis, sarcoidosis
Myeloid vs Lymphoid
Myeloid progenitors give rise to red blood cells, granulocytes, monocytes, and platelets.
Lymphoid progenitors give rise to lymphocytes and NK cells
Significance of reticulocyte count
measure of red cell prod.
Know the main components of blood that can be transfused and their indications.
indications for rbc transfusion
1. acute severe anemia
2. improve QoL w/ anemia
3. Prepare pt for sx or speed up recovery
4. reverse dmg by own red cells
indications for PLT
1. massive haemorrhage
2. BM failure
3. sx prophylaxis
4. cardiopulmonary bypass
FFP
1. massive haemorrhage
2. DIC with bleeding
3. prophylax.
Understand why blood groups restrict how blood can be transfused.
a
Understand when to send samples to blood bank, the principles of what happens to
samples within the laboratory and when/how blood is made available.
- group and screening
- coombs test: detect the presence of antibodies against circulating red blood cells (RBCs) in the body, which then induce hemolysis
- direct: auimm haemolytic anemia, passi e antiD
- indirect: cross matching
Know the main hazards of blood transfusion.
initiating immune response
group a => Ab against B
B => Ab against A
O => Ab against A and B
AB = no Ab against A and B
- RhD negative individuals can make anti-D if exposed to RhD+ cells
Understand the pathophysiology of haemolytic disease of the newborn and how it is
prevented.
*Transfusion or pregnancy
Anti-D can cause transfusion reactions or haemolytic disease of the newborn
- anti-d sensitisation dt igG crossing placenta
> prophylactic anti-D, sensitising events
If you’re Rh negative and have not been sensitized, you’ll get a medicine called Rh immunoglobulin (RhoGAM)
+ similar process for NAIT
Be aware of future cellular therapies.
LEUCAPHERESIS
- bm harvests
OTHER BANKS
- bone, milk, tendons, heart valves, cells etc.
GENE THERAPIES
Outline pathophysiological or morphological approaches to the assessment of anaemia.
genetic defects may lead to congneital anemias
* red cell membrane: maintained by skeletal proteins
* metabolic pathways - enzyme ensure energy
* in haemoglobin
* haem synth defect
= haemolysis if red cell not viable
Describe the symptoms 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
+J aundice
+ Splenomegaly/Lymphadenopathy
Discuss the appropriate investigations for iron deficiency anaemia.
1) DAGT - DIRECT ANTIGLOBULIN TEST: antihuman IgG, anti-complement; causes agglutination implying immune basis for haemolysis.
+ = imm mediated, - = non-imm med.
Outline the structure of haemoglobin and the basis of the haemoglobinopathies and thalassaemias.
- A1 and A2 chains, B1 and B2 chains
+ 4 Fe atoms - reduced/absent globin chain prod
= THALASSAEMIA - mutations leading to abnormal chain
= HbS = sickle cell - autosomal recessive inheritance
Describe the breakdown of haemoglobin to bilirubin and discuss the value of direct and
indirect bilirubin measurement.
- red cell breakdown in reticuloendothelial system
- macrophages in spleen, liver, LN, lungs
- bilirubin bound to albumin in plasma
Outline the principle and uses of the direct antiglobulin test in assessing haemolysis
The direct antiglobulin test (DAT) is a laboratory test that detects immunoglobulin and/or complement on the surface of red blood cells. The utility of the DAT is to sort hemolysis into an immune or nonimmune etiology
Discuss the causes of inherited anaemias in terms of membranes, enzymes or
haemoglobin.
a
hereditary spherocytosis
skeletal membrane protein dysfunction = spherical rbc
> folic acid
transfusion
splenectomy: severe anemia
red cell enzymatic dysunfction
- G6PD def. = commonest disease enzymopathy in the world, leading to vulnerability to oxidative dmg.
- malarial protection
- X-linked: affects males, female carriers
- infective trigger to haemolysis, as well as acute illness, and drugs, and broad beans
- blister/bite cells
sickle cell disease
B chains have point mutation
* commonest inherited disorder
* autosomal recessive inheritance
= haemoglobin polymerisation, vaso-occlusion, endothelial dysfunction, sterile inflammation
- painful vaso-occlusion
- chest crisis, stroke
- increased infection risk with hyposplenism
- chronic hemolytic anemia: gallstone
- sequestration crises. = ACUTE CHEST SYNDROME
> opiates for painful crises
hydration, oxygen
?abx
> vaccination, penicillin prophylaxis, folic acid
blood transfusion
Thalassemia minor and major
Thalassemia mn. = commonest, carrier state
* hypochromic microcytic red cell indices
Beta thalassaemia mj = severe aneamia
* 3-6mos onwards
* ineffective BM expansion = bony deformities
+ splenomegaly
+ growth retardation
Mgmt of B Thal. Mj.
> Chronic transfusion support, 4-6w
!iron overloading = early death in 2nd/3rd decade dt heart liver endocrine failure
> Iron chelation therapy
- s/c desferrioxamine infusion
- oral deferasirox
=> normal life expectancy with good adherence
> BM TRANSPLANTATION = CURATIVE
Sideroblastic anemia
rare defect in haaem synth
| hereditary, commonest form of myelodysplasia
results in porphyrias
Hb Normal Reference Values
MALE 12-70yo = 140-180
MALE >70yo = 116-156
FEMALE 12-70yo = 120-160
FEMALE >70yo = 108-143
Significance of indirect bilirubin
sign of rbc breakdown (normal), creating unconjugated bilirubin
Red cell indices
MCH = Mean cell haemoglobin
MCV = Mean cell volume (cell size)
-normochromic = hypo
- normocytic = hypo, macro
Causes of Hypochromic and hypocytic
- serum ferritin test
= Hypochromic microcytic anaemia
LOW FERRITIN = Fe Def.
NORMAL/INCREASED FERRITIN =
Thalassaemia
Secondary Anaemia
Sideroblastic anaemia
Fe Metabolism
Iron absorbed in duodenum - Fe2+ > Fe3+
ferroportin transports from duo. to cells
transferrin transports from plasma to cells.
*FERRITIN WITHIN CELLS
*Hepcidin synthesised in hepatocytes in response to ↑iron levels and inflammation – blocks ferroportin
Clinical signs & causes & mgmt of Fe Def.
- hypochromic microcytic red cells
- pencil/rod cell
- koilonychia
- atrophic tongue
- angular chelitis
dt
- GI blood
- menorrhagia
- malabs: gastrectomy; coeliac
> oral fe, IV, transfusion
correct cause
Normochromic normocytic anaemia
⇧reticulocyte count = acute blood loss, haemolysis
normal/⇩ reticulocyte count = 2º anemia, hypoplasia, marrow infiltration
2º anemia = chronic disease, inflammation = increased hepcidin
Haemolytic anemia
Normochromic normocytic anaemia
*accelerated RBC destruction, compensated by BM
= ⇧retics.
Haemolytic Anemia: Types & Mgmt
1) IMMUNE; extravasc.
* spherocytes
warm agglutination = auImm, drugs, CLL
cold agglutination = CHAD, infections, lymphoma
allo agglutination = transfusion reaction
2) NON-IMM; intravasc.
* red cell fragments, shistocytes
> folic acid supports marrow
correct cause
- immsuppr.
- remove site of rbc destr.
- sepsis, leaky valve, malignancy
?transfusion
Macrocytic anemia
via B12/folate assay, blood film
megaloblastic = B12 def., folate def.
* pernicious anemia
* gastric/ileal disease; GI pathology
* dietary
non-megaloblastic = myelodysplasia, marrow infiltraation, drugs
Megaloblastic anemia presentation and mgmt
- lemon yellow tinge
- bilirubin, LDH (rbc destruction & BM destruction)
- red cell friable
> replace vitamin
B12 injection, loading dose then every 3mos.
Oral folate replacement
Pernicious anemia
commonest cause of B12 def in west, AuImm.
Ab against IF (diagnostic), gastric parietal cells
= malabs of B12
