Haematology Flashcards
what are the components of plasma
ions
water
proteins
nutrients
waste
gases
What does haematocrit mean?
Ratio of RBC : plasma
Sites of bone marrow production?
- bone marrow
- vertebrae/pelvis (axial skeleton)*
- sternum
- ribs
- lymph node
- femur
what is anaemia
low hb concentration
what is Mean cell volume (MCV)
the average volume of RBCs (microcytic, normocytic, macrocytic)
what is polycythaemia or (erythrocytosis)
too many/increase in RBC, Hb concentration or haematocrit
what is a recticulocyte
the final stage of RBC development before full maturation (a brand new RBC that has just left the marrow)
what is haemoglobinopathy
mutation in the globin genes leading to abnormal haemoglobin synthesis - either form or number (e.g. sick cell - form or thalassamia - number of chains)
microcytic causes of anaemia (MCV)
- common ones
iron deficiency anaemia
thalassaemia (haemoglobinopathies)
Leukopenia means?
Low total WBC count
all WBCs or specific
- neutropenia
- lymphopenia
leucocytosis meaning?
high total WBC count
either all or specific types
- neutrophilia
- eosinophilia
-lymphocytosis
what does thrombocytopenia mean?
a reduced platelet count
- decreased production or increased consumption of platelets
thrombocytosis
high platelet count
- increased production(response to inflammation)
- decreased consumption (hyposplenism)
pancytopenia
all cell lineages are low
- anaemia
- thrombocytopenia (bleeding)
- -leucopenia (infection)
bone marrow failure
vancomycin can cause decrease in platelets (Thrombocytopenia)
a. true
b. false
a. true
difference between acute v chronic leukaemias
acute - blast cells accumulate in the bone marrow and crowd out normal haematopoiesus
- cause bone marrow failure early one
- blasts circulate in the blood and can cause enlarged liver or spleen
chronic - lymphocytes (CLL) or granulocytes (CML) spill into the blood and infiltrate the liver, spleen, lymph nodes (CLL)
- marrow failure later in disease
what is lymphoma
**cancer of the lymphocytes in the lymph nodes!!
**
and extra nodal areas (slpeen, liver, bone marrow etc)
if enters bone marrow can find cells in blood
symptoms of issues with platelets in coagulation system
brusing
mucosal bleeding
nose bleeds
symptoms of problems with clotting factors in caogulation system
bleeding into joints, muscles, brain
what is PT (prothrombin time)
time taken for sample of blood to clot after tissue factor and calcium are added
(normal 10-13.5 seconds)
Tests extrinsic and common pathway (PeT)
what does PT test for
time for blood to clot - extrinsic and common pathway
- problems with factors 2,5, 7, 10
- problems with fibrinogen (deficiency or inhibitor)
- warfarin use/Vit K deficiency
- Liver disease ++++
- DIC disseminated intravascular coagulation
what does APTT test for
time taken for the sample of blood to clot after a contact activator and Ca2+ have been added
normal 25-35 seconds
prolonged in
- factor 2 , 5, 8, 9 , 10, 12 or fibrinogen deficiency or inhibitor
- heparin therapy
- lupus anticoagulant
- APL syndrome
- liver disease +
- DIC
what pathway affected if PT raised
extrinisic pathway
what pathway affected if APTT raised
intrinsic
what pathway if PT and APTT raised
global defect or common pathway
do not assess for vWF or platelet problems
what are anti-coagulants
interfere with secondary haemostasis (i.e. coagulation factors)
different to platelets and thrombolytic agents
what is a group and screen?
tells
1. blood group
2. screens for presence of antibodies
blood group used in emergency
O negative
What is a cross-match
detects low frequency antigens
tells if compatible (mixes with patients blood in test tube)
45 minutes
What components can be transfused?
RBCs - anaemia, bleeding, increase 02 stats
Platelets - low and bleeding
Fresh frozen plasma - clotting factors, major haemorrhage protoccol, so don’t dilute clotting factors (factor, 8,9, 10 usually)
An allogenic stem cell transplant
patient receives stem cells from a genetically matched donor
what is primary haemostasis
platelets form a plug at the site of endothelium (vessel wall damage - exposes collagen -> cytokines)
- vasoconstiction
- platelet adhesion (to subendothelial collagen)
- platelet aggregation
final step in coagulation
insoluble fibrin formation
and fibrin cross-linking
h
how is fibrin broken down
by plasmin
fibrin -> fibrinogen
(fibrin degradation products detected by d-dimer)
virchows triad
- stasis
- hypercoagulability
- vessel wall damage
what are blood products screened for
Hep B/C/E
HIV
syphillis
HTLV
(sometimes malaria, west nile virus and zika, CMV)
indications for RBC transfusion
correct severe acute anaemia
prepare for surgery or speed up recovery
reverse damage of sickle cell disease
GI bleed/RTA
if blood group A .. antibodies against?
B
if blood group B.. antibodies against?
A
if blood group O antibodies against?
A and B blood groups
if blood group AB, have no antibodies against A or B
a. true
b. false
a. true
RhD negative individuals can make anti-D antibodies if exposed to RhD+ cells
a. true
b. false
a. true
can cause haemoyltic disease of the newborn
which blood group given in emergencies
O negative
how soon do acute tranfusion reactions occur
within 24 hours of adminstration of blood products
what does the primary haeomstatic response to bleeding involve?
platelet plug formation
platelets, vWF,
what does the secondary haemostatic response to bleeding involve?
fibrin plug formation
biggest predictor for reoccurence of VTE
if unprovoked ? need long term anti-coagulation
basic structure of immunoglobulinsf
Y shapes (antigen binding portion - Fab and Fc portion which doesnt vary)
2 heavy chains
2 light chains
the Fc portion of immunoglobulin is made of heavy chains
a. true
b. false
a. true
what are the 5 types of heavy chain
gamma IgG
alpha IgA
mu IgM
Delta - IgD
Epsilon - IgE
GAMDE
what is the first antibody released in the acute phase of reactions
IgM
(mum is younger) than granny
- initial phase of antibody production
IgG (2nd and is the most prevalent antibody subclass - 75% of total antibodies)
most prevalent of the antibody subclasses
IgG
antibody mainly found in the mucous membranes
IgA
antibody involved in anaphylaxis
IgE
parasite immune responses, hypersensitivt
the light chain part of an antibody can either belong to 1 of 2 groups which are?
kappa or lambda (b-cells)
- random selection for each cell
- but each cell will only make 1 type of light chain with ` specificity
- free light chains are also found in the blood - at low levels
should be in balance 50:50!!!!!
which region of an antibody is constant?
the Fc region - defines the subclass (5 options GAMDE)
which region of antibody is variable?
Fab region
defines the target binding
what is a paraprotein?
monoclonal (identical) immunoglobulin found in the blood OR urine
(if present it tells us that there is monoclonal proliferation of a b-lymphocyte/plasma cell somewhere in the body)
how does serum protein electropheresis work
it separates protein based on the size and charge
form
how are total immunoglobulin levels measured?
using Ig subclasses by
heavy chains (Fc portion)
what is electrophoresis used for?
to assess antibody diversity
identifies paraprotein
what is immunofixation used for
identifies what class of paraprotein is present (IgG, IgM)
why measure light chains?
assess imbalance /excessof light chains in the urine/serum
hormonal factors required for RBC production
EPO
GM-CSF
androgens
thyroxine
vitamins needed to make RBC
B12, folic acid, thiamine B1, Vitamin B6, C, E,
what is EPO
hormone synthesised in the kidney in response to hypoxia
-> increased secretion stimulates production of RBCs
lifespan of RBC normally
120 days
(broken down by reticuloendothelial system - spleen , liver, lymph nodes, lungs) - extravascular
what are RBC broken down into
globin -> AAs reutilised
haem -> biliverdin -> biliruben
or iron recycled back into haemoglobiin
unconjugated biliruben binds to?
albumin in the plasma
describe the shape of a healthy RBC
bi-concave
(contains, membrane, enzymes, Hb)
normal Hb structure - adult HbA
2 alpha chains (genes chro 16)
2 beta chains (genes Chro 11)
how is the amount of iron in body balanced?
dietry intake is absorbed (duodenum)
most of the bodys iron is recycled (is in Hb)
control is by the amount absorbed because iron is NOT excreted!! (no pathway for excess iron excretion)
how is iron utilised?
muscle - myoglobin
bone marrow
circulating erythrocytes (Hb)
recticuloendotheial macrophages
liver parenchyma
how is iron lost
sloughed mucosal cells
desquamnation
mentruation
other blood loss
(1-2mg per day)
how is iron stored?
as ferritin
mainly in the liver
where is iron absorbed?
duodenum (Fe2+ > Fe3+)
how is iron transported
from enterocytes and macrophages by Ferroportin
in the plasma bound to transferrin
stored as ferritin
what is hepcidin
is synthesised in the hepatocytes in response to increased iron levels and inflammation
blocks ferropotin (so reduces the intestinal absorption and mobalization of reticuloendothelial cells)
where is B12 absorbed and how
binds to intrinsic factor (secreted by gastric parietal cells)
complex is absorbed by IF receptors in the distal ILEUM
(b12 is bound by transcobalamin 2 in portal circulation for transport to marrow and other tissues)
why do Haemolytic anaemias predispose a person to gallstones,
haemolysis –> increased bilirubin which is excreted in the bile.
A 34-year-old male donates a unit of blood. It is stored at 4 oC. After 72 hours which of the following clotting factors will be most affected?
Factor V as it is one of the most labile coagulation factors and is particularly sensitive to storage conditions. Factor V has a half-life of approximately 12-36 hours and rapidly deteriorates when blood is stored at 4°C. This significant decline in Factor V activity is one of the earliest changes observed in stored blood products, making it a crucial indicator of blood product viability.
A 55-year-old man comes to the general practitioner complaining of night sweats and weight loss. He also mentions that he is getting tired quicker than usual. On examination, the physician notices marked splenomegaly. Laboratory investigations reveal an increased number of white blood cells and a translocation between two chromosomes.
What 2 chromosomes are most likely translocated in this patient?
CML - Philadelphia chromosome - t(9:22)
A 50-year-old male complains of pain in his upper abdomen, with fever, night sweats and weight loss. Examination reveals enlargement of his liver and spleen. A full blood count shows raised basophils, eosinophils and neutrophils.
what condition
CML
t9:22 marker of diagnosis
translocation of BCR-ABL1 (philadephia chromsome)
characterised by the Philadelphia chromosome, where a translocation between chromosome 9 and 22 causes the formation of the BCR-ABL gene.
chronic myeloid leukaemia (CML).
drugs that cause folate deficiency
phenytoin
methatrexate
-> macrocytic anaemia
Hyperkalaemia is a significant risk associated with out-of-date units
a. true
b. false
a. true
Potassium is an intracellular ion which is released upon lysis of cells, something which happens to old red cells in storage.
The most common form of leukaemia in adults is
CLL
Chronic lymphocytic leukaemia is the most common adult leukaemia
The curve is shifted to the left when there is a decreased oxygen requirement by the tissue. This includes:
The curve is shifted to the left when there is a decreased oxygen requirement by the tissue. This includes:
1. Hypothermia
2. Alkalosis
3. Reduced levels of DPG:
DPG is found in erythrocytes and is reduced in non exercising muscles, i.e. when there is reduced glycolysis.
4. Polycythaemia
Reed Sternberg cells are seen in
Hodgkins lymphoma disease
key features of hodgkins lymphoma
reed sternberg cells - large cancerous lymphocytes with 2+ nucleus and prominent nuclei (owl with large eyes)
young men
pain in lymph nodes after drinking /increase in size
2 main ways of categorising non hodgkins lymphoma
- high grade (DBCL)
- Low grade (follicular)
main targeted treatment for non hogkins lymphoma
rituximab - anti b-cell
A 18-year-old female is referred with excessive bruising and bleeding gums. You are concerned about the extrinsic pathway of coagulation.
What investigation will you order?
The extrinsic pathway of the clotting cascade is assessed by measurement of PT
The intrinsic pathway is best assessed by the
Prolonged aPTT can be seen in haemophilia and use of heparin.
A 50:50 mixing study is used to assess if
a prolonged PT or aPTT is due to factor deficiency or a factor inhibitor.
vWF deficiency -> aPTT corrects (APTT is prolonged but corrects after)
D-dimer is a fibrin degradation product which is elevated in the presence of blood clots.
a. true
b. false
a. true
generic term for WBC
leukocytes
all White blood cells !!! (myeloid or lymphoid)
Which cells are the most important mediators of graft versus host disease?
Graft versus host disease (GVHD) is caused by T cells in the donor tissue (the graft) mount an immune response toward recipient (host) cells
mechanism of acute haemolytic transfusion reactions
host IgM antibody destruction of ABO-incompatible red blood cells (RBCs),
Acute haemolytic transfusion reactions typically occur due to human error, giving patients ABO-incompatible blood products (in some cases, however, these reactions are mediated by incompatibility of other blood characteristics other than ABO type). Subsequent haemolysis of donated RBCs results in hypotension, fever, and abdominal-and-or-chest pain.
CRAB features of myeloma
C - Calcium (elevated)
R - Renal failure (raised creatinine)
A - Anaemia (normocytic and normochromic)
B - Bone lesions and bone pain
tests in myeloma
Serum protein electrophoresis (to detect paraproteinaemia)
Serum-free light-chain assay (to detect abnormally abundant light chains)
Urine protein electrophoresis (to detect the Bence-Jones protein)
Bone marrow biopsy is required to confirm the diagnosis and perform cytogenetic testing.
