2
o Graft rejection process occurring; if whole blood from one individual is fused
with that of another individual. T-cells get activated and may recognise
recipient as foreign, so graft attacks host
Fixed as white cells are removed prior to transfusion
haemostasis n. keep blood at a constant level
o Larger blood vessels have a lot of smooth muscle, which can spasm and close
off blood flow
o vWF involved in starting platelet adhesion process; effective clotting is a
result of decent platelet levels and coagulation
Platelets should be attracted to endothelium; adhere to exposed
collagen when a damaged blood vessel is present
Will lead to clot formation
o Result of blood coagulation is to turn soluble fibrinogen into insoluble fibrin;
fibrin forms spider-web and holds cells and platelets together, causing a
clot
Intrinsic pathway relates to blood vessel injury
Extrinisic pathway relates to tissue injury
Warfarin is an anticoagulant (blood thinner)
Heparin stops blood from clotting; acts on activated components of
the clotting cascade
o coagulopathy n. condition in which the bloods ability to coagulate is
impaired
o Clot will then contract to squeeze out the fluid
o Clot will then get removed via various enzyme processes
Lymphomas remain in the lymph nodes BUT leukaemias occur in the blood
o Cell retention in marrow can lead to issues with platelet production
Many cancers driven by abnormal signal transduction
CML:
o Caused by translocation (n. abnormality caused by rearrangement of parts
between non-homologous chromosomes) between two chromosomes
o homologous chromosomes n. chromosome pairs (one from each parent)
that are similar in length, gene position and centromere location
o All people with CML have a miniature chromosome
o Translocation between gene on chromosome 22 (BCR) and a tyrosine kinase
containing gene on chromosome 9 (ABL); leads to a hybrid protein
Tyrosine kinase activity no longer regulated in new protein
3
Tyrosine kinase essentially acts as a permanently switched on
growth factor receptor
o Tyrosine kinase binds to ATP, transfers phosphate to a tyrosine of a
substrate; which can then promote survival, proliferate etc.
To model this, imatinib created to bind to ATP binding pocket,
preventing the above from occurring