preview:● Glanzmann’s thrombasthenia – autosomal recessive so you have to inherit a faulty gene from mum and dad, and it is quite rare roughly around 1 in a million.
● Because it is an inherited condition patients will present with symptoms following birth therefore earlier in their life a...
● Pathology of platelet disorders including how we classify them.
● Diagnosis – role of the BMS, what are the diagnostic test that we perform.
● Inherited – number of different conditions.
● Acquired – broader, a number of different conditions can give rise to acquired platelet
disorders. Examples include scarring of the liver (cirrhosis) and haematological malignancies
which can impair platelet function.
● Glanzmann’s thrombasthenia – autosomal recessive so you have to inherit a faulty gene
from mum and dad, and it is quite rare roughly around 1 in a million.
● Because it is an inherited condition patients will present with symptoms following birth
therefore earlier in their life and these include nosebleeds, extensive bruising, bleeding
gums, excessive bleeding during periods.
● It arises as we get defects in the glycoprotein 2b3a complex.
● Platelets express a number of molecules or receptors on their surface and one such example
is the glycoprotein 2b3a complex.
● In vessel injury we get the exposure of collagen – that gets bound by vWf – one of the
receptors upon platelets that binds that vWf is the glycoprotein 2b3a complex.
● In patients with Glanzmann’s – not only do they have impaired binding to vWf mediated by
this complex, but they also have impaired binding to fibrinogen.
● If we out the patient sample through an analyser we would find that they have a normal
platelet count and if we were to look at the blood under the microscope you would find
normal platelet morphology.
● How can we diagnose it them? – generally its based on the sample being sent in the first
place because patients will have symptoms – we will perform a full blood count and a blood
film, and we will also perform a functional test.
● Functional test – here we will expose the patients’ platelets to a number of agonists which
are meant to activate them so ADP, collagen, adrenaline and we find that we get impaired
platelet aggregation, and we get increased bleeding time.
● Bernard-Soulier syndrome – typical around 1 in a million.
● It also involves a glycoprotein but this time it is 1b.
● Platelets express a number of receptors on their surface and one such example is the
glycoprotein 1b – that will bind to vWf – it performs a really key role in forming a platelet
plug.
, 8. Coagulation Disorders
● Patients will have slight or mild thrombocytopenia – slight reduction in platelet count we can
do a full blood count and when we look at the cells under the microscope unlike
Glanzmann’s where the morphology is normal in Bernard-Soulier you will see the presence
of giant platelets.
● Bleeding can be sever – because glycoprotein 1b plays an essential role in he binding of
platelets to vWf and therefore plays a really important role in platelet aggregation and
activation and formation of a primary platelet plug we find that defects in glycoprotein 1b
can have quite sere repercussions and have quite sever symptoms – this include excessive
bleeding (could be during pregnancy for example and during delivery or if they were to
develop a gastric ulcer where we get damage to the stomach lining due to the stomach acid
therefore we get damage to the blood vessels within the stomach and excessive bleeding).
● Anti-platelet drugs – there are a number of them, but aspirin is one the most well known
and widely taken one.
● Aspirin exerts its anti-platelet effects by inhibiting cyclo-oxygenase 1 (COX-1) – that
interference or inhibition of COX-1 is irreversible.
● COX-1 normally facilitates the conversion of arachidonic acid to producing prostaglandin H2
and that will go on to firm thromboxane A2.
● Thromboxane A2 is a potent vasoconstrictor but it also facilitates platelet aggregation.
● Because it is irreversible the effects of aspirin last for the remainder of the platelet’s
lifespan.
● Aspirin exerts its effect at 80-150 milligrams – it exerts its biological effects around 1 hour
after taking it and it is absorbed through the stomach.
● Patients who go onto develop chronic renal failure (end stage renal disease) will also have
impaired platelet function – this is due to the fact that the kidneys are no longer working
correctly we get the accumulation of uremic toxins within the blood or within the plasma,
examples of this include urea and phenolic acid.
● Phenolic acid has a negative effect on platelet function because it impairs ADP mediated
activation of platelets leading to the aggregation.
● Other compounds such as nitric oxide potentially will inhibit platelet function – we can see
on the diagram that the formation of nitric oxide leads to platelet disaggregation.
● They may also experience anaemia – we get a drop within normal red cell counts so we get a
reduction in the erythrocyte count.
● In health as red cells are flowing through the circulation, they cause platelets to be displaced
towards the edges of that circulation so when we have injury to the vasculature, they are in
a prime position to mediate the formation of a clot – when we get reductions in
erythrocytes, we get less of the platelets flowing within the circulation towards the edges of
the vasculature therefore that can interfere with their function as well.
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