W1 Haemostasis, Platelets and Coagulation Part 1 and 2 Flashcards
what area is a blood clot limited to?
the site of injury
what is haemostasis?
the process in which coagulation is initiated and terminated in a regular way, with the removal of the clot
haemostasis is a physiological process that stops bleeding at the site of injury whilst maintaining what?
blood flow elsewhere in the circulation
what is haemostasis in response to?
a defence mechanism in response to injury in order to preserve the integrity of the vascular system
what are the four steps of haemostasis?
- vasoconstriction restricting blood flow to the damaged vessel
- platelet aggregation and plug formation (primary haemostasis)
- generation of the enzyme thrombin that proteolyzes soluble fibrinogen to insoluble fibrin (secondary haemostasis)
- removal of the clot in a controlled way known as fibrinolysis restores function
what are the five major components of the haemostatic system?
- blood vessels
- platelets
- coagulation factors
- coagulation inhibitors
- fibrinolytic factors (clot dissolving components)
in a high pressure vascular system why does the response need to be rapid but regulated?
to prevent inappropriate clot formation and ensure it is localised to prevent loss of blood
what impact does clotting have on microbes?
prevents them from gaining entry to the body
what are potential problems of inappropriate blood coagulation?
may block vessels which can restrict blood flow, starve tissues of oxygen and thus cell death
what is haemophillia?
failure to be able to generate a fibrin clot (life threatening)
what is DVT?
deep vein thrombosis
what is PE?
pulmonary embolism
what enables coagulation to be so rapid?
platelets are produced in bone marrow and circulate in large numbers, proteins involved in generating fibrin clots are produced in the liver primarily and all components are pre-synthesised and most circulate in the blood
why is coagulation so localised, give three reasons?
any three of:
- platelets sense proteins only at exposed sites of vascular injury
- activated platelets at injury sites expose a surface the promotes assembly of complexes which lead to thrombin generation
- thrombin generation network is triggered by exposure of blood to cellular receptors
- the unperturbed endothelium presents an anticoagulant response that dampens down any inappropriate activation of coagulation
- the anticoagulant response of endothelium limits spread of the response beyond the site of injury and occlusion of injured vessel
platelets are anucleate cells, what does this mean and where are they produced?
they have no nucleus, produced in the bone marrow via budding off from megakaryocytes
what is thrombocytopenia?
a deficiency of circulating platelets due to decreased platelet formation
what is platelet formation regulated by and where is it produced?
thrombopoietin which is produced in the liver and kidney
what percentage of dogs admitted to vet hospitals have low platelet count?
5% according to some surveys
what percentage of king charles spaniels are effected by macrothrombocytopenia which is an inhertied disorder?
around 50%
what shape and colour are resting platelets?
round to oval in shape, they have visible red-pink granules
what are the key binding partners to platelets?
collagen and von Willebrand factor (VWF)
binding to ligands results in the release of granules containing what, that activate platelets?
ADP and thromboxane
activated platelets change shape and generate what?
generation of filopodia
what is VWF?
von Willebran factor, a large protein 250kDa forming multimers of 80 subunits
where is VWF found?
in plasma, platelet storage granules and in endothelial cells
what is VWF associated with?
collagen and laminins found in the subendothelial matrix
under normal conditions is VWF in globular or non-globular form?
globular form that does not bind with platelets