HAEMOSTASIS Flashcards
What is haemostasis?
he cellular and biochemical processes that enables both the specific and regulated cessation of bleeding in response to vascular insult
prevention of blood loss
what is the initial response at the site of injury?
vessel constriction to limit blood flow
formation of an unstable platelet plug
-platelet aggregation and adhesion
what is secondary haemostasis?
the coagulation cascade
stabilisation of the platelet plug with fibrin
what anticoagulant molecules are there on the endothelial cell wall?
thrombo modulin, EPCR (endothelial cell protein C receptor), TFPI
what substances circulating in the blood are involved in haemostasis?
von willebrand factor platelets protein C protein S FII (prothrombin), FV, FVII, FVIII, FIX, FXI
What are platelets- what are their features?
small (2-4um) anuclear cells
life span of ~10days
Platelet count: 150-350 x 109/L
where do platelets come from?
haematopoetic stem cells from the bone marrow proliferate into a megakaryocyte
Each megakaryocyte produces ~4000 platelets.
what do the platelet alpha-granules contain?
growth factors fibrinogen VWF FV cytokines
specifically released when platelet activated
what do the platelet dense granules contain?
ADP ATP serotonin Ca2+ polyphosphates
what is recruitment of the platelets to the site of damage dependant on?
briefly describe the process
von willebrand factor
circulates in blood in a folded up structure which conceals the binding sites to platelets
when there is vessel injury the VWF recognises the exposed collagen and this causes a structural change in the VWF into an extended confirmation
this exposes all of the binding sites that recognise platelets
allowing the platelets to anneal to the VWF at the site of injury
what are platelets activated by?
gpVI
how do platelets aggregate?
they bind to each other via gpIIb/IIIa
what happens when the platelet is activated?
it releases its granular contents and changes confirmation to optimise aggregation
what is von willebrands disease?
mutation in the protein VWF which means platelets cant be recruited to vessel damage so the patients bleed
what are the co factors?
tissue factor
factor Va
factor VIIIa
what is the first step of the extrinsic pathway of the coagulation cascade?
FVII is activated to FVIIa when it interacts with tissue factor
what is tissue factor?
an integral membrane protein
which are the Gla domain containing proteins?
FVII
FX
Prothrombin
FIX
Protein C
Protein S
what is the gla domain?
gives the proteins the ability to interact with negatively charged phospholipid cell or platelet surfaces
what does wafarin do?
indirect anticoagulant
it is a vitamin K antagonist so
prevents the body from gamma carboxylating the clotting factors
so the clotting fasctors produced dont have a functional gla domain so cant bind to phosopholipid surfaces
diminishing the function of a number of clotting factors
what factor cleaves prothrombin to thrombin?
factor Xa
what regulates the coagulation cascade?
tissue factor pathway inhibitor (TFPI)
what is the protein C pathway?
protein C is activated by thrombin- TM complex
activated protein C (APC) inhibits thrombin generation by proteolytically inactivating procoagulant cofactors FVa and FVIIIa
it down regulates thrombin generation but it does not inhibit thrombin
how does heparin work?
indirect anticoagulant
binds to antithrombin and enhances the efficiency in which antithrombin can inhibit FXa, thrombin, FIXa, FXIa
