Platelets and Haemostasis Flashcards
what are platelets
what is their function
small cell fragments formed by megakaryocytes
clotting
how are platelets formed
describe their origin cells
shed off from megakaryocytes
extraordinarily large bone-marrow cells
describe clot formation when a vessel is injured
- circulating platelets adhere to and are activated by exposed collagen
- Von Willebrand factor activates platelets causing them to have protrusions
- activated platelets release ADP and thromboxane A2
- these further activate more platelets to join the newly forming plug and release further ADP and thromboxane A2
how soon after injury does a blood vessel constrict
vasoconstriction occurs within seconds
what prevents platelet aggregation under normal conditions and confines aggregation to plug sites
normal uninjured endothelium releases prostacyclin and nitric oxide to inhibit it
what is the effect of aspirin
acts as a blood thinner by inhibiting the COX1 pathway which normally releases prostaglandins that stimulate clotting
what is haemostasis
what is the functions
arrest of bleeding from a broken blood vessel; stopping a haemorrhage
prevents blood loss from damaged small vessels
features of platelets
no nucleus
some organelles round when inactive, protrusions when active
how does blood clot formation get triggered
chain reaction involving plasma clotting factors
fibrinogen
plasma protein important for clotting but must be converted to fibrin
when is prothrombin converted to thrombin
when blood clotting is desirable
what is the clotting cascade
what is the final step
series of sequential reactions that occurs until thrombin catalyses the conversion of fibrinogen to fibrin
describe the formation of fibrin mesh
- thrombin cleaves fibrinogen to make a fibrin monomer
- thrombin also cleaves factor 13 -> 13a
- fibrin monomers cross link into a fibrin strand
- cross linked stands form a mesh stabilised by factor 13 cross linking
intrinsic clotting pathway
precipitates clotting within damaged vessels, and clotting of blood samples e.g. in test tubes
extrinsic pathway
initiates clotting blood that has escaped into the tissues
clot retraction
platelets trapped within the clot contract and shrink the fibrin mesh
pulls the edges of the damaged vessel closer together allowing healing
at what point do the intrinsic and extrinsic pathway converge
factor 10 activation
factor 10 function
together with Ca2+ and factor 5 converts prothrombin to thrombin
what activates factor 13
thrombin
what are the results of thalassaemia and haemophilia
poor blood clotting and excessive bleeding
how is the extrinsic pathway activated when there is damage from outside
- tissue thromboplastin (factor 3) is released from damaged tissue
- acts together with factor 7 and Ca2+ to activate factor 10
when damage affects both pathways, which activates factor 10 first
extrinsic
what other factors does factor 10 require to act
factor 5 and Ca2+
how is the intrinsic pathway activated
- when factor 12 (Hageman factor) is activated by contact with exposed collagen at the surface of damaged vessels
- or by contact with a foreign surface (glass in test tubes)
order of factor activation in the intrinsic pathway
12, 11, 9, 10
what factor is required between factor 11 and 9
what factor is required between factor 9 and 10
4
8
where are clotting factors synthesised
what vitamin do many of them require
liver
vitamin K
what cells form a scar at vessel defects
fibroblasts
what dissolves clots
how
plasmin
becomes trapped in the clot and later dissolves it by slowly breaking down the fibrin meshwork
what is the continuous role of plasmin
preventing inappropriate clot formation
why would you want to pharmacologically inhibit tissue plasminogen activator
it cleaves plasminogen into active plasmin
when you want clotting e.g. haemophilia
why would you want to pharmacologically inhibit plasmin
what is the physiological inhibitor of plasmin when does it act
when you want clotting
alpha2-antiplasmin, when plasmin in blood is 6-8X exceeding therapeutic dose
what is a thrombus
what is a thromboembolism - what can they cause
abnormal intravascular clot attached to a vessel wall
free floating abnormal intravascular clot - stroke
causes of strokes
thromboembolism, brain bleed, hypoxia
why is liver disease a blood clotting disorder
liver synthesises procoagulants and most clotting factors
also produces bile to absorb fat and vitamin K
why is vitamin K deficiency a blood clotting disorder
essential for the synthesis of clotting factors
why does long term antibiotic use result in bleeding disorders
results in vit K deficiency because half of our Vit K comes from gut bacteria (other half diet)
thrombocytopenia definition
results
cause
treatment
number of circulating platelets is too low
spontaneous, widespread haemorrhage, visible by small purple spots on the skin
caused by damaged bone marrow or cancer
treated with whole blood transfusions or platelet transfusion
thrombosis definition
causes
results
inappropriate clotting
caused by roughened surface of a vessel, endothelial cell injury (collagen exposed), disrupted flow (stasis - no laminar flow)
can cause DVT, ischemia, and tissue death
coronary thrombosis
cerebral thrombosis
thrombus in a blood vessel of the heart can cause a heart attack
thrombus in a blood vessel of the brain can cause a stroke
atherosclerosis
build up of oxidised LDL, fatty plaques in vessels
what do blood types depend on
surface antigens on erythrocytes
when does haemolytic disease of the new-born occur
explain why
- occurs when the mother is Rh- during the second or later pregnancies with a Rh+ child
- when Rh+ blood from previous pregnancy caused her body to synthesise anti-Rh Abs
- mothers Abs cross the placenta and cause agglutination and haemolysis of foetal RBCs
how is haemolytic disease of the new-born prevented
injected anti-Rh antibodies eliminate Rh+ cells