Principles Flashcards
What components interact in haemostasis?
platelets coagulation factors coagulation inhibitors fibrinolytic processes blood vessels/endothelium/cell membranes
What are the steps haemostasis + what is their timefram
Seconds -> minutes (immediate)
= Primary haemostasis
- get platelet plug
Minutes
= Secondary haemostasis
- fibrin network secures clot in place
Mins -> Hrs
Fibrinolysis
- lysis of clot
What occurs in primary haemostasis?
- damaged vessel wall -exposes collagen
=> platelets are activated when bind collagen
platelets release ADP and 5-HT (serotonin)
5-HT = serotonin (5-HT) - powerful vasoconstrictor
ADP - causes other platelets to activate and change shape
- platelet adhesion + aggregation -> plug
platelets also synthesise other mediators - eg thromboxane from arachadonic acid => stimulate further activation of platelets
via what mechanism do platelets aggregate and adhere
fibrinogen bridging between GPIIb/IIIa receptors
What happens in secondary haemostasis?
- activation of coagulation factors
- formation of fibrin -> fibrin network => secure clot into place
What happens in fibrinolysis
lysis of clot -> back to smooth surface on endothelium wall
What are the components of Virchow’s triad
Vessel wall
Blood composition
Blood flow
Virchow’s triangle - vessel wall - describe
what effects can it have on haemostasis
endothelial surface of vessel wall is dynamic + active - interacts with blood/subcutaneous tissue
can be anti or pro-thrombolytic (depending on expression of surface proteins/secreted proteins)
the lining differs with location and age
Which components of Virchow’s triad can we test to look at clotting/bleeding disorders
Blood composition (cells, plasma)
Blood flow (cardio factors, function)
Can’t test vessel wall integrity
Virchow’s triad - blood composition; what components are important
Blood cells
- RBC
- WBC
- platelets
Plastma - coagulation/clotting system
What are the 2 key components of the coagulation system?
tissue factor - is released by vessel wall, kicks things off
thrombin - key enzyme that must be controlled
- converts fibrinogen -> fibrin
What are the phases of the coagulation model? What are the steps within each phase
(1) Initiation phase
- vessel wall injury - contact between subendothelial cells + blood
- tissue factor is exposed
- tissue factor binds FVIIa - and this activates FIX + FX
- FXa then binds Fva on cell surface
(2) Amplification phase
- the FXa/FVa complex converts a small amount of prothrombin -> thrombin
thrombin activates FVIII, FV, FXI and platelets
then FXIa converts FIX to FIXa
the activated platelets bind FVa, FVIIIa, FIXa
(3) propagation phase = thrombin burst
FVIIIa/FIXa comple activates FX on activated platelet surface
FXa + FVa convert a large amount of prothrombin -> thrombin
=> this leads to the formation of a stable fibrin clot
why is thrombin esential for clot formation?
converts fibrinogen -> fibrin
- clot formation
- reinforcement of platelet plut
what happens if there is too much thrombin?
or too little?
too much = thrombosis
too little = bleeding
how does inactivation of thrombin occur
Thrombin inactivation:
(1) negative feedback
= thrombin binds thrombomodulin -> activates protein C
- APC inhibits VIIIa and Va
- APC also inactivates the inhibitor of tissue plasminogen (allowing fibrinolysis)
(2) Other mechanisms
a. enzyme inhibitors
= antithrombin - binding induces irreversible inhibition (accelerated 1000fold by heparin)
b. binding to heparin co-factor II, dermatan sulphate, a-2 macroglobulin
how does heparin work
accelerates antithrombin-thrombin binding (irreversible inhibition of thrombin)
what is a fault of haemostatic testing?
isn’t a true measure of physiology - usually we are testing one part of the system in isolation
- however it can hopefully predict clinical ehaviour
what kinds of tests can we use to test haemostasis?
can’t test blood vessel wall
can test platelets - number, function, appearance
we have a range of tests for the coagulation system
what are some tests of the coagulation system
tests of risk of bleeding
- APTT, INR etc
we can do specific assays on clotting factors, fibrinogen, specific assays
and we can genotype for disorders of clotting
What are some examples of global functional assays for haemostasis?
PT = prothrombin time - initiate clotting (calcium, heating) + measure time to make a clot
INR = standardisation of PT
APTT - activated partial thromboplastin time - similar to PT
Why is INR used?
Different labs will have different results for prothrombin time (PT) due to use of different reagents
INR gives a way to standardise these results = international normalised ration
INR = (patient PT/mean normal PT)^ISI
where ISI = sensitivity index
INR is used to monitor warfarin use
what can APTT tell you about?
factor deficiencies (XII, XI, IX, X)
lupus anticoagulant
heparin monitoring
Haemostatic disorders what are type I and type II
Type I - low amount and function
Type II - normal amount, but non-functioning
How does fibrinolysis occur
plasmin - dissolves fibrin
