haemostasis

Question 1

What 3 processes take part in haemostasis

Answer 1

vasoconstriction, primary haemostasis, secondary haemostasis (coagulation)

Question 2

describe primary haemostasis

Answer 2

Formation of a platelet plug:
platelet adhesion, platelet release reaction, platelet aggregation

Question 3

what are platelets

Answer 3

non-nucleated, granule-containing cells formed from the fragmentation of megakaryocyte cytoplasm

Question 4

mechanism of adhesion

Answer 4

injury to vessel walls –> platelets stick to damaged endothelium- on collagen, the GPIb receptor or indirectly through VWF which then binds to GPIb receptor

adhesion changes platelet shape from a disc to rounded with spicules

Question 5

What happens to platelets after platelet adhesion?

Answer 5

they get activated
contents of alpha and dense granules released
through invaginated membrane

Question 6

components of alpha and dense granules in platelets?

Answer 6

ADP, fibrinogen, von Willebrand factor

Question 7

What is thromboxane A2?

Answer 7

vasoconstrictor

involved in platelet aggregation

prostaglandin

derived from arachidonic acid in cell membrane

Question 8

what happens after granular release in primary haemostasis?

Answer 8

platelet activation causes conformational change in GPIIb/IIIa receptor on endothelial cells to allow for fibrinogen binding

fibrinogen has a key role in linking platelets to form the platelet plug

Question 9

how are the effects of primary haemostasis counterbalanced?

Answer 9

active flow of blood and the release of prostacyclin PGI2 from endothelial cells

prostacyclin is a powerful vasodilator and suppresses platelet activation

Question 10

name anti platelet drugs

Answer 10

aspirin, clopidgrel

Question 11

how does aspirin work?

Answer 11

irreversibly binds to platelets, inhibiting them (single dose aspirin effects persist for around 7 days)

aspirin binds specifically to cycle-oxygenase COX

Question 12

how does clopidogrel work

Answer 12

irreversible blocking of ADP receptor on platelet cell membranes (effects also last for 7 days)

Question 13

what is the VWF?

Answer 13

glycoprotein synthesised by endothelial cells and megakaryoctes

mediates adhesion of platelets to sites of injury, promotes platelet-platelet aggregation

also specific carrier for factor 8

Question 14

What’s secondary haemostasis?

Answer 14

coagulation - formation of a stable fibrin clot

Question 15

where are most clotting factors synthesised?

Answer 15

the liver

factor VIII and VWF are made by endothelial cells

Question 16

Which factors are dependent on vitamin K for function, and therefore effected by warfarin?

Answer 16

factors II, VII, IX and X
2 5 7 10

vit K needed for carboxylation of glutamic acid residues on them

Question 17

What does calcium do in coagulation?

Answer 17

plays an important role in the binding of activated clotting factors to the phospholipid surfaces of platelets

Question 18

What is the trigger to initiate coagulation?

Answer 18

Tissue factor (TF)

found only in tissue so does not come into contact with blood until vascular injury occurs

Question 19

What is the initiation phase in coagulation?

Answer 19

TF binds to VIIa, triggering factor X and IX to be activated- this leads to the activation of factor II (prothrombin) being activate to form small amounts of thrombin (factor IIa)

Question 20

What is the amplification phase in coagulation?

Answer 20

small amount of thrombin mediates activation of factors V and VIII (co-factors) and the zymogen factor X11 (11) and platelets.

Factor XI activates factor IX to IXa, which, with factor VIIIa, amplifies the conversion of factor X to Xa

Question 21

What is the propagation phase in coagulation?

Answer 21

a rapid burst in thrombin generation

cleaves circulating fibrinogen to form insoluble fibrin (the clot)

Question 22

inhibitory mechanism ensuring coagulation is confined to site of injury? (anticoagulation pathway)

Answer 22

antithrombin inhibits thrombin and factor Xa

protein C activated by binding of thrombin thrombodulin on endothelial cell surfaces to form APC

APC inactivates factors Va and VIIIa in the presence of co-factor protein S

Question 23

anticoagulant drugs

Answer 23

heparin, warfarin, direct oral anticoagulants

Question 24

heparin

Answer 24

mixture of glycosaminylglycan chains extracted from porcine mucosa

works indirectly- potentiates action of antithrombi, leading to inactivation of factors Xa and IIa (thrombin)

administered intravenously/subcutaneous injection

Question 25

warfarin

Answer 25

vit K antagonist- reduces synthesis of factors II, VII, IX and X by liver oral tablet, effect must be regularly monitored takes several days for effect

Question 26

 Direct oral anticoagulants (DOACs)

Answer 26

Orally available drugs that directly inhibit either thrombin or factor Xa (i.e. without the involvement of antithrombin) ​These do not usually require monitoring

Question 27

what's fibrinolysis?

Answer 27

breakdown of fibrin to generate fibrin-degradation produces (FDPs)

Question 28

what is the principal fibrinolytic enzyme?

Answer 28

plasmin (zymogen form plasminogen) activation of plasmin is mediated by tissue plasminogen activator, t-PA

Question 29

how do thrombolytic agents work?

Answer 29

e.g. recombinant t-PA generate plasmin to lyse clots- administered intravenously to patients w ischaemic stroke high risk of bleeding

Question 30

what does tranexamic acid do?

Answer 30

binds to plasminogen (it is similar to lysine) competitively prevents activation of plasminogen to plasmin less fibrinolysis

Question 31

when is tranexamic acid used mainly

Answer 31

to treat bleeding in trauma and surgical patients, and patients with inherited blood disorders

Question 32

what's the intrinsic pathway

Answer 32

where all the factors are found inside the blood- XII-> XI -> VIII and IX then common common is V X --> II --> fibrinogen to fibrin

Question 33

what's the extrinsic pathway

Answer 33

kicked off by TF, then common

Question 34

what's prothrombin time(PT)?

Answer 34

measures integrity of extrinsic pathway

Question 35

mechanism of the PT test?

Answer 35

blood collected in bottle with sodium citrate stops blood from clotting by chelating calcium in sample sample spun to produce platelet poor plasma TF and phospholipid added to the citrated plasma with calcium to start the reaction time taken for clotting is measured

Question 36

when is PT prolonged?

Answer 36

when there is a reduction in factors VII, X, V, II or fibrinogen

Question 37

how are results expressed when PT is used to monitor via K antagonist anticoagulant therapy (eg warfarin)?

Answer 37

INR - international normalised ratio involves correction for diff thromboplastin reagents sued by diff labs around the world- so all labs have the same INR result for a given sample

Question 38

what does Activated partial thromboplastin time (APTT) measure?

Answer 38

integrity of intrinsic pathway

Question 39

mechanism of APTT?

Answer 39

performed by contact activation of factor XIIa by a surface like glass, or using a contact activator like silica or kaolin contact activator and phospholipid added to citrated plasma followed by calcium time for clotting measured

Question 40

when is APTT prolonged?

Answer 40

where there is a reduction in a single or multiple clotting factors- in the latter there could be a prolonged PT as well isolated prolonged APTT is seen in patients w haemophilia A, B and factor XI deficiency (sometimes also by factorXII deficiency which doesn't result in bleeding)

Question 41

what can bleeding be caused by?

Answer 41

reduction in platelet number or function reduction in coagulation factors increased fibrinolysis

Question 42

what is haemophilia a

Answer 42

deficiency of factor VIII (x linked)

Question 43

what is haemophilia B

Answer 43

factor IX deficiency, x linked

Question 44

acquired causes of reduced coagulation factors?

Answer 44

liver disease anticoagulant drugs disseminated intravascular coagulation

Question 45

what Is thrombosis

Answer 45

term used to describe formation of a blood clot where it is not needed

Question 46

3 contributory factors to thrombosis?

Answer 46

blood, vessel wall, blood flow

Question 47

which factors increase the risk of venous thrombosis?

Answer 47

1. reduced levels of anticoagulant proteins - -reduced fibrinolytic activity 2. increased levels of clotting factors/ platelets 3. hyperviscosity (e.g. due to polycythaemia)