Haemostasis

Question 1

Haemostasis what

Answer 1

arrest of blood loss from damaged vessels. Platelets aggregate become stabilized by fibrin and arrest bleeding from severed vessels

Question 2

Thrombosis what does it cause

Answer 2

Formation of occlusive thrombi lead to MI, ischaemic stroke

Question 3

Draw flow diagram for the vascular control of platelet function

Answer 3

ref. notes and include mediators

Question 4

Process of platelet plug formation

Answer 4

damage to blood vessel->exposure of platelets to collagen and vWF in extracellular matrix and exposure to thrombin->platelets adhere and activate->release of mediators->vasoconstriction+aggregation of platelets->formation of soft platelet plug

Question 5

Extrinsic and intrinsic pathway cascade draw flow chart

Answer 5

ref. notes 7a:TF, Va:Xa, (vwf:VIII), VIIIa:IXa, Va:Xa

Question 6

What does thrombin activate

Answer 6

FV, VIII, IX, X takes place on activated platelets. Changes shape of platelet

Question 7

Initiation where

Answer 7

TF-expressing cells in tissues after blood, with its clotting factors leak out of the blood vessels

Question 8

3 categories leading to thrombosis

Answer 8

Stasis, vessel wall injury, hypercoagulability

Question 9

Arterial thrombosis

Answer 9

white clots, usually associated with atherosclerosis, form at site of vascular injury, disturbed blood flow. Large platelet component. Antiplatelet drugs. MI and strokes

Question 10

Venous thrombosis

Answer 10

stasis/turbulent flow of blood, vascular injury, hypercoagulability of blood. Platelet component, large fibrin component and RBC. Anticoagulants.Pulmonary embolism

Question 11

what do you have to make sure when treating thrombosis

Answer 11

balance clot formation risk and risk of haemorrhage

Question 12

Antiplatelet drug what does it do and example

Answer 12

limits growth/decreases risk of arterial thrombosis. aspirin, P2Y12 antagonists, GPIIb-IIIa antagonists

Question 13

Aspirin what does it do

Answer 13

irreversible inhibition of COX-1 which prevents production of TXA2 (potent platelet agonist, vasoconstrictor, mitogen) but PGI2 production not affected because COX-2 can be produced. TXA2/PGI2 PGI2 action dominates

Question 14

GPIIB-IIIa antagonist

Answer 14

Fab fragment (Abciximab, tirofiban), small molecule inhibitor (eptifibatide), use i.v. very potent block restenosis following angioplasty, inhibits aggregation. Major thrombocytopaenia risk

Question 15

Anti platelet drug use

Answer 15

Mostly secondary prevention, block restenosis following angioplasty. But multiple pathways to platelet activation limit effect of specific inhibition. So sometimes dual therapy e.g. aspirin+clopidogrel

Question 16

Anticoagulant and fibrinolytic therapy

Answer 16

Inhibit coagulation cascade, prevent propagation of blood clot but do not dissolve clot. Heparin, warfarin

Question 17

What does intrinsic system comprise of

Answer 17

XII, XI, IX, VIII, X

Question 18

What does intrinsic system comprise of

Answer 18

XII, XI, IX, VIII, X

Question 19

What does thrombin accelerate

Answer 19

XI, VIII, XIII (fibrin stabilising factor), V,

Question 20

What happens when thrombin+thrombomodulin

Answer 20

Protein C->Ca+protein S degrade Va and VIIIa

Question 21

What happens when thrombin+thrombomodulin

Answer 21

Protein C->Ca+protein S degrade Va and VIIIa

Question 22

How does fibrinogen turn into blood clot

Answer 22

Fibrinogen (thrombin)->fibrin monomers (Ca2+)->fibrin polymers(FXIII)->blood clot

Question 23

What does heparin inhibit

Answer 23

Intrinsic system production of serine-protease factors (XIIa, XIa, IXa, Xa, thrombin) by direct method and potentiation of plasma serine-protease inhibitor and antithrombin III

Question 24

Unfractioned heparin Pro+cons

Answer 24

Pro: effective, cheap, short half life, reversible with protamine
Con: continuous infusion, variable bioavailability, monitoring required, haemorrhage

Question 25

Low molecular weight heparin pros+cons

Answer 25

Pro: bioavailability increase, T1/2 increase, risk of HIT decrease Con: expensive, partial reversal with protamine, haemorrhage

Question 26

Factor Xa inhibitor how administered

Answer 26

Injection (fondaparinux, indraparinux) act indirectly via antithrombin I.v or s.c. (100% bioavailability), more predictable PK than heparin), HIT rarely observed (does not bind to PF-4), superior to LMWH Oral (rivaroxaban, apixaban) directly inhibit FXa, favourable safety does not require frequend blood monitoring

Question 27

Thrombin inhibitor how administered

Answer 27

block active site of thrombin, both clot bound and free. i.v (hirudin, lepirudin, lepirudin, desirudin), = effective LMWH, used for anticoagulant therapy of patients with HIT Oral (dabigatran) as erffective as warfarin, less chance of haemorrhage

Question 28

How to prevent inappropriate clot formation

Answer 28

Endothelial cell NO and prostacyclin (inhibit platelet activation+aggregation), Tissue factor pathway inhibitor (inactivates and forms a complex with Factor Xa which inactivates TF-VIIa complex), APC (activated by thrombin-thrombomodulin with co-factor protein S inactivating Factor Va VIIIa), antithrombin (activated by heparan and heparin, inactivates thrombin, IXa, Xa, XIa and XIIa when not in clot or combined with prothrombinase

Question 29

Draw out the relations between APC, fibrinolysis, plasmin

Answer 29

ref. notes

Question 30

Draw flow chart fibrinolytic system

Answer 30

tPA- bound to fibrin->plasminogen->plasmin->clot breaks into soluble fragments.

Question 31

Fibrinolytic purpose, risk, how administered, antidote, examples

Answer 31

activate plasminogen, high risk of haemorrhage, i.v infusion, severe haemorrhage treated with transexamic acid, streptokinase=bind and activate plasminogen-> plasmin, Alteplase=only activvate plasminogen bound to fibrin in thrombus