Haemostasis Flashcards

1
Q

Haemostasis what

A

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

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2
Q

Thrombosis what does it cause

A

Formation of occlusive thrombi lead to MI, ischaemic stroke

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3
Q

Draw flow diagram for the vascular control of platelet function

A

ref. notes and include mediators

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4
Q

Process of platelet plug formation

A

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

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5
Q

Extrinsic and intrinsic pathway cascade draw flow chart

A

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

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6
Q

What does thrombin activate

A

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

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7
Q

Initiation where

A

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

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8
Q

3 categories leading to thrombosis

A

Stasis, vessel wall injury, hypercoagulability

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9
Q

Arterial thrombosis

A

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

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10
Q

Venous thrombosis

A

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

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11
Q

what do you have to make sure when treating thrombosis

A

balance clot formation risk and risk of haemorrhage

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12
Q

Antiplatelet drug what does it do and example

A

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

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13
Q

Aspirin what does it do

A

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

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14
Q

GPIIB-IIIa antagonist

A

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

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15
Q

Anti platelet drug use

A

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

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16
Q

Anticoagulant and fibrinolytic therapy

A

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

17
Q

What does intrinsic system comprise of

A

XII, XI, IX, VIII, X

18
Q

What does intrinsic system comprise of

A

XII, XI, IX, VIII, X

19
Q

What does thrombin accelerate

A

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

20
Q

What happens when thrombin+thrombomodulin

A

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

21
Q

What happens when thrombin+thrombomodulin

A

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

22
Q

How does fibrinogen turn into blood clot

A

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

23
Q

What does heparin inhibit

A

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

24
Q

Unfractioned heparin Pro+cons

A

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

25
Q

Low molecular weight heparin pros+cons

A

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

26
Q

Factor Xa inhibitor how administered

A

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

27
Q

Thrombin inhibitor how administered

A

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

28
Q

How to prevent inappropriate clot formation

A

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

29
Q

Draw out the relations between APC, fibrinolysis, plasmin

A

ref. notes

30
Q

Draw flow chart fibrinolytic system

A

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

31
Q

Fibrinolytic purpose, risk, how administered, antidote, examples

A

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