coagulation

Question 1

what is haemostasis

Answer 1

arrest of blood loss from a damaged vessel at the site of injury

Question 2

what is involved in the sequence of haemostasis

Answer 2

1. vascular wall damage which exposes collagen and tissue factor
2. primary haemostasis
3. activation of blood clotting and formation of a stable clot

Question 3

what is involved in primary haemostasis

Answer 3

local vasoconstriction

platelet adhesion, activation, and aggregation by fibrinogen

Question 4

what do activated platelets release

Answer 4

thromboxane A2 (TXA2)

Question 5

what does TXA2 bind to, what does this cause

Answer 5

1. platelet GPCR TXA2 receptors (TP receptors) which causes mediator release
2. vascular smooth muscle cell TXA2 receptors causing vasoconstriction

Question 6

what mediators are released by TXA2 binding

Answer 6

5-HT (aka serotonin)

ADP

Question 7

what does ADP bind to in primary haemostasis, what does this cause

Answer 7

platelet GPCR purine receptors (P2Y12)

binding causes: further platelets to be activated, aggregation of platelets into a ‘soft plug’, and exposure of acidic phospholipids on the platelet surface that initiates coagulation of blood and solid clot formation

Question 8

describe the coagulation cascade

Answer 8

X is converted to Xa + Va (together known as prothrombinase) by IXa and VIIIa (together known as tenase). prothrombinase then converts II (prothrombin) to IIa (thrombin). thrombin then cleaves fibrinogen to form fibrin (solid clot)

Question 9

what is thrombosis

Answer 9

pathological haemostasis, a haematological plug in the absence of bleeding

Question 10

what is an arterial thrombus

Answer 10

mainly platelets in a fibrin mesh

Question 11

what is an arterial thrombus also known as

Answer 11

a white thrombus

Question 12

what does an arterial thrombus form if it detaches

Answer 12

an embolus which then lodges in an artery (causing stroke) or other organ

Question 13

how is an arterial thrombus treated

Answer 13

antiplatelet drugs

Question 14

what is a venous thrombus

Answer 14

white head, jelly-like red tail.. fibrin rich

Question 15

what is a venous thrombus also known as

Answer 15

red thrombus

Question 16

what does a venous thrombus form if it detaches

Answer 16

an embolus that usually lodges in the lung

Question 17

how is a venous thrombus treated

Answer 17

anticoagulants

Question 18

what drug works on factor X

Answer 18

warfarin

Question 19

what drug works on factor II

Answer 19

warfarin

Question 20

what drug works on factor Xa

Answer 20

orally active inhibitors

heparin/LWMH/fondaparinux

Question 21

what drug works on factor IIa

Answer 21

orally active inhibitors

heparin/LWMH/fondaparinux

Question 22

what is warfarin’s mechanism of action

Answer 22

inactivates factors II, VII, IX, and X

Question 23

how is warfarin administered

Answer 23

orally

Question 24

what is used to treat an warfarin overdose

Answer 24

vitamin K (as phytomenadione)

Question 25

what is orally active inhibitor's mechanism of action

Answer 25

directly inhibit thrombin or factor Xa

Question 26

give an example of an orally active inhibitors

Answer 26

dabigatran (inhibits thrombin) | rivaroxaban (inhibits factor Xa)

Question 27

what is the mechanism of action of heparin

Answer 27

inhibits factors Xa and IIa

Question 28

what is the mechanism of low molecular weight heparin (LWMH)

Answer 28

inhibits factor Xa

Question 29

what are the serine proteases in the coagulation cascade

Answer 29

VIIa IXa Xa

Question 30

what does anti-thrombin III (ATIII) do

Answer 30

important inhibitor of coagulation as it neutralised ALL serine protease factors in the coagulation cascade

Question 31

explain the link between heparin and ATIII

Answer 31

heparin binds to ATIII which increases its binding affinity especially for factors Xa and IIa which increases their rate of inactivation

Question 32

how does heparin inactivate IIa

Answer 32

by binding to ATIII AND factor IIa

Question 33

how does heparin inactivate Xa

Answer 33

by binding to ATIII

Question 34

what are anticoagulants used to treat

Answer 34

AF DVT post-op thrombosis patients with artificial heart valves

Question 35

give examples of low molecular weight heparin (LMWH)

Answer 35

"-parin" | fondaparinux "-pariniux"

Question 36

how is LMWH administered

Answer 36

subcutaneously (SC) = injection

Question 37

how is heparin administered

Answer 37

``` IV = immediate onset of action SC = onset delayed by 1 hour ```

Question 38

when is heparin preferred over LMWH, why?

Answer 38

renal failure LMWH is excreted via the kidneys, heparin is not

Question 39

what is given in if a heparin haemorrhage has occurred

Answer 39

protamine sulfate IV

Question 40

what are anticoagulants used for

Answer 40

venous thrombosis

Question 41

what are antiplatelets used for

Answer 41

arterial thrombosis

Question 42

give examples of antiplatelets

Answer 42

aspirin clopidogrel tirofiban

Question 43

what is the mechanism of action of clopidogrel

Answer 43

links to the P2Y12 receptor via disulphide bond producing irreversible inhibition

Question 44

when would clopidogrel be used

Answer 44

most often given in patients intolerant to aspirin

Question 45

what is the mechanism of action of aspirin

Answer 45

irreversibly blocks cycloxygenase (COX) in platelets preventing TXA2 synthesis also blocks COX in endothelial cells inhibiting production of antithrombotic prostaglandin I2 (PGI2)

Question 46

what cascade opposes the coagulation cascade

Answer 46

fibrinolytic cascade

Question 47

describe the fibrinolytic cascade

Answer 47

plasminogen is converted to plasmin via endogenous tissue plasminogen activator (tPA). Plasmin then converts fibrin to fibrin fragments which are involved in clot lysis

Question 48

where do fibrinolytic drugs act

Answer 48

act on the conversion on plasminogen to plasmin

Question 49

give examples of fibrinolytic drugs

Answer 49

streptokinase alteplase duteplase

Question 50

what is streptokinase

Answer 50

a protein extracted from strep cultures

Question 51

when is streptokinase contraindicated

Answer 51

in a patient with a recent strep infection or an allergy

Question 52

what are alteplase and duteplase

Answer 52

recombinant tissue plasminogen activators (rt-PAs)

Question 53

how can haemorrhage caused by alteplase or duteplase be treated

Answer 53

oral tranexamic acid which inhibits plasminogen activation