Haemostasis/Anti-platelets

Question 1

what is haemostasis?

Answer 1

the arrest of bleeding from damaged blood vessels

Question 2

how many stages of haemostasis are there?

Answer 2

3

unofficially 4

Question 3

what are the stages of haemostasis?

Answer 3

1. Blood vessel constriction
2. Formation of a platelet plug
3. Formation of a clot
   (4) . Remodelling clot

Question 4

how do the main stages of haemostasis work?

Answer 4

endothelial damage causes vascular spasm
platelet aggregation causes platelet plug formation
coagulation cascade causes clot formation

vascular spasm also leads platelet aggregation which leads to clot formation

endothelial damage can lead to platelet aggregation which leads to coagulation cascade, or to coagulation cascade directly.

Question 5

what is the anatomy of a blood clot?

Answer 5

thrombus: platelets in fibrin thread, erythrocytes in mesh

Question 6

what is the aim of the coagulation phase?

Answer 6

make fibrin

Question 7

a severed blood vessel- what is the first response? why?

Answer 7

contraction of smooth muscle - vasoconstrict

Question 8

how does a severed blood vessel constrict?

Answer 8

release of Thromboxane A2 from platelets

Question 9

what does TXA2 stand for?

Answer 9

Thromboxane A2

Question 10

what is Thromboxane A2?

Answer 10

potent vasoconstrictor

Question 11

what 3 things does Thromboxane A2 do?

Answer 11

1. slows blood flow
2. reduces pressure
3. brings cut surfaces together (only permanent closure in small blood vessels)

Question 12

in the platelet plug formation, what do platelets adhere to?

Answer 12

collagen

Question 13

how do platelets adhere to collagen?

Answer 13

by binding to

Question 14

where is von Willebrand’s factor secreted?

Answer 14

platelets and endothelium

Question 15

what 3 granules do activated platelets release?

Answer 15

ADP
5-HT
TXA2

Question 16

what does ADP stand for?

Answer 16

adenosine diphosphate

Question 17

what does 5-HT stand for?

Answer 17

serotonin

Question 18

what do the granules secreted by activated platelets do?

Answer 18

cause more platelets to come to increase aggregation

Question 19

what is the change in platelets in platelet aggregation?

Answer 19

discoid platelets -> activated platelets

Question 20

how is the loose platelet plug reinforced?

Answer 20

by fibrin meshwork which traps the blood cells

Question 21

how is the fibrin formed?

Answer 21

fibrinogen →→(thombin)→→ fibrin

Question 22

what are coagulation factors?

Answer 22

INACTIVE proenzymes which are synthesised from the liver

Question 23

what are the 2 pathways that coagulation factors are activated?

Answer 23

1. intrinsic pathway

2. extrinsic pathway

Question 24

what is the intrinsic pathway?

Answer 24

Components are contained within the blood

Question 25

what is the extrinsic pathway?

Answer 25

Component needed for initiation (tissue | factor) comes from outside the blood.

Question 26

how is the intrinsic pathway initiated?

Answer 26

blood trauma

Question 27

how is the extrinsic pathway initiated?

Answer 27

tissue trauma

Question 28

how long does the intrinsic pathway take?

Answer 28

minutes

Question 29

how long does the extrinsic pathway take?

Answer 29

seconds

Question 30

what kind of 'blood trauma' initiates the intrinsic pathway?

Answer 30

Blood exposure to glass Blood exposure to collagen Platelet exposure to damaged cells

Question 31

what is released when the extrinsic pathway is initiated?

Answer 31

tissue factor

Question 32

what happens when the clotting factors from the intrinsic and extrinsic pathways are activated?

Answer 32

they activate the production of thrombin from prothrombin

Question 33

what happens when thrombin is activated from the coagulation cascade?

Answer 33

fibrinogen is converted to fibrin which forms the clot

Question 34

which factor is missing from the coagulation cascade?

Answer 34

factor VI

Question 35

what is fibrinolysis?

Answer 35

dissolving of a clot once repair begins

Question 36

what system(s) cause fibrinolysis?

Answer 36

fibrinolytic or thrombolytic

Question 37

what breaks down fibrin?

Answer 37

plasmin

Question 38

how is plasmin formed?

Answer 38

plasminogen →→→ plasmin via plasminogen activators

Question 39

give an example of a plasminogen activator

Answer 39

tissue plasminogen activator (tPA)

Question 40

what does plasmin do?

Answer 40

Plasmin remodels the thrombus and limits the extent of thrombosis by breaking down the fibrin

Question 41

what is thrombosis?

Answer 41

the normal haemostatic processes are activated inappropriately which results in the formation of a clot (thrombus) which may cause block the blood vessels or the heart

Question 42

what predisposes thrombus formation?

Answer 42

Virchow’s triad

Question 43

what is Virchow’s triad?

Answer 43

1. endothelial injury 2. abnormal blood flow 3. hypercoagulability

Question 44

what are the consequences of arterial occlusion?

Answer 44

myocardial infarction stroke peripheral ischaemia

Question 45

what are the causes of arterial occlusion?

Answer 45

endothelial injury due to underlying | arterial wall pathology, e.g. atherosclerosis

Question 46

what does arterial thrombi mainly consist of?

Answer 46

platelets

Question 47

what are the consequences of venous occlusion?

Answer 47

deep venous thrombosis and pulmonary embolism

Question 48

what are the causes of venous occlusion?

Answer 48

blood stasis, allowing build-up of platelets and | fibrin.

Question 49

what does venous thrombi mainly consist of?

Answer 49

fibrin

Question 50

what is the primary trigger of arterial thrombosis?

Answer 50

atherosclerotic plaque ruptire

Question 51

how does an atherosclerotic plaque rupture?

Answer 51

disruption of the endothelium and release of constituents | of the plaque

Question 52

how does a venous thrombi form?

Answer 52

Endothelium remains intact but converted from a | surface with anticoagulant properties to one with procoagulant properties

Question 53

what do antiplatelet drugs do?

Answer 53

inhibit platelet aggregation

Question 54

5 examples of antiplatelet drugs

Answer 54

``` Aspirin Clopidogrel Abciximab Eptifibatide Tirofiban ```

Question 55

what do anticoagulant drugs do?

Answer 55

inhibit coagulation cascade

Question 56

give 2 examples of anticoagulant drugs

Answer 56

heparin, warfarin

Question 57

what do fibrinolytic drugs do?

Answer 57

dissolve the clot once formed

Question 58

at the receptor level, how does platelet aggregation actually occur?

Answer 58

1. fibrinogen crosslinks platelets to one another by binding to GPIIb-IIIa receptors on their membranes 2. ADP and TXA2 are released from platelets that are attached to the collagen 3. further platelets are recruited to the platelet plug and cause them to aggregate by activating their GPIIb-IIIa receptors

Question 59

how does aspirin prevent platelet aggregation?

Answer 59

blocks platelet TXA2 synthesis

Question 60

how does clopidogrel prevent platelet aggregation?

Answer 60

blocks platelet ADP receptors

Question 61

how do Abciximab, Eptifibatide and Tirofiban prevent platelet aggregation?

Answer 61

block platelet GPIIb/IIIa receptors

Question 62

how does heparin inhibit clotting factors?

Answer 62

inhibits clotting factors directly

Question 63

how was warfarin inhibit clotting factors?

Answer 63

inhibit synthesis of clotting factors in the liver

Question 64

* Effective immediately * Effective in external circuits, cannulae and blood specimen containers Heparin or Warfarin?

Answer 64

Heparin

Question 65

what does heparin inactivate?

Answer 65

thrombin and factors XIIa, XIa, Xa, IXa

Question 66

what is Antithrombin III?

Answer 66

is part of the coagulation cascade system that regulates clotting

Question 67

how does heparin inhibit the coagulation cascade?

Answer 67

accelerates the actions of antithrombin | III - inhibiting coagulation

Question 68

how does heparin accelerate antithrombin III?

Answer 68

Antithrombin III forms a 1:1 complex with | thrombin - Heparin increases the rate at which the complex forms 100-fold

Question 69

what is a low molecular weight heparin?

Answer 69

mixture of large mucopolysaccharide molecules - fragments of heparin

Question 70

give an example of a low molecular weight heparin

Answer 70

Enoxaparin (Clexane)

Question 71

how are the effects of LMW heparin different to heparin?

Answer 71

A more predictable doseeffect relationship Longer duration of action

Question 72

how does warfarin act indirectly on the coagulation cascade?

Answer 72

Inhibits synthesis of vitamin K-dependent | clotting factors in the liver

Question 73

• in vivo • when circulating clotting factors have been sufficiently depleted Heparin or Warfarin?

Answer 73

Warfarin

Question 74

what is vitamin K?

Answer 74

co-factor for the production of four clotting factors in the liver

Question 75

how does warfarin inhibit the synthesis of vitamin K-dependent clotting factors in the liver?

Answer 75

warfarin is similar to part of vitamin K molecule warfarin inhibits vitamin K epoxide reductas

Question 76

what does vitamin K epoxide reductase do?

Answer 76

normally reduces inactive vitamin K to its active form

Question 77

does warfarin have a small therapeutic window or a large therapeutic window?

Answer 77

small

Question 78

what is the biggest predictor of warfarin dose?

Answer 78

VKORC1* polymorphisms

Question 79

what drug interactions does warfarin have?

Answer 79

aspirin

Question 80

heparin and warfarin time of onset?

Answer 80

heparin - immediately (i.v.) | warfarin - 1-3 days

Question 81

what is the clinical use of heparin?

Answer 81

Treatment of deep vein thrombosis and pulmonary embolism Prevention of postoperative thromboses and MI Rapid anti-coagulation until warfarin becomes effective

Question 82

what is the clinical use of warfarin?

Answer 82

Prevention and treatment of thromboembolytic disease Prevention of systematic embolism

Question 83

– Lepirudin – Desirudin – Argatroban (USA) what are these drugs?

Answer 83

Direct Thrombin Inhibitors

Question 84

– Fondaparinux – Idraparinux what are these drugs?

Answer 84

Selective Factor Xa Inhibitors

Question 85

– Ximelagatran (withdrawn – toxicity) – Dabigatran – (BNF) what are these drugs?

Answer 85

Direct Thrombin Inhibitors

Question 86

– Rivaroxaban – (BNF) what is this drug?

Answer 86

Selective Factor Xa Inhibitors

Question 87

what is streptokinase?

Answer 87

Bacterial protein from beta-haemolytic streptococci

Question 88

what does streptokinase do?

Answer 88

increases production of plasmin from circulating plasminogen

Question 89

what are the adverse effects of streptokinase?

Answer 89

A full allergic response

Question 90

why do you often need to give a high dose of streptokinase?

Answer 90

Antibodies against it are often present in the patient's blood

Question 91

give and example of a Tissue Plasminogen Activators (t-PA)

Answer 91

Alteplase

Question 92

what is Alteplase used for?

Answer 92

non-antigenic substitution for streptokinase with less side effects