Drugs Affecting Coagulation

Question 1

What is thrombosis?

Answer 1

The pathological formation of a haemostatic plug in a blood vessel in the absence of blood loss

Question 2

What kind of cells are present in a arterial thrombus?

Answer 2

Platelets, white blood cells, fibrin

Question 3

What kind of cells are present in a venous thrombus?

Answer 3

Platelets, red blood cells, fibrin

Question 4

What is the first step in haemostasis?

Answer 4

Vasoconstriction - an initial vasoconstriction occurs because of the release of endothelin from the epithelium

Question 5

What is the second step in haemostasis?

Answer 5

Primary haemostasis - the formation of the initial platelet plug - the exposed collagen in the damaged blood vessel causes platelets to adhere, activate and aggregate

Question 6

What is the third step in haemostasis?

Answer 6

Secondary haemostasis - activation of the coagulation cascade to convert fibrinogen to fibrin - initiated by the exposure of tissue factor in the damaged endothelium which activates thrombin which converts fibrinogen to fibrin

Question 7

What is present in the subendothelial ECM which when exposed causes platelets to adhere to the blood vessel?

Answer 7

Von willebrands factor - a factor which binds to platelets via GpIb platelet receptor

Question 8

What causes platelet activation?

Answer 8

Platelet adhesion (binding to vWF via GpIb), thromboxane A2 and ADP

Question 9

What happens when platelets are activated?

Answer 9

They release their granule contents (calcium and ADP and serotonin) and synthesise thromboxane A2 and express the GpIIb-IIIa receptor

Question 10

What is the role of calcium released by platelets?

Answer 10

It is a cofactor in many reactions in the coagulation cascade

Question 11

What is the role of ADP released by platelets?

Answer 11

It activates other platelets

Question 12

What is the role of serotonin released by platelets?

Answer 12

vasoconstriction

Question 13

What is platelet aggregation?

Answer 13

Where fibrinogen binds to GpIIb-IIIa receptors on platelets to form a bridge

Question 14

How are endothelial cells activated to release tissue factor?

Answer 14

By cytokines such as IL-1 and TNF or by bacterial products such as endotoxin

Question 15

How is coagulation controlled?

Answer 15

By enzymes which inhibit the cascade e.g. antithrombin or by lysis via plasmin

Question 16

What are the three factors which lead to thrombosis (Virchow’s triad)?

Answer 16

blood stasis, hyper coagulability, vessel damage

Question 17

When does blood stasis occur?

Answer 17

in atrial fibrillation or deep vein thrombosis

Question 18

When does vessel damage occur?

Answer 18

atherosclerosis

Question 19

What is heparin?

Answer 19

A drug which enhances the activity of antithrombin III (which inhibits factor Xa and thrombin)

Question 20

What are the pharmacokinetics of heparin?

Answer 20

It has a high molecular weight and is not orally available

Question 21

What is low molecular weight heparin?

Answer 21

A lower molecular weight version of heparin with less effect on thrombin that has a longer half life - used for patients self administration

Question 22

What test is used to monitor heparin?

Answer 22

The APTT test (intinsic pathway)

Question 23

What are the adverse effects of heparin?

Answer 23

haemorrhage, platelet deficiency, osteoporosis

Question 24

Which factors are vitamin K dependent?

Answer 24

II, VII, IX, X - these factors require gamma carboxylation after synthesis which requires reduced vitamin K as a cofactor

Question 25

What is warfarin?

Answer 25

A drug which inhibits the reduction of vitamin K so inhibits gamma carboxylation of factors II, VII, IX and X

Question 26

What are the properties of warfarin?

Answer 26

It is only active in vivo, has a delayed onset of action and doesn’t effect already active factors

Question 27

What are the adverse effects of warfarin?

Answer 27

haemorrhage

Question 28

What test is used to monitor warfarin?

Answer 28

INR (extrinsic pathway)

Question 29

What happens if you administer vitamin K and warfarin?

Answer 29

vitamin K will outcompete and overcome the warfarin

Question 30

What are the pharmacokinetics of warfarin?

Answer 30

orally active, rapidly absorbed, strongly bound to plasma protein

Question 31

What causes increased warfarin activity?

Answer 31

vitamin K deficiency, hepatic disease, hyper metabolic state, drug interactions

Question 32

What drugs interact with warfarin to increase activity ?

Answer 32

Drugs which affect platelet aggregation (aspirin), drugs which compete for plasma protein binding (NSAIDs), drugs which compete for the cytochrome p450 pathway (alcohol)

Question 33

What causes decreased warfarin activity?

Answer 33

pregnancy, drug interactions

Question 34

What drugs interact with warfarin to decrease activity?

Answer 34

drugs which induce liver enzymes - e.g. barbiturates or chronic alcohol use and also vitamin K supplements

Question 35

Why are new anticoagulants needed?

Answer 35

To have a lower molecular weight so they can be given orally, to get a more predictable dose-response relationship and to reduce laboratory monitoring

Question 36

What drugs affect platelet activation and adhesion?

Answer 36

ADP receptor antagonists (clopidigrel), thromboxane synthesis inhibitors (aspirin), glycoprotein receptor antagonists (abciximab)

Question 37

What is aspirin?

Answer 37

An irreversible COX inhibitor - leads to decreased platelet activation and vasoconstriction

Question 38

What drugs are used to cause fibrinolysis?

Answer 38

streptokinase and alteplase

Question 39

What does streptokinase do?

Answer 39

It activates plasminogen

Question 40

Why can streptokinase only be used once?

Answer 40

Because it is antigenic (derived from bacterium)

Question 41

What does alteplase to?

Answer 41

Activates fibrin bound plasminogen (clot selective)

Question 42

Can alteplase be given more than once?

Answer 42

Yes