Lecture 14 Haemostasis and Thrombosis

Question 1

What is the difference between haemostasis and thrombosis?

Answer 1

haemostasis is appropriate coagulation

thrombosis is inappropriate coagulation

Question 2

haemostasis - name the factors involved in primary/secondary haemostais and the treatments

Answer 2

primary factors - platelets and VWF
primary treatment - platelet transfusion, desmopressin, VWF concentrate
secondary factors - clotting factors
secondary treatment - specific clotting factors

Question 3

thrombosis - name the factors involved in arterial/venous thrombosis and the treatments

Answer 3

arterial factors - high pressure platelets
arterial treatment - antiplatelet drugs
venous factors - clotting factors
venous treatment - anticoagulants

Question 4

What benefits are there from fresh whole blood?

Answer 4

platelets
red blood cells
plasma - multiple factors

Question 5

What factors are found in fresh frozen plasma?

Answer 5

I, VII, VIII, VWF, IX, X, XI, XIII

Question 6

What are the two mechanism of repair when a vessel is injured?

Answer 6

local vasoconstriction - platelet adhesion - platelet aggregation - haemostatic plug - fibrinolytic activity - repair of the vessel damage

local vasoconstriction - activation of coagulation cascade - fibrin formation - haemostatic plug - fibrinolytic activity - repair of the vessel damage

Question 7

In primary haemostasis what three proteins/factors interact?

Answer 7

platelet
VWF
collagen

Question 8

What causes platelet bleeding disorders?

Answer 8

inherited or acquired
thrombocytopenia - reduced platelet number
abnormal/reduced function of platelets

Question 9

How are platelet bleeding disorders treated?

Answer 9

platelet transfusion

Question 10

Give an example of a platelet bleeding disorder

Answer 10

Von Willebrand Disease

Question 11

Give the pathophysiology, epidemiology and treatment of Von Willebrand Disease

Answer 11

most common inherited bleeding disorder ~1% population
autosomal dominant inheritance
milder than haemophilia
sites of bleeding - bruising, cuts, gyms, epistaxis, menorrhagia, post-operative, post-trauma
treatment - desmopressin and intermediate purity (from plasma) FVIII (IV)

Question 12

Give examples of coagulation factor disorders

What are they deficient in?

Answer 12

haemophilia A (X-linked) - FVIII deficiency
haemophilia B (X-linked) - FIX deficiency

Question 13

Give the pathophysiology of haemophilia

Answer 13

autosomal recessive inherited condition - sex-linked
deficiency of fibrinogen - FII, FV, FVII, FX, FXI, FXIII
severity <1% severe/1-4% moderate/>5% mild
risks - haemarthorosis, haematoma

Question 14

What is clotting factor I?

Answer 14

fibrinogen

Question 15

What is clotting factor II?

Answer 15

prothrombin

Question 16

What is the only non-plasma derived clotting factor?

Answer 16

clotting factor V

Question 17

What are the three recombinant clotting factors?

Answer 17

clotting factors VII, VIII and X

Question 18

What are the two types of thrombosis?

Answer 18

arterial - arterial circulation which is high-pressure system and platelet-rich
venous - venous circulation which is low-pressure and fibrin-rich

Question 19

What are clinically linked to arterial thrombosis?

Answer 19

myocardial infarction

thrombotic stroke

Question 20

What are clinically linked to venous thrombosis?

Answer 20

deep vein thrombosis (leg)

pulmonary embolism

Question 21

Give examples of antiplatelet drugs

Answer 21

aspirin
clopidogrel
prasugrel
ticagrelor
cangrelor
abcisimab
eptifibatide
tirofiban

Question 22

Give examples of anticoagulant drugs

Answer 22

intravenous - unfractionated heparin
subcutaneous - low MW heaparin
oral - warfarin, dabigatran, rivaroxaban, apixaban, edoxaban

Question 23

What is the most commonly prescribed vitamin K antagonist?

Answer 23

warfarin

Question 24

What factors does unfractionated heparin and low molecular weight heparin act on?

Answer 24

clotting factors IXa, Xa and IIa

Question 25

What is the pharmacokinetics of heparin?

Answer 25

glycosaminoglycan - binds to antithrombin to increase its activity indirect thrombin inhibitor monitor with APTT test given by continuous infusion

Question 26

What is the pharmacokinetics of low MW heparin?

Answer 26

``` smaller molecular made from heparin less variation in dose given subcutaneously renally excreted give once/day weight adjusting dosing treatment thrombosis and prophylaxis (preventative) ```

Question 27

What is the pharmacokinetics of warfarin?

Answer 27

oral drug - completely and rapidly absorbed 99% plasma protein bound inhibit production of factors II, VII, IX and X peak effect 3-4 days after start of treatment effect still present after 4-5 of stopping treatment side effects - bleeding and embryopathy

Question 28

Why is it important to personalise the dosage of warfarin in patients?

Answer 28

genotype CYP2C9 and VKORC1 mutations CYP2C9 *1, *2, 3* mutation increases sensitivity VKORC1 G-to-A mutation increases sensitivity increased sensitivity required more monitoring and lower dosage

Question 29

What other factors are important to take into account with dosing warfarin?

Answer 29

``` age sex ethnicity weight height smoking liver/kidney disease INR (international normalised ratio) multidrug interactions - amiodarone and statins ```

Question 30

What are the pharmacokinetics for Dabigatran?

Answer 30

anticoagulant - IIa inhibitor renal excretion 80% half life 13-18 hours protein binding 35%

Question 31

What are the pharmacokinetics for Rivaroxaban?

Answer 31

anticoagulant - Xa inhibitor renal excretion 67% half life 5-9 hours healthy / 11-13 hours elderly protein binding 95%

Question 32

What are the pharmacokinetics for Apixaban?

Answer 32

anticoagulant - Xa inhibitor renal excretion 25% half life 8-13 hours protein binding 87%

Question 33

What are the pharmacokinetics for Edoxaban?

Answer 33

anticoagulant - Xa inhibitor renal excrtion 35% half life 9-11 hours protein binding 50%

Question 34

Give a specific example of direct oral anticoagulant reversal agents

Answer 34

dabigatran - idarucizumab - humanised monoclonal antibody fragment rivaroxaban/apixaban/edoxaban - andexanet - recombinant modified inactive factor Xa molecule (not licensed yet)

Question 35

What are the advantages of direct oral anticoagulants compared to warfarin?

Answer 35

rapid onset of action fixed oral dosing - predictable anticoagulant effect low potential for food/alcohol intolerance low potential for drug interactions no need for blood monitoring

Question 36

What are the disadvantages of direct oral anticoagulants compared to warfarin?

Answer 36

renal elimination no specific antidotes for Xa inhibitors licensed only specific individuals