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CDL301 > Lecture 14 Haemostasis and Thrombosis > Flashcards

Lecture 14 Haemostasis and Thrombosis Flashcards

1
Q

What is the difference between haemostasis and thrombosis?

A

haemostasis is appropriate coagulation

thrombosis is inappropriate coagulation

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2
Q

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

A

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

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3
Q

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

A

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

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4
Q

What benefits are there from fresh whole blood?

A

platelets
red blood cells
plasma - multiple factors

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5
Q

What factors are found in fresh frozen plasma?

A

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

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6
Q

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

A

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

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7
Q

In primary haemostasis what three proteins/factors interact?

A

platelet
VWF
collagen

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8
Q

What causes platelet bleeding disorders?

A

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

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9
Q

How are platelet bleeding disorders treated?

A

platelet transfusion

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10
Q

Give an example of a platelet bleeding disorder

A

Von Willebrand Disease

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11
Q

Give the pathophysiology, epidemiology and treatment of Von Willebrand Disease

A

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)

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12
Q

Give examples of coagulation factor disorders

What are they deficient in?

A 
haemophilia A (X-linked) - FVIII deficiency
haemophilia B (X-linked) - FIX deficiency
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13
Q

Give the pathophysiology of haemophilia

A

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

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14
Q

What is clotting factor I?

A

fibrinogen

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15
Q

What is clotting factor II?

A

prothrombin

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16
Q

What is the only non-plasma derived clotting factor?

A

clotting factor V

17
Q

What are the three recombinant clotting factors?

A

clotting factors VII, VIII and X

18
Q

What are the two types of thrombosis?

A

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

19
Q

What are clinically linked to arterial thrombosis?

A

myocardial infarction

thrombotic stroke

20
Q

What are clinically linked to venous thrombosis?

A

deep vein thrombosis (leg)

pulmonary embolism

21
Q

Give examples of antiplatelet drugs

A 
aspirin
clopidogrel
prasugrel
ticagrelor
cangrelor
abcisimab
eptifibatide
tirofiban
22
Q

Give examples of anticoagulant drugs

A

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

23
Q

What is the most commonly prescribed vitamin K antagonist?

A

warfarin

24
Q

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

A

clotting factors IXa, Xa and IIa

25
Q

What is the pharmacokinetics of heparin?

A

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

26
Q

What is the pharmacokinetics of low MW heparin?

A 
smaller molecular made from heparin 
less variation in dose
given subcutaneously 
renally excreted 
give once/day 
weight adjusting dosing 
treatment thrombosis and prophylaxis (preventative)
27
Q

What is the pharmacokinetics of warfarin?

A

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

28
Q

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

A

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

29
Q

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

A 
age
sex
ethnicity
weight
height 
smoking
liver/kidney disease
INR (international normalised ratio)
multidrug interactions - amiodarone and statins
30
Q

What are the pharmacokinetics for Dabigatran?

A

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

31
Q

What are the pharmacokinetics for Rivaroxaban?

A

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

32
Q

What are the pharmacokinetics for Apixaban?

A

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

33
Q

What are the pharmacokinetics for Edoxaban?

A

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

34
Q

Give a specific example of direct oral anticoagulant reversal agents

A

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

35
Q

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

A

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

36
Q

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

A

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

CDL301 (14 decks)

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