Haemostasis and thrombosis

Question 1

What is appropriate coagulation?

Answer 1

Haemostasis:
primary haemostasis
secondary haemostasis

Question 2

What is inappropriate coagulation?

Answer 2

Thrombosis:
arterial
venous

Question 3

What happens when you have an injury?

Answer 3

Vessel injury
-platelet adhesion
platelet aggregation
-activation of coagulation cascade
fibrin formation 
*haemostatic plug 
fibrinolytic activity 
repair of vessel damage

Question 4

What occurs in primary haemostasis?

Answer 4

when vessel wall is injured- exposes collagen

platelets stick to the collagen via von Willebrand factors

Question 5

Types of platelet bleeding disorder and treatment used

Answer 5

• Due to a reduced number of platelets- inherited of acquired
• Due to abnormal function- can be inherited or acquire d (antiplatelet drugs used for thrombosis etc)
• tretament= platelet transfusion

Question 6

What is Von Willebrand disease and what are its symptoms?

Answer 6

VWFs are missing- a common bleeding disorder
autosomal dominant
3 subtypes
milder bleeding than in haemophilia
main symptom= heavy periods
also:
bruising, cuts, gum bleeding, nose bleeds, post operative bleeding

Question 7

How do you treat Von Willebrand disease?

Answer 7

1. Intermediate purity factor 8 (plasma derived)

2. Desmopressin- makes the body release VWF from endothelial cells

Question 8

Examples of coagulation factor disorders

Answer 8

Haemophilia a= factor 8 deficiency
Haemophilia b= factor 9 deficiency
-others- deficiency of fibrinogen, factor 2,5,7,10
*just giving plasma isnt ideal- need a more precise treatment

Question 9

What are the symptoms of heamophilia?

Answer 9

clinical features of a & b is the same
sites of bleeding: joints, muscles, post trauma, postoperative
bleed into joint= hemarthrosis- lots of bleeds- erodes cartilage- bone on bone

Question 10

How do we make clotting factor concentrates?

Answer 10

Plasma derived
Made using recombinant technology
-not enough demand to make all the clotting factors via recombinant technology (factor 5 etc.)

Question 11

What are the treatments for primary haemostasis?

Answer 11

Platelet transfusion
demsopressin
VWF concentrate

Question 12

What are the treatments for secondary haemostasis?

Answer 12

Specific clotting factors

Question 13

What are the 2 types of thrombosis and what are their characteristics? What are their clinical presentations?

Answer 13

Arterial
-high-pressure system 
-platelet rich
myocardial infarction, thrombotic stroke 
Venous
-low pressure 
-fibrin rich- problem on coagulation cascade 
DVT, pulmonary embolism

Question 14

How are the 2 types of thrombosis treated?

Answer 14

Arterial- antiplatelet drugs

Venous- anticoagulant drugs

Question 15

Examples of antiplatelet drugs

Answer 15

used to be: aspirin and clopidogrel

prasugrel, ticagrelor, cangrelor

Question 16

What are the 3 types of anticoagulant drugs, examples of each type

Answer 16

Intravenous- unfractionated heparin
subcutaneous- low MW heparin
oral- warfarin
direct oral anticoagulants- dabigatran, rivaroxaban, apixaban, edoxaban

Question 17

How does heparin work?

Answer 17

Binds to and activates antithrombin-

inhibits the coagulation cascade more efficiently

Question 18

How is glycosaminoglycan antithrombotic?

Answer 18

Indirectly inhibits thrombin
effects anti thrombin
monitored with APTT test
given by continuous infusion

Question 19

What is low molecular weight heparin, when is it used?

Answer 19

Smaller molecule made from heparin- easier for body to take
given subcutaneously
renally excreted
weight based
given once daily
-can be used as a treatment or in preventing thrombosis
-in hospital, over 45 years old, thrombosis risk high enough= put on this drug

Question 20

What the pharmacology of warfarin?

Answer 20

Completely and rapidly absorbed 
inhibits vitamin K dependent clotting factors 
slow on and off action 
warfarin inhibits factors: 2,7,9 and 10
side fx:
bleeding and embryopathy

Question 21

How is warfarin monitored?

Answer 21

test used to monitor the effect of warfarin= international normalized ration
dose based on INR
frequency of monitoring depends on INR
blood test every week/ 8 weeks for rest of life
NO single dose for every person= personalised medicine
dose you need is genetically controlled

Question 22

What is the cyclin involving s-warfarin, VKOR and GGCX?

Answer 22

Hypofunctional factors need to be carboxylated by the enzyme GGCX
GGCX requires vitamin k- when vitamin k is activated it is oxidized
VKOR recycles reduced vitamin K
S-warfarin inhibits VKOR- GGCX doesn’t work- clothing factors remain hypofunctional
CYP2C9 breaks down warfarin

Question 23

Which 3 enzymes control your warfarin dose?

Answer 23

VKOR
GGCX
CYP2C9

Question 24

How do people differ in warfarin digestion?

Answer 24

Some people break down warfarin rapidly, others dont
if we could identify the polymorphisms in the enzymes-
could work out the dose youd need

Question 25

Characteristics of DOACs?

Answer 25

Direct oral anticoagulants 
no monitoring needed*
oral
aiming to replace heparin and warfarin 
no alcohol/food interactions 
standard dosing*
very few drug interactions 
short half life 
more expensive than warfarin

Question 26

Examples of DOACS

Answer 26

Targeting factor Xa:
rivaroxaban 
apixaban 
edoxaban 
Targeting factor 2a:
dabigatran 
-They're new drugs- currently going through clinical trials

Question 27

Can you reverse the actions of DOACS?

Answer 27

Currently only dabigatran

via humanised monoclonal antibody= idarucizumab

Question 28

Advantages of DOACs?

Answer 28

rapid onset of action
fixed oral dosing with predictable coagulant effects
low potential for food/alcohol interactions
low potential for drug interactions
no need for blood monitoring

Question 29

Disadvantages of DOACs?

Answer 29

Renal elimination
no specific antidotes for the Xa inhibitors
licensed for only specific indications
recently introduced