Haemostasis and Thrombosis

Question 1

Main 3 components of coagulation?

Answer 1

Coagulation - making the clot
Anticoagulants - limiting the size of the clot
Fibrinolysis - remodel the clot and resolve the clot

Question 2

What can contribute to clotting?

Answer 2

Endothelial surface (when activated)
Platelets
Von Willebrand factors
Coagulation Factors

Question 3

What can aid bleeding?

Answer 3

Natural anticoagulants (help control the clot)

Question 4

What is the function of fibrinolysis?

Answer 4

Remodel or remove clot

Question 5

If there is a problem with clotting how will this manifest?

Answer 5

Patient has bleeding tendency

Question 6

If there is a problem with natural anticoagulants/bleeding how will this manifest?

Answer 6

Patient has clotting tendency

Question 7

First response to injury?

Answer 7

Vasoconstriction

Question 8

During vasoconstriction how do platelets react?

Answer 8

Release serotonin and thromboxane A2 which activates them - forms platelet plug

Question 9

Why do we feel pain during vasoconstriction?

Answer 9

Sympathetic interpretation to help vasoconstriction

Question 10

What is the next step of clotting after vasoconstriction

Answer 10

Formation of platelet plug

Question 11

How is a platelet plug formed?

Answer 11

When collagen is exposed platelets release serotonin and thromboxane A2 which activates them - they change shape and become adhesive

Question 12

When does the first response to injury occur in terms of clotting?

Answer 12

When collagen is exposed (damaged endothelium)

Question 13

How can platelets bind directly to the endothelium?

Answer 13

Von Willebrand factor

Question 14

What does the platelet plug bind to?

Answer 14

Exposed collagen

Question 15

What are the 3 parts of the coagulation cascade?

Answer 15

Intrinsic Extrinsic and common

Question 16

What is the first clotting factor of the common pathway?

Answer 16

10

Question 17

What activates the extrinsic pathway?

Answer 17

Tissue factor

Question 18

What is the end result of the common pathway?

Answer 18

Clotting factors activate thrombin which activates fibrin

Question 19

What 4 things do we need to healthy coagulation?

Answer 19

Platelets - number and function
Von willebrand factor
coagulation factor
Clot stability

Question 20

What type of condition is Haemophilia? How does it cause problems?

Answer 20

X-linked condition - genetic = deficiency of clotting factor 8 and 9

Question 21

How is haemophilia classified?

Answer 21

Severity based on normal concentration of coagulation factor %

Question 22

How does a patient with very severe haemophilia (concentration of coagulation factor less than 1%) react?

Answer 22

Spontaneous bleeding

Question 23

How does a patient with moderately severe haemophilia react?

Answer 23

Severe bleeding after surgery

Question 24

Risk of haemophilia in young?

Answer 24

Not yet diagnosed so spontaneous bleeding in joints leads to arthritis

Question 25

How is haemophilia now treated?

Answer 25

Recombinant gene therapy treatment - gene cloned

Question 26

How is haemophilia C transmitted?

Answer 26

Blood transfusion

Question 27

Hemlibra is a new gene therapy for haemophilia treatment. How does it work?

Answer 27

It is an antibody that binds factor 9 and 10 and leads to activation and formation of fibrin

Question 28

Why is hemlibra (new gene therapy treatment) better than previous treatments?

Answer 28

Doesn't get injected into the vein only under the skin once every 2 weeks = less often so better quality of life

Question 29

How does von Willebrand disease present?

Answer 29

Mucosal bleeding - bruising, nosebleeds, heavy periods, GI bleeding

Question 30

Function of Von Willebrands factor?

Answer 30

Helps bind Platelets to endothelium and each other

Question 31

How can Von Willebrand disease be classified?

Answer 31

Type I = mild deficiency in VWD Type II - normal number but mutation effecting the function of VWD Type III - severe deficiency

Question 32

How can problems with platelets be classfied?

Answer 32

Low number or functional defects

Question 33

What drugs is given to treat functional defects of platelets?

Answer 33

Aspirin

Question 34

In general how should a patient with bleeding disorders be managed during surgery (5)

Answer 34

Close liaison with haemophilia centre Platelets transfusion or DDAVP (increase VWF) Atraumatic technique to secure local haemostasis Oral tranexamic acid = antifibrinolytic = stabilise clot

Question 35

Warfarin mechanism of action?

Answer 35

inhibit thrombin (vit K reductase inhibitor)

Question 36

How is warfarin dealt with in surgery?

Answer 36

Don't alter - check INR

Question 37

Why is it advisable to not stop warfarin treatment (especially when INR is normal)?

Answer 37

Can increase risk of thrombosis

Question 38

Name 2 type of DOAC?

Answer 38

Direct thrombin inhibitors | Xa inhibitors

Question 39

Dabigatran is a direct thrombin inhibitor, describe its mechanism of action?

Answer 39

Reversible thrombin inhibitor

Question 40

Mechanism of action fo Xa inhibitors?

Answer 40

Bind to activated factor 10