Coagulation Disorders

Question 1

What are the two most important receptors on the surface of platelets?

Answer 1

integrin alpha2beta3 (also called glycoprotein IIbIIIa) which binds fibrinogen when platelet is activated
glycoproteinIb/V/IX which binds von willebrand factor

Question 2

What is the mechanism of action of aspirin as an antiplatelet?

Answer 2

inhibits arachadonic acid to stop TXA2 generation

Question 3

What is the mechanism of action of ticagrelor/clopidogrel?

Answer 3

P2Y12 antagonists

Question 4

What is primary haemostasis?

Answer 4

platelet aggregation

Question 5

What is secondary haemostasis?

Answer 5

fibrin rich clot

Question 6

What is required for secondary haemostasis?

Answer 6

a negatively charged surface
replete with coagulation factor and fibrinogen
calcium and correct temperature

Question 7

What does INR assess?

Answer 7

the ‘extrinsic’ pathway - factors II, V, VII, X

Question 8

What does APTT assess?

Answer 8

the ‘intrinsic’ pathway - all factors except XIII and VII

Question 9

What is the end point of the coagulation cascade?

Answer 9

cleavage of fibrinogen into fibrin

Question 10

What is the bleeding pattern of a platelet function disorder?

Answer 10

mucosal bleeding and petechiae

Question 11

What is the bleeding pattern of a coagulopathy?

Answer 11

deep haematomas

Question 12

What is the role of von willebrand factor?

Answer 12

mediates initial adhesion of platelets at sites of vascular injury and binds factor VII in the circulation

Question 13

What things increase the level of VWF?

Answer 13

increased age
african race
non-O blood group
adrenaline
inflammatory mediators
exogenous oestrogen

Question 14

What is the typical inheritance of von willebrands disease?

Answer 14

autosomal dominant

Question 15

What is type 1 von willebrand disease?

Answer 15

partial quantity deficiency of VWF (most common)

Question 16

What is type 2 von willebrand disease?

Answer 16

qualitative deficiency of VWF

Question 17

What is type 3 von willebrand disease?

Answer 17

almost complete deficiency of VWF

Question 18

What is the treatment to prevent or control bleeding in VWD?

Answer 18

release endogenous VWF through stimulatiom of endothelial cells with DDAVP
human plasma derived VWF
antifibrinolytics (TXA)

Question 19

What is the issue with DDAVP?

Answer 19

limited to a few doses or will get tachyphylaxis
need to fluid restrict or will cause hyponatraemia
only works for type 1 VWD

Question 20

What is the treatment for haemophilia?

Answer 20

prophylaxis with regular infusions of clotting factor concentrate to prevent joint bleeds

Question 21

What is the mechanism of action of emicizumab?

Answer 21

mimics the function of factor VIII (still in clinical trials)

Question 22

What is the mechanism of action of fitusiran?

Answer 22

stop production of anti thrombin (still in clinical trials)

Question 23

What is the most sensitive test to detect presence of dabigatran?

Answer 23

thrombin time

Question 24

What test do you need to find the drug level of dabigatran?

Answer 24

dilute thrombin time (but don’t know how the drug level correlates to risk of bleeding)

Question 25

What test do you need to find the drug level of apixaban?

Answer 25

chromogenic anti-Xa assay

Question 26

What is the antidote for dabigatran?

Answer 26

idarucizumab (monoclonal Ab that binds thrombin with greater affinity than dabigatran)

Question 27

Can NOACs be used in malignancy associated VTE?

Answer 27

yes