Haematology 2S - Coagulation

Question 1

Anti-coagulant factors

Answer 1

anti-thrombin, proteinC/S, tissue factor pathway inhibitor

Question 2

Vessel injury stimulates three responses…

Answer 2

1. Vasoconstriction (neural)
2. Platelet aggregation (primary haemostasis)
3. Activation of coagulation cascade

Question 3

How is the endothelium involved in haemostasis?

Answer 3

It prevents the exposure of all the pro-coagulant subendothelial structures to the blood

Question 4

What do endothelial cells produce?

Answer 4

Prostaglandins, vWF, thrombomodulin, plasminogen activators

Question 5

Lifespan of a platelet

Answer 5

10 days

Question 6

How long do anti-platelet drugs e.g. aspirin and clopidogrel halt platelet activity for?

Answer 6

10 days

Question 7

How soon before surgery should patients aspirin be stopped?

Answer 7

7-10 days

Question 8

2 methods of platelet adhesion

Answer 8

Direct: GlpIa
Indirectly: vWF via GlpIb

Question 9

Platelet aggregation

Answer 9

Once platelets adhered to endothelium, release of mediators such as ADP and TxA2 which promote platelet aggregation. Platelets aggregate using glycoproteins GlpIIb/IIIa + fibrinogen + Ca2+

Question 10

MOA of clopidogrel

Answer 10

ADP receptor inhibitor

Question 11

Aspirin MOA

Answer 11

Irreversibly inhibits COX

Question 12

2 end products of arachidonic acid pathway and their functions

Answer 12

Thromboxane A2 - induces platelet aggregation

PGI2 - Inhibits platelet aggregation

Question 13

Rate limiting step for fibrin production

Answer 13

Factor Xa

Question 14

4 roles of thrombin (IIa)

Answer 14

Fibrinogen –> fibrin
Activates plts
Activates factors 5+8
Activates zymogen (Factos 7,11,13)

Question 15

What causes the production of thrombin?

Answer 15

Prothrombinase complex

Question 16

What is the most important step in the coagulation cascade

Answer 16

Production of thrombin

Question 17

Final step in the coagulation cascade

Answer 17

Thrombin breaks down fibrinogen –> fibrin –> stable fibrin clot

Question 18

Three phases of clotting

Answer 18

1. initiation
2. amplification
3. propagation

Question 19

Initiation phase

Answer 19

Factor Xa binds to factor Va

Question 20

Extrinisc pathway initiation

Answer 20

Damage to vessel wall + tissue factor + factor 7

Question 21

Initiation phase in people with factor V Leiden

Answer 21

Factor Va cannot bind to factor Xa

Question 22

Amplification phase

Answer 22

Factor Va and Xa binding –> small production of thrombin, activates platelets, activates factors 8,9,11, activates more factor 5a
These activated factors bind to platelet (5,8,9)

Question 23

What is the propagation phase?

Answer 23

The factor 5/8/9 complex on activated platelets will activate factor X –> THROMBIN BURST–> fibrinogen –> fibrin –> stable clot

Question 24

Investigations for extrinsic pathway

Answer 24

INR, PT

Question 25

Most common cause of vitamin K deficiency?

Answer 25

WARFARIN

Question 26

Fibrinolysis pathway

Answer 26

tissue plasminogen activator (tPA) and urokinase convert plasminogen --> plasmin. Plasmin then breaks down fibrin in to its degradation products

Question 27

What is plasmin inhibited by?

Answer 27

alpha-2-anti-plasmin | alpha-2-macroglobulin

Question 28

What is the most thrombogenic condition?

Answer 28

Lack of antithrombin III

Question 29

MOA of antithrombins?

Answer 29

Directly bind to and inactivate thrombin to be excreted in the kidney

Question 30

How is activated protein C formed?

Answer 30

Thrombomodulin (activated by thrombin) binds to protein C --> APC

Question 31

How is APC fully activated?

Answer 31

Protein S is the co-factor

Question 32

Function of APC?

Answer 32

Inactivates Factors 5a and 8a

Question 33

TFPI - What does it stand for and its function?

Answer 33

Tissue factor pathway inactivator (TFPI) - inhibits factor 7a

Question 34

What would immediate bleed suggest?

Answer 34

Issue with primary haemostatic plug: platelets, vWF, ednothelium

Question 35

Differentiating platelet and coagulation disorders

Answer 35

Platelet: petechiae, purpura, skin and mucous membranes Coagulation: haemarthrosis, joints, muscles, large and deep echhymosis,

Question 36

Effects of clopidogrel

Answer 36

ADP-R blocker, reduce GlpIIb/IIIa crosslinking of platelets

Question 37

Non immune mediated causes of ITP

Answer 37

DIC, MAHA

Question 38

Population of people who get chronic or acute ITP

Answer 38

Acute: children, follows viral illness, self-limiting and severe Chronic: adults, F>M

Question 39

Treatment of idiopathic immune ITP

Answer 39

Depends on platelet count and bleeding. If bleeding, give steroids + IVIG, if not bleeding --> Steroids

Question 40

Inherited and acquired disorders of coagulation

Answer 40

Inherited: haemophilia A/B, vWD | Acquired, liver disease, vitamin K deficiency, warfarin, DIC

Question 41

Coagulation studies in haemophilia

Answer 41

Prolonged aPTT, normal PT as intrinsic pathway involved

Question 42

Treatment of haemophilia

Answer 42

Clotting factor replacement required for life

Question 43

What is the most common coagulation disorder?

Answer 43

vWD

Question 44

Inheritance pattern of vWD

Answer 44

AD (Except for type III which is AR)

Question 45

Classification of vWD

Answer 45

Type I - low quantity Type II - Low quality type III - TOTAL quantitative deficiency

Question 46

Treatment of vitamin K deficiency

Answer 46

Vitamin K, FFP

Question 47

Reversal of warfarin

Answer 47

PCC (prothrombinase complex concentrate) - prompt reversal, IV vitamin K takes longer

Question 48

DIC pathophysioogy

Answer 48

Systemic activation of coagulation --> fibrin deposition in microvasculature (thrombosis) and depletion of platelets and coagulation factors --> bleeding

Question 49

Treatment for low fibrinogen

Answer 49

Cryoprecipitate

Question 50

Benefit of warfarin over dOACs?

Answer 50

Can rapidly reverse the bleeding