Thrombosis

Question 1

Virchow’s triad

Answer 1

Blood - hypercoagulability
Blood flow - statis
Vessel wall - injury/trauma

Question 2

Factors which increase the chances of hypercoagulability

Answer 2

High platelets
High haematocrit - myelodysplastic syndromes, polycythemia

Question 3

Factors which increase the chance of stasis

Answer 3

Compression - Pregnancy and malignancy
Immobility - surgery, travel, paraparesis
Viscosity - paraprotein, polycythemia
Congenital vascular abnormalities

Question 4

Factors which increase the chances of vessel wall dysfunction

Answer 4

COVID-19
Inflammatory states

Question 5

Is the vessel wall naturally pro or anticoagulatory? How? What factors does it contain? What does it express? What does it not express?

Answer 5

Naturally anti-coagulatory - contains:
Thrombomodulin
Prostacyclin (PGI2)
Heparans
Endothelial protein C receptor (EPCR)

Also secretes antiplatelet factors such as nitric oxide and prostacyclin

Doesn’t express tissue factor (this is subendothelial, along with collagen)

Question 6

Name three naturally occurring anti-thrombotic factors

Answer 6

Antithrombin
Protein C,S and thrombomodulin
TFPI - tissue factor pathway inhibitor

Question 7

What does anti thrombin do?

Answer 7

Directly inhibits thrombin and factor 10a?

Question 8

What does protein C need to be binded to become activated?

Answer 8

Thrombomodulin

Question 9

What does protein C and protein S inhibit?

Answer 9

Factor 5a and factor 8a

Question 10

What is factor 5a’s function?

Answer 10

It’s a confactor for factor 10a, aka for thrombin

Question 11

What is the function of factor 8a’s function?

Answer 11

It is a cofactor for factor 9a, to make factor 10a

Question 12

State three things which increase the risk of thrombosis in order of most risk to least risk

Answer 12

Family history < Factor 5 Leiden < Antithrombin deficiency

Question 13

What is factor 5 Leiden?

Answer 13

A single point mutation means that protein C can’t bind and inhibit it, so it can’t be switched off, leading to thrombosis

Question 14

How can we classify management of thrombosis?

Answer 14

Immediate and delayed
Direct and indirect

Question 15

Name immediate antithrombotic drugs, based on classification

Answer 15

Immediate DIRECT - factor Xa or 2a inhibitors
for example dabigatrin (factor 2a inhibitor), or factor Xa - apixaban aka DOACs

Immediate INdirect - heparIN - activates antithrombin

Question 16

Name delayed antithrombotic drugs based on classification

Answer 16

Delayed direct
Delayed indirect (warfarin)

Question 17

What is the disadvantage of heparins?

Answer 17

They must be monitored
You need injections

Question 18

How does heparin work?

Answer 18

Immediately activates antithrombin (indirect form of anticoagulation)

Question 19

What is warfarin and its complication?

Answer 19

Warfarin is a LONG ACTING anticoagulant because it has DELAYED, indirect effects

Question 20

Mechanism of action of warfarin

Answer 20

Vitamin K antagonist - therefore reduces factors 2, 7, 9 and 10

Question 21

What is the problem with warfarin?

Answer 21

Narrow therapeutic window
Dose response is variable

Question 22

What measurement is used to monitor warfarin?

Answer 22

INR

Question 23

Normal INR for someone on warfarin

Answer 23

Between 2 and 3

Question 24

INR over 3.5 means

Answer 24

High risk of bleeding

Question 25

Thromboprophylaxis

Answer 25

TED stockings LMWH low dose DOACs

Question 26

When would you give TED stockings?

Answer 26

Before surgery or if heparin is contraindicated

Question 27

What is the advantage of giving LMWH for thromboprophylaxis

Answer 27

You don't need to monitor the dose as it is a low dose e.g. enoxaparin 40mg

Question 28

Treating thrombosis - how does the management change compared to thromboprophylaxis?

Answer 28

You give higher doses

Question 29

Future prevention of thrombosis - when is it most useful to give long term anticoag?

Answer 29

If someone has had idiopathic clots - they have the highest risk of recurrence

Question 30

State the risk of recurrence of venous clots based on location

Answer 30

Distal - less likely Proximal (above popliteal) - more likely

Question 31

If someone has a clot after surgery, what is the risk of recurrence? Would you anticoagulate?

Answer 31

Low risk, no need for long term antithrombosis

Question 32

If someone has a clot after taking the COCP, a flight or trauma, what is the risk of recurrence? Would you anticoagulate?

Answer 32

Medium risk, so you would give three months of long term anticoagulation (e.g. a DOAC), but this could be for longer depending on other risk factors

Question 33

Idiopathic clot - recurrence risk + would you prescribe LTA?

Answer 33

HIGH RISK, DEFO GIVE LONG TERM ANTICOAGULATION, maybe DOAC

Question 34

Why don't we just give DOACs to everyone instead of Warfarin?

Answer 34

It doesn't work for everyone, e.g. people with heart valve transplants / metallic heart valves or antiphospholipid syndrome - it would just increase risk of clots. Therefore we still use warfarin. Otherwise some people are given DOACs long term.

Question 35

RA for VTE when someone comes into hospital

Answer 35

Patient factors - age over 60, previous VTE, Cancer, lung disease, chronic heart failure, lower limb paralysis, acute infection, BMI over 30. Procedural factors - hip or knee replacement, hip fracture, long surgery over 30 mins, plaster cast immobilisation of lower limb

Question 36

Can you prescribe warfarin to a pregnant person?

Answer 36

Absolutely not. Risk of teratogenicity.