thrombosis

Question 1

What are the most common Consequences of thromboembolism?

Answer 1

In order:

Thrombophlebitic syndrome

Recurrence

Death

Pulmonary hypertension

Question 2

what is Virchow’s triad?

Answer 2

blood coagulability
vessel wall /endothelial damage
blood flow/stasis

Question 3

which of the factors in the coagulation pathway are NOT procoagulant?

Answer 3

7, 12

Question 4

which are the endogenous anticoagulant factors ?

Answer 4

Affect the coagulation pathway:

• TFPI
• Protein C,S
• Antithrombin

Thrombomodulin
EPCR
Fibrinolysis

Question 5

in which ways is The vessel wall is normally antithrombotic?

Answer 5

Expresses anticoagulant molecules:
Thrombomodulin
Endothelial protein C receptor
Tissue factor pathway inhibitor
Heparans 

Does not express tissue factor

Secretes antiplatelet factors
Prostacyclin
NO

Question 6

what makes the vessel wall prothrombotic?

Answer 6

inflammation / injury causes the following:

Anticoagulant molecules (eg TM) are down regulated
TF may be expressed
Prostacyclin production decreased
Adhesion molecules upregulated

Von Willebrand factor release from endothelial cells:
Platelet and neutrophil capture
Neutrophil extracellular traps (NETS) form

Question 7

what are the Causes of stasis?

Answer 7

Immobility - Surgery, Paraparesis, Travel

Compression - Tumour, pregnancy

Viscosity - Polycythaemia, Paraprotein

Congenital - Vascular abnormalities

Question 8

what is the MOA of Anticoagulant drugs ? give exampls of each.

Answer 8

Immediate action:
Heparin
Unfractionated heparin
Low molecular weight heparin

• > Increase anticoagulant activity
• > All act by directly activating antithrombin

Direct acting anti-Xa and anti-IIa (DOAC)

Delayed action:
Vitamin K antagonists
Warfarin
-> Reduce procoagulant activity

Question 9

What are some benefits of using DOACs over heparin?

Answer 9

oral admin

No monitoring needed*

Question 10

dabigatran is a ___?

Answer 10

anti-IIa

Question 11

how do fXa and fIIa inhibitors work?

Answer 11

Binds to fxa enzyme - do directly to the enzymes not just on the factor

Question 12

what is the MOA of warfarin? if ivx, what will levels of fx show?

Answer 12

Indirect effect by preventing recycling of Vit K - Vit K antagonists
Therefore onset of action is delayed

Levels of procoagulant factors II, VII, IX & X fall
Levels of anticoagulant protein C and protein S also fall

Question 13

which drugs are co-factors for antithrombin?

Answer 13

Heparins

Question 14

How must some1 on heparin be monitored?

Answer 14

LMWH – none

UFH – APTT/antiXa

Question 15

how would you reverse the effect of warfarin?

Answer 15

Factor concentrate

Vitamin K

Question 16

Which patients are at increased risk of thrombosis and why?

Answer 16

Medical in patients
Infection/inflammation, immobility (inc stroke), age

Patients with cancer
Procoag molecules, inflammation, flow obstruction

Surgical patients
Immobility, trauma, inflammation

Previous VTE, Family history, genetic traits
Obese
Elderly

Question 17

list different methods of thrombophrophylaxis?

Answer 17

Low molecular weight heparin (LMWH)
Eg: Tinzaparin 4500u/ Enoxaparin 40mg od
Not monitored

TED Stockings (for surgery or if heparin C/I)
Intermittent pneumatic compression (increases flow)

Sometimes DOAC +/- aspirin (orthopaedics)

Question 18

what is the risk of clot after the following and is long term anticoagulation needed?

1. After surgical precipitant
2. VTE
3. After minor precipitants (COCP, flights, trauma)

Answer 18

Risk: Very low after surgical precipitant
No need for long term anticoagulation

High after idiopathic VTE (10-20% in 2yrs)
Consider long term anticoagulation – esp with DOAC

After minor precipitants (COCP, flights, trauma)
Usually 3 months of anticoagulation is adequate