Haematology 8 - Thrombosis: aetiology and management

Question 1

What is Virchow’s triad?

Answer 1

1. blood
2. vessel wall
3. stasis

Question 2

What are the procoagulant factors?

Answer 2

Factors 2, 5, 8, 9, 10, 11

fibrinogen

platelets

Question 3

What are the anticoagulant factors?

Answer 3

TFPI

Protein C and S

Thrombomodulin

EPCR

Antithrombin

Fribrinolysis

Question 4

draw the coagulation cascade, with the coagulation regulators

Question 5

Is the vessel wall pro or anti thrombotic and what makes it either?

Answer 5

antithrombotic

Expresses anticoagulant molecules:

Thrombomodulin

Endothelial protein C receptor

TF pathway inhibitor (NO tissue factor)

Heparans

and antiplatelet factors:

Prostacyclin (PGI2) from vessel wall

NO

Question 6

What catalyses the conversion of fibrinogen to fibrin?

Answer 6

Thrombin

Question 7

How does inflammation affect the blood vessel wall?

Answer 7

It makes it prothrombotic

↓ anticoagulants (e.g. TM)

↑ adhesion molecules

TF expression

↓ prostacyclin

vWF release

• platelet + neutrophil capture
• neutrophil extracellular traps (NETs) form

Question 8

How do neutrophils contribute to immunothrombosis?

Answer 8

Neutrophils release DNA, which is procoagulant

Question 9

What is the mechanism of action of clopidogrel?

Answer 9

Inhibits ADP receptors

Question 10

Give 4 ways in which blood stasis promotes thrombosis

Answer 10

1. Accumulation of activated factors
2. Promotes platelet adhesion
3. Promotes leukocyte adhesion and transmigration
4. Hypoxia produces inflammatory effect on endothelium

Question 11

What are some causes of blood stasis?

Answer 11

Immobility

surgery, paraparesis, travel

Compression

tumour, pregnancy

Viscosity

polycythaemia, paraprotein

Congenital

vascular abnormalities

Question 12

Rank these factors in order of highest risk thrombosis: factor V leiden, Protein C or S deficiency, antithrombin deficiency

Answer 12

Antithrombin (highest) > Protein C/S deficiency > FVL

Question 13

What is used for immediate vs delayed anticoagulant therapy?

Answer 13

immediate = heparin

delayed = warfarin

Question 14

What is the broad mechanism of action of heparins?

Answer 14

Potentiate antithrombin (anti-IIa) - ↑anticoag

Question 15

What is one risk of long term heparin use?

Answer 15

Injections, risk of osteroporosis, variable renal dependance

Question 16

Routes of administration for 1. unfractionated heparin, 2. LMWH and 3. penrasaccharide:

Answer 16

IV - required monitoring

SC

SC

Question 17

Give an example of an anti-Xa drug

Answer 17

Anti Xa (rivaroxaban, apixaban, edoxaban)

Question 18

Give an example of an anti-IIa drug

Answer 18

Dabigatran

Question 19

How to monitor heparin therapy?

Answer 19

APTT

anti Xa assay

Question 20

What is the mechanism of action of warfarin?

Answer 20

↓ procoagulant activity (2,7,9,10) vitamin K epoxide reductase(VKER) inhibitor

Indirect effect by preventing recycling of vit K = delayed onset

Question 21

Which procoagulant factors fall as a result of warfarin medication?

Answer 21

II, VII, IX and X
Also Protein C and Protein S

Factor 7 and Protein C drop first

Question 22

How is warfarin monitored?

Answer 22

INR derived from prothrombin time

Question 23

Why should warfarin never be given to pregnant women?

Answer 23

It is teratogenic as it crosses the placenta

Question 24

How would you reverse the effects of warfarin?

Answer 24

Give vitamin K if high INR (12 hours)

Quickly (1 minute) – 2,7,9,10 infusion

Question 25

What is the route of administration of warfarin?

Answer 25

oral

Question 26

Give an example of an LMWH

Answer 26

Enoxaparin/ Tinzaparin

Question 27

What scoring system is used to calculate risk of thrombosis?

Answer 27

Chads-vasc

Question 28

Which surgeries carry the highest risk of thrombosis?

Answer 28

Orthopaedic

Question 29

Which surgeries carry highest risk of bleeding?

Answer 29

Neuro, spinal or eye surgery

Question 30

Which class of anti-coagulants carries a significantly lower risk of intracranial bleeding?

Answer 30

DOACs

Question 31

What is the best drug to use as a long-term anticoagulant in a patient who has had an idiopathic VTE?

Answer 31

DOACs

Question 32

Recall the order in which the different coagulation factors in the intrinsic pathway catalyse each other?

Answer 32

12 11 9 8 10

Question 33

Which coagulation measure is used to monitor heparin therapy?

Answer 33

APTT

Question 34

Which coagulation measure is used to monitor warfarin therapy?

Answer 34

PT (INR)

Question 35

Which factor does the extrinsic pathway start with?

Answer 35

Seven

Question 36

What is the triad of symptoms in thrombophlebitic syndrome?

Answer 36

Recurrent pain Swelling Ulcers

Question 37

which factors increase the risk of recurrence of thrombosis?

Answer 37

idiopathic thrombosis M\>F proximal (above knee) \> distal (calf)

Question 38

After someone has suffered a thrombosis due to a minor precipitant (COCP, flights, trauma), how long should they be anti-coagulated for?

Answer 38

3 months

Question 39

After someone has suffered idiopathic thrombosis how long should they be anti-coagulated for?

Answer 39

long term anticoag - DOAC

Question 40

After someone has suffered post op thrombosis how long should they be anti-coagulated for?

Answer 40

no need long term

Question 41

33M collapses - has PE. Most appropriate first line treatment?

Answer 41

Therapeutic dose LMWH