Haem: Thrombosis - aetiology and management

Question 1

What is the triad of symptoms in thrombophlebitic syndrome?

Answer 1

Recurrent pain

Swelling

Ulcers

Question 2

What catalyses the conversion of fibrinogen to fibrin?

Answer 2

Thrombin

Question 3

Which anticoagulant molecules are expressed on the blood vessel wall?

Answer 3

Thrombomodulin

Endothelial protein C receptor

Tissue factor pathway inhibitor

Heparans

NOTE: it does not normally produce tissue factor

Question 4

Recall 5 effects of inflammation on the blood vessel wall

Answer 4

1. Anticoagulant molecules are downregulated
2. TF expressed
3. Prostacyclin decreased
4. Adhesion molecules upregulated
5. VWF released (leading to neutrophil capture, and formation of NETs)

Question 5

How do neutrophils contribute to immunothrombosis?

Answer 5

Neutrophils release DNA, which is procoagulant

Question 6

Give 4 ways in which blood stasis promotes thrombosis

Answer 6

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

Question 7

What is the broad mechanism of action of heparins?

Answer 7

Potentiate antithrombin

Question 8

Give an example of an LMWH

Answer 8

Enoxaparin/ Tinzaparin

Question 9

How is unfractionated heparin monitored?

What about LMWH?

Answer 9

Unfractionated heparin: it has variable pharmacokinetics and a variable dose-response

Must be monitored with APTT or anti-Xa levels

LMWH: reliable pharmacokinetics so monitoring usually not required

Monitor anti-Xa levels if there is renal failure, extreme weight or extreme risk

Question 10

What are the disadvantages of heparin?

Answer 10

Administered by injection

Risk of osteoporosis

Variable renal dependence

Risk of heparin-induced thrombocytopaenia

Question 11

How does warfarin affect vit K?

Answer 11

Warfarin inhibits vitamin K epoxide reductase

Prevents recycling of Vit K

Question 12

Which procoagulant factors fall as a result of warfarin medication?

Answer 12

II, VII, IX and X

*Also impairs Protein C and Protein S (which are natural anticoagulant molecules)*

Question 13

How can the action of warfarin be reversed?

Answer 13

Administering vitamin K – takes 12 hours

Giving factors 2, 7, 9 and 10 – immediate

Question 14

How is warfarin monitored?

Answer 14

Pro-thrombin time/INR

Question 15

What are the problems with warfarin?

Answer 15

Teratogenic so cannot give during pregnancy

Initial hypercoagulable state due to inhibition of protein C and protein S - that’s why heparin is co-administered until INR stabilises

Question 16

List some properties of DOACs

Answer 16

Oral administration

Immediate action (peak = 3-4 hours)

Useful in long-term

Short half-life

No monitoring needed

NOTE: contra-indicated in valvular AF

Question 17

Which DOAC inhibits factor IIa?

Which DOACs inhibit factor Xa?

Answer 17

IIa: Dabigatran

Xa: Rivaroxiban Apixaban Edoxaban

Question 18

Which surgeries carry the highest risk of thrombosis?

Answer 18

Orthopaedic

Question 19

Which of these factors are associated with a higher risk of recurrence of DVT?

Male sex

Female sex

Proximal thrombosis

Distal thrombosis

Post surgery

Idiopathic

Answer 19

Male sex

Proximal thrombosis

Idiopathic

Question 20

Risk factors for thrombosis

Answer 20

Cancer

Surgery

Obesity

Elderly

Immobility

*Antithrombin deficiency confers the highest risk*

Question 21

What should all patients > 60 years old with idiopathic thromboembolic disease be offered?

Answer 21

CT scan to check for an underlying cause

Question 22

Outline the treatment of DVT/PE.

Answer 22

Start LMWH (e.g. tinzaparin 175 u/kg) + warfarin

Stop LMWH when INR > 2 for 2 days

ALTERNATIVE: start a doac

These should be continued for:

• Known cause: 3 months
• Unknown cause or cancer VTE: 3-6 months
• Thrombophilic/recurrent: lifelong

Question 23

How do you prevent venous thrombosis recurrence?

Answer 23

After a surgical precipitant: no long-term anticoagulation needed

After a minor precipitant: 3 months anticoagulation usually adequate

If idiopathic cause: long-term anticoagulation (10-20% recurrence within 2 years)