0330 - Approach to Thrombosis

Question 1

What is thrombophilia?

Answer 1

Hard to define. Clinically used to describe patients who:
Develop VTE spontaneously
VTE is disproportionate to recognised stimulus
Recurrent VTE
VTE at early age

Question 2

What are the components of Virchow’s triad?

Answer 2

Hypercoagulability
Abnormal Blood flow/(thrombosis = stasis)
Endothelial damage

Question 3

What are some possible outcomes of venous thrombosis?

Answer 3

Ischaemia
Embolisation
Resolution
Recanalisation
Propagation (growth)

Question 4

What are the three parts of the coagulation cascade?

Answer 4

Intrinsic (PTT/INR - from surface/foreign body contact, but all factors are in the blood)
Extrinsic (PT - tissue derived, not in blood)
Common (starting at factor X)

Question 5

Outline the common coagulation cascade.

Answer 5

X->Xa
V->Va (Is only a cofactor, V fits in the X)
Prothrombin->thrombin (Factor II)
fibrinogen->fibrin

Question 6

Outline the intrinsic (aPTT/INR) clotting cascade.

Answer 6

aPTT is a TENET of Haematology

XII->XI>IX->VIII->X

Question 7

Which clotting factor is deficient in Haemophilias A, B, C?

Answer 7

A = Eight
B = Nine
C = Eleven
Thinking back to the TENET pathway - CBA = ENE

Question 8

What is the interplay between thrombosis and cancer?

Answer 8

Thrombosis considered a complication of cancer.
20% of VTE cases are associated with active cancer, and 4-6 fold higher risk of VTE in cancer patients.
Causes - Endothelial dysfunction, procoagulant malignant cells, and tissue factor released by macrophages.

Question 9

What are the three acquired forms of thrombophilia?

Answer 9

Pregnancy
Cancer
Antiphospholipid syndrome/antibodies

Question 10

How does pregnancy interact with Virchow’s triad?

Answer 10

Blood - Increased procoagulants (FV, FVIII), reduced anticoagulants (protein S)
Flow - Stasis secondary to pelvic mass
Vessels - Vascular damage during delivery.

Question 11

How does cancer interact with Virchow’s triad?

Answer 11

Blood - procoagulants and other factors in malignant cells.
Flow - Venous Catheters
Vessels - Venous catheters, chemotherapy effects.

Question 12

How do antiphospholipid antibodies interact with Virchow’s triad?

Answer 12

Blood - interact with coag and anticoag pathways, and can activate platelets
Blood flow - NA
Vessels - activate the endothelium.

Question 13

What are the most common causes of inherited thrombophilias?

Answer 13

Biggest 2:
Activated Protein C Resistance
Prothrombin Gene 20210A Mutation
Protein C deficiency
Protein S deficiency
Antithrombin deficiency

Question 14

Briefly outline Activated Protein C resistance

Answer 14

Present in 5-8% of caucasians
Factor Va resists cleavage by activated protein C complex, therefore is not denatured.
85-90% of cases - factor V gene Leiden mutation.

Question 15

Briefly outline the prothrombin gene mutation that causes thrombophilia.

Answer 15

2% incidence in caucasian population.
Mutation at gene position 20210 (like 90210 but not)
Leads to increased amounts of circulating thrombin.

Question 16

What is Protein C? What does it do?

Answer 16

Vitamin K dependent anticoagulant, synthesised in liver.
Activated by thrombin-thrombomodulin complex, and neutralises Factors V and VIII
Also induces fibrinolysis.

Question 17

What is Protein S? What does it do?

Answer 17

Vitamin K dependent anticoagulant, synthesised in liver.
Only exists in active form. Exists in Free (40%) and bound (60%) forms.
Free Protein S acts as co-factor for Protein C (so assists in cleaving Va and VIIIa)

Question 18

What are the risk factors for recurrence of thrombophilia?

Answer 18

Cannot be reliably predicted.
Active Cancer
Proximal DVT/PE (vs distal DVD)
Male
High BMI