Venous Thrombosis, Thrombophilia & APS

Question 1

Compare an arterial vs venous thrombus

Answer 1

Arterial - platelet rich thrombus
Venous - fibrin rich thrombus

Question 2

Where does a venous thrombus usually form

Answer 2

In the venous valve pockets
(& other sites of stasis)

Question 3

Using Virchow’s triad, list risk factors for venous thrombosis

Answer 3

Stasis
- Left ventricular dysfunction
- Immobility (e.g. trauma, surgery, long flights) or paralysis
- Venous obstruction (e.g. tumour, obesity, pregnancy, age)
- Venous insufficiency/ varicose veins

Endothelial (valve) damage
- Venous valvular damage (from previous DVT/PE)
- Age
- Indwelling catheter

Hyper-coagulability
- Oestrogen therapy
- Pregnancy, peripartum
- Malignancy, sepsis/infection, trauma/surgery
- Thrombophilia

Question 4

Malignancy, infection, trauma, surgery, pregnancy, oestrogen therapy etc can cause hypercoagulability. Why is this?

Answer 4

They are associated with release of tissue factor
They are also associated with increased VWF & factor VIII

Question 5

What is thrombophilia & what are the 4 potential mechanisms for thrombophilia

Answer 5

• Familial or acquired disorder
• of haemostatic mechanisms
• that predispose to thrombosis

4 mechanisms
- Increased platelet coagulation
- Increased fibrin coagulation
- Decreased fibrinolytic activity
- Decreased anti-coagulant activity

Question 6

What is hereditary thrombophilia and what are the 5 most common types/causes

Answer 6

• Factor V Leiden (protein C can’t inhibit factor V/Xa)
• Prothrombin 20210 mutation (increased prothrombin)
• Antithrombin deficiency
• Protein C deficiency
• Protein S deficiency

Question 7

When would you consider screening for hereditary thrombophilia

Answer 7

Recurrent venous thrombosis
Unusual venous thrombosis
<45 yrs old venous thrombosis
Family history of venous thrombosis

Question 8

Hereditary thrombophilia management

Answer 8

• Advice on avoiding risk
• Short term prophylaxis during periods of known risk
• Short term anticoagulation to treat thrombotic events
• Long term anticoagulation if recurrent thrombotic events

Question 9

One cause of acquired thrombophilia is anti-phospholipid antibody syndrome, what is this?

Answer 9

• Autoimmune disorder
• Anti-phospholipid antibodies
• Activation of primary & secondary haemostasis

Question 10

What is APS associated with

Answer 10

SLE (& other rheumatic or autoimmune conditions)

Question 11

APS clinical presentation

Answer 11

• Arterial (TIA, MI, stroke) & venous (DVT, PE) thrombosis
• Pulmonary hypertension (due to recurrent PE)
• Sterile (libman-sacks) valvular endocarditis
• Miscarriage (recurrent early or late spontaneous foetal loss)
• Mild thrombocytopenia
• Migraine
• Livedo reticularis (capillary blood clot)

Question 12

APS diagnostic investigations

Answer 12

One of the following on two occasions 12 weeks apart:
- Anti-cardiolipin
- Anti-β2-GPI antibodies
- Positive lupus anticoagulation assay

Question 13

APS FBC & clotting screen findings

Answer 13

• FBC - thrombocytopenia
• Clotting screen - prolongation of APTT

Question 14

APS management

Answer 14

Antibodies & one thrombotic episode
- acute LMWH then warfarin or aspirin prophylaxis

Antibodies but no thrombotic episode
- no anti-coagulation

During pregnancy in patients with recurrent miscarriage
- LMWH & aspirin

Question 15

Describe APS pathophysiology

Answer 15

• Antiphospholipid antibodies bind to phospholipids like cardiolipin and blood proteins like βGPI (that bind to anionic phospholipids).
• This disrupts the membrane of endothelial cells which then activates haemostasis (thrombosis).
• This also affects platelets, causing them to clump together and also causing them to decrease in numbers (thrombocytopenia).
• This also reduces the availability of phospholipids, which prolongs the time it takes for blood to clot (prolonged APTT).
• This also damages the heart valves (Libman-sacks (sterile) endocarditis)