Chapter 133

### Introduction

Thrombosis is an ugly thought;

Dicumarol and heparin,

Statistics show, prevent most ills

Like thrombus of the coronary, infarction of the heart

And tests are made so many times

That arms turn blue and blood runs thin

David Littman, ‘The Good Old Days’, N Engl J Med, 1965

A thrombus is defined as a clot formed in the circulation from the constituents of the blood, whereas emboli are fragments of thrombus that break off and block vessels downstream. Almost half of adult deaths in Western countries are due to thrombosis of coronary arteries or cerebral arteries and to pulmonary embolism.1 A thrombus is the result of a cascade of events involving platelets, RBCs, coagulation factors and the vessel wall.

Conditions predisposing to thrombosis:

• thrombophilia

• thrombocytosis (platelets)

• polycythaemia rubra vera

##### Thrombophilia2

Thrombophilia refers to a disorder of haemostasis in the form of a primary coagulopathy leading to a tendency to thrombosis. This should be considered in patients with major unprecipitated venous thromboembolism with or without a strong family history of venous thrombosis. There are several causes that can be tested. The factors are both inherited and acquired:

• inherited:

• factor V Leiden gene mutation (activated protein C resistance)

• prothrombin gene mutation

• protein C deficiency

• protein S deficiency

• antithrombin deficiency

• acquired:

• antiphospholipid antibodies (anticardiolipin or anti-ß2 GPI)

• elevated homocysteine level

• lupus anticoagulant

The above factors can all be measured in the laboratory with specific genetic tests, coagulation or antibody-based tests. Other acquired causes (regarded as risk factors) include malignancy, OCP, HRT, immobilisation, obesity, smoking, pregnancy and major surgery. Consideration should be given to screening patients with a DVT, especially in travellers at possible risk. Referral to a haematologist if thrombophilia is proved or suspected is advisable. Of particular interest is factor V Leiden, which occurs in about 5% of Caucasians, and the risk of venous thrombosis is increased three to seven times in heterozygotes and 80 times in homozygotes.2

Indications for investigation

• Recurrent or unusual thrombosis

• Venous thromboembolism <40 years

• Arterial thrombosis <30 years

• Skin necrosis, especially on warfarin

• Recurrent fetal loss

• Familial thromboembolism

##### Venous thromboembolism

A feature of venous thrombosis is that it develops in normal vessels, with key factors being stasis and increased coagulability including thrombophilia. The classic example is deep venous thrombosis of the leg veins. Another poorly recognised thrombosis is axillosubclavian venous thrombosis, which is associated with pulmonary embolism in 30% of cases.3

Other sites of deep vein thrombosis are the pelvic/ovarian veins, which should be suspected in a person at risk with pelvic pain and swollen upper thighs, mesenteric venous thrombosis and cerebral sinus thrombosis, which are usually due to thrombophilia.

##### Deep venous thrombosis

Past history is very important.

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