Stagnation within the veins is the most important factor in initiating venous thrombosis. Calf muscles act as a venous pump returning blood to the heart. Failure of the calf pump due to enforced immobility (e.g. postoperative bed rest, plaster cast, paralysed limb) leads to venous stasis. This is a particular problem in the elderly, the obese and those with varicose veins: in these patients even 3 or 4 days of immobility can be critical.

Thrombosis is triggered by the activation of clotting mechanisms that occurs when there is damage to the vein wall – indeed, this is the normal mechanism for preventing bleeding at the sites of trauma. Typical situations that lead to vein damage are pressure injuries to the calf from the operating theatre table and the deterioration that occurs in the veins as a result of recurrent venous thrombosis.

There are several inherited and acquired abnormalities of the clotting mechanisms that increase the risk of venous thromboembolic disease (→Box 7.1). The most common acquired abnormalities are those associated with the oral contraceptive pill, hormone replacement therapy, pregnancy and the presence of malignant disease.

Inherited clotting abnormalities (‘thrombophilias’) are increasingly recognised as underlying the cause of recurrent DVTs, particularly in younger patients and in those with a positive family history. The most important of several inherited coagulation abnormalities, known as Factor V Leiden, is present in 5% of the population and increases the risk of thrombosis by ten times the normal rate. One in five patients with their first DVT are Factor V Leiden positive. Recent estimates suggest up to half of all patients who present with a venous thromboembolic episode, either DVT or pulmonary embolus, may have a single or multiple inherited abnormalities of their clotting. In these individuals, each episode can be triggered by trivial external events such as minor surgery or immobility. In the future, increasing attention will be paid to identifying these inherited risk factors.

In most situations in which the chances of a venous thrombosis are high there are multiple risk factors. Thus in major orthopaedic procedures to the leg there is vein damage and immobility; in pregnancy there is abnormal clotting and stagnation of blood due to intraabdominal mechanical effects; and in prolonged air travel there is immobility, often associated with a degree of dehydration. The combination of the oral contraceptive pill and the presence of Factor V Leiden increases the risk of a DVT 30-fold.

In a patient with suspicious symptoms, the presence of major risk factors (those that increase the risk by between 5 and 20 times normal) makes the diagnosis of a pulmonary embolism much more likely.

Confirmatory tests are chosen according to the clinical likelihood of a PE and the presence or absence of major risk factors (page 254). If the clinical picture is consistent with a PE, and the patient has no other obvious alternative diagnosis such as pneumonia or COPD, the presence of a major risk factor makes the probability of a PE high. If the clinical picture is consistent with a PE but the patient has either no obvious alternative diagnosis or a major risk factor, the probability of a PE is intermediate. If the clinical picture would fit a PE but there is an obvious alternative diagnosis and no major risk factor, the probability of a PE is low. High probability patients should start heparin immediately and need a definitive test (CTPA or isotope lung scan) – patients where the probability of a PE is intermediate or low should have the screening blood test (D-dimer) which, if it is normal, rules out a PE. A normal D-dimer test can give false reassurance in cases where the clinical suspicion is scored high – in this situation the test should not be done.

A number of tests are available to identify venous thromboembolic disease (→Table 7.1). They are described in more detail below.

The investigation of possible pulmonary emboli has been revolutionised by the introduction of the CTPA. It is superior to both the isotope lung scan and the conventional angiogram. A negative CTPA rules out a significant pulmonary embolus and often gives additional information on alternative causes of the patient’s symptoms.

Lung scans are easy to perform and, when used in conjunction with the clinical details, are useful in the diagnosis of pulmonary emboli. Although positive scans are also seen in other conditions and have to be interpreted with care, a normal scan result is very helpful, as it rules out the possibility of a pulmonary embolus.

D-dimers are fragments of dissolving blood clots that can be identified from a blood sample whenever a thromboembolic process is under way. A positive test is also seen after surgery, in infections, after myocardial infarction and in malignant disease: a positive D-dimer test is not therefore in itself diagnostic. D-dimer tests are most useful for ruling out thromboembolism when the initial clinical assessment suggests a low or intermediate suspicion of the diagnosis. For example a patient who is breathless may have a major risk factor such as recent hip surgery, but has other possible causes of breathlessness such as COPD: in this situation, a negative D-dimer means there is another cause for the breathlessness. When the clinical suspicion is high, D-dimers are not helpful, because a negative result under these circumstances is not reliable enough to rule out the diagnosis (an example would be a patient who is breathless, with no alternative explanation, plus a major risk factor for pulmonary embolus).

This looks at compressibility of the vein with an ultrasound probe and also examines venous blood flow using colour Doppler. Compression ultrasound is accurate for thigh vein thrombosis, but not for thrombosis in the pelvis or calf. It is also unreliable at picking up recurrent thrombotic episodes. In spite of these drawbacks, ultrasound is a simple, rapid and very effective diagnostic tool, particularly when combined with clinical assessment and initial screening by the measurement of D-dimers. If a DVT is thought likely (based on clinical assessment in the form of a scoring system – page 265 and an elevated D-dimers) but a compression scan is negative, the scan should be repeated in seven days in case a calf vein thrombosis (not dangerous) has extended above the knee to involve the thigh veins (dangerous).

The venogram examines the veins of the legs and pelvis and the inferior vena cava and is considered to be the ‘gold standard’ for the identification of venous thrombosis. An invasive test and unpleasant for the patient, its use is confined to difficult cases, particularly those in which active intervention with a vena cava filter is under consideration. The pulmonary angiogram was the ‘gold standard’ investigation for diagnosing pulmonary emboli, but it has been replaced by the CT pulmonary angiogram.

In this test, the flow of blood out of the calf is impeded by inflating a thigh cuff. The cuff is then suddenly let down and the flow of blood out of the calf is measured to assess the degree of venous obstruction. The term ‘impedance’ refers to the technique of deriving a measure of blood flow from sensors placed over the calf.

Ultrasound and plethysmography are reliable for proximal deep vein thrombosis, but are poor at identifying calf vein thrombosis. However, in practical terms (i.e. the risk of pulmonary embolus) thrombosis in the calf only becomes important if it spreads to the thigh – so if the initial clinical suspicion is high it is prudent to repeat either test after a few days, in case a missed calf vein thrombosis has extended proximally to the thigh.