Venous thrombosis

Venous thrombosis of the deep veins is a serious life-threat­ening condition which may lead to sudden death in the short term or to long-term morbidity due to the development of a post-thrombotic limb and venous ulceration. The most fre­quent location of deep vein thrombosis is in the lower limb. This condition may arise spontaneously or after injury to the limb. In modern medical practice the most common cause of lower limb venous thrombosis is following hospital admis­sion for treatment of medical or surgical conditions. In 10 per cent of patients who die in hospital, the cause of death is pulmonary embolism following a lower limb deep vein thrombosis.

Factors which lead to venous thrombosis

These were originally described by Virchow over a century ago. He suggested that the following factors may lead to clotting in the veins.

1. Changes in the vessel wall with damage to the endothelium due to injury or inflammation. This is known to happen following previous deep vein thrombosis.
2. Diminished rate of blood flow in the veins. In modern medical practice this occurs during and after operations, and in debilitating conditions such as strokes and myo­cardial infarction.
3. Increased coagulability of the blood. This also occurs following surgery and in the presence of infection or systemic malignancy.

Much more is now understood about the clotting cascade that results in the deposition of thrombus, as well as the fibrinolytic system that removes thrombus. Congenital deficiencies in either of these systems may result in increased susceptibility to thrombosis in that individual.

Thrombophilia

Severe deficiencies of antithrombin III, protein C or protein S lead to severe or fatal episodes of venous thrombosis at anearly age. More mild deficiencies may present as recurrent episodes of venous thrombosis in later life. Activated protein C resistance results in only a modest increase in the risk of venous thrombosis, perhaps presenting as deep vein thrombosis in the lower limb following hospital treatment for some other condition. However, this abnormality is fairly common, occurring in 6—7 per cent of Caucasian people. In any patient presenting with an episode of venous thrombosis a family history of thrombotic episodes should be sought.

Spontaneous venous thrombosis may occur following injury to the leg such as a severely sprained ankle, as the consequence of an infection or following a period of immobility. Long-haul air travel is recognised as the cause for venous thrombosis in a number of people who are obliged to spend long periods in conditions permitting little movement of the legs. Long car journeys may also cause venous thrombosis in the lower limbs in susceptible individuals. In a proportion of patients an underlying malignancy appears to be the precipitating factor. In a patient who develops venous thrombosis in the absence of any identifiable cause clinical examination and special investigations should be arranged to detect common malignancies (leg, lung, stomach, large bowel).

Patients receiving treatment in hospital are at increased risk of venous thrombosis. This includes patients being treat­ed surgically or for medical conditions. The factors which result in increased risk of venous thrombosis include advanc­ing age and greater complexity of surgical treatment. Orthopaedic operations on the lower limbs (hip and knee replacements) are especially likely to result in venous throm­bosis. However, medical patients are also at risk, particularly those being treated for strokes and other neurological conditions. Any patient with myocardial infarction or any serious illness runs the risk of venous thrombosis of the lower limb. Should this thrombus detach and become a pulmonary embolism, the result may be fatal. A large number of medical conditions, in addition to those mentioned above, may lead to venous thrombosis.

Prevention of deep vein thrombosis

All patients admitted to hospital or being treated for a serious illness should be assessed for the risk of deep vein thrombosis. These patients may he considered at low risk, moderate risk or high risk:

• low risk — young patients, minor illnesses, operations lasting for less than 30 minutes with no additional risk factors;
• moderate risk — patients over the age of 40 years with debilitating illnesses, undergoing major surgery but no additional risk factors;
• high risk — patients over the age of 40 years with serious medical conditions, such as stroke and myocardial infarc­tion, and undergoing major surgery with additional risk factor, such as a past history of venous thromboembolism, extensive malignant disease or obesity.

Both mechanical and pharmacological methods are effective in preventing deep vein thrombosis. Graduated compres­sion stockings (TED stockings) have been shown in clinical trials to reduce the incidence of deep vein thrombosis. Sequential pneumatic compression devices have also been shown to reduce the incidence of deep vein thrombosis in patients. Their efficacy is enhanced if graduated compression stockings are worn as well.

Pharmacological methods evaluated include: low-dose heparin, low-molecular-weight heparin, dextran and adjusted dose warfarin. There is now good scientific evidence that low-dose heparin is effective in reducing the incidence of deep vein thrombosis and pulmonary embolism. Most studies suggest that the use of 5000 units of heparin, given subcutaneously two or three times a day, is effective. This should be continued for at least 5 days. The risk of develop­ing a deep vein thrombosis following hospital discharge has now been recognised, and deep vein thrombosis prophylaxis probably ought to be extended into the postdischarge period. Low-molecular-weight heparin is effective in reducing the incidence of deep vein thrombosis. It has been shown to be more effective than low-dose heparin in orthopaedic patients and as effective in patients undergoing general surgical procedures. The advantages of low-molecular-weight heparin over standard heparin include once a day administration and a lower risk of bleeding complications, making it more suitable for out of hospital use.

Pulmonary embolism

Pulmonary embolism is a potentially fatal complication of lower limb deep vein thrombosis. A clot from the lower limb veins becomes detached from its site of formation and passes via the inferior vena cava and right heart to the pulmonary arteries. Here it may totally occlude the perfusion to part or all of one or both lungs. This leads to collapse or sudden death in some patients and is a medical emergency. Treatment includes full, immediate anticoagulation with intravenous heparin combined with standard methods of resuscitation. Large emboli may be treated by infusion of fibrinolytic drugs into the pulmonary arteries via catheters inserted via arm or leg veins.

Diagnosis of deep vein thrombosis

The most significant findings are tenderness in the calf and oedema at the ankle. However, these may also be attributable to other conditions. Pain in the calf on dorsiflexion of the ankle (Homan’s sign) has been described in many textbooks. However, this is a very misleading clinical sign and provides no useful informa­tion about the presence or otherwise of a lower limb venous thrombosis. It should no longer be used. Some patients with deep vein thrombosis of the lower limb may have no symptoms in the leg, but present with severe dyspnoea due to pulmonary embolism.

Signs and symptoms of deep vein thrombosis

Objective diagnosis of deep vein thrombosis

The only reliable way to detect venous thrombosis is using an imaging investigation. The test of choice is duplex ultrasono­graphy because it is a noninvasive, hazard-free method of investigation. If this is not available, then ascending phlebo­graphy should be undertaken. For diagnosis of pulmonary embolism, enhanced helical computerised tomography (CT) scanning is considered the standard test and is replacing isotope imaging studies. Treatment with anticoagulants is potentially hazardous and should not be commenced until a definite diagnosis has been made.

Treatment of deep vein thrombosis

In treating an established deep vein thrombosis it is important to make the correct diagnosis. Twenty per cent of patients with clinical signs and symptoms of a deep vein thrombosis have normal deep veins. The differential diagnosis includes ruptured Baker’s cyst, superficial thrombophlebitis, calf muscle haematomas and a ruptured plantaris tendon. All of these diagnoses can be demonstrated on ultrasonography, which has the advantage of allowing the examination of the soft tissues, something which venography is unable to do.

Having made the diagnosis of a deep vein thrombosis and confirmed it by duplex ultrasound imaging or venography, treatment should be instituted. Standard treatment involves intravenous heparin with the dose adjusted according to the weight of the patient and controlled by the activated partial thromboplastin time (APTT). The duration of heparin treatment should be at least 5 days. The aim is to minimise the risk of pulmonary embolism and encourage the thrombus to resolve. At the same time, the patient should be commenced on warfarin. The aim here is to reduce the risk of a further recurrence of venous thrombosis. Warfarin does not remove the clot from blocked veins and the duration of treatment (usually 3—6 months) is selected to prevent further episodes of venous thrombosis. Warfarin dosage is controlled by mea­suring the international normalised ratio (INR) by regular blood tests. The INR should be prolonged to between 2.5 and 3.5 times the control value. Patients with recurrent venous thromboembolic problems should be anticoagulated for life.

The use of subcutaneous injections of low-molecular-weight heparin for the treatment of deep vein thrombosis is an alternative method of anticoagulation. The dose is based on the patient’s weight and treatment given without blood tests to control the dose. This has been found to produce reliable anticoagulation without the risk of haemorrhage. This may in future become a very convenient way to manage patients with acute deep vein thrombosis, either in hospital or at home. Warfarin treatment is commenced at the same time and controlled using the INR in the same way as for the intravenous heparin regime.

Venous thrombectomy

Occasionally massive venous thrombosis in the lower limb leads to severe impairment in the blood supply to the limb, leading to ischaemia and, eventually, gangrene. This is a surgical emergency and requires rapid relief of the venous obstruction. This can be achieved surgically by opening the femoral vein via an incision in the groin and removing all clot from the deep veins of the leg and pelvis. This operation used to be more widely performed on the assumption that it would reduce the severity of post-thrombotic vein damage following a deep vein thrombosis. However, very few surgeons now perform this operation. The more modern treatment of thrombolysis, achieved by passing a catheter into the affected vein and infusing a fibrinolytic drug such as streptokinase or tissue plasminogen activator (TPA), is reducing the need for this operation.

Prevention of pulmonary embolism

In some patients the risk of pulmonary embolism is very great, e.g. a large venous thrombosis in the lower limb where anticoagulation is contraindicated (e.g. following a haemorrhagic stroke). In others, pulmonary embolism occurs despite full anticoagulation with warfarin. Pulmonary embolism may be prevented by the insertion of an inferior vena cava filter which traps large thrombi in its wires and prevents them from occluding the pulmonary arteries. These filters are usu­ally placed by a radiologist via the femoral or jugular vein under X-ray control without the need for an open surgical procedure.

Superficial vein thrombosis

Venous thrombosis (thrombophlebitis) often occurs in superficial veins. This is a frequent complication of varicose veins and may follow cannulation of a vein for an intravenous infusion. Spontaneous superficial thrombo­phlebitis may occur in the presence of polycythaemia, polyarthritis and Buerger’s disease and may also herald the presence of a visceral cancer. This condition does not carry the severe risks of deep venous thrombosis and is normally treated symptomatically. Patients benefit from simple analgesics and anti-inflammatory drugs. Occasionally deep vein thrombosis may complicate superficial venous thrombosis and should be investigated where there is a clinical suspicion that thrombosis may have reached the deep veins. Patients with varicose veins should be advised to undergo surgical treatment for their varices as further episodes are likely in these patients.

Axillary vein thrombosis

Thrombosis of the axillary vein may occur following excessive exercise or as a complication of thoracic outlet syndrome. It is occasionally associated with a cervical rib. The arm becomes swollen and the superficial veins are distended. Early treatment with anticoagulants may result in rapid resolution. In severe cases the use of fibrinolytic therapy, streptokinase or TPA may be considered. Definitive treat­ment of the thoracic outlet syndrome by surgical decompres­sion of the subclavian vein may be needed, for example by resection of the first rib.