Venous thrombosis/pulmonary embolism

>> How high is my risk of venous thrombosis?
>> How can I avoid venous thrombosis?
>> What is the state of art in diagnosis and treatment?
>> For how long do I have to take vitamin K antagonists?

How high is my risk of thrombosis?

The risk of thrombosis depends upon the interaction of hereditary and acquired risk factors. The larger the number of risk factors and the stronger their potency, the higher is the risk of thrombosis. The thrombosis risk hence differs from patient to patient.

The most important acquired risk factors are surgery and trauma (in particular trauma of the leg), immobility, pregnancy, use of oestrogen containing oral contraceptives, hormone replacement therapy during menopause, cancer or cardiac insufficiency. Long-haul flights are also associated with an increased risk of thrombosis. The thrombosis risk is increased among individuals with the lupus anticoagulant or high homocysteine blood levels.

Following major surgery, in particular surgery of the knee or hip, or after an injury of the leg which is treated with a plaster cast, patients receive usually anticoagulant treatment with a low molecular weight heparin. This procedure substantially lowers the risk of thrombosis. Nevertheless, venous thrombosis is sometimes encountered despite heparin treatment.

Patients who are bedridden because of a severe medical illness are at an increased thrombosis risk, which can be lowered by anticoagulant treatment.

Oral contraceptives that contain estrogens are associated with a 4-fold increased risk of thrombosis. Hormone replacement therapy during menopause confers a 2- to 3-fold increase of the thrombosis risk. Pregnancy and in particular the postpartum period confer an increased risk of thrombosis.

Reasons for the increased risk of thrombosis associated with long-haul flights are immobility, reduced cabin pressure, intake of alcoholic beverages or sleeping pills. Prevention strategies consist of general measures such as ambulation during flight, use of compression stockings, fluid intake and, in selected cases only application of a low molecular weight heparin.

Antiphospholipid antibodies are proteins, which are directed against certain molecular structures on the surface of blood vessels and blood cells. The mechanisms, which eventually lead to thrombus formation, are not fully understood. The lupus anticoagulant is a risk factor for both arterial and venous thrombosis and can also be associated with adverse pregnancy outcome and reduced levels of platelets (thrombocytopenia).

The association between cancer and venous thrombosis is well known. About 10% of patients with venous thrombosis suffer from (sometimes occult) cancer. Conversely, 10% of patients with cancer experience venous thrombosis during the course of the disease. Patients with cancer and thrombosis are no longer treated with vitamin K antagonists (Marcoumar, Sintrom), but should receive long-term treatment with low molecular weight heparin.

The most important congenital risk factors are APC resistance (factor V Leiden mutation), the G20210A mutation in the prothrombin gene (prothrombin mutation), or antithrombin-, protein C- or protein S deficiency.

Factor V Leiden is named after the Dutch city of Leiden where it was discovered in the mid 90ies. Factor V Leiden is the most frequent congenital abnormality in haemostasis and is found in 5-10% of the population and in approx. 30% of patients with venous thrombosis. Carriers of heterozygous factor V Leiden have a 7-fold increased risk of thrombosis and those with homozygous factor V Leiden a 30-fold increased risk. Factor V Leiden, however, is not a risk factor for recurrence of venous thrombosis. The risk of thrombosis among individuals with factor V Leiden is increased by oestrogen containing oral contraceptives. Nevertheless, oral contraceptives are not necessarily contraindicated in women with factor V Leiden.

The prothrombin mutation is found in about 2% of the population and in approx. 15% of patients with venous thrombosis. Heterozygous carriers have a 2 to 3-fold increased risk of thrombosis. Use of oestrogen containing oral contraceptives increases the risk in women with the mutation. Nevertheless, oral contraceptives are not necessarily contraindicated in women with the heterozygous mutation.

Antithrombin, protein C and protein S are natural inhibitors of several coagulation factors. Patients with a reduced plasma level of one of these substances have a tendency towards venous thrombosis and pulmonary embolism.

How can I avoid venous thrombosis?

The risk of thrombosis can be reduced by a healthy lifestyle consisting of regular physical activity and avoidance of overweight. Safety measures during risk situations such as surgery, trauma, plaster casts and long-haul flights have been already addressed.

What is the state of art in diagnosis and treatment?

Typical symptoms of venous thrombosis are swelling of the leg, calf pain and leg pain while walking. The diagnosis on the basis of clinical symptoms only is not warranted. The clinical judgement is usually followed by measurement of D-Dimer, an indicator of haemostatic system activation, in venous blood. If D-Dimer is positive, either ultrasound of the leg or venography has to be performed.

The typical symptoms of pulmonary embolism are dyspnoea at rest or with minimal exertion or chest pain. In case of clinical symptoms indicative for pulmonary embolism, D-Dimer measurement is necessary. If D-Dimer testing is positive or in case of a high clinical suspicion, a CT of the lung or a lung scan has to be performed.

Treatment of venous thrombosis and pulmonary embolism consists of anticoagulants. Anticoagulant treatment is started with low molecular weight heparin overlapped and followed by vitamin K antagonists. Vitamin K antagonists have to be monitored by laboratory testing (INR).

For how long do I have to take vitamin K antagonists?

The duration of anticoagulation varies from patient to patient and is dependent upon the presence of risk factors including a history of prior venous thromboembolism, thrombosis of the proximal veins (= veins above the knee), male gender and other clinical patient characteristics. Patients in whom venous thrombosis is associated with a temporary risk situation such as surgery, trauma or use of oestrogen containing oral contraceptives, or patients with calf vein thrombosis have a low risk of recurrence and should be treated for a limited period of time. Patients with unprovoked venous thrombosis of the proximal veins or patients with pulmonary embolism are candidates for indefinite treatment. For this patient group, the risk of recurrent venous thrombosis can be calculated by the use of the “Vienna prediction model”.