Factor V Leiden: How great is the risk of venous thromboembolism?
ABSTRACTThe factor V Leiden mutation, the most common inherited cause of thrombophilia, causes a mild hypercoagulable state. We describe a 29-year-old man, heterozygous for factor V Leiden, who developed extensive pulmonary emboli with concomitant bilateral deep venous thrombosis, likely provoked by prolonged immobility during a car trip. We then review the diagnosis, therapy, screening, and prognosis of venous thromboembolism related to factor V Leiden.
KEY POINTS
- The pathogenesis of venous thromboembolism is complex and multifactorial, often reflecting the interplay between environmental, clinical, and genetic factors.
- Factor V Leiden increases the risk of venous thromboembolism but by itself does not appear to increase the risk of arterial thrombosis.
- Often, people with factor V Leiden may have additional risk factors that increase the rate of venous clots, such as older age, surgery, obesity, immobility, prolonged travel, hospitalization, oral contraceptive use, hormonal replacement therapy, pregnancy, and malignancy.
- General measures and precautions are needed to minimize the risk of venous thromboembolism in people with the factor V Leiden mutation, especially when modifiable factors are present, such as obesity and long periods of immobilization.
HOW LONG TO GIVE ANTICOAGULATION AFTER VENOUS THROMBOEMBOLISM?
Patients who have had an episode of venous thromboembolism have to be treated with anticoagulants.
In general, the initial management of venous thromboembolism in patients with heritable thrombophilias is no different from that in any other patient with a clot. Anticoagulants such as warfarin are given at a target INR of 2.5 (range 2.0–3.0).32 The duration of treatment is based on the risk factors that resulted in the thrombotic event.
After a first event, some authorities recommend anticoagulant therapy for 6 months.32 A shorter period (3 months) is recommended if there is a transient risk factor (eg, surgery, oral contraceptive use, travel, pregnancy, the puerperium) and the thrombosis is confined to distal veins (eg, the calf veins).32
Factor V Leiden does not necessarily increase the risk of recurrent events in patients who have a transient risk factor. Therefore, people who are heterozygous for this mutation do not usually need to be treated lifelong with anticoagulants if they have had only one episode of deep vein thrombosis or pulmonary embolism, given the risk of bleeding associated with anticoagulation, unless they have additional risk factors.
Conditions in which indefinite anticoagulation may be required after careful consideration of the risks and benefits are:
- Life-threatening events such as near-fatal pulmonary embolism
- Cerebral or visceral vein thrombosis
- Recurrent thrombotic events
- Additional persistent risk factors (eg, active malignant neoplasm, extremity paresis, and antiphospholipid antibodies)
- Combined thrombophilias (eg, combined heterozygosity for factor V Leiden and the prothrombin G20210A mutation)
- Homozygosity for factor V Leiden.32,46,48
Factor V Leiden by itself or combined with other thrombophilic abnormalities is not associated with a higher risk of recurrent venous thromboembolism during warfarin therapy (a possible exception is the combination of factor V Leiden plus antiphospholipid antibodies).32,34 Furthermore, current evidence suggests that no thrombophilic defect is a clinically important risk factor for recurrent venous thromboembolism after anticoagulant therapy is stopped. All these facts indicate that clinical factors are probably more important than laboratory abnormalities in determining the duration of anticoagulation therapy.32,35,36,61–63
PRIMARY PROPHYLAXIS IN PATIENTS WITH FACTOR V LEIDEN
Factor V Leiden is only one of many risk factors for deep vein thrombosis or pulmonary embolism. If carriers of factor V Leiden have never had a blood clot, then they are not routinely treated with an anticoagulant. Rather, they should be counseled about reducing or eliminating other factors that may add to their risk of developing a clot in the future.
Usually, the effect of risk factors is additive: the more risk factors present, the higher the risk.46,50 Sometimes, however, the effect of multiple risk factors is more than additive.
Some risk factors, such as genetics or age, are not alterable, but many can be controlled by medications or lifestyle modifications. Therefore, general measures and precautions are recommended to minimize the risk of thrombosis. For example:
Losing weight (if the patient is overweight) is an important intervention for risk reduction, since obesity is probably the most common modifiable risk factor for developing blood clots.
Avoiding long periods of immobility is recommended. For example, if the patient is taking a long car ride (more than 2 hours), then stopping every few hours and walking around for a few minutes is a good way to keep the blood circulating. If the patient has a desk job, getting up and walking around the office periodically is advised. On long airplane trips, a walk in the aisle every so often and preventing dehydration by drinking plenty of fluids and avoiding alcohol are recommended.
Wearing elastic stockings with a graduated elastic pressure may prevent deep venous thrombosis from developing on long flights.63–65
Staying active and getting regular exercise through such activities as walking, bicycling, or swimming are helpful.
Avoiding smoking is critical.50,63
Thromboprophylaxis is recommended for most acutely ill hospitalized patients, especially those confined to bed with additional risk factors. Guidelines for prophylaxis are based on an individualized risk assessment and not on thrombophilia status. Prophylactic anticoagulation is routinely recommended for patients undergoing major high-risk surgery, such as an orthopedic, urologic, gynecologic, or bariatric procedure. Any excess thrombotic risk conferred by thrombophilia is likely small compared with the risk of surgery, and recommendations on the duration and intensity of thromboprophylaxis are not based on thrombophilic status.46,48
Education. Pain, swelling, redness of a limb, unexplained shortness of breath, and chest pain are the most common symptoms of deep vein thrombosis and pulmonary embolism.46,50 It is crucial to teach patients with factor V Leiden to recognize these symptoms and to seek early medical attention in case they experience any of them.
SCREENING FAMILY MEMBERS FOR THE FACTOR V LEIDEN MUTATION
Factor V Leiden by itself is a relatively mild thrombophilic defect that does not cause thrombosis in all carriers, and there is no evidence that early diagnosis reduces rates of morbidity or mortality. Therefore, routine screening of all asymptomatic relatives of affected patients with venous thrombosis is not recommended. Rather, the decision to screen should be made on an individual basis.50,66
Screening may be beneficial in selected cases, especially when patients have a strong family history of recurrent venous thrombosis at a young age (younger than 50 years) and the family member has additional risk factors for venous thromboembolism such as oral contraception or is planning for pregnancy.32,48,49,66
