VTE Facts
It is estimated that more than 250,000 patients are hospitalized for venous thromboembolism (VTE) in the United Sates each year.1 The number of VTE cases annually in this country ranges from 600,000 to 2 million.2,3 The most common causes of VTE include surgery, trauma, hospital or nursing home confinement and malignant neoplasm.4
Unnecessary studies. Some authorities recommend a chest radiograph in the routine evaluation for occult malignancy,9 but its clinical utility for patients without pulmonary symptoms has not been clearly demonstrated. Because of their expense and low test yield, we do not advocate the use of more elaborate screens for occult malignancy, such as computerized tomography, magnetic resonance imaging, or serologic tumor markers.
Caveat. In the past, nearly all patients with pulmonary embolism or DVT were hospitalized to receive treatment with continuous intravenous heparin. Presumably these patients routinely received a careful history evaluation, physical examination, and standard blood work.
With increased use of low-molecular-weight heparins (given subcutaneously once or twice daily), many individuals with VTE are candidates for treatment partially or totally on an outpatient basis.14,15 Be sure that individuals receiving outpatient treatment for idiopathic VTE receive the same attention and routine work-up as hospitalized patients.
Coagulation disorders and Venous Thromboembolism
With advances in laboratory testing, more than half of idiopathic VTE cases can be attributed to a specific coagulation disorder. Data show that in a randomly selected group of patients with newly discovered DVT, 24% to 37% have an inherited predisposition to thrombosis.16-19
Deficiencies in protein C, protein S, and antithrombin were the first causes of inherited thrombophilia to be identified;20-22 however, these deficiencies are not particularly common. The most common causes of thrombophilic coagulation disorders are activated protein C resistance, the prothrombin gene G20210A mutation, and hyperhomocysteinemia.
When to look for prothrombotic defects
If, after ruling out occult malignancy, the cause of VTE remains uncertain, be judicious in deciding whether to run more tests for prothrombotic defects. We advocate pursuing further testing for patients likely to have an underlying hypercoagulable disorder, and for whom the identification of such a disorder would have management implications.
A decision to pursue testing with other patients should be made on a case-by-case basis. The yield in testing is low for many prothrombotic disorders, some tests are affected adversely by anticoagulation therapy, and the influence of a positive test result on patient management decisions remains unclear in many cases. Finally, serologic evaluation for thrombophilia would be costly if conducted for all patients with VTE, and the potential clinical benefit would be small.
Although large epidemiologic studies are lacking to help identify patients at increased risk of a hypercoagulable disorder, patients with clinically significant inherited thrombophilia tend to have VTE at a young age.23-25
In addition, advanced age alone is often regarded as an identifiable risk factor for DVT. A recent retrospective study demonstrated the risk for DVT rose rapidly during the 6th through 8th decades of life.26
We generally recommend testing for hypercoagulable disorders upon discovering one of the following findings:
- The first thrombotic event occurs when the patient is younger than 50 years
- A family history of VTE exists
- Episodes of unexplained VTE recur (SOR=C).
Activated protein C resistance (Factor V Leiden mutation)
Prevalence. Approximately 90% of cases of activated protein C resistance are due to a substitution of glutamine for arginine at position 506 on the factor V gene, the so-called Leiden mutation.27
Factor V Leiden mutation varies greatly by race. In North America, this mutation is found in the heterozygous form in approximately 5% of Caucasians, 2% of Hispanics, 1% of African Americans, and less than 0.5% of Asians.28 Persons heterozygous for factor V Leiden have approximately a 7-fold increase in the relative risk;29 persons homozygous for the mutation have approximately an 80-fold increase in the relative risk.30
Detection. Activated protein C resistance is typically assessed by mixing patient plasma with factor V-deficient plasma. This clotting assay is not affected by oral anticoagulation medication but is affected by heparin. A positive test result for activated protein C resistance typically warrants a polymerase chain reaction assay to distinguish the factor V Leiden mutation from other causes of activated protein C resistance.
Testing considerations. Although factor V Leiden mutation is the cause of activated protein C resistance in most cases, we recommend that activated protein C resistance testing be done first, as it is a less expensive and more widely available test than the DNA-based factor V Leiden mutation test. However, if a patient is taking heparin at the time of evaluation for thrombophilia, it may be necessary to defer activated protein C resistance testing or proceed directly to factor V Leiden DNA-based testing.