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Four Ps of Thrombophilia Testing

Venous thromboembolism (VTE) is a major cause of morbidity and mortality. Approximately 900,000 cases of pulmonary embolism and deep vein thrombosis occur in the United States each year, causing 60,000 to 300,000 deaths.

Once a diagnosis of VTE has been established, physicians must decide if additional thrombophilia testing is warranted. One thoughtful approach to testing is the 4 Ps which include:

  • Patient selection
  • Pretest counseling
  • Proper laboratory interpretation
  • Provision of education and advice

The first step in patient selection is to determine if the VTE was provoked or unprovoked. Provoked VTE are due to known, temporary risk factors such as surgery, trauma, fracture, long distance travel, hormone therapy, malignancy, chemotherapy, rheumatologic disease, nephrotic syndrome, central venous catheter and inferior vena cava filter. Testing for thrombophilia should not be performed in these cases. Testing should also not be ordered if the patient is already receiving indefinite anticoagulation therapy and additional testing will not change the management plan. Thrombophilia testing may be considered in patients with unprovoked VTE, especially if VTE occurs in unusual sites or causes recurrent pregnancy loss.  Patients with unprovoked VTE have a twofold higher risk of recurrence than patients with provoked VTE.

Even in cases of unprovoked VTE, there is no clear consensus regarding which patients should be tested for thrombophilia. Experts recommend that patients who express a desire to be tested receive pretest counseling. The implications of finding a genetic diagnosis should be reviewed with the patient and family members. The American Board of Internal Medicine’s Choosing Wisely campaign strongly recommends consultation with an expert in thrombophilia prior to ordering testing. 

Proper test interpretation includes selection of the correct thrombophilia tests. Ordering large hypercoagulability panels is discouraged. Specimens for initial testing should be collected at the proper time. This means not testing during acute episodes of VTE or during anticoagulation therapy. Direct oral anticoagulants can cause false negative or false positive results with many thrombophilia tests. Testing should not be performed during pregnancy or treatment with oral contraceptives. Many hospitals forbid inpatient thrombophilia testing. If one of the initial tests is abnormal, guidance should be provided to insure that appropriate confirmatory tests are ordered.

Patients and family members should be provided with education at an appropriate health literacy level that explains the meaning of their test results and how it will affect their future care. While positive results may help to explain why a patient experienced an unprovoked VTE, they can also cause unnecessary worry about having a genetic disease and the risk of death.

More comprehensive information is available in an excellent review article that was recently published by physicians at the Cleveland Clinic.

Rendon P. et al. Optimizing diagnostic testing for venous thromboembolism. Cleveland Clinic Journal of Medicine, July 2017;84:545-554.

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