Thrombophilia: How To Test? How To Manage?

By Julie Hambleton, MD

Print This | TOC | Previous | Next

Approach to the Patient With an Unprovoked DVT/PE

Approximately 250,000 patients are diagnosed annually with acute VTE disease. The major morbidity relates to acute PE, the postphlebitic syndrome (characterized by intermittent pain, swelling, or recurrent skin ulceration), and recurrent disease with renewed risk for both of these complications on a repeated basis. The initial assessment of a patient with an unprovoked DVT/PE should include a thorough evaluation of the medical history, physical findings, and initial laboratory screening results. Hormonal therapy, the incidental finding of a mass, a prolonged prothrombin time, evidence of a myeloproliferative disease, or nephrotic syndrome should alert the clinician to the presence of a secondary thrombophilia risk factor. A history of recurrent unprovoked VTE in either the patient or the patient's biological family raises suspicion for the presence of an underlying genetic risk factor. Presence of a DVT or PE should be confirmed with the appropriate radiographic tests, including ultrasound, venogram, ventilation/perfusion study, or chest spiral CT scan.⁸

Identification of a thrombophilic risk factor during the acute presentation of VTE disease rarely influences the initial approach to therapy.^3,8 However, many clinicians are in the habit of ordering a variety of tests before initiating therapy (Table 3). DNA-based tests, such as factor V Leiden and prothrombin gene testing, can be performed at any time. Testing for AT, PC, and PS deficiencies may be affected by the acute thrombotic event due to consumption of these factors as an effect rather than a cause of the disease process. Additionally, these levels are lowered in the setting of liver disease and DIC. AT levels may be lowered in the setting of heparin therapy as a result of binding to either unfractionated heparin or low–molecular weight heparin. PC and PS levels are lowered by warfarin therapy, as their synthesis is dependent on vitamin K, and PS levels may be lowered in pregnancy, with the use of estrogen therapy, or in the presence of the lupus anticoagulant. Homocysteine levels rise with advancing age, renal insufficiency, smoking, certain medications such as phenytoin, and B vitamin deficiency. Homocysteine levels are best measured in the fasting state. A methionine load may identify a subset of patients at risk for hyperhomocysteinemia missed by random screening.

Print This | TOC | Previous | Next

3300 Dundee Road • Northbrook, Illinois 60062-2348 • (847) 498-1400 • (800) 343-2227
Copyright ©1999-2008 American College of Chest Physicians. All Rights Reserved.
ACCP Privacy Policy | ACCP Web Site Terms of Use