Pulmonary embolism risk factors

Associate Editors-in-Chief: Ujjwal Rastogi, MBBS [mailto:urastogi@perfuse.org]

Overview
The most common sources of pulmonary embolism are proximal leg deep venous thrombosis (DVTs) or pelvic vein thromboses. Any risk factor for DVT also increases the risk of pulmonary embolism, thus DVT and PE are together considered as VTE. Approximately 15% of patients with a DVT witll develop a pulmonary embolus. The conditions of DVT and pulmonary embolism are generally regarded as a continuum termed venous thromboembolism (VTE).

Risk Factors
The development of thrombosis is classically due to a group of causes named Virchow's triad (alterations in blood flow, factors in the vessel wall and factors affecting the properties of the blood). Often, more than one risk factor is present.



Figure : Virchow's triad encompasses three broad categories of factors that are thought to contribute to venous thrombosis.

Medical conditions included in the trid are:
 * Alterations in blood flow: immobilization (after surgery, injury or long-distance air travel), pregnancy (also procoagulant), obesity (also procoagulant)
 * Factors in the vessel wall: of limited direct relevance in VTE
 * Factors affecting the properties of the blood (procoagulant state):
 * Estrogen-containing hormonal contraception
 * Genetic thrombophilia (factor V Leiden, prothrombin mutation G20210A, protein C deficiency, protein S deficiency, antithrombin deficiency, hyperhomocysteinemia and plasminogen/fibrinolysis disorders).
 * Acquired thrombophilia (antiphospholipid syndrome, nephrotic syndrome, paroxysmal nocturnal hemoglobinuria)

Risk Factors Identified in the PIOPED Study Independent risk factors identified in prospective investigation of pulmonary embolism diagnosis (PIOPED) include:
 * Immobilization, paresis, or paralysis
 * Surgery within the last 3 months, and stroke were also risk factors, but may also relate to immobility.
 * History of venous thromboembolism.
 * Malignancy, especially lung cancer; found in up to 17% of patients with an idiopathic deep vein thrombosis (DVT).
 * Current or past history of thrombophlebitis
 * Trauma to the lower extremities and pelvis during the past 3 months
 * Smoking
 * Central venous instrumentation within the past 3 months
 * Prior pulmonary embolism
 * Heart failure
 * Chronic obstructive pulmonary disease
 * Travel of 4 hours or more in the past month

Risk Factors from the Nurses' Health Study
 * Obesity: RR 2.9
 * Smoking: 25 – 34 cigarettes / d (RR 1.9), > 35 cig / d (RR 3.3)
 * Hypertension: RR 1.9
 * Oral contraceptives: RR ~ 2 – 3
 * Hormone replacement therapy: RR ~ 2

Risk Factors from the Physician's Health Study
 * Anticardiolipin antibody level above the 95th percentile.
 * Factor V Leiden: RR 2.7, found in 40% of patients with idiopathic DVT.
 * Use of oral contraceptives by a person with the Factor V mutation increases the risk of venous thromboembolism 35 fold.
 * Hyperhomocysteinemia increases the risk of a DVT by a factor of 3.
 * Hyperhomocysteinemia with Factor V increases the risk of a DVT by 10 fold.
 * Lupus anticoagulant was found in 8.5% of patients with idiopathic DVT.

Other risk factors include:
 * Venous stasis
 * Hypercoagulable states
 * Pregnancy
 * Hereditary factors resulting in a hypercoagulable state
 * Acute medical illness
 * Drug abuse (intravenous [IV] drugs)
 * Hemolytic anemias
 * Homocystinuria
 * Hyperlipidemias
 * Phenothiazines
 * Thrombocytosis
 * Varicose veins
 * Venography
 * Venous pacemakers
 * Warfarin (first few days of therapy)
 * Inflammatory bowel disease