History and exam

Key diagnostic factors

common

previous VTE, thrombophilia, malignancy, postoperative setting, trauma, and indwelling central catheter

These are key strong risk factors for VTE.

chronic medical conditions, paresis, increasing age, obesity, estrogen-containing birth control pills and hormone replacement therapy, varicose veins, pregnancy and up to 6 weeks postpartum, first-degree relative with a history of VTE, extended travel, and admission to intensive care

These are additional, weaker risk factors for VTE.

Risk factors

strong

previous VTE (deep vein thrombosis [DVT] and/or pulmonary embolism [PE])

Previous VTE is a strong independent predictor of new VTE. Patients with previous VTE are 8 times more likely than patients who have never had a VTE to develop a new VTE in a high-risk situation.[14] In a case-control study, previous VTE increased the risk of having a second VTE 4.7-fold.[15] Patients with 2 or more episodes of VTE carry an extremely high risk of recurrence. Notably, in cases where a definite provocation (such as surgery) of VTE can be identified, the risk of recurrence is lower than it is for patients without an easily identifiable risk factor.

thrombophilia

Several thrombophilic disorders have been associated with VTE occurrence. Patients with thrombophilia have a 1.65 relative risk for recurrent VTE versus patients without thrombophilia.[16]​ Reported risks of VTE with the different thrombophilias vary widely. In acquired thrombophilias, the risk of VTE is doubled with anticardiolipin antibodies and 5.6-fold greater with lupus anticoagulant.[17] With hereditary thrombophilias, the risk is markedly higher in family studies than in case-control studies. For deficiencies of antithrombin, protein C, and protein S, the risk is increased 1.7- to 6.5-fold in case-control studies versus 5.0- to 42.8-fold in family studies. For factor V Leiden (heterozygote), the risk is increased 5- to 10-fold in case-control studies and 2.5- to 16-fold in family studies. For patients with prothrombin mutation, the risk is increased three- to fourfold versus patients without the mutation.[17] A combination of thrombophilias or homozygote status confers a greater risk of VTE than that associated with individual thrombophilias or heterozygote status.[17]

malignancy

The association between malignancy and VTE has been well documented. Compared with noncancer patients, patients with cancer have a four- to sevenfold increased risk of VTE.[18][19]

Risk varies according to cancer type, cancer stage, and use of chemotherapy.[20][21] Cancer types most strongly associated with VTE vary from study to study. In a study involving 9 million patients admitted to the hospital, cancer types most strongly associated with VTE were uterine, brain, ovarian, and pancreatic.[20] Higher cancer stage at diagnosis is a strong independent risk factor for VTE within the first year after diagnosis.[21] Treatment with chemotherapy further increases risk of VTE.[22][23] In a case-control study, chemotherapy in a cancer population was associated with a 6.5-fold greater risk of VTE.[24] Patients receiving thalidomide or lenalidomide with chemotherapy or dexamethasone have a high risk of venous thrombosis.​[25]​​

postoperative setting

Surgery is a strong risk factor for VTE. As a general estimate, the risk of VTE following surgery is increased 4- to 22-fold.[17][24] Certain types of surgery (e.g., orthopedic) confer a higher risk of VTE than others.

trauma

One of the strongest risk factors for VTE. In a case-control study, recent trauma was associated with a 13-fold increased risk of VTE.[24]

indwelling central catheter (upper or lower extremity)

Increases likelihood of deep vein thrombosis (DVT) and pulmonary embolism (PE) by occupying the lumen of the vein and impeding blood flow. Central venous catheter and transvenous pacemaker were associated with a 5.5-fold increased risk of PE or upper-extremity DVT in a case-control study.[24] Femoral venous catheters increase the risk of iliofemoral DVT in a similar manner in critically ill patients.[26]

immobility

Patients admitted to the hospital are increasingly disease-burdened, and immobilization contributes to making them prime candidates to develop VTE. VTE is one of the most common and preventable complications of hospitalization. The rate of asymptomatic hospital-acquired deep vein thrombosis, if thromboprophylaxis is not used, is 10% to 40% after general surgery and 40% to 60% after hip surgery. The rate of symptomatic VTE is up to 5% (or more) of medical and surgical patients if thromboprophylaxis is not used.[3]​​

weak

myeloproliferative diseases

Myeloproliferative diseases have been linked to a statistically increased risk of venous thrombosis (especially intra-abdominal clot) in some studies but not in others.[27][28][29]

congestive heart failure

Congestive heart failure is generally considered to be an independent risk factor for VTE, but 2 studies did not confirm a significant relationship in multivariate analyses.[17][19][24]

chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease is not a strong independent risk factor for VTE because no significant relationship was found in various studies.[19][29]

inflammatory bowel disease (IBD)

Patients with IBD have a two- to threefold increased risk of VTE compared with the general population. In hospitalized patients with IBD, the overall risk of VTE has been reported to be 4.3%.[30] Several modifiable risk factors for VTE are inherently more frequent in IBD patients compared with the general population, such as dehydration, indwelling catheters, prolonged immobilization, hyperhomocysteinemia, surgical interventions, and active disease with an inflammatory burden.[31]

neurologic disease with extremity paresis

Often results in immobilization and is thus an important risk factor for VTE. In a case-control study, neurologic disease with extremity paresis was associated with a tripled risk of VTE.[24]

increasing age

Independent risk factor for VTE, with a 1.7- to 1.9-fold increase per decade.[18][32]

obesity

The relationship between VTE and obesity is controversial. No association was found in the Heart and Estrogen/Progestin Replacement Study (HERS), but a 2.9-fold increase in pulmonary embolism with a body mass index >29 kg/m² was documented in the Nurses' Health Study.[19][33]

estrogen-containing birth control pills, hormone replacement therapy (HRT), and androgen deprivation therapy

Hormone therapy has been documented to be a risk factor for VTE in numerous studies. With respect to age-matched nonusers, the risk of VTE with birth control pill use is estimated to increase two- to fourfold.[34] The risk is highest in the first year of birth control pill use.[35] Postmenopausal HRT also doubles or triples the VTE risk.[19][36] The absolute risk of VTE is much higher with HRT than with birth control pill use because the baseline risk of VTE is higher in postmenopausal than in younger women.[37] In one study, patients receiving androgen deprivation therapy for prostate cancer had an 84% increase in their VTE risk.[38]

history of varicose veins

Inconsistent link to VTE in various studies. In one study, varicose veins increased the risk of deep vein thrombosis by a factor of 2.6.[39] In another study, the risk of VTE associated with varicose veins varied with age. It was increased fourfold in 45-year-old patients and doubled in 60-year-old patients; it was not increased in 75-year-old patients.[29] Finally, in the Framingham study, varicose veins were not an independent predictor of pulmonary embolism at autopsy.[40]

pregnancy/postpartum

In Western countries, pulmonary embolism is the leading cause of maternal death during pregnancy.[41] Pregnancy was an independent risk factor for VTE in various studies.[37][42] In the Sirius study, the increase in VTE associated with pregnancy was 11-fold.[43]

extended travel

There seems to be a mild risk of VTE associated with prolonged travel.[44] In a univariate analysis, extended travel was 2.4 times more frequent in outpatients presenting with a deep vein thrombosis.[43] Long flights (>8-10 hours) are more strongly associated with VTE.[45] However, not all studies found a significant relationship between extended travel and development of VTE.[46]

lower leg immobility

Patients with lower leg trauma and lower leg immobility with a plaster cast or brace are at increased risk of developing deep vein thrombosis (DVT). One Cochrane review of 8 randomized controlled trials found a 60% risk reduction in symptomatic DVT in patients with lower leg immobility with daily prophylaxis with low molecular weight heparin compared with those without prophylaxis or with placebo.[47] However, the primary outcome of these studies included asymptomatic DVT confirmed by screening venography or ultrasonography, and one trial showed no benefit with low molecular weight heparins to prevent symptomatic DVT.[48] Thus, routine thromboprophylaxis in patients with lower leg immobility is currently not recommended, but scores to individualize prophylaxis are being studied.[49]

first-degree relative with a history of VTE

In a Swedish study, the risk of recurrent hospitalization for idiopathic VTE was 1.20 (95% confidence interval [CI] 1.10 to 1.32) for people whose parents had a history of VTE, and 1.30 (95% CI 1.14 to 1.49) for those with affected siblings. The risk of recurrent VTE hospitalization in people with 2 affected parents was 1.92 (95% CI 1.44 to 2.58).[50]

admission to intensive care

In critically ill patients, the baseline risk of symptomatic deep vein thrombosis is around 58 per 1000 and the risk of pulmonary embolism is around 42 per 1000.[51]​ These risks vary with preexisting medical illnesses, the nature of the acute illness, as well as the presence of surgery, catheters, and anesthesia.​[51]

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