What is the recommended approach for the diagnostic evaluation of Venous Thromboembolism (VTE) risk factors?

Diagnostic Evaluation of VTE Risk Factors

The diagnostic evaluation of VTE risk factors should be systematically categorized into three domains: patient-related factors (intrinsic and extrinsic), disease-related factors, and treatment-related factors, with risk assessment performed at hospital admission and reassessed during hospitalization. 1

Risk Factor Categories and Assessment Framework

Patient-Related Risk Factors (Intrinsic)

Age and Demographics:

• Age >60 years is an independent predictor of VTE risk and should be documented at admission 1
• Advanced age (≥75 years) carries additional risk in acutely ill medical patients 1
• Obesity (BMI ≥35 kg/m²) increases VTE risk and should be calculated 1

Prior VTE History:

• A history of prior VTE is one of the strongest independent risk factors, with 12-month cumulative recurrence rates of 20.7% in cancer patients versus 6.8% in non-cancer patients 1
• Previous VTE should be documented with details of timing, location, and whether provoked or unprovoked 1

Inherited Thrombophilias:

• Known thrombophilia (antithrombin deficiency, protein C/S deficiency, factor V Leiden, prothrombin mutation) should be documented if previously diagnosed 1
• Routine testing for factor V Leiden and prothrombin mutations is NOT recommended for adults with idiopathic VTE or their asymptomatic family members, as identification does not change management outcomes 1
• Testing for inherited thrombophilias should be reserved for specific scenarios: VTE at young age (<50 years), VTE at unusual sites, recurrent VTE, or strong family history 2

Patient-Related Risk Factors (Extrinsic/Acquired)

Immobility and Functional Status:

• Immobility ≥7 days is a critical risk factor that should be assessed both at admission and during hospitalization 1, 3
• Acute paresis or lower-limb paralysis significantly increases risk 1
• Severe immobilization at study entry was present in 99.9% of high-risk medical patients 4

Medical Comorbidities:

• Acute infections are an important risk factor not included in many widely-used models and should be specifically evaluated 1
• Active malignancy increases VTE risk 2-6 fold and is associated with higher mortality 1
• Heart failure (NYHA class III or IV) 4
• Acute respiratory insufficiency 4
• Renal failure (creatinine clearance <30 mL/min) 4

Hospitalization Status:

• Critical illness requiring ICU or coronary care unit admission is an independent risk factor 1, 3
• Hospitalized adults have VTE rates of 239 per 100,000 persons hospitalized annually 1

Laboratory Parameters to Evaluate

Hematologic Markers:

• Prechemotherapy thrombocytosis and leukocytosis predict VTE in patients undergoing chemotherapy 1
• Hemoglobin <10 g/dL is predictive of VTE, though this may be confounded by ESA use 1
• D-dimer >2× upper limit of normal was present in 43.7% of high-risk medical patients 4
• D-dimer requires further research to confirm its role in VTE risk assessment models 1

Disease-Specific Risk Factors

Cancer-Related Factors:

• Type of malignancy (pancreatic, brain, lung, gastric, gynecologic cancers carry highest risk) 1
• Cancer stage and presence of metastatic disease 1
• Direct vascular compression by tumor 1

Multiple Myeloma-Specific Assessment:

• For myeloma patients, count individual risk factors: obesity, history of VTE, central venous catheter, immobility, surgery, erythropoietin use, infection, renal disease, cardiac disease, clotting disorders 1
• Patients receiving thalidomide/lenalidomide with high-dose dexamethasone (≥480 mg/month) or multiagent chemotherapy require enhanced risk stratification 1

Treatment-Related Risk Factors

Chemotherapy and Medications:

• Specific chemotherapeutic regimens increase VTE risk 1
• Antiangiogenic therapy (thalidomide, lenalidomide) 1
• Erythropoiesis-stimulating agents 1
• Hormone replacement therapy or oral contraceptives 1

Surgical and Procedural Factors:

• Recent surgery (within 30 days) 1
• Central venous catheter use 1

Structured Risk Assessment Approach

At Hospital Admission

The admission VTE risk score should include:

• Age >60 years 1, 3
• Previous VTE 1, 3
• Known thrombophilia 1, 3
• Active malignancy 1, 3

At admission, 67% of medical patients have a risk score ≥1 3

During Hospitalization

The in-hospital VTE risk score should add:

• Acute infections 1
• Immobility ≥7 days 1, 3
• Acute paresis 1
• Critical illness (ICU/CCU admission) 1, 3

During hospitalization, 31% of patients have a score ≥2; for scores of 2-3, VTE risk is 1.5% versus 5.7% for scores ≥4 3

Clinical Probability Assessment Tools

For suspected DVT, use Wells' Criteria for DVT 1, 5

For suspected PE, use:

• Wells' Criteria for PE 1, 5
• Geneva score 1
• Pulmonary Embolism Rule-Out Criteria (PERC) in emergency department settings 1, 5

These tools classify patients into low, intermediate, or high pretest probability, which guides subsequent diagnostic testing 1

Common Pitfalls to Avoid

Do not routinely test for inherited thrombophilias (factor V Leiden, prothrombin mutation) in adults with idiopathic VTE, as this does not change management 1

Do not evaluate VTE risk factors in isolation—risk is cumulative across all three categories (patient, disease, treatment-related) 1

Do not overlook acute infection as a risk factor, as it is frequently missed in standard risk assessment models 1

Do not assume that factor V Leiden or prothrombin mutations increase VTE risk in cancer patients—a prospective study found no association 1

Do not test for thrombophilia during acute thrombosis or while on anticoagulation, as results will be unreliable 2

Recognize that 45% of VTE events occur after hospital discharge, necessitating post-discharge risk assessment 3

Remember that VTE risk assessment is dynamic—reassess during hospitalization as clinical status changes 1, 3