What is the clinical application of the Khorana score and Wells score in assessing and managing venous thromboembolism (VTE) risk?

Clinical Application of Khorana and Wells Scores in VTE Risk Assessment and Management

The Khorana score is strongly recommended for risk stratification of venous thromboembolism (VTE) in ambulatory cancer patients receiving systemic therapy, while the Wells score remains the standard for general VTE diagnosis in both cancer and non-cancer populations. 1

Khorana Score: Cancer-Associated VTE Risk Assessment

Purpose and Validation

The Khorana score was specifically developed to predict VTE risk in cancer outpatients receiving chemotherapy. It has been extensively validated through multiple independent studies and meets criteria for a Level 1 clinical decision rule 1.

Components of the Khorana Score

Patient characteristics	Risk score
Very high risk cancer site (stomach, pancreas)	2
High risk cancer site (lung, lymphoma, gynecologic, bladder, testicular)	1
Prechemotherapy platelet count ≥350,000/mm³	1
Hemoglobin <10 g/dL or use of red cell growth factors	1
Prechemotherapy leukocyte count >11,000/mm³	1
BMI ≥35 kg/m²	1

Risk Stratification

• Low risk: Score 0
• Intermediate risk: Score 1-2
• High risk: Score ≥3

Clinical Application Algorithm

1. Assess all cancer patients for VTE risk at initiation of systemic therapy and periodically thereafter 1
2. Calculate Khorana score using baseline laboratory values (within 2 weeks of starting chemotherapy)
3. Determine risk category:
   • High risk (score ≥3): Consider thromboprophylaxis
   • Intermediate risk (score 1-2): Individual assessment needed
   • Low risk (score 0): Routine thromboprophylaxis not recommended

Effectiveness and Limitations

• The Khorana score has demonstrated ability to predict VTE risk in multiple settings:

  • Ambulatory cancer patients (original validation)
  • Hospitalized cancer patients (OR 3.9 for high vs. low risk) 2
  • Central venous catheter insertion patients

• However, performance varies by cancer type:

  • Less predictive in lung, pancreatic, hepatocellular, and gastric cancers 1
  • Better performance in lymphoma and germ cell tumors 1

• A large validation study of 40,218 patients showed 6-month VTE risks of:

  • 1.5% for low-risk patients
  • 2.8% for intermediate-risk patients
  • 4.1% for high-risk patients 3

Wells Score: VTE Diagnostic Assessment

Purpose

The Wells score is used for clinical probability assessment of DVT or PE in patients with suspected VTE, guiding the diagnostic pathway.

Wells Score for DVT

Points assigned for:

• Active cancer (+1)
• Paralysis, paresis, or recent immobilization (+1)
• Recently bedridden >3 days or major surgery within 12 weeks (+1)
• Localized tenderness along deep venous system (+1)
• Entire leg swollen (+1)
• Calf swelling >3 cm compared to asymptomatic leg (+1)
• Pitting edema (+1)
• Collateral superficial veins (+1)
• Alternative diagnosis as likely or greater than DVT (-2)

Wells Score for PE

Points assigned for:

• Clinical signs of DVT (+3)
• Alternative diagnosis less likely than PE (+3)
• Heart rate >100 beats/min (+1.5)
• Immobilization or surgery in previous 4 weeks (+1.5)
• Previous DVT/PE (+1.5)
• Hemoptysis (+1)
• Malignancy (+1)

Clinical Application Algorithm

1. Calculate Wells score in patients with suspected VTE
2. Determine pretest probability:
   • For DVT: Low (≤0), Intermediate (1-2), High (≥3)
   • For PE: Low (<2), Intermediate (2-6), High (>6)
3. Select diagnostic pathway based on pretest probability:
   • Low probability: D-dimer testing first
   • Intermediate/high probability: Imaging studies (ultrasound for DVT, CT angiography for PE)

Diagnostic Accuracy

• DVT prevalence by Wells score: 10% (low), 25% (intermediate), 50% (high) 1
• PE prevalence by Wells score: 5% (low), 20% (intermediate), 50% (high) 1

Integration of Khorana and Wells Scores in Clinical Practice

When to Use Each Score

• Khorana score: Prospective risk assessment for primary prevention in cancer patients starting chemotherapy
• Wells score: Diagnostic assessment when VTE is suspected in any patient (including those with cancer)

Practical Implementation

1. For cancer patients starting chemotherapy:

   • Calculate Khorana score at baseline
   • For high-risk patients (score ≥3), consider thromboprophylaxis 1
   • For patients with advanced pancreatic cancer, consider thromboprophylaxis regardless of score 1

2. For patients with suspected VTE:

   • Calculate Wells score
   • Follow diagnostic algorithm based on pretest probability
   • Note that cancer patients automatically receive points on Wells score

Impact on Mortality

• VTE is associated with increased mortality in cancer patients
• Patients with high Khorana scores have 5.7 times higher odds of six-month mortality 4
• Patients who develop VTE have 4 times higher odds of death 4

Pitfalls and Caveats

1. Khorana score limitations:

   • Underestimates VTE risk in certain cancer types (lung, pancreatic) 1
   • Requires laboratory values within 2 weeks of chemotherapy initiation
   • May perform poorly in specific surgical settings (e.g., radical cystectomy) 5

2. Wells score considerations:

   • Subjective components (e.g., "alternative diagnosis as likely")
   • All cancer patients automatically receive points, potentially reducing specificity

3. Competing risk of death:

   • Not accounting for death as a competing risk may overestimate VTE incidence by up to 23% 3
   • Important consideration in advanced cancer patients

4. Timing considerations:

   • Khorana score best predicts VTE risk in first 3-4 months of chemotherapy
   • Risk assessment should be repeated periodically during treatment 1

By systematically applying these risk assessment tools, clinicians can identify patients who would benefit most from thromboprophylaxis or expedited diagnostic testing, potentially reducing morbidity and mortality from VTE in cancer and non-cancer populations.