What investigations should be done to assess thrombosis in a patient with suspected thrombosis and risk factors such as cancer, obesity, or recent immobilization?

Investigations to Assess Thrombosis

Initial Clinical Assessment and Risk Stratification

Begin with the Wells Score to determine pretest probability before ordering any imaging, as clinical assessment alone is unreliable for diagnosing or excluding deep vein thrombosis 1, 2. A Wells score ≥2 indicates DVT is "likely" (53% prevalence), while <2 indicates "unlikely" (5% prevalence) 1.

Key Risk Factors to Document

• Active malignancy (present in ~10% of unprovoked VTE) 2
• Recent immobilization (>1 week), surgery (especially orthopedic, abdominal, pelvic), or trauma 3, 1
• Prior venous thromboembolism 3, 2
• Obesity, pregnancy, or estrogen therapy 2
• Age >60 years 1

Laboratory Investigations

Essential Baseline Tests

Obtain complete blood count with platelet count, PT, aPTT, liver function tests, and kidney function tests as part of the initial workup 2. Kidney function is critical for determining appropriate dosing of low-molecular-weight heparin and direct oral anticoagulants 2.

D-Dimer Testing Strategy

For LOW pretest probability (Wells <2), use high-sensitivity D-dimer testing first—if negative, DVT is excluded without imaging 1, 4. The negative predictive value of a normal D-dimer combined with low clinical probability is 99.4% 4.

Do NOT use D-dimer as a standalone test in high pretest probability patients or those with active cancer, as false-positive rates are unacceptably high in these populations 1, 2. In cancer patients, proceed directly to imaging 1.

Coagulation Screen for Specific Scenarios

If vaccine-induced immune thrombocytopenia and thrombosis (VITT) is suspected, perform a coagulation screen including Clauss fibrinogen assay and blood film to confirm true thrombocytopenia and identify alternative diagnoses 3.

Imaging Investigations

Ultrasound (First-Line for DVT)

Complete duplex ultrasound from inguinal ligament to ankle is the preferred imaging modality for suspected DVT 3, 1, 2. The diagnostic criterion is inability to fully collapse the femoral or popliteal vein under gentle probe pressure (sensitivity 94.2%, specificity 93.8% for proximal DVT) 1.

Compression must be performed at 2-cm intervals with spectral and color Doppler imaging 1. For upper extremity DVT, ultrasound duplex Doppler is most appropriate for veins peripheral to the brachiocephalic vein 3.

Serial Imaging Protocol

For INTERMEDIATE/MODERATE pretest probability, if initial proximal ultrasound is negative, perform serial imaging at days 3 and 7 1. This approach safely detects clinically significant thrombi that extend proximally over time 5, 6.

Advanced Imaging for Specific Locations

When thrombosis is suspected but ultrasound is inadequate or for central venous structures, consider:

• CT venography or MR venography for full assessment from hand to right atrium, or for central venous structures 3
• Head CT venogram or MR angiography to identify cerebral venous sinus thrombosis 3
• Abdominal ultrasound or venogram for portal or splanchnic vein thrombosis 3
• Transesophageal echocardiography or MRI for patients with suboptimal transthoracic windows or posterior thrombi 3

Pulmonary Embolism Assessment

Evaluate for concurrent PE if the patient has ANY respiratory symptoms 2. The combination of unexplained acute dyspnea, hypoxia, and normal chest radiograph strongly indicates PE 3.

For suspected PE:

• Perform CT pulmonary angiography if PE is likely based on clinical probability 3, 2
• Use clinical probability assessment combined with D-dimer if PE is unlikely 2
• Duplex imaging based on symptom location to confirm thrombosis site 3

Risk-Stratified Investigation Algorithm

LOW Risk (Wells <2)

1. High-sensitivity D-dimer test
2. If negative → STOP, no imaging needed 1, 4
3. If positive → proceed to ultrasound

MODERATE Risk

1. Whole-leg ultrasound OR
2. Proximal ultrasound with serial imaging at days 3 and 7 if initially negative 1

HIGH Risk (Wells ≥2)

1. Complete duplex ultrasound immediately 1
2. Do not rely on D-dimer alone 1

Cancer Patients

Proceed directly to imaging without D-dimer testing due to high false-positive rates 1.

Critical Pitfalls to Avoid

• Never rely on clinical examination alone—physical findings are unreliable 1, 2
• Do not accept limited proximal-only ultrasound without serial follow-up in moderate-risk patients 1
• Do not forget to assess renal function before selecting anticoagulation 2
• Do not overlook bilateral symptoms—consider alternative diagnoses like heart failure, venous insufficiency, or lymphedema 2
• Remember that 5% of VITT patients have normal platelet counts initially that subsequently fall—repeat platelet count after 2-3 days if high clinical suspicion remains 3

Special Populations

Post-Surgical/Immobilized Patients

Patients with recent surgery (especially orthopedic, abdominal, pelvic), immobilization >1 week, or lower limb fractures have 15-75% DVT incidence depending on procedure type 3, 1. These patients warrant lower threshold for imaging.

Unprovoked DVT

Determine if thrombosis is provoked or unprovoked, as this impacts duration of anticoagulation and need for cancer screening 2. Perform age-appropriate cancer screening in patients with unprovoked DVT 2.