Should I consider the underlying cause of a blood clot in a patient presenting with thrombosis?

Yes, You Must Investigate the Underlying Cause of Thrombosis

When a patient presents with a blood clot, you should always investigate potential underlying causes, as this directly impacts treatment decisions, duration of anticoagulation, and risk of recurrence. 1

Why Investigation is Critical

The distinction between provoked and unprovoked thrombosis fundamentally determines your management strategy:

• Provoked by major transient factors (surgery >30 minutes, hospitalization with bed confinement ≥3 days, cesarean section): Annual recurrence risk <1% after 3 months of anticoagulation—extended therapy generally not needed 1

• Unprovoked thrombosis (no identifiable risk factors): Annual recurrence risk >5%—requires consideration for long-term or indefinite anticoagulation 1

• Provoked by persistent factors (active cancer, antiphospholipid syndrome, inflammatory bowel disease): Highest recurrence risk—typically requires indefinite anticoagulation 1

Mandatory Initial Assessment

For All Patients with VTE

Confirm therapeutic anticoagulation status first: Check INR if on warfarin to verify the patient is actually therapeutically anticoagulated before assuming breakthrough thrombosis 1

Assess compliance: Verify the patient is actually taking their anticoagulation as prescribed, as noncompliance is a frequent cause of apparent "breakthrough" events 1

Evaluate for drug-drug and drug-food interactions that may be interfering with anticoagulant efficacy 1

For Acute Arterial Thrombosis

All patients, particularly those with atypical presentations, should be evaluated for hypercoagulability including: 1

• Prothrombin time
• Partial thromboplastin time
• Platelet count
• Factor V Leiden
• Factor II (prothrombin) G20210A
• Anti-cardiolipin antibody
• Protein C level
• Protein S level
• Anti-thrombin III level

For Breakthrough VTE on Anticoagulation

Consider heparin-induced thrombocytopenia (HIT) if the patient was recently treated with UFH or LMWH before starting VKA therapy 1

Investigate for underlying conditions such as: 1

• Active malignancy
• Antiphospholipid syndrome (may require LMWH over DOAC)
• Vasculitis
• Chronic inflammatory conditions

Common Pitfalls to Avoid

Do not assume all clots are the same: The American College of Radiology emphasizes that septic emboli require fundamentally different management than VTE—do not extrapolate VTE guidelines to septic thrombosis 2

Do not overlook hormone-associated VTE in women: Thrombosis occurring on estrogen-containing oral contraceptives or hormone replacement therapy has approximately 50% lower recurrence risk compared to truly unprovoked VTE, but only if hormones are discontinued 1

Do not miss cancer-associated thrombosis: These patients require different anticoagulation strategies (typically LMWH preferred over warfarin) and have higher bleeding risks requiring individualized assessment 1

Do not forget to assess bleeding risk: In cancer patients, evaluate platelet count, renal function, liver function, and potential bleeding sources before initiating anticoagulation—therapeutic LMWH generally requires platelets >50 × 10⁹/L 1

Clinical Algorithm for Investigation

1. Immediate assessment: Verify current anticoagulation status, compliance, and appropriate dosing 1

2. Categorize the thrombosis: Determine if provoked (transient vs. persistent factors) or unprovoked 1

3. Screen for thrombophilia in patients with: 1

   • Unprovoked VTE at young age (<50 years)
   • Recurrent VTE
   • VTE in unusual locations
   • Strong family history
   • Atypical presentations

4. Evaluate for malignancy in unprovoked VTE, especially if age-appropriate cancer screening is not up to date 1

5. Adjust anticoagulation duration based on findings: 3 months for major transient factors, indefinite for unprovoked or persistent factors 1