Workup for Clotting Disorder in a Patient with Two DVTs in One Year
For a patient with two unprovoked DVTs within one year, you should initiate extended anticoagulation immediately and perform thrombophilia testing, as this represents a second unprovoked VTE with high recurrence risk requiring indefinite anticoagulation. 1
Immediate Management
Extended anticoagulation is strongly recommended for patients with a second unprovoked VTE who have low bleeding risk (Grade 1B), and suggested for those with moderate bleeding risk (Grade 2B). 1 This takes priority over completing the thrombophilia workup, as the presence or absence of specific thrombophilias will not change the recommendation for indefinite anticoagulation after two unprovoked events. 2
Anticoagulation Choice
- Direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists for extended therapy in patients without cancer. 3, 4
- If warfarin is used, maintain INR 2.0-3.0 (target 2.5) for all treatment durations. 1, 2
- For cancer-associated thrombosis, low molecular-weight heparin is preferred over warfarin (Grade 2B). 1
Thrombophilia Testing Panel
The following tests should be ordered to identify inherited or acquired thrombophilias, though results will not alter the decision for extended anticoagulation after two unprovoked events: 2
Inherited Thrombophilias
- Factor V Leiden mutation 2
- Prothrombin 20210 gene mutation 2
- Antithrombin deficiency 2
- Protein C deficiency 2
- Protein S deficiency 2
- Elevated Factor VIII levels (>90th percentile) 2
- Homocysteine levels 2
Acquired Thrombophilias
- Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies, anti-β2-glycoprotein I antibodies) 2
Timing Considerations
Ideally, test for inherited thrombophilias when the patient is off anticoagulation for at least 2 weeks, as warfarin can affect Protein C and S levels. However, Factor V Leiden and prothrombin gene mutations can be tested at any time. 2 Antiphospholipid antibodies require confirmation with repeat testing at least 12 weeks apart. 2
Bleeding Risk Assessment
Assess bleeding risk using the following criteria to guide the intensity of anticoagulation monitoring: 5, 4
Low Bleeding Risk
- Age <70 years 5
- No prior bleeding episodes 5
- Good INR control during initial treatment (if on warfarin) 5
- No concomitant antiplatelet therapy 5
High Bleeding Risk
- Advanced age (>70 years) 5
- Previous bleeding episodes 5
- Concomitant antiplatelet drugs 5
- Renal or hepatic impairment 5
- Poor INR control 5
For patients with high bleeding risk and a second unprovoked VTE, extended anticoagulation is still suggested over stopping at 3 months (Grade 2B), though this is a weaker recommendation. 1
Additional Workup
Malignancy Screening
Screen for occult malignancy in patients with unprovoked VTE, as cancer-associated thrombosis requires different management. 1
- Age-appropriate cancer screening (colonoscopy, mammography, etc.) 6
- CT chest/abdomen/pelvis if clinically indicated 6
- Consider PET scan in select cases with high suspicion 6
D-Dimer Testing
Measure D-dimer 1 month after stopping anticoagulation (if anticoagulation is ever stopped) to help predict recurrence risk. 4, 7 Elevated D-dimer favors extended anticoagulation. 4, 7
Residual Vein Thrombosis Assessment
Compression ultrasound to assess for residual vein thrombosis can help predict recurrence risk, though routine repeat imaging is not necessary for treatment decisions. 1, 5 A ≥4 mm increase in residual venous diameter suggests recurrent DVT. 1
Long-Term Management
Reassess the need for continued anticoagulation at least annually, considering: 1, 5, 4
- Ongoing bleeding risk 5, 4
- Patient preference and quality of life 5
- New provoking factors or comorbidities 5
- Changes in health status 5
Post-Thrombotic Syndrome Prevention
Prescribe compression stockings for 2 years following DVT to prevent post-thrombotic syndrome. 3
Common Pitfalls to Avoid
Do not delay anticoagulation while waiting for thrombophilia test results. The presence of specific thrombophilias does not change the recommendation for extended anticoagulation after two unprovoked events. 2
Do not stop anticoagulation at 3 months in a patient with two unprovoked DVTs, even if a specific thrombophilia is not identified. The recurrence risk remains high (>5% annually) regardless of thrombophilia testing results. 1, 7
Do not order thrombophilia testing during acute thrombosis or while on anticoagulation if accurate results are needed for genetic counseling purposes. However, for clinical management after two unprovoked DVTs, the timing of testing is less critical since indefinite anticoagulation is already indicated. 2