What laboratory studies should be ordered to assess for a hypercoagulable state in a patient with ulcerative colitis and a history of spontaneous Deep Vein Thrombosis (DVT) after discontinuing Eliquis (apixaban)?

Laboratory Studies for Hypercoagulable State Assessment in a Patient with Ulcerative Colitis and History of Spontaneous DVT

For patients with ulcerative colitis who have experienced a spontaneous DVT and completed 6 months of anticoagulation with apixaban, comprehensive thrombophilia testing should be performed to assess for underlying hypercoagulable states. 1

Recommended Laboratory Tests

First-line Testing

• Factor V Leiden mutation (R506Q) testing 1, 2
• Prothrombin gene mutation (G20210A) testing 1, 2
• Protein C activity and antigen levels 2
• Protein S activity and antigen levels 2
• Antithrombin III activity 2
• Lupus anticoagulant 1
• Anticardiolipin antibodies 1
• Anti-β2-glycoprotein-1 antibodies 1
• Factor VIII levels 1

Additional Testing

• Homocysteine levels (particularly if considering MTHFR mutations) 3
• Complete blood count with platelet count 1
• Comprehensive metabolic panel including liver function tests 1
• C-reactive protein (to assess inflammatory activity) 1
• Fecal calprotectin (to assess disease activity) 1

Timing of Testing

• Testing should be performed at least 2-4 weeks after discontinuation of apixaban to avoid interference with results 2
• Protein C, Protein S, and antithrombin testing should be conducted when the patient is not in an acute inflammatory phase of ulcerative colitis, as inflammation can affect these results 1

Rationale and Evidence

Increased Risk in Inflammatory Bowel Disease

• Patients with ulcerative colitis have approximately twice the risk of venous thromboembolism compared to the general population 1
• The risk of recurrent thrombosis is increased in IBD patients compared to non-IBD patients 1
• Inflammatory and thrombotic processes are interconnected in IBD, creating a vicious cycle that can maintain inflammation 4

Genetic Testing Considerations

• The American College of Medical Genetics recommends testing for Factor V Leiden and prothrombin G20210A mutations in individuals with a first episode of spontaneous venous thrombosis, especially when occurring at a young age 1, 2
• Genetic thrombophilias may have synergistic effects with IBD-related hypercoagulability 1
• MTHFR gene mutations have been reported in IBD patients with thrombotic complications 3

Acquired Thrombophilia Assessment

• Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein-1) should be tested as they represent important acquired risk factors for thrombosis 1
• Elevated Factor VIII levels are common in inflammatory states and represent an independent risk factor for recurrent thrombosis 1

Clinical Implications

• Results of thrombophilia testing may influence decisions regarding extended anticoagulation therapy 1
• Patients with unprovoked DVT and identified thrombophilia may benefit from indefinite anticoagulation, especially after a second thrombotic event 1
• For patients with ulcerative colitis and identified thrombophilia, more aggressive management of IBD activity may be warranted to reduce thrombotic risk 1, 4
• Positive thrombophilia results may have implications for family members who could benefit from testing and risk assessment 1, 2

Common Pitfalls to Avoid

• Testing during acute inflammation or while still on anticoagulation can lead to false results 2
• Failure to consider both genetic and acquired causes of thrombophilia 1
• Not accounting for the synergistic effect of multiple risk factors (e.g., oral contraceptives in patients with Factor V Leiden can increase thrombotic risk 30-fold) 2
• Overlooking the need for comprehensive IBD disease activity assessment, as active disease significantly increases thrombotic risk 1