Repeat Screening for Protein C Deficiency in Asymptomatic Patients
A single confirmatory test is sufficient for asymptomatic patients with protein C deficiency identified through family screening—routine repeat testing is not necessary once the diagnosis is established.
Initial Diagnostic Confirmation
When protein C deficiency is first identified through family screening, the initial low result should be confirmed with repeat testing to exclude laboratory error or transient causes 1, 2, 3. However, once hereditary protein C deficiency is confirmed in an asymptomatic individual:
- No routine repeat screening is indicated after the diagnosis is established with confirmatory testing 1, 2
- The diagnosis is permanent and levels will remain consistently low in hereditary deficiency 4, 5
- Repeat testing does not change management for asymptomatic carriers 6, 7
Key Diagnostic Principles
Confirmation Requirements
- Measure protein C activity (functional assay) as the primary test 2, 3
- Confirm with repeat testing if initially low, ensuring normal prothrombin levels or positive family history to establish inherited deficiency 1, 6
- Both clot-based and chromogenic methods are acceptable for measuring protein C activity 2, 3
When NOT to Test
Avoid testing during conditions that cause acquired deficiency, which would yield falsely low and non-diagnostic results 6, 2, 3:
- During acute thrombosis
- During anticoagulant therapy (warfarin artificially lowers protein C)
- During acute illness or liver disease
- During pregnancy (for protein S specifically)
Management of Asymptomatic Carriers
Clinical surveillance without prophylactic anticoagulation is the appropriate approach for asymptomatic individuals with confirmed protein C deficiency 7, 8:
- No anticoagulation is indicated in the absence of thrombotic events 7
- Prophylactic anticoagulation should be considered only during high-risk situations 7:
- Major surgery
- Prolonged immobilization
- Pregnancy and postpartum period (particularly with family history of VTE)
Clinical Penetrance and Risk Stratification
The phenotypic expression of protein C deficiency is highly variable 5, 9:
- Not all carriers will develop thrombosis, even with very low protein C levels 5
- Asymptomatic homozygotes have been documented into adulthood 5
- Additional risk factors typically need to interact for clinical thrombosis to occur 5
- First thrombotic events typically occur in young adults when they do manifest 6, 4
Critical Pitfalls to Avoid
- Do not repeat testing routinely once hereditary deficiency is confirmed—this provides no clinical benefit and wastes resources 1, 2
- Do not initiate anticoagulation based solely on laboratory diagnosis in asymptomatic patients 7, 8
- Do not test during acute illness or anticoagulation, as results will be unreliable 6, 2, 3
- Recognize that family history matters: patients with both protein C deficiency and a family history of VTE have higher risk and may warrant more aggressive prophylaxis during high-risk periods 7, 8
When Repeat Testing IS Indicated
The only scenario requiring repeat protein C testing in a known carrier would be 2, 3:
- If the patient develops thrombotic symptoms and you need to assess current anticoagulation status
- Pre-operatively if considering prophylactic anticoagulation strategies
- These are clinical assessments, not routine screening