What are the diagnostic tests for Protein C (PC) deficiency?

From the Guidelines

Testing for protein C deficiency involves a functional protein C activity assay as the initial screening test, which measures how well protein C works in the blood, and should be performed when the patient is not taking anticoagulants like warfarin, ideally at least two weeks after any acute thrombotic event, as recommended by recent guidelines 1. To diagnose protein C deficiency, the following steps should be taken:

• The initial screening test is a functional protein C activity assay, which measures how well protein C works in the blood.
• If this test shows low levels, a protein C antigen test may be performed to confirm the diagnosis and determine if the deficiency is quantitative (low amounts) or qualitative (dysfunctional protein).
• Testing should be done when the patient is not taking anticoagulants like warfarin, which can artificially lower protein C levels, and ideally at least two weeks after any acute thrombotic event.
• For accurate diagnosis, testing should be repeated on a separate occasion to confirm results, as protein C levels can be temporarily reduced during certain conditions like liver disease, vitamin K deficiency, or acute thrombosis.
• Genetic testing may also be used to identify specific mutations in the PROC gene responsible for hereditary protein C deficiency, as suggested by recent studies 1. Key considerations in testing for protein C deficiency include:
• Avoiding anticoagulants like warfarin, which can interfere with test results.
• Waiting at least two weeks after any acute thrombotic event to ensure accurate results.
• Repeating tests on a separate occasion to confirm results, as protein C levels can fluctuate.
• Considering genetic testing for individuals with a personal or family history of unexplained blood clots, especially at a young age or in unusual locations, as protein C deficiency increases the risk of venous thromboembolism, as highlighted in recent recommendations 1.

From the Research

Testing for Protein C Deficiency

To test for protein C deficiency, the following methods can be used:

• Functional (activity) assays, which may be clotting time based or chromogenic 2
• Immunologic assays to measure protein C antigen levels 3
• Chromogenic protein C assay, which is recommended due to its good specificity 4
• Clotting-based assay of protein C, which can detect type 2b deficiency but has reduced specificity 4

Types of Protein C Deficiency

There are two types of protein C deficiency:

• Type I: due to the absence or reduced presence of protein C molecules 3
• Type II: caused by the presence of an abnormal protein C molecule with strongly reduced functional activity 3

Factors Affecting Test Results

The following factors can affect test results:

• Age: protein C levels vary with age, and adult reference ranges cannot be applied to babies or children 4
• Pre-analytical variables in the specimen: can affect measurement of protein C and can be assay-dependent 4
• Direct oral anticoagulants: can falsely raise protein C level in the clotting-based assay but do not affect the standard chromogenic assay 4
• Oral anticoagulant treatment: can affect protein C activity and antigen levels 5

Diagnostic Approach

The diagnostic approach for protein C deficiency involves:

• Initial testing with a functional (activity) assay 2
• Confirmation of hereditary deficiency by excluding acquired causes of protein C deficiency 2
• Use of protein C activity tests, which have a higher discriminative power than antigen determination 5