How is protein C deficiency diagnosed in patients taking warfarin?

Updated: Jan 04, 2019
  • Author: Shamudheen Rafiyath, MD; Chief Editor: Perumal Thiagarajan, MD  more...
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Answer

Because protein C is a vitamin K–dependent protein, its levels are reduced with warfarin administration. Therefore, protein C testing is not recommended unless the patient has been off vitamin K antagonist therapy for at least 2 weeks. If the patient has a severe thrombotic diathesis that does not permit discontinuation of anticoagulation, the patient may be temporarily transitioned to low molecular weight heparin (LMWH) for testing purposes or, alternatively, the diagnosis may be inferred through testing of family members.

Several investigators have developed ratio methods for diagnosing protein C deficiency in the context of warfarin therapy by comparing the protein C level with that of other vitamin K–dependent clotting factors. [66, 67] However, such methods have not been broadly validated.

The clotting-based assays may be affected by anticoagulants, including heparin and direct oral anticoagulants (DOAC), whereas the chromogenic assay generally is unaffected by anticoagulants. Vitamin K antagonists can lower the activity of any assay. [68]

The direct thrombin inhibitors (DTIs; argatroban, dabigatran) do not impact the results of functional assays using snake venom to activated protein C and a chromogenic substrate to measure enzymatic activity.  DTIs may interfere with the functional assays that use a clotting-based endpoint.  DTIs do not interfere with antigenic assays of protein C. [68]


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