Diagnostic considerations in protein C deficiency and protein S deficiency
| . | Protein C deficiency . | Protein S deficiency . |
|---|---|---|
| Genetic mutation | PROC gene | PROS1 gene |
| Types of deficiency | Type 1 quantitative defect, low PC antigen and activity Type 2 qualitative defect, normal PC antigen but low activity • Type 2A • Type 2B—not detected by amidolytic assays | Type 1 quantitative defect; low total and free PS antigen, low activity Type 2 qualitative defect; normal total and free PS, low activity Type 3 selective quantitative defect; normal total PS, low free PS antigen, low activity |
| Activity assays | PC activity: • Clotting end point • Amidolytic end point (uses a chromogenic substrate) | PS activity: • Clotting end point |
| Antigen assays | PC antigen: immunoassays • Helps distinguish deficiency type, not required for diagnosis | PS antigen: immunoassays Free PS antigen—ELISA, latex immunoassays; initial test for diagnosis Total PS antigen—helps distinguish deficiency type, not required for diagnosis |
| Diagnostic threshold | PC activity <65%-70% | Free PS antigen <33% (in general population) <40%-50% (with patients with prior VTE or strong family history) |
| Laboratory interference | Clot-based assays: lupus anticoagulants, heparins, direct thrombin inhibitor, oral factor Xa inhibitors, elevated FVIII:C, FVL mutation, and hyperlipidemia | Clot-based assays: lupus anticoagulants, heparins, direct thrombin inhibitor, oral factor Xa inhibitors, elevated FVIII, FVL mutation, and PC deficiency |
| Conditions with acquired deficiency | Liver disease, DIC, vitamin K antagonist, vitamin K deficiency, recent surgery or trauma, acute inflammatory illnesses, oral contraceptive pills, or acquired antibodies | Liver disease, DIC, vitamin K antagonist, vitamin K deficiency, nephrotic syndrome, L-asparaginase therapy, oral contraceptive pills, pregnancy, or acquired antibodies |
| . | Protein C deficiency . | Protein S deficiency . |
|---|---|---|
| Genetic mutation | PROC gene | PROS1 gene |
| Types of deficiency | Type 1 quantitative defect, low PC antigen and activity Type 2 qualitative defect, normal PC antigen but low activity • Type 2A • Type 2B—not detected by amidolytic assays | Type 1 quantitative defect; low total and free PS antigen, low activity Type 2 qualitative defect; normal total and free PS, low activity Type 3 selective quantitative defect; normal total PS, low free PS antigen, low activity |
| Activity assays | PC activity: • Clotting end point • Amidolytic end point (uses a chromogenic substrate) | PS activity: • Clotting end point |
| Antigen assays | PC antigen: immunoassays • Helps distinguish deficiency type, not required for diagnosis | PS antigen: immunoassays Free PS antigen—ELISA, latex immunoassays; initial test for diagnosis Total PS antigen—helps distinguish deficiency type, not required for diagnosis |
| Diagnostic threshold | PC activity <65%-70% | Free PS antigen <33% (in general population) <40%-50% (with patients with prior VTE or strong family history) |
| Laboratory interference | Clot-based assays: lupus anticoagulants, heparins, direct thrombin inhibitor, oral factor Xa inhibitors, elevated FVIII:C, FVL mutation, and hyperlipidemia | Clot-based assays: lupus anticoagulants, heparins, direct thrombin inhibitor, oral factor Xa inhibitors, elevated FVIII, FVL mutation, and PC deficiency |
| Conditions with acquired deficiency | Liver disease, DIC, vitamin K antagonist, vitamin K deficiency, recent surgery or trauma, acute inflammatory illnesses, oral contraceptive pills, or acquired antibodies | Liver disease, DIC, vitamin K antagonist, vitamin K deficiency, nephrotic syndrome, L-asparaginase therapy, oral contraceptive pills, pregnancy, or acquired antibodies |
DIC, disseminated intravascular coagulation; PC, protein C; PS, protein S.