Testing for Protein C and S in Acute Ischemic Stroke
Routine testing for protein C and protein S levels is not warranted in the acute phase of ischemic stroke, as these levels are altered during the acute stroke period and do not change immediate management. 1
When Testing Should Be Deferred
Protein C, protein S, and antithrombin levels should be deferred or repeated at least 4 to 6 weeks after the acute stroke because these protein levels are altered during the acute stroke phase, rendering acute measurements unreliable. 1
Acute stroke triggers massive activation of coagulation factors, which artificially lowers protein C levels and does not reflect true hereditary deficiency. 2
Protein S levels may be normal on admission but decrease significantly in subsequent weeks, further complicating interpretation. 3
Clinical Scenarios Where Testing May Be Considered (After Acute Phase)
Testing for inherited thrombophilias including protein C and S deficiencies should be considered in highly selected patients with the following characteristics:
Young patients (<45 years old) with no identifiable stroke cause after comprehensive evaluation. 1
Personal or family history of unprovoked venous thrombosis (deep vein thrombosis or pulmonary embolism). 1
History of prior spontaneous abortion or recurrent pregnancy loss. 1
Coexistence of systemic signs and symptoms suggestive of hypercoagulability. 1
Stroke with confirmed unprovoked deep vein thrombosis, as this combination suggests paradoxical embolism through a right-to-left shunt (often via patent foramen ovale). 1
Critical Management Principles
If inherited thrombophilia testing is pursued, patients must first be fully evaluated for alternative stroke mechanisms (cardiac sources, large vessel atherosclerosis, small vessel disease) before attributing stroke to thrombophilia. 1
In the absence of venous thrombosis, either anticoagulant or antiplatelet therapy is reasonable for patients with proven thrombophilia and arterial stroke. 1
If deep vein thrombosis is identified in a patient with inherited thrombophilia and stroke, anticoagulation is indicated according to standard DVT treatment guidelines. 1
For patients with spontaneous cerebral venous thrombosis and inherited thrombophilia, long-term anticoagulation is probably indicated. 1
Evidence Quality and Practical Considerations
The prevalence of hereditary protein C, protein S, or antithrombin III deficiencies in young stroke patients is extremely low (0-2%) when acquired causes are excluded. 4
Most abnormal levels detected acutely represent acquired deficiencies (pregnancy, estrogen use, acute inflammation, liver disease) rather than hereditary conditions. 4
There is no evidence that testing for these hematologic traits benefits secondary stroke prevention in the absence of a diagnosis that would change treatment. 1
Measurements do not correlate with stroke etiology, predict recurrence, or guide management in typical stroke patients. 3
Common Pitfalls to Avoid
Do not delay standard acute stroke treatment (thrombolysis, thrombectomy, antiplatelet therapy) to obtain thrombophilia testing. 1
Do not test during acute hospitalization as results will be unreliable and will not influence immediate management decisions. 1
Do not order thrombophilia panels routinely in older patients (>45 years) with typical vascular risk factors, as the yield is negligible and does not change management. 1
If testing is performed and abnormal, repeat testing 4-6 weeks after stroke to confirm true deficiency versus acute-phase alterations. 1