Can protein S deficiency be tested for during pregnancy?

Testing for Protein S Deficiency During Pregnancy

Protein S deficiency testing should not be performed during pregnancy as it can lead to misdiagnosis and inappropriate treatment due to physiological decreases in protein S levels that occur naturally during pregnancy. 1, 2

Physiological Changes in Protein S During Pregnancy

• Pregnancy is a physiological hypercoagulable state with increased risk of thromboembolic events 2
• Protein S levels naturally decrease during pregnancy to 40-50% of normal levels 3
• This decrease is progressive throughout pregnancy, with the most significant reduction occurring in the third trimester 2
• By the third trimester, all pregnant women may have functional protein S levels well below the lower limit of the reference range 1

Testing Limitations

• Functional protein S assays (clot-based) show dramatic decreases during pregnancy, with all third-trimester patients having levels below the normal reference range 1
• Free protein S antigenic levels also decrease but to a lesser extent than functional assays 1, 2
• The discrepancy between functional and antigenic assays increases as pregnancy progresses 2
• Testing during pregnancy could result in false diagnosis of protein S deficiency in normal pregnant women 1

Recommendations for Diagnosis

• Protein S deficiency testing should be deferred until at least 6 weeks postpartum when protein S levels return to baseline 4
• For women with suspected thrombophilia, comprehensive thrombophilia testing (including protein S) should be conducted outside of pregnancy 5
• If testing is absolutely necessary during pregnancy, results must be interpreted with extreme caution and in the context of pregnancy-specific reference ranges 2

Management of Known Protein S Deficiency During Pregnancy

• For pregnant women with known protein S deficiency but no prior VTE or family history of VTE, the American Society of Hematology suggests antepartum clinical surveillance rather than prophylactic anticoagulation 5, 4
• For pregnant women with protein S deficiency and a family history of VTE, postpartum prophylaxis with prophylactic or intermediate-dose LMWH for 6 weeks is suggested 5, 4
• Women with protein S deficiency and prior VTE should receive both antepartum and postpartum prophylaxis 5

Clinical Implications

• Protein S deficiency may be associated with pregnancy complications including recurrent miscarriages, intrauterine growth restriction, and stillbirths 6, 3
• Anticoagulant therapy can be successful in managing pregnancies in women with known protein S deficiency 3
• The decision to use anticoagulant prophylaxis should be based on comprehensive risk assessment including personal history of VTE, family history, and additional risk factors 5

Key Pitfalls to Avoid

• Avoid testing for protein S deficiency during pregnancy as physiologic decreases can lead to misdiagnosis 1, 2
• Do not initiate long-term anticoagulation based on protein S levels measured during pregnancy 1
• Remember that oral contraceptives can also decrease protein S levels, which should be considered when testing women of reproductive age 7