Management of Protein S Activity Level 55% at Postpartum Day 2
Do not diagnose protein S deficiency based on this postpartum day 2 value, as protein S levels are physiologically reduced during pregnancy and the immediate postpartum period, making interpretation unreliable at this time. 1, 2, 3
Critical Context: Physiologic Changes in Protein S During Pregnancy and Postpartum
Protein S activity decreases significantly during normal pregnancy to approximately 38% ± 17.3% compared to non-pregnant levels of 97% ± 31.6%, and remains depressed in the immediate postpartum period 1
Free protein S antigen levels drop to approximately 62-66% during the third trimester, with functional protein S falling even further to 26-44% by the third trimester 2, 4
The observed level of 55% on postpartum day 2 falls within the expected physiologic range for the immediate postpartum period and does not necessarily indicate true protein S deficiency 1, 2
Testing for definitive diagnosis of protein S deficiency should be delayed until at least 6 weeks postpartum when levels normalize to non-pregnant ranges 3
Immediate Management Algorithm
Step 1: Assess for Family History and Additional Risk Factors
If there is NO family history of VTE, the American Society of Hematology suggests against antithrombotic prophylaxis in the postpartum period for women with protein S deficiency 5
If there IS a family history of VTE, the American Society of Hematology suggests postpartum prophylaxis with prophylactic- or intermediate-dose LMWH for 6 weeks 5
Step 2: Evaluate for Additional Thrombotic Risk Factors
Consider postpartum prophylaxis if the patient has any 2 or more of the following risk factors (each carrying <1% absolute VTE risk in isolation): 5
- BMI ≥30 kg/m² at first antepartum visit
- Smoking >10 cigarettes per day antepartum
- Preeclampsia
- Intrauterine growth restriction
- Placenta previa
- Emergency cesarean section
- Peripartum or postpartum blood loss >1 L or need for blood product replacement
- Preterm delivery
- Stillbirth
- Maternal disease (cardiac disease, systemic lupus erythematosus, sickle cell disease, inflammatory disease, varicose veins, gestational diabetes)
Step 3: Clinical Surveillance vs. Prophylaxis Decision
For patients WITHOUT family history of VTE and <2 additional risk factors:
- Clinical surveillance is appropriate (no pharmacologic prophylaxis) 5
For patients WITH family history of VTE OR ≥2 additional risk factors:
- Initiate prophylactic- or intermediate-dose LMWH for 6 weeks postpartum 5
Common Pitfalls to Avoid
Do not diagnose protein S deficiency based on levels obtained during pregnancy or the immediate postpartum period, as physiologic reductions will lead to false-positive results and unnecessary anticoagulation 1, 2, 3, 4
Do not confuse the physiologic decrease in protein S with acquired deficiency from warfarin, which also reduces protein S activity and can cause redistribution to inactive forms 6
Do not order repeat protein S testing in the immediate postpartum period, as levels will remain physiologically depressed; defer testing until at least 6 weeks postpartum 3
Recognize that functional protein S assays fall more dramatically than free protein S antigen during pregnancy (functional PS 26-44% vs. free PS antigen 62-66% in third trimester), making functional assays particularly unreliable for diagnosis during this period 4
Follow-Up Plan
Schedule protein S testing at 6 weeks postpartum or later if there is clinical suspicion for true protein S deficiency based on personal or family history of thrombosis 3
If the patient has a family history of VTE or develops thrombotic symptoms, maintain LMWH prophylaxis for the full 6-week postpartum period and arrange hematology consultation for long-term management planning 5
Document the presence or absence of family history of VTE and additional risk factors to guide future pregnancy management, as this will determine whether antepartum and postpartum prophylaxis is indicated in subsequent pregnancies 5