Protein S reference ranges

How low can protein S drop during pregnancy? Good question 💯

The level of anticoagulant protein S decreases physiologically in almost all pregnant women 💁🏼‍♀️, so they appear to have a protein S deficiency if judged by reference ranges established for the general population. If a patient develops venous thromboembolism (VTE) during pregnancy and hereditary thrombophilia is suspected, protein S testing should be postponed until after delivery. For most pregnant women with VTE, thrombophilia testing is not required, since both the treatment and its duration will be the same regardless of whether thrombophilia is present.

❓So what level of protein S should be considered normal outside of pregnancy and during pregnancy❓

Of the three main parameters (total protein S, free protein S, and protein S activity), free protein S is the best indicator of true deficiency ☝️

There is no perfect cutoff level that reliably distinguishes individuals with and without protein S deficiency. The reference value depends on the type of assay, clinical context, patient’s age, and physiological states such as pregnancy.

🔴 For patients with a history of VTE, or with a strong family history of VTE, a plasma total or free protein S level below 60–65 international units/dL is considered a deficient range. 🔴 For asymptomatic individuals, or those with a first VTE and no significant family history, a lower free protein S level (e.g., <33 units/dL) is a stronger predictor of increased VTE risk.

Eleanora Rhee et al. (2005) published a small study of 39 healthy pregnant women between 26 and 39 weeks of gestation. Results: 📢 Mean protein S activity (% of normal): 37.2 (95% CI 33 – 40.5) 📢 Mean total protein S: 89.1 (83.6 – 94.7) 📢 ❗Mean free protein S antigen: 52.6 (48.8 – 56.4)

Aspirin for the Prevention of Pregnancy Loss Antiphospholipid Syndrome (APS)