From the Guidelines
Based on your protein S levels, your risk of blood clots appears to be low, but taking estrogen would significantly increase this risk. Your protein S levels (total protein S of 133 and free protein S of 146) are within or above the normal range, suggesting adequate protein S activity, which is protective against clot formation. However, estrogen therapy is known to increase the risk of venous thromboembolism (VTE) by 2- to 6-fold, as reported in various studies 1.
Key Points to Consider
- Estrogen alters the balance of clotting factors in the blood, increasing factors that promote clotting while decreasing natural anticoagulants like protein S 1.
- The risk of VTE is highest within the first year of estrogen therapy use, with a relative risk of 3.49 (95% CI, 2.33 to 5.59) 1.
- The US Preventive Services Task Force concluded that there is good evidence that hormone replacement therapy (HRT) increases the risk for venous thromboembolism 1.
Recommendations
- If you're considering estrogen therapy, discuss this blood clot risk with your healthcare provider, who may recommend additional monitoring or alternative treatments depending on your overall health profile and other risk factors for thrombosis.
- Given the potential risks, it's essential to weigh the benefits of estrogen therapy against the increased risk of blood clots and consider alternative treatments or close monitoring if estrogen therapy is initiated.
From the Research
Protein S and Blood Clot Risk
- Protein S is an anticoagulant protein that circulates in plasma in complex with C4b-binding protein (C4BP) or in free form 2.
- Deficiency of protein S increases the risk of venous thrombosis 3.
- Measurement of free protein S, as compared to total levels, has been shown to be superior for prediction of protein S deficiency 3.
Interpretation of Protein S Levels
- A protein S level of 133 and a free protein S level of 146 are within the normal range, but the exact normal range may vary depending on the laboratory and assay used 2, 3.
- Free protein S levels less than the 5th percentile (< 41 IU/dL) or less than the 2.5th percentile (< 33 IU/dL) are associated with a higher risk of first venous thrombosis 4.
Effect of Estrogen on Protein S Levels
- Estrogen can decrease protein S levels, which may increase the risk of blood clots 5.
- However, the exact effect of estrogen on protein S levels and blood clot risk in individuals with normal protein S levels is not well established 5.
Blood Clot Risk
- The risk of blood clots is influenced by multiple factors, including protein S levels, estrogen use, and other genetic and environmental factors 2, 3, 5, 4.
- Individuals with low free protein S levels (< 41 IU/dL or < 33 IU/dL) are at higher risk of venous thrombosis, but the risk for individuals with normal protein S levels is not well established 4.