Protein S in Pregnancy
Protein S, also known as Protein C, is an essential vitamin K-dependent plasma protein that plays a critical role in regulating blood coagulation and preventing thrombosis. During pregnancy, the female reproductive system undergoes significant changes that alter the coagulatory system. This is particularly true during the postpartum period when there is a shift towards an anticoagulant state. Protein S levels are altered accordingly, and understanding these changes is crucial for the prevention and management of coagulopathy during pregnancy.
During normal pregnancy, protein S levels typically decline by approximately 38% due to the increased production of coagulation factors and decrease in fibrinolytic factors. This reduction in protein S activity is counterbalanced by an increase in the amount of free protein S that is complexed with C4b-binding protein, resulting in a stable equilibrium between functionally active free protein S and its complexed form. The net result of this equilibrium is that the overall level of protein S activity is maintained within thenormal range for nonpregnant females.
However, women with inherited protein S deficiency, either type I (decrease in free and total protein S) or type III (low free protein S levels with normal total protein S), may be at higher risk for both venous andarterial thrombosis due to their decreased APC-cofactor activity. Protein S deficiency is caused by mutations in the PROS1 gene, which encodes for protein S synthesis.Type I protein S deficiency is characterized by a total and free protein S level below normal, while Type III deficiency is characterized by low free protein S levels and normal total protein S levels.
Acquired protein S deficiency can occur due to a variety of conditions, such as vitamin K deficiency, consumption from ongoing thrombosis, disseminated intravascular coagulation (DIC), or invasive procedures. It can also be related to certain medications or medical conditions, such as oral estrogens or sickle cell anemia.
To manage protein S deficiency during pregnancy, healthcare providers often recommend prophylactic anticoagulation with low molecular weight heparin (LMWH) to reduce the risk of venous thromboembolism (VTE). Prophylaxis usually starts early in the second trimester and continues until delivery. Heparin is a medication that prevents the formation of blood clots by enhancing the activity of antithrombin III (ATIII), which acts as a natural protein C inhibitor. A direct oral anticoagulant (DOAC) may be an alternative to heparin for certain patients.
In some women with recurrent pregnancy loss, who have a history of protein S deficiency but have not experienced a blood clot, the use of LMWH may be necessary during pregnancy to prevent further pregnancy loss. Other medical conditions, such as deep vein thrombosis (DVT) or pulmonary embolism, may necessitate treatment with LMWH or Warfarin in addition to dietary changes and lifestyle modifications., understanding the changes in protein S levels during pregnancy is essential for the prevention and management of coagulopathy. Healthcare providers should monitor protein S levels regularly and adjust the treatment plan accordingly to optimize outcomes for women with protein S deficiency and to minimize the risk for VTE and other complications during pregnancy and the postpartum period.