• A. Factor V Leiden
  • B. Antithrombin deficiency
  • C. Antiphospholipid antibodies
  • D. Protein S deficiency ✓


Protein S deficiency is a thrombophilic condition that can lead to an increased risk of blood clot formation. During pregnancy, the levels of protein S naturally decrease, making it challenging to definitively diagnose a pre-existing protein S deficiency during this time. This difficulty arises because the normal physiological changes in protein S levels during pregnancy can mask underlying deficiencies. Therefore, a definitive diagnosis of protein S deficiency is typically made outside of pregnancy or after delivery when the levels return to baseline.

Protein S deficiency is an inherited disorder that affects the anticoagulation pathway in the blood. Protein S acts as a cofactor for protein C, which helps regulate blood clotting by inhibiting factors V and VIII. When there is a deficiency in protein S, the regulation of blood clotting is impaired, leading to an increased risk of thrombosis.

Diagnosing protein S deficiency involves measuring the levels of free and total protein S in the blood. However, during pregnancy, these levels are naturally lower due to increased production of other proteins that bind to protein S. This makes it challenging to differentiate between a true deficiency and the normal physiological changes that occur during gestation.

In other words, Thrombophilia refers to a group of conditions that predispose individuals to abnormal blood clotting. Protein S deficiency is one such thrombophilic condition that can lead to an increased risk of developing blood clots. Protein S is a natural anticoagulant protein that plays a crucial role in regulating blood clot formation.

Challenges in Diagnosing Protein S Deficiency During Pregnancy:

During pregnancy, the maternal hemostatic system undergoes significant changes to support the growing fetus and prepare for childbirth. These changes can complicate the diagnosis of thrombophilic conditions like protein S deficiency. Several factors contribute to the challenges in definitively diagnosing protein S deficiency during pregnancy:

  1. Physiological Changes: Pregnancy itself is associated with alterations in various coagulation factors, including an increase in certain proteins that promote blood clotting. These changes can mask the underlying deficiency of protein S, making it difficult to accurately diagnose the condition during pregnancy.
  2. Hormonal Influence: Hormonal fluctuations during pregnancy can further impact the interpretation of laboratory tests used to diagnose protein S deficiency. Estrogen, which is elevated during pregnancy, can affect the levels of protein S in the blood, leading to potential misinterpretation of test results.
  3. Interference with Testing: Standard laboratory assays used to measure protein S levels may be affected by pregnancy-related factors, such as increased plasma volume and changes in protein concentrations. These alterations can influence test results and make it challenging to establish a definitive diagnosis of protein S deficiency during pregnancy.
  4. Gestational Age Considerations: The timing of testing during pregnancy is crucial for accurate diagnosis. Protein S levels fluctuate throughout gestation, with lower levels often observed in late pregnancy. Therefore, interpreting test results requires consideration of gestational age to avoid misdiagnosis or underestimation of protein S deficiency.

Clinical Management and Monitoring:

Despite the diagnostic challenges posed by pregnancy, healthcare providers may still suspect protein S deficiency based on clinical history or family background. In cases where a definitive diagnosis cannot be made during pregnancy, close monitoring and follow-up after delivery are essential to assess the need for ongoing anticoagulant therapy or other interventions to manage the risk of thrombotic events.