What is the Origin of Activated Protein C Resistance?

The clinical concept of APCR was first formally described in the early 1990s, emerging from hematology research focused on unexplained thrombophilia. Its etymology is purely descriptive, combining the function of the regulatory enzyme, "Activated Protein C," with the observed pathological state of "Resistance." The discovery of the underlying Factor V Leiden mutation provided the definitive molecular basis for the majority of clinically relevant APCR cases. This diagnostic entity has since become a standard consideration in pre-treatment screening for high-risk patients.

What is the Mechanism of Activated Protein C Resistance?

The fundamental mechanism involves a defect in the Factor V molecule, which is normally inactivated by APC to slow the coagulation cascade. In the presence of the Factor V Leiden mutation, the altered Factor V (Factor Va) becomes resistant to cleavage and inactivation by APC. This resistance allows the coagulation cascade to proceed unchecked for a longer duration, resulting in an increased generation of thrombin and subsequent clot formation. The persistent procoagulant state shifts the hemostatic balance toward thrombosis, underscoring the importance of genetic and functional testing for this resistance in clinical endocrinology.

Activated Protein C Resistance

Meaning

Activated Protein C Resistance (APCR) is a hypercoagulable state characterized by a diminished anticoagulant response to Activated Protein C (APC), a natural plasma protein that normally regulates blood clotting. This condition increases an individual’s predisposition to venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism. The most common genetic cause of APCR is a specific mutation in the Factor V gene, known as Factor V Leiden, leading to a structural change in the clotting factor. Clinical evaluation of APCR is vital in hormonal health, particularly when considering therapies that may inherently elevate thrombosis risk, such as certain estrogen or testosterone regimens.