Acquired APC resistance and oral contraceptives: differences between two functional tests.

Area of Science:

• Coagulation and Thrombosis
• Pharmacology
• Biochemistry

Background:

• Activated protein C (APC) resistance is a risk factor for thrombosis.
• Factor V Leiden mutation is the most common cause of inherited APC resistance.
• Acquired APC resistance is observed in women using oral contraceptives (OC).

Purpose of the Study:

• To compare the response to APC in plasma from normal individuals, factor V Leiden carriers, and OC users.
• To evaluate functional APC-resistance tests based on endogenous thrombin potential (ETP) and activated partial thromboplastin time (aPTT).

Main Methods:

• Functional APC-resistance assays quantifying the effect of APC on ETP and aPTT.
• Comparison of test results between non-OC users, OC users, and factor V Leiden carriers.

Main Results:

• Both ETP and aPTT assays effectively distinguished between individuals with and without factor V Leiden among non-OC users.
• The ETP-based assay revealed significant differences in APC sensitivity between non-OC users and OC users, and between users of different OC generations.
• The aPTT-based test did not show these distinctions.
• Poor correlation in APC sensitivity between the two assays was observed in non-carriers, OC users, and factor V Leiden carriers.

Conclusions:

• The ETP and aPTT assays measure different aspects of APC resistance.
• Oral contraceptives appear to alter plasma components that modulate APC's effect on thrombin generation.
• Further investigation is needed to identify plasma proteins affected by OC use that influence APC resistance.