Резистентність фактора V до активованого протеїну C (APC)

ЗаMichael B. Streiff, MD, Johns Hopkins University School of Medicine
Переглянуто/перевірено серп. 2023

Mutations of factor V make it resistant to its normal cleavage and inactivation by activated protein C, and they also predispose to venous thrombosis.

Ресурси за темою

(See also Overview of Thrombotic Disorders.)

Activated protein C (APC), in complex with protein S, degrades coagulation factors Va and VIIIa, thus inhibiting coagulation (see figure Pathways in Blood Coagulation). Any of several mutations to factor V make it resistant to inactivation by APC, increasing the tendency for thrombosis.

Factor V Leiden is the most common of these mutations. Homozygous mutations increase the risk of thrombosis more than do heterozygous mutations.

Шляхи згортання крові

Factor V Leiden as a single gene defect is present in about 5% of White Americans, but it rarely occurs in native Asian or African populations (1). It is present in 20 to 60% (depending on patient selection) of patients with "spontaneous" venous thrombosis (2).

Довідкові матеріали загального характеру

  1. 1. Ridker PM, Miletich JP, Hennekens CH, Buring JE. Ethnic distribution of factor V Leiden in 4047 men and women. Implications for venous thromboembolism screening. JAMA 1997;277(16):1305-1307.

  2. 2. Eichinger S, Weltermann A, Mannhalter C, et al. The risk of recurrent venous thromboembolism in heterozygous carriers of factor V Leiden and a first spontaneous venous thromboembolism. Arch Intern Med 2002;162(20):2357-2360. doi:10.1001/archinte.162.20.2357

Diagnosis of Factor V Resistance to APC

  • Plasma coagulation assay

Diagnosis is based on

  • The activated protein C resistance assay

  • Genetic mutation analysis of the factor V gene using DNA-based assays

The activated protein C resistance assay is a screening test for the presence of factor V Leiden. Activated protein C is added to a 5-fold dilution of patient plasma, and the coagulation time is measured. In patients with homozygous or heterozygous factor V Leiden resistance, the prolongation of the clotting time is significantly reduced because their factor V is resistant to cleavage by activated protein C.

Confirmation of factor V Leiden is then done by DNA-based testing for the mutation.

Treatment of Factor V Resistance to APC

  • Anticoagulation

Direct oral anticoagulants are at least as effective as warfarin for the treatment of venous thromboembolism in patients with thrombophilia including factor V Leiden (1).

Довідковий матеріал щодо лікування

  1. 1. Campello E, Spiezia L, Simion C, et al. Direct Oral Anticoagulants in Patients With Inherited Thrombophilia and Venous Thromboembolism: A Prospective Cohort Study. J Am Heart Assoc 2020;9(23):e018917. doi:10.1161/JAHA.120.018917