What is Factor V Leiden (PCR)?

Also Known As: Activated Protein C Resistance, APC Resistance, Factor V R506Q, PT G20210A, Factor II 20210, Factor II Mutation

Formal Name: Factor V Leiden Mutation|Prothrombin 20210 Mutation

Factor V Leiden and prothrombin 20210 (PT 20210 or Factor II mutation) are genetic mutations that are associated with an increased risk of developing inappropriate blood clots. These mutations are tested by two separate tests that evaluate a person’s DNA to look for the mutations. The two tests are often performed together to help determine if an individual has an inherited risk for excessive clotting.

Factor V and prothrombin are coagulation factors (sometimes called clotting factors), two of a group of proteins essential for proper blood clot formation. When an injury occurs and bleeding starts, a process called hemostasis begins to form a plug at the injury site to help stop the bleeding. Blood cells called platelets adhere to and aggregate at the injury site, and a coagulation cascade begins to activate coagulation factors in sequence. Eventually, a blood clot forms. Once the area has healed, the blood clot dissolves.

There must be an adequate number of each of the coagulation factors, and each must function normally in order for a stable blood clot to form and then dissolve when no longer needed. A deficiency in clotting factors (quantitative defect) or clotting factors that do not work properly (qualitative defect) can lead to excessive bleeding or clotting (thrombosis).

Factor V Leiden and PT 20210 are two mutations that individuals may inherit from their parents that may cause an increased risk of excessive clotting. They are inherited in an autosomal dominant manner. A person may inherit one mutated gene copy and be heterozygous or may inherit two mutated gene copies and be homozygous. This may determine to what extent the person is affected. (For additional details, read the section on Autosomal Dominant Inheritance in the Genetic Disorders article.)

These two mutations are independent and are tested separately, but the tests are often performed at the same time as part of the investigation of a blood clot (thrombotic episode) in someone who is suspected of having an inherited risk factor for an excessive clotting (hypercoagulable) disorder. Each test is used to identify whether or not the specific mutation is present and to determine whether the person has one copy (heterozygous) or two copies (homozygous) of that mutation.

• During blood clotting, factor V is normally inactivated by a protein called activated protein C (APC) to prevent the blood clot from growing too large. But a factor V Leiden genetic mutation can lead to an altered factor V protein that resists inactivation by APC. The result is that clotting remains more active than usual, increasing the risk of a blood clot forming in the deep veins of legs (DVT) or breaking off and blocking a vein (venous thromboembolism or VTE).
• During blood clotting, an enzyme converts prothrombin to form thrombin. A mutation in the gene that codes for prothrombin called prothrombin 20210 can lead to the increased amount of prothrombin and therefore abnormal clotting and an increased risk of a DVT or VTE.