Factor II Prothrombin Mutation

Prothrombin gene mutation (also known as Factor II mutation or Prothrombin G20210A) is a hereditary condition that increases the likelihood of developing abnormal blood clots in the veins, such as deep vein thrombosis (DVT) and in the lungs, known as pulmonary embolism (PE). This occurs because the body produces an excess amount of Factor II (prothrombin) protein, which is essential for normal blood clotting. When blood clots form and obstruct blood flow, it can lead to serious complications as the cells are deprived of oxygen.

Although most individuals never experience a blood clot in their lifetime, this mutation is caused by a particular gene mutation where guanine (G) is replaced by adenine (A) at position 20210 in the prothrombin gene code. Other mutations in blood clotting pathways that increase the risk of clots comprise factor V Leiden.


The heterozygous prothrombin gene mutation is present in approximately 1 out of 50 white people in Europe and North America, making it the second most frequent inherited clotting disorder after Factor V Leiden. In contrast, about 1 out of 250 Black people in America has the prothrombin gene mutation.

Women who are heterozygous carriers of this mutation and who take combined birth control pills have a 15-fold increased risk of venous thromboembolism, and those who are also heterozygous for factor V Leiden have a 20-fold increased risk.


Signs and Symptoms

Prothrombin G20210A is a genetic variation that can increase the risk of blood clots, including deep vein thrombosis and pulmonary embolism. The variant causes higher levels of prothrombin in the blood, which can lead to a state of hypercoagulability or an increased risk of clotting. However, this variation does not appear to significantly increase the risk of arterial thrombosis or coronary disease.

Symptoms of DVT in your arm or leg include pain, swelling, skin that looks purple or red, and skin that feels warm. Symptoms of a PE in your lung are chest pain, shortness of breath, very fast heartbeat, fainting, and cough with or without blood.


The diagnosis of prothrombin G20210A mutation is easily done through genetic testing (i.e., Real-Time PCR) as it involves a single point mutation that is not affected by other illnesses or anticoagulant use. The prothrombin gene mutation (G20210A) occurs in a region that does not code for proteins, specifically in the nucleotide 20210 of the 3′ untranslated region. This results in a substitution of adenine for guanine, which is located near the site where the pre-mRNA receives its poly-A tail. Protein C and Protein S deficiencies can further increase the risk of blood clots in carriers of this mutation.

Genetic testing for G20210A is not typically recommended for individuals who have developed unprovoked venous thromboembolism or for asymptomatic family members of carriers. The results of thrombophilia tests are also unlikely to play a role in determining the length of treatment for those who develop blood clots.


Individuals who carry the mutation can pass it on to their children. While most carriers do not require treatment, they should exercise caution during periods of increased risk, such as during pregnancy, after surgery, or during long flights. In some cases, blood-thinning medication may be recommended to reduce the risk of clotting.

Patients with the prothrombin G20210A mutation are typically treated similarly to those with other forms of thrombophilia, with anticoagulation therapy for a minimum of three to six months. Patients with the prothrombin G20210A mutation who have not had a thromboembolic event typically do not require routine anticoagulation. However, counseling patients on how to manage situations that increase their risk of thrombosis is recommended, such as during pregnancy, surgery, and acute illness. Women with the mutation should generally avoid oral contraceptives as they increase the risk of thrombosis.

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