Factor II Leiden Genetic Mutation

A new genetic marker for Thrombophilia, Factor II was identified in 1969 by the same group that identified Factor V Leiden. Wikipedia describes this mutation as, Substitution of adenine for guanine at position 20210 of the prothrombin gene, known as the prothrombin 20210a mutation, prothrombin 20210 mutation and less precisely just factor II mutation, leads to hypercoagulability and may be a factor that contributes to infertility. To understand this genetic mutation we have to understand how prothombin works. "Prothrombin is a protein in the blood that is required for the blood to clot. It is also called factor II. Blood clots are composed of a combination of blood platelets and a meshwork of the blood clotting protein fibrin. Prothrombin is a blood clotting protein that is needed to form fibrin. If somebody has too little prothrombin, he or she has a bleeding tendency. If an individual has too much prothrombin, blood clots may form when they shouldn't."

Factor II is an inherited predisposition to develop blood clots which can affect other family members. Everyone inherits two copies of the prothrombin gene, one from your father and one from your mother. If only one of those genes are mutated, you are heterozygous for the gene mutation. If both genes are mutated, you are homozygous. Heterozygous prothrombin mutations are found in about 2% of the US white population and is most common in those with southern European ancestry. It is theorized that the mutation originated with one common ancester. The mutation is rarely found in African Americans, Asians, or Native Americans. The homozygous form (two inherited mutated genes) is considered uncommon, with an expected occurrence of approximately one (1) in ten thousand (10,000) individuals. The prothrombin 20210 mutation is found in both men and in women and has nothing to do with blood type. This mutation is a major risk factor for venous thrombosis and certain arterial thrombotic conditions.

There are some definitive health risks for those with the genetic mutation. It increases the risk of developing  deep vein thrombosis (DVT). Typically blood clots occur in the deep veins and are considered dangerous because they can damage the veins, and lead to pain and swelling. In some instances it can even result in disability. The risk factor of DVT increases with age.

Women increase their risk of (DVT) when using estrogen-containing oral contraceptives. It is theorized that this may be a contributing factor to stillbirth, second trimester pregnancy loss, placental abruption, and preeclampsia.

DNA testing for the prothrombin mutation is recommended for all patients with deep vein thrombosis, pulmonary embolism, cerebral vein thrombosis, and premature ischemic stroke, and women with premature myocardial infarction. If this mutation is found in one family member, all members of the immediate family should be tested.

MY STORY
I had an early morning meeting and shortly after the meeting started I began feeling short of breath. Having asthma, I used my inhaler a number of times, but continued to have problems. After the meeting I walked several blocks back to work and realized that something else must be wrong. When I reached my office I asked the department manager to re-assign my afternoon appointments. He insisted on taking me the the emergency room. I very calmly told the receptionist that I was having a heart attack. It was hours before the cardiologist arrived. His initial diagnosis was a typical one; he believed I was having a panic attack. My internist decided to be cautious and admitted me for observation.

Early the next morning I had a second heart attack. The duty nurse told me that my bloodwork,from the night before, confirmed that I had a heart attack when I went to the emergency room. A skilled nursing staff quickly brought the attack under control with morphine. A few hours later number three hit and that one hurt! It was a Saturday and the heart catheter team wasn't available. I am thankful that a very angry nurse who called the doctor and insisted he do something. The team was brought in and the test revealed clotting in veins in the lower left ventrical. The real mystery was why? I had an exceptionally healthy heart, with clean wide caliper veins and arteries. The doctors best guess was that I had Prinzmetal angina.

A few months later my sister had a very similar heart attack and her cardiologist tested her for the hereditary gene mutation and she had it! She was also diagnosed with Prinzmetal angina. It was only then that I was tested and found that I had it too, which explained my mysterious heart attacks. Many of my direct ancestors died of heart attacks. It made me wonder just how many of them carried the mutation and could have lived a much longer life with the proper medication.

I have six siblings and so far three out of seven have tested positive for the prothrombin (factor II) mutation 20210. Two of the next generation have tested positive, but sadly some family members refuse to be tested, saying they don't want to know.

Coronary heart disease is America's No. 1 killer. It is very important to be tested if you have had any problem with deep vein clots or a history of heart attacks in your family. Women are at a higher risk when taking birth control. And if you are a woman reading this, we don't have the same warnings signs as men! For women it may seem like indigestion or in my case a problem with my asthma.

The good news is there are tests to determine if you have hereditary hypercoagulability and it can be treated with blood thinners. If you have an hereditary hypercoagulability disorder and have had a heart attack or deep vein thrombosis, please share your story in the comments section. If enough people are interested, I will start an online forum for discussion and add the link here.

NOTE: 50% of the royalties earned by this Squidoo lens goes to the American Heart Association.

The American Heart Association published this list of warning signs:

For more information and some great references on this top, please read the article published by the American Heart Association. They recommended  the following reference materials:

1. DeStefano V, Martinelli I, Mannucci P, et al. The risk of recurrent deep venous thromboembolism among heterozygous carriers of the G20210A prothrombin gene mutation. Br J Hematol. 2001; 113: 630-635. [CrossRef] [Medline] [Order article via Infotrieve]
   
2. Hellmann EA, Leslie N, Moll S. Knowledge and information satisfaction of individuals with factor V Leiden mutation. J Thromb Hemost. 2003; 1: 2335-2339.
   
3. Martinelli I, Taioli E, Bucciarelli P, et al. Interaction between the G20210A mutation of the prothrombin gene and oral contraceptive use in deep vein thrombosis. Arterioscler Thromb Vasc Biol. 1999; 19: 700-703.[Abstract/Free Full Text]
   
4. McGlennen R, Key N. Clinical and laboratory management of the prothrombin G20210A mutation. Arch Pathol Lab Med. 2002; 126: 1219-1325.[Medline] [Order article via Infotrieve]
   
5. Ornstein, D, Cushman M. Factor V Leiden. Circulation. 2003; 107: e94-e97.[CrossRef] [Medline] [Order article via Infotrieve]
   
6. Reich L, Bower M, Key N. Role of the geneticist in testing and counseling for inherited thrombophilia. Gen Med. 2003; 5: 133-143.
   
7. Ridker PM, Hennekens C, Miletich J. G20210A mutation in prothrombin gene and risk of myocardial infarction, stroke, and venous thrombosis in a large cohort of US men. Circulation. 1999; 99: 999-1004.[Medline] [Order article via Infotrieve]
   
8. Rosendaal F, Vessey M, Rumley A, et al. Hormonal replacement therapy, prothrombotic mutations and the risk of venous thrombosis. Br J Hematol. 2002; 16: 851-854.
   
9. Vandenbroucke J, Rosing J, Bloemenkamp K, et al. Oral contraceptives and the risk of venous thrombosis. N Engl J Med. 2001; 344: 1527-1535.[Free Full Text]
   
10. Deborah Okner Smith. Factor V Leiden/Thrombophilia Support Page. Available at: http://www.fvleiden.org. Accessed May 18, 2004.