Posted by by Matt Pengelly
In this course, we have studied disorders of the blood as well as functions and underlying processes of the circulatory system. The ability of the human body to heal itself and repair damage has been covered extensively, but very little time was spent on the clotting process. I wanted to spend some time studying a condition that has significantly affected my life for the last fifteen years, and that condition is the Factor V Leiden clotting disorder.
Factor V Leiden is a genetic mutation in the F5 gene that increases the risk of abnormal blood clotting (thrombophilia) in the human body. It is one of the most common blood clotting disorders in the world and it primarily affects individuals of European descent. Individuals that are heterozygous for the trait have a slightly elevated risk of blood clots, and individuals that are homozygous for the trait are at even higher risk of abnormal clotting (Pastori, 1999). This genetic mutation alters Factor V clotting protein in a way which makes it resistant to inactivation by what is known as Activated Protein-C (APC). Activated Protein-C is essentially a key regulator of blood coagulation, and Activated Protein-C resistance has been shown to contribute to the development of venous thrombosis (Zuniga, 2023). Factor V Leiden is the leading causes of Activated Protein-C resistance (Bahraini, 2024). This deficiency most commonly manifests itself as deep vein thrombosis (DVT) or as a pulmonary embolism (PE), however, depending on risk factors, clots may appear in other locations as well (Pastori, 1999). The effect of this interruption on Activated Protein-C action is that the clotting mechanism is not shut off properly, and, therefore, dangerous clots can form in sensitive parts of the body. In this scenario, the normal clotting mechanism is not easily shut off and thrombin formation continues in an unabated runaway chain reaction. In a standard scenario, the normal clotting reaction is cleaved or interrupted by a response from Activated Protein-C which has anticoagulant properties.
Just above is a video that shows what happens in a normal clotting regimen when our friend A-Peeps-C (Activated Protein-C) is able to inactivate the clotting mechanism and affect a normal anticoagulant response. This essentially begins to dissolve the clot before it represents a threat to the individual. In this scenario, the APC effectively stops the coagulation cascade.
The second video is of a domino train which represents an uninterrupted clotting cascade in which our friend A-Peeps-C (representing Activated Protein-C) fails to deactivate the chain reaction. This video demonstrates what happens when Activated Protein-C is bypassed because of the Factor V Leiden deficiency. Essentially, the APC is sidelined in the reaction and thus is unable to stop the coagulation cascade.
Consequently, Factor V Leiden is a very serious disorder with the potential for ramifications throughout one’s life. Extended anticoagulation therapy is often necessary depending on a variety of other factors (Pastori, 1999), and it is not uncommon to have to take oral anticoagulants for the rest of one’s life. People who are heterozygous for Factor V Leiden are as much as four times more likely than the general population to suffer from a venous thromboembolism (Tsalta-Mladenov, 2022). When someone is exposed to other risk factors such as surgery, injury, or severe dehydration, that risk can go significantly higher. It is important for people who may have genetic predisposition to this deficiency be screened at an early age for Factor V Leiden mutations.
REFERENCES
Bahraini, M., Fazeli, A., & Dorgalaleh, A. (2024). Laboratory Diagnosis of Activated Protein C Resistance and Factor V Leiden. Seminars in thrombosis and hemostasis, 50(8), 1067–1083. https://doi.org/10.1055/s-0043-1770773
Pastori, D., Menichelli, D., Valeriani, E., & Pignatelli, P. (1999). Factor V Leiden Thrombophilia. In M. P. Adam (Eds.) et. al., GeneReviews®. University of Washington, Seattle.
Tsalta-Mladenov, M., Levkova, M., & Andonova, S. (2022). Factor V Leiden, Factor II, Protein C, Protein S, and Antithrombin and Ischemic Strokes in Young Adults: A Meta-Analysis. Genes, 13(11), 2081. https://doi.org/10.3390/genes13112081
Zuniga, L., Davis, M., Movahed, M. R., Hashemzadeh, M., & Hashemzadeh, M. (2023). Association between Factor-V Leiden and occurrence of acute myocardial infarction using a large NIS database. American journal of blood research, 13(6), 207–212. https://doi.org/10.62347/XQBZ7374
I really liked this project! I learned that there is an abnormal blood clotting disorder and it is called Factor V Leiden. Factor V Leiden is a gene mutation that primarily affects those of European descent and is the most common of blood clotting disorders. The author used dominoes to show the effect of how blood flows through the body and how it is supposed to clot. He also showed how Factor V Leiden affects that clotting procedure. He used a video to show the process. You can tell that this project was well researched and has impacted his life in a significant way. He goes on to say that this shows up as Deep Vein Thrombosis, however, the blood clots can show up anywhere in the human body. This is caused by a deficiency in activated Protein C which is a key regulator in blood clotting. I did not know any of this before reading this project, so this is all very interesting to learn. He also stated that Factor V Leiden is the leading cause of the deficiency in Activated Protein C. It can also appear as a pulmonary embolism. Blood clots in the body can be serious because they interrupt the blood flow which can cause a person to lose a limb or worse, die. Activated Protein C is supposed to dissolve the clot before it can form, however, with this deficiency, the clot would be allowed to form anywhere in the body causing serious problems for the individual. Overall this project was well done and I learned from it.