The Clotting Problem Of Hemophilia

Original Paragraph: 
1. Blood is carried throughout the body within a network of blood vessels. When tissues are injured, damage to a blood vessel may result in leakage of blood through holes in the vessel wall. The vessels can break near the surface, as in a cut. Or they can break deep inside the body, making a bruise or an internal hemorrhage.

Platelets are small cells circulating in the blood. Each platelet is less than 1/10,000 of a centimeter in diameter. There are 150 to 400 billion platelets in a normal liter of blood. The platelets play an important role in stopping bleeding by clumping together and forming a plug, thereby beginning the repair of injured blood vessels. Clotting factors like factor VIII and IX are then needed to glue the plug in place thus forming a clot.

When one of the proteins, for example, factor VIII, is absent, the dominos stop falling, and the chain reaction is broken. Clotting does not happen, or it happens much more slowly than normal. The platelets at the site of the injury do not mesh into place to form a permanent clot. The clot is 'soft' and easily displaced. Without treatment, bleeding will continue until the pressure outside the broken vessel is equal to the pressure inside. This can take days and sometimes weeks.

2. Hemophilia is a family of clotting disorders. Most patients born with hemophilia are not able to form blood clots efficiently. Any modest injury can trigger excessive bleeding that can endanger life. Patients with severe hemophilia experience life-threatening spontaneous bleeds, unrelated to trauma. Some patients have a mild form of the disease in which a minor injury is not critical, but major trauma, such as car accidents and surgery, pose a significant risk.

Hemophilia is caused by mutations in one of the proteins involved in blood clotting (predominantly Factor VIII or Factor IX). Most patients, roughly 85%, have Hemophilia A and produce too little or no Factor VIII. Factor VIII is a relatively large protein and mutations occur as large deletions (6%), point mutations (43%), or as inversions in which part of the DNA is flipped backwards (intron 22A, intron 1). Patients with Hemophilia B have a defect in their Factor IX gene, such as deletions of variable length or point mutations. Patients with mild hemophilia maintain low levels of the clotting factor (5%-40% of the normal level in blood).

Key Ideas: 
- Platelets are small cells circulating in the blood, these platelets play an important role in stopping bleeding by clumping together and forming a plug
- Clotting factors like factor VIII and IX are then needed to glue the plug in place thus forming a clot
- When one of the proteins is absent, the chain reaction is broken. 
- Without treatment, bleeding will continue until the pressure outside the broken vessel is equal to the pressure inside. This can take days and sometimes weeks
- Hemophilia is a family of clotting disorders
- Patients with severe hemophilia experience life-threatening spontaneous bleeds, unrelated to trauma
- Patients have a mild form of the disease in which a minor injury is not critical, but major trauma, such as car accidents and surgery, pose a significant risk.
- Hemophilia is caused by mutations in one of the proteins involved in blood clotting
- There are two kinds of Hemophilia: Hemophilia A and Hemophilia B

Source:

1. "The Clotting Problem in Hemophilia." - Canadian Hemophilia Society. N.p., n.d. Web. 8 Oct. 2014. <http://www.hemophilia.ca/en/bleeding-disorders/hemophilia-a-and-b/the-clotting-problem-in-hemophilia/>.

2. "Hemophilia." ASGCT. N.p., n.d. Web. 8 Oct. 2014. <http://www.asgct.org/general-public/educational-resources/gene-therapy-and-cell-therapy-for-diseases/hemophilia>.

Paraphrasing: 

Hemophilia is an inherited disease that prevents the patient from forming blood clots effectively. People who are not infected with hemophilia have a normal way of recovering. When their tissues in the body, both inside and outside, are injured and damaged, blood vessels might get injured as well, thus the blood is exposed and leaks out from the hole of the cut, bruise or internal hemorrhage. When people experience being injured, the platelets that flow in the blood are extremely essential cells that are required to cluster and cover the hole of the injury, enabling the blood to stop flowing out.

However when one has hemophilia, injuries may result to continuous bleeding that can possibly be detrimental to one’s life.  The patient may experience one of the two effects. The first being life-imperiling bleeding injuries that have no relation to traumas, and the other being light forms of the disease with non-critical minor injuries, however major traumas may occur that highly risks the patient’s well being, in which these include car accidents and surgery.

In addition, for a patient to have hemophilia means to have a gene mutation in their body. In other words, the proteins responsible for blood clotting must have experienced substitution, inversion, deletion or insertion. Blood clotting proteins of Factor VIII and IX are predominantly the factors that were mutated. Estimated to be around 85% of the Hemophilia patients are infected with Hemophilia A, in which the body produces too little or no Factor VIII. Mutations of this particular factor are 6% due to large deletions, 43% due to substitution or 51% due to inversions. On the other hand, Hemophilia B is a case where in the patient has a flaw in their Factor IX gene, in which it is caused by deletions or substitution.

Figure 1: How Hemophilia Works
http://www.hemophilia.ca/en/bleeding-disorders/hemophilia-a-and-b/the-clotting-problem-in-hemophilia/