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Factor Viii Research Paper

In a galaxy far, far away… or in blood vessels far, far away awaits a powerful superhero Factor VIII. Yea, when this guy detects damage to his known territory, which is the entire blood vessel galaxy, he is out to risk his life to maintain the balance of the Hemostasis Empire. This superhero never sleeps. He is in constant circulation, circulating the blood vessels of the human body. Factor VIII though does not work alone when circulating the blood vessels when in inactive form. Factor VIII and his sidekick vWF both are bound together looking for damage and awaiting for injury that may arise at any second.

When injury happens (Intrinsic Pathway) vWF and Factor VIII splits. Factor VIII goes into action (going into VIIIa) interacting with another superhero named IX. This interaction sets off a chain of additional chemical reactions that help in the formation of a blood clot to save the day. This Factor VIII and IX interaction is apart of the intrinsic pathway the last step of the coagulation cascade just before the common pathway initiation. Factor VIII participates in blood coagulation; it is a cofactor for factor IXa which, in the presence of Ca2+ and phospholipids forms a complex that converts factor X to the activated form Xa.

This part is known as the tenase complex. So now you know who and what this superhero is all about, but what makes him so powerful during the cascade process? Well you already know about his sidekick vWF, who helps him keep an eye on everything in circulating the blood stream. When Factor VIII goes into active form, you have to watch out because he turns into a beast. What makes him really powerful is his suit that he puts on when he goes into action. His suit is made up of smaller subunits of proteins that is a part of his superpowers. The key that makes this suit so powerful and strong during coagulation is ionized calcium and PF3.

Calcium and PF3 help aids into the activation into the common pathway, which is the start of factor X. The name of his suit is VIII:C. The “C” stands for coagulation. This VIII:C suit is responsible for the clotting or procoagulation activity of VIII. This suit is functionally active in the coagulation cascade of the intrinsic pathway. When factor VIII senses a problem in the Hemostasis Empire, he goes into active form, puts on his powerful suit, and he is ready for action. But there was one detail that was left out. Factor VIII is one fast superhero because of thrombin.

Thrombin is a catalyst that speeds up the activation of VIII to VIIIa by making binding sites. Fibrin is also a big part that helps the superhero stick to the walls of the damaged area of the blood vessels. During the VIII to VIIIa coagulation step, the superhero brings in his army. That’s right platelets. These guys are very small, but together they are unstoppable and unmatchable. Escaping blood is no match for this army of platelets. Platelets are activated during the fight to help proceed into the common pathway, which later eventually forms a stable clot. *note: when Factor VIII goes into active form, vWF is not bound to VIII. ) So what about vWF? Let’s talk about him for a second since he is apart of Factor VIII.

Mr. Von Willebrand plays an important role in stopping the escape of blood from vessels a little differently than Factor VIII, but they work together in the fight. vWF works by mediating the adherence of platelets to one another and to sites of vascular damage. vWF binds to a protein complex made up of the glycoproteins Ib, IX, and V on the surfaces of platelets.

The binding of VWF to this complex facilitates the activation and aggregation of platelets and the interaction of platelets with components such as collagen in the damaged vessel lining. These actions are important in the formation of a blood clot that halts bleeding. Also vWF, as said from other studies, has an affect over Factor VIII’s suit (VIII:C) by protecting it from proteolytic activity. Proteolysis activity is the breakdown of proteins into smaller polypeptides or amino acids in which vWF stops this from happening during the fight. So to say, the secret identity of Factor VIII is his sidekick.

Without Mr. Von Willebrand, Factor VIII would not be as strong. Factor VIII’s habitat is all throughout the bloodstream. He particularly does not have a hide out because he is always patrolling with all eyes wide open. Factor VIII’s headquarters or base is all over, circulating blood vessels. Factor VIII was born from the edge of the galaxy, from the sub endothelial cells. “Factor VIII is synthesized by various tissues, including liver, kidney, and spleen, as an inactive single-chain protein. After extensive posttranslational processing, factor VIII is released into the circulation as a set of heterodimeric proteins.

This heterogenous population of factor VIII molecules readily interacts with vWF, which is produced and secreted by vascular endothelial cells (bloodjournal. org). ” Factor VIII’s side kick, vWF, is also from the edge of the galaxy, the sub endothelial cells. Like all of us human beings, we depend on vitamins to make sure our body functions properly. So yes, superheroes have to take vitamins too. Factor VIII is dependent on vitamin K. this gives him the ability to coagulate. Factor VIII in plasma has the highest molecular weight of any coagulation factor when he is added with his sidekick.

So together, they do rule the galaxy. “The activation (or activator) of factor VIII results from limited proteolysis catalyzed by thrombin or factor Xa, which binds the factor VIII substrate over extended interactive surfaces. The proteases efficiently cleave factor VIII at three sites, two within the heavy chain and one within the light chain resulting in alteration of its covalent structure and conformanntion and yielding the active cofactor, factor VIIIa. The role of factor VIIIa is to markedly increase the catalytic efficiency of factor IXa in the activation of factor X (NCBI). ”

There are some enemies out there that Factor VIII may have to go up against. In addition, there are some hemostasis empires out there who do not have VIII patrolling their galaxy. Hemophilia A is a big problem. This is a factor VIII deficiency (X-linked) which is a genetic disorder caused by missing or defective factor VIII. It is known to be passed down from parents to children, however, about 1/3 of cases are caused by a spontaneous mutation or a change in a gene. “According to the US Centers for Disease Control and Prevention, hemophilia occurs in approximately 1 in 5,000 live births.

There are about 20,000 people with hemophilia in the US. All races and ethnic groups are affected. Hemophilia A is four times as common as hemophilia B while more than half of patients with hemophilia A have the severe form of hemophilia (hemophilia. org). ” Symptoms of people with hemophilia A often, bleed longer than other people. Bleeds can occur internally, into joints and muscles, or externally, from minor cuts. How frequently a person bleeds and the severity of those bleeds depends on how much FVIII is in the plasma, the straw-colored fluid portion of blood.

Anti-C2 antibodies is an archenemy of the superhero. This antibody disrupt the binding of FVIII to phospholipid and vWF. Also there are antibodies to A2 and A3 interfere with FVIII binding to factor X and factor IXa. So there are alloantibodies out there circulating the galaxy that holds Factor VIII hostage. These though are very rare, so not very many hemostasis empires face this problem. There are laboratory tests to determine deficiencies of factor VIII. Tests known are Factor VIII assay and Partial Thromboplastin Time test (PTT).

So this is the Factor VIII & the vWF Super Pack. These two circulates and activates to help win the war against escaping blood to bring the Hemostasis Empire back in to balance. Together the sole theme of Factor VIII and vWF is that they give everything they have to the Hemostasis Empire to save the day. These two are so strong and so powerful together. Without vWF, VIII would not be as strong and without VIII, blood cannot clot properly. So next time when you get cut on your arm, thank vWF and VIII, because they play a big role in the blood clotting cascade

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