Case Report On Factor X Deficiency

According to the National Hemophilia Foundation (n.d.), von Willebrand disease (VWD) is a genetic disorder caused by missing or defective von Willebrand factor (VWF), a clotting protein. VWF binds factor VIII, a key clotting protein, and platelets in blood vessel walls, which help form a platelet plug during the clotting process. The condition is named after Finnish physician Erik von Willebrand, who first described it in the 1920s (National Hemophilia Foundation, n.d.). The seriousness of the bleeding varied between family

Initiation of the common pathway requires the activation of Factor X and the formation of prothrombinase by the extrinsic and or intrinsic pathways.

Hemophilia A is an X-linked disorder caused by a deficient or defective clotting factor VIII (FVIII) protein, and characterized by spontaneous or traumatic bleeding into joints and muscles [Ragni]. It causes afflicted individuals to not be able to coagulate their blood very efficiently or at all when getting an injury in which blood is exposed either internally or externally. This disease can be very dangerous and fatal because major blood loss can occur if the patient has not received treatment.

Hemophilia A is a known X-linked recessive disorder. This condition or bleeding disorder is characterized by a deficiency in the activity of a coagulation factor, which in this case is F8 or coagulation factor VIII. This condition is clinically known to be heterogeneous and its severity depends on the plasma level of the coagulation factor VIII. Varying levels of hemophilia exist which are categorized based on percentage of coagulation factor within blood plasma compared to normal levels.

Mutations lead to a genetic deficiency in clotting factor VIII, causing increased bleeding and affects males a majority of the time. HA can occur in homozygous females. 5-10% of patients with HA have dysfunctional proteins (factor VII) and 90% to 95% of HA cases are characterized by a quantitative deficiency pf factor VII. Patients usually experience bleeding episodes: the most serious bleeding sites include, joints, muscles, digestive tract, and brain. 30% of cases are caused by new mutations. Medications are prescribed to prevent bleeding episodes and for more severe cases blood coagulate and blood plasma treatments are

Andexanet appears to be an effective antidote for the reversal of factor Xa inhibitor anticoagulants.

It inhibits thrombosis by inactivating co-factors Va, and VIIIa (Neyrinck, 2009). When deficient, Factor V can cause excessive blood clotting and Factor VIII, being an essential clotting factor, can cause blood to profusely move out of tissues once cut or damaged (Faust, 2001 and Yan, 2001). Thrombin may become limited, one reason being the decrease of plasma D-dimer, which again stimulates fibrinolysis (Bernard, 2001).

Factor V Leiden is the most common inherited form of thrombophilia (Stammers, Dorion, Trowbridge, Yen, Klayman, Murdock & Gilbert, 2005). Between 3 and 8 percent of people with European ancestry carry one copy of the factor V Leiden mutation in each cell, and about 1 in 5,000 people have two copies of the mutation (Stammers, Dorion, Trowbridge, Yen, Klayman, Murdock & Gilbert, 2005). People who inherit two copies of the mutation, one from each parent, have a higher risk of developing a clot than people who inherit one copy of the mutation. Considering that about 1 in 1,000 people per year in the general population will develop an abnormal blood clot, the presence of one copy of the factor V Leiden mutation increases that risk to 3 to 8 in 1,000, and having two copies of the mutation may raise the risk to as high as 80 in 1,000 (Stammers, Dorion, Trowbridge, Yen, Klayman, Murdock & Gilbert, 2005). Although, only about 10 percent of individuals with the factor V Leiden mutation ever develop

This organ system has a number of functions namely, to keep a constant body temperature as well as to ensure coagulation occurs specifically at the site of injury, as well as to ensure no added blood loss occurs to cause life-threatening effects. This process of blood coagulation is explained in three interconnected phases. In the first phase, the enzyme thrombokinase is activated due to the damage of tissue and the breaking down of platelets. Prothrombin is converted into thrombin by the disintegration of the thrombocytes, electrically charged calcium ions and other coagulation factors, as well as the blood activator and tissue activator which become involved in the coagulation process. The second phase includes production of the thrombin that transforms fibrinogen in the blood plasma into fibrin. The thrombus (or blood clotting) is formed by a fibrilliform mesh that encloses the blood cells. Lastly, the third phase, which takes place as retraction occurs of the fibres of the fibrin mesh. Solidification of the fibrous mesh takes place which closes the defect in the vascular wall. Coagulation is then followed by fibrinolysis (re-dissolution of the clot).

Binding of vWF to platelets is mediated primarily by the GpIb/IX/V complex. Collagen also binds to platelets via the GpIb/IX/V complex as well as through other collagen binding receptors on the platelet surface (like GpIa/IIa and GpVI). The GpIb/IX/V complex also binds to other proteins like thrombin and other proteins in the coagulation cascade and is critical for initial platelet response (50-52). These vWF/collagen bound platelets form a monolayer of activated platelets that secrete their granules and activate other platelets, which triggers the extension phase. Important mediators in this process include thromboxane A2 (inhibited by aspirin), ADP (inhibited by P2Y12-inhibitors) and thrombin ( inhibited by bivalirudin, dabigatran, heparin and low-molecular weight heparin) ( 53). The final downstream step of platelet activation is the expression of to bind other activated platelets (52,53). The platelet clot formation afterwards undergoes the stabilization phase, wherein the platelets form a close network. Several receptors have been implicated in this process, including the previously mentioned GPIIb/IIIa-receptors as well as CD40 and its ligand (CD40L) (51). The final step in thrombus formation is the activation of the coagulation cascade with the deposition of fibrin to stabilize the thrombus. This process is started by exposure of tissue factor to the coagulation system, thrombin generation and final conversion of insoluble fibrinogen into fibrin

Human beings contain tens of thousands of genes that decide what characteristic will each person have from the color of their eyes to their risk of contracting various disease. Amazingly, one misplaced gene can change a person life forever. For instance,is a rare bleeding disorder in which the blood doesn't clot normally. Hemophilia is a genetic disease where there is a defect in the series of protein that forms blood clots. The series of proteins is called the coagulation cascade in which each factor activate each other in chain reaction. The last to to activate is factor 10a which in turn activates thrombin. Thrombin is an enzyme that converts fibrinogen to fibrin. The large amounts of fibrin then forms long strands and merges with platelets

The active ingredient in Alprolix is a recombinant Fc fusion protein containing the Human Coagulation Factor IX concentrate (Biogen Idec) and is expressed in a human embryonic kidney cell line. It is indicated in adults and children with hemophilia B; a rare hereditary bleeding disorder caused by the deficiency of Coagulation Factor IX. Blood clotting factor IX is located on the X chromosome, therefore, hemophilia B is an X-linked inheritance that predominately affects males. Although there is no cure for patients with hemophilia B, there are available products marketed to replace defective clotting factor such as Alprolix.

Baxter Healthcare Corporation (Baxter) has developed a coagulation factor IX recombinant drug product named RIXUBIS, which is intended for the treatment and prevention of bleeding episodes, routine prophylaxis, and perioperative management of haemophilia B patients. Baxter’s recombinant coagulation factor IX is a glycoprotein secreted by genetically engineered mammalian cells derived from a Chinese hamster ovary (CHO) cell line.

Coagulation has 4 main parts, the first is constriction, this involves the narrowing of blood vessels to slow blood flow, the next is the activation of platelets by thrombin, which accumulate at the site of the injury to form an impermanent, platelet plug. Fibrinogen is the main protein used in platelet clumping. Then a fibrin mesh (clot) is formed and ensnares the plug to give it stability. Finally the clot must dissolve to return blood flow to its original state, this occurs after the tissue has been repaired to a suitable standard. A haemophiliac lacks the proteins needed to ensure this process at the normal pace, this means that the clotting process is slowed enough that the bleeding time has extended passed the normal rate. Depending on the severity of the protein deficiency this can be a very large or very small time

Occasionally a baby is born with this disorder and no family history of it. When this happens, it could be caused by a hidden gene, which is when several generations of female carry it, and it has not affected any male members of the family or a spontaneous mutation. With each pregnancy, a woman who is a carrier has a 25% possibility of having a son born with hemophilia. Since the father's X chromosome is what determines if the unborn child will be a girl, all of the daughters born of a man with hemophilia will be carriers. None of his sons, which is determined by the father through his Y chromosome, will have hemophilia. Individuals who suffer from mild hemophilia may choose to use a non-blood product known as Desmopressin acetate (DDAVP) to help treat the small bleeds and/or scrapes. For deep cuts or internal bleeding, the treatment called DDAVP may not be enough and therefore, may need a much more complex treatment. The clotting factor must be replenished so the affected person can form a clot to stop the bleeding. Plasma is one of the ‘human blood products’ than is used for factor replacement. Another factor replacement option is using the recombinant factor, which is produced in a laboratory.