Haemophilia, or hemophilia, is a mostly inherited genetic disorder that impairs the body's ability to make blood clots, a process needed to stop bleeding. This results in people bleeding for a longer time after an injury, easy bruising, and an increased risk of bleeding inside joints or the brain. Those with a mild case of the disease may have symptoms only after an accident or during surgery. Bleeding into a joint can result in permanent damage while bleeding in the brain can result in long term headaches, seizures, or a decreased level of consciousness.
Haemophilia A is a blood clotting disorder caused by a genetic deficiency in clotting factor VIII, thereby resulting in significant susceptibility to bleeding, both internally and externally. This condition occurs almost exclusively in males born to carrier mothers due to X-linked recessive inheritance. Nevertheless, rare isolated cases do emerge from de novo (spontaneous) mutations.
Haemophilia B, also spelled hemophilia B, is a blood clotting disorder causing easy bruising and bleeding due to an inherited mutation of the gene for factor IX, and resulting in a deficiency of factor IX. It is less common than factor VIII deficiency.
Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism of coagulation involves activation, adhesion and aggregation of platelets, as well as deposition and maturation of fibrin.
Von Willebrand disease (VWD) is the most common hereditary blood-clotting disorder in humans. An acquired form can sometimes result from other medical conditions. It arises from a deficiency in the quality or quantity of von Willebrand factor (VWF), a multimeric protein that is required for platelet adhesion. It is known to affect several breeds of dogs as well as humans. The three forms of VWD are hereditary, acquired, and pseudo or platelet type. The three types of hereditary VWD are VWD type 1, VWD type 2, and VWD type 3. Type 2 contains various subtypes. Platelet type VWD is also an inherited condition.
Haemophilia C (also known as plasma thromboplastin antecedent deficiency or Rosenthal syndrome) is a mild form of haemophilia affecting both sexes, due to factor XI deficiency. It predominantly occurs in Ashkenazi Jews. It is the fourth most common coagulation disorder after von Willebrand's disease and haemophilia A and B. In the United States, it is thought to affect 1 in 100,000 of the adult population, making it 10% as common as haemophilia A.
Factor VIII (FVIII) is an essential blood-clotting protein, also known as anti-hemophilic factor (AHF). In humans, factor VIII is encoded by the F8 gene. Defects in this gene result in hemophilia A, an X-linked coagulation disorder. Factor VIII is produced in the liver’s sinusoidal cells and endothelial cells outside the liver throughout the body. This protein circulates in the bloodstream in an inactive form, bound to another molecule called von Willebrand factor, until an injury that damages blood vessels occurs. In response to injury, coagulation factor VIII is activated and separates from von Willebrand factor. The active protein interacts with another coagulation factor called factor IX. This interaction sets off a chain of additional chemical reactions that form a blood clot.
Coagulation factor VII is one of the proteins that causes blood to clot in the coagulation cascade, and in humans is coded for by the gene F7. It is an enzyme of the serine protease class. Once bound to tissue factor released from damaged tissues, it is converted to factor VIIa, which in turn activates factor IX and factor X.
Protein C, also known as autoprothrombin IIA and blood coagulation factor XIV, is a zymogen, that is, an inactive enzyme. The activated form plays an important role in regulating anticoagulation, inflammation, and cell death and maintaining the permeability of blood vessel walls in humans and other animals. Activated protein C (APC) performs these operations primarily by proteolytically inactivating proteins Factor Va and Factor VIIIa. APC is classified as a serine protease since it contains a residue of serine in its active site. In humans, protein C is encoded by the PROC gene, which is found on chromosome 2.
Factor X, also known by the eponym Stuart–Prower factor, is an enzyme of the coagulation cascade. It is a serine endopeptidase. Factor X is synthesized in the liver and requires vitamin K for its synthesis.
Factor V is a protein of the coagulation system, rarely referred to as proaccelerin or labile factor. In contrast to most other coagulation factors, it is not enzymatically active but functions as a cofactor. Deficiency leads to predisposition for hemorrhage, while some mutations predispose for thrombosis.
Factor XI or plasma thromboplastin antecedent is the zymogen form of factor XIa, one of the enzymes of the coagulation cascade. Like many other coagulation factors, it is a serine protease. In humans, Factor XI is encoded by the F11 gene.
Congenital afibrinogenemia is a rare, genetically inherited blood fibrinogen disorder in which the blood does not clot normally due to the lack of fibrinogen, a blood protein necessary for coagulation. This disorder is autosomal recessive, meaning that two unaffected parents can have a child with the disorder. The lack of fibrinogen expresses itself with excessive and, at times, uncontrollable bleeding.
Prothrombin complex concentrate (PCC), also known as factor IX complex, sold under the brand name Kcentra among others, is a combination medication made up of blood clotting factors II, IX, and X. Some versions also contain factor VII. It is used to treat and prevent bleeding in hemophilia B if pure factor IX is not available. It may also be used for reversal of warfarin therapy. It is given by slow injection into a vein.
Factor VIII is a medication used to treat and prevent bleeding in people with hemophilia A and other causes of low factor VIII. Certain preparations may also be used in those with von Willebrand's disease. It is given by slow injection into a vein.
The EGF-like domain is an evolutionary conserved protein domain, which derives its name from the epidermal growth factor where it was first described. It comprises about 30 to 40 amino-acid residues and has been found in a large number of mostly animal proteins. Most occurrences of the EGF-like domain are found in the extracellular domain of membrane-bound proteins or in proteins known to be secreted. An exception to this is the prostaglandin-endoperoxide synthase. The EGF-like domain includes 6 cysteine residues which in the epidermal growth factor have been shown to form 3 disulfide bonds. The structures of 4-disulfide EGF-domains have been solved from the laminin and integrin proteins. The main structure of EGF-like domains is a two-stranded β-sheet followed by a loop to a short C-terminal, two-stranded β-sheet. These two β-sheets are usually denoted as the major (N-terminal) and minor (C-terminal) sheets. EGF-like domains frequently occur in numerous tandem copies in proteins: these repeats typically fold together to form a single, linear solenoid domain block as a functional unit.
An obligate carrier is an individual who may be clinically unaffected but who must carry a gene mutation based on analysis of the family history; usually applies to disorders inherited in an autosomal recessive and X-linked recessive manner.
Moroctocog alfa is a recombinant antihemophilic factor genetically engineered from Chinese hamster ovary (CHO) cell line. Chemically it is a glycoprotein. It is manufactured by Genetics Institute, Inc. and used to control and prevent hemorrhagic bleeding and prophylaxis associated with surgery or to reduce the number of spontaneous bleeding episodes in patients with hemophilia A. It is partially a recombinant coagulation factor VIII since it has an amino acid sequence which compares to the 90 + 80 kDa form of factor VIII (BDDrFVIII). It also has posttranslational modifications which are similar to those of the plasma-derived molecule. It can not prevent hemorrhagic bleeding associated with von Willebrand's disease since it is not a von Willebrand factor.
Recombinant factor VIIa (rfVIIa) is a form of blood factor VII that has been manufactured via recombinant technology. It is administered via an injection into a vein. It is used to treat bleeding episodes in people who have acquired haemophilia, among other indications. There are several disimilar forms, and biosimilars for each. All forms are activated.
Efmoroctocog alfa, sold under the brand name Elocta among others, is a medication for the treatment and prophylaxis of bleeding in people with hemophilia A. Efmoroctocog alfa is a recombinant human coagulation factor VIII, Fc fusion protein (rFVIIIFc). It is produced by recombinant DNA technology in a human embryonic kidney (HEK) cell line.
