Factor IX complex

Factor IX complex treatment of hemophilia B and other coagulation 57 5 X 10-"... 

Proplex T (Factor IX Complex)—used for factor VIII inhibitors, and factor VII or IX deficiency... 

Factor IX complex, human (AlphaNine SD, Bebulin VH, BeneFix, Konyne 80, Mononine, Profilnine SD, Proplex T, Proplex SX-T)... 

Factor IX complex -fromblood fractionation [FRACTIONATION,BLOOD - PLASMAFRACTIONATION] (Volll)... 

For patients with high titre factor VIII inhibitors, standard factor IX complex products are first-line therapy but activated factor IX complex concentrates may be necessary for continued, more frequent or more severe bleeding. Porcine factor VIII or recombinant human factor Vila may be necessary for major bleeds or elective surgery. 

Tabor E, Aronson DL, Gerety RJ. Removal of hepatitis-B-virus infectivity from factor-IX complex by hepatitis-B immune-globulin. Experiments in chimpanzees. Lancet 1980 2(8185) 68-70. 

Boulis NM, Bobek MP, Schmaier A, Hoff JT. Use of factor IX complex in warfarin-related intracranial hemorrhage. Neurosurgery 1999 45(5) 1113-19. 

Factor IX complex, a blood derivative with hemostatic properties, is used in factor IX deficiency (hemophilia B or Christmas disease) in patients with factor VIII inhibition, in factor VII deficiency, and in overdosage with anticoagulant (see also Tables 17 and 18 and Figure 92). 

Factor IX complex (human), Konyne, Propter, Hemoplex (obsolete). A mixture of human factors II, Vll, IX, and X. 

Factor IX complex In a retrospective chart review of 28 patients treated with intravenous factor IX complex for warfarin-induced coagulopathy, the INR was reduced from 5.1 to 1.9 within a mean of 14 minutes there were no early thrombotic events or allergic reactions [67 ]. 

Factor IX. This factor is dependent on the presence of vitamin K for its activity as a biologicaUy functional procoagulant glycoprotein. Factor IX is converted to its active form by XIa in the classic scheme of the intrinsic pathway. However, it can also be activated via interaction with Factor Xa or the complex Factor III plus Factor VII in the presence of calcium. 

Figure 51-1. The pathways of blood coagulation. The intrinsic and extrinsic pathways are indicated. The events depicted below factor Xa are designated the final common pathway, culminating in the formation of cross-linked fibrin. New observations (dotted arrow) include the finding that complexes of tissue factor and factor Vila activate not only factor X (in the classic extrinsic pathway) but also factor IX in the intrinsic pathway, in addition, thrombin and factor Xa feedback-activate at the two sites indicated (dashed arrows). (PK, prekallikrein HK, HMW kininogen PL, phospholipids.) (Reproduced, with permission, from Roberts HR, Lozier JN New perspectives on the coagulation cascade. Hosp Pract [Off Ed] 1992Jan 27 97.)...

Factor IX Replacement Hemophilia B therapy may include recombinant (produced via transfection of mammalian cells with the human factor IX gene) or plasma-derived (concentrate from pooled plasma) factor IX (see Table 64-2). Guidelines for choosing the factor-concentrate formulation for hemophilia B are similar to the guidelines for hemophilia A. However, older-generation factor IX concentrates containing other vitamin K-dependent proteins (e.g., factors II, VII, and IX), called prothrombin complex concentrates (PCCs), have been associated with thrombogenic side effects. Consequently, these products are not first-line treatment for hemophilia B.11... 

The activity of factor Vila is enhanced astronomically (10 millionfold) upon binding to tissue factor. The VII or VHa-tissue factor complex activates factors IX and X and autoactivates factor VII. Although the activity of the tissue factor-factor VII complex is expressed without the presence of the negatively charged phosphatidylserine, the activity can be enhanced by its presence (9). 

Intact factor VIII, as usually purified from the blood, consists of two distinct gene products factor VIII and (multiple copies of) von Willebrand s factor (vWF Figure 12.6). This complex displays a molecular mass ranging from 1 to 2 MDa, of which up to 15 per cent is carbohydrate. The fully intact factor VIII complex is required to enhance the rate of activation of factor IX of the intrinsic system. 

Some 5-25 per cent of individuals suffering from haemophilia A develop anti-factor VIII antibodies, and 3-6 per cent of haemophilia B sufferers develop anti-factor IX antibodies. This complicates treatment of these conditions and, as mentioned previously, one approach to their treatment is direct administration of factor Vila. The therapeutic rationale is that factor Vila could directly activate the final common steps of the coagulation cascade, independently of either factor VIII or IX (Figure 12.1). Factor Vila forms a complex with tissue factor that, in the presence of phospholipids and Ca2+, activates factor X. 

This complex catalyzes the activation of factor IX or factor X as a part of the overall coagulation cascade. 

Platelet membrane phosphatidylserine is critical to the formation of the tenase complex since on its surface activated factor VIII (Villa) generates a high-afflnity binding site for activated factor IX (IXa) in the presence of calcium. Subsequently, this complex activates factor X (2, 13). Platelet membrane phosphatidylserine similarly anchors activated factor V (Va), favoring the calcium-dependent binding of activated factor X (Xa). The prothrombinase complex is generated on the surface of the anionic platelet membrane phosphatidylserine when factor Va binds prothrombin. The prothrombinase complex cleaves prothrombin to produce thrombin, which has a multifunctional role (14). 

Purification entails use of an immunoaffinity column containing immobilized murine antifactor VII antibody. It is initially produced as an unactivated, single chain 406 amino acid polypeptide, which is subsequently proteolytically converted into the two-chain active factor Vila complex. After sterilization by filtration, the final product is aseptically filled into its final product containers and freeze-dried. The excipients present in the product include sodium chloride, calcium chloride, polysorbate 80, mannitol and glycylglycine. When freeze-dried in the presence of these stabilizing substances and stored under refrigerated conditions, the product displays a shelf-life of at least 2 years. It has proved effective in the treatment of serious bleeding events in patients displaying anti-factor VIII or IX antibodies. 

Hemostasis begins with the formation of the platelet plug, followed by activation of the clotting cascade, and propagation of the clot. One of the major multicomponent complexes in the coagulation cascade consists of activated factor IX (factor IXa) as the protease, activated factor VIII (factor Villa), calcium, and phospholipids as the cofactors, and factor X as the substrate. Factor IXa can be generated by either factor Xa activation of the intrinsic pathway or by the tissue factor/factor Vila complex. 

II Prothrombin deficiency 30-40% 3 days Prothrombin complex concentrates (intermediate purity factor IX concentrates)... 

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