Factor VIII replacement

Spiegel PC Jr, Stoddard BL. Optimization of factor VIII replacement therapy can structural studies help in evading antibody inhibitors Br J Haematol 2002 119(2) 310-22. 

Because the half-life of factor IX is approximately 24 hours, dosing can be less frequentthan with factor VIII. Table 100-5 provides general guidelines for dosing factor IX, based on the site and severity of the bleeding episode. As with factor VIII replacement therapy, individual pharmacokinetics may vary, and monitoring the patient s factor IX levels helps optimize therapy. 

A New Technology Standard for Safety and Efficacy in Factor VIII Replacement Therapy Designing an Advanced Category rFVIII Concentrate... 

Antihemophilic factor [9001-28-9] (AHF) is a protein found in normal plasma that is necessary for clot formation. It is needed for transformation of prothrombin to thrombin. Administration of AHF by injection or infusion can temporarily correct the coagulation defect present in patients with hemophilia. Antihemophilic factor VIII (Alpha Therapeutic) has been approved by the FDA as replacement therapy in patients with hemophilia B to prevent bleeding episodes, and also during surgery to correct defective hemostasis (178). 

Type 1 patients unresponsive to desmopressin, patients with types 2 and 3 von Willebrand s disease, and major surgery patients require replacement therapy with plasma-derived intermediate- and high-purity factor VIII virus-inactivated factor VIII concentrates containing von Willebrand factor. 

TABLE 64-3. Guidelines for Replacement Dosing with Factor VIII and Factor IX... 

Factor VIII and IX inhibitors are antibodies that develop in 20% and 12% of hemophilia A and hemophilia B patients, respectively, in response to replacement therapy. These antibodies bind to and neutralize the activity of infused factor concentrates. Although the inhibitors do not increase hemorrhage frequency, their existence challenges the treatment of bleeding episodes. Titers of inhibitors are measured and... 

Haemophilia A is also known as classical and is caused by lack of factor VIII. It is now treated by replacement with factor VIII which, when prepared from human blood, was not without its problems. It is now prepared by genetic engineering. 

Therapy is determined by the level of factor VIII deficiency. Severely affected patients have concentrations less than 1 %, in moderate disease this is present between 1 and 5 % whereas plasma levels between 5 and 30 % may be associated with bleeding only after trauma such as dental extraction. Additionally, the choice of replacement is modified by the site of bleeding and the presence or absence of inhibitors that interfere with the function of the factor. Cryoprecipitate or lyophilised concentrate is becom-... 

No patient experienced a significant adverse effect related to the procedure. None developed antibodies against factor VIII, and there was no cellular immune response to the fibroblasts. Four months later, four patients had higher levels of factor VIII than they had at baseline, although none was able to completely forgo replacement therapy. The findings are a first step toward clinical application, but many issues need to be clarified, especially why two patients failed to show any response. 

Replacement of deficient gene products or even of organs is also utilized in the treatment of genetic disorders for example, replacement of coagulation factor VIII in hemophilia A, of or-antitrypsin in persons deficient in this factor or of pancreatic islet cells in some forms of diabetes mellitus. 

An uncomplicated hemorrhage into a joint should be treated with sufficient factor VIII or factor IX replacement to maintain a level of at least 30-50% of the normal concentration for 24 hours. Soft... 

The visualization method also worked with a 500-L perfusion reactor system for production of recombinant human coagulation factor VIII (hFVIII) in Chinese hamster ovary (CHO) cells [36,37]. Despite the diluted concentration of CHO cells and low titer of hFVIII in the medium, the nose could differentiate between the batch phase, medium replacement phase, and the high and low productivity phases during the five-week long cultivations (Fig. 10). The low concentration of hFVIII makes it credible to believe that there are other components associated with the product formation that the electronic nose responds to. 

In the past, hemophiliacs were treated with transfusions of a concentrated plasma fraction containing factor VIII. This therapy carried the risk of infection. Indeed, many hemophiliacs contracted hepatitis and AIDS. A safer preparation of factor VIII was urgently needed. With the use of biochemical purification and recombinant DNA techniques, the gene for factor VIII was isolated and expressed in cells grown in culture. Recombinant factor VIII purified from these cells has largely replaced plasma concentrates in treating hemophilia. 

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