Factor VIII concentrate products available

Clinical trials have demonstrated excellent efficacy with recombinant human factor VIII concentrates available as Recombinate and Kogenate. These recombinant factor VIII products are purified from the cell culture of plasmids, not viral DNA-transfected hamster cells and therefore do not express viral sequences. The addition of human serum albumin for stabilization, constitutes the sole possible source for human viral contamination. More recently recombinant factor IX has been genetically engineered by insertion of the human factor IX gene into a Chinese hamster ovary cell line. It has been proved to be safe and effective in the treatment of patients with hemophilia B. 

Protein purification, introduced in the 1990s, produced high-purity concentrates with increased amounts of factor VIII or factor IX relative to the product s total protein content. Recombinant factor VIII and then factor IX also became available. The first-generation recombinant factor VIII products utilize human and animal proteins in culture and add human albumin as a protein stablilizer. Second-generation recombinant factor VIII concentrates removed albumin as a protein stabilizer, and the third-generation products lack human and animal proteins in the culture media. Finally, gene therapy for the treatment of hemophilia is now in the early stages of clinical trials. 

Factor VIII concentrates can be classified according to their level of purity, which refers to the specific activity of factor VIII in the product. Cryoprecipitate is a low-purity product, containing a specific factor VIII activity level of less than 5 units/mg of protein. This product is no longer considered a primary treatment for factor VIE deficiency in countries where factor VEI concentrates are available, because cryoprecipitate does not undergo a viral inactivation process. Intermediate-purity products have a specific activity of factor VIE of 1 to 10 units/mg of protein, while high-purity products have a specific activity of 50 to 1,000 units/mg of protein. Ultrahigh-purity plasma-derived products are prepared with monoclonal antibody purification steps and have a specific activity of 3,000 units/mg of protein prior to the addition of albumin as a stabihzer. 

Von Willebrand factor/factor VIII concentrates play a key role in the treatment of patients with von Willebrand disease. The von Willebrand factor multimer fraction is very effective in achieving hemostasis. The available products differ in production techniques, von Willebrand factor multimer content, and activity. No serious adverse events have been related to Haemate P/Humate P in clinical trials. Non-serious adverse events include allergic symptoms in under 6% of patients, chills, phlebitis, edema, pain in the limbs, and pseudothrombocytopenia in a few patients. No cases of thrombosis have been reported in clinical trials, although caution should be taken in patients with von Willebrand disease who have other thrombotic risk factors [8 ]. 

Cryoprecipitate may also be used for patients with factor VIII deficiency and von Willebrand disease if desmopressin is not indicated and a pathogen-inactivated, recombinant, or plasma-derived product is not available. The concentration of factor VIII and von Willebrand factor in cryoprecipitate is not as great as that found in the concentrated plasma fractions. Moreover, cryoprecipitate is not treated in any manner to decrease the risk of viral exposure. For infusion, the frozen cryoprecipitate unit is thawed and dissolved in a small volume of sterile citrate-saline solution and pooled with other units. Rh-negative women with potential for childbearing should receive only Rh-negative cryoprecipitate because of possible contamination of the product with Rh-positive blood cells. 

Prothrombin complex concentrates are available in three main types the most effective are four-factor concentrates containing factors II, VII, IX, and X. Three-factor concentrates (mainly in use in the USA) lack factor VII and are less effective in reversing oral anticoagulation therapy. The third type consists of activated products, such as factor VIII inhibitor bypassing activity (FEIBA) these products are not indicated for reversal of oral anticoagulation, but they are indicated for treatment of inhibitors (anti-factor VIII antibodies) in patients with hemophilia A [31 ]. FEIBA is associated with thrombotic events [67 ]. 

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