factor concentrates
Although coagulation factor concentrates were known to transmit hepatitis when they first became available, the risk has been reduced over the years by improvements to the donor history, the addition of laboratory tests for transmissible agents, and the introduction in the mid‐1980s of methods to treat the concentrates to separate and inactivate viruses [95, 96, 99]. The major methods of viral inactivation for plasma‐derived concentrates are: (a) dry heating, in which the sealed final vial is heated between 80°C and 100°C; (b) pasteurization, in which the concentrate is heated to 60°C while still in solution before lyophilization; (c) vapor heating, in which the lyophilized powder is exposed to steam before bottling; and (d) solvent–detergent (SD) treatment, in which the organic solvent tri‐n‐butyl‐phosphate and the detergent Tween 80 or Triton X‐100 are added at intermediate processing steps. Currently, the SD method is most commonly used. The pasteurization and vapor heating methods result in substantial loss of factor VIII activity [99, 100].
Table 5.10 Plasma‐derivative products.
Source: From information provided by the Plasma Protein Therapeutics Association; and modified from Burnouf T. Transfus Med Rev 2007; 21(2):101–117.
| Plasma product | Indication |
|---|---|
| Albumin | |
| Serum human albumin Plasma protein fraction | Restoration of plasma volume subsequent to shock, trauma, surgery, burns, and therapeutic plasma exchange |
| Immunoglobulins | |
| Immunoglobulin (intravenous and intramuscular) | Treatment of agammaglobulinemia and hypogammaglobulinemia; passive immunization for hepatitis A and measles |
| IgM‐enriched immune globulin | Treatment and prevention of septicemia and septic shock due to toxin liberation in the course of antibiotic treatment |
| Cytomegalovirus immune | Passive immunization subsequent to exposure to globulin cytomegalovirus |
| Hepatitis B immune globulin | Passive immunization subsequent to exposure to hepatitis B |
| Rabies immune globulin | Passive immunization subsequent to exposure to rabies |
| Rubella immune globulin | Passive immunization subsequent to exposure to German measles |
| Tetanus immune globulin | Passive immunization subsequent to exposure to tetanus |
| Vaccinia immune globulin | Passive immunization subsequent to exposure to smallpox |
| Varicella‐zoster immune | Passive immunization subsequent to exposure to globulin chicken pox |
| RhO(D) immune globulin | Treatment and prevention of hemolytic disease of fetus and newborn resulting from Rh incompatibility and incompatible blood transfusions |
| Protease inhibitors | |
| Alpha1 proteinase inhibitor | Used in the treatment of emphysema caused by a genetic deficiency |
| C1‐esterase inhibitor | Hereditary angioneurotic edema |
| Coagulation proteins | |
| Antithrombin III | Treatment of bleeding episodes associated with liver disease, antithrombin III deficiency, and thromboembolism |
| Antihemophilic factor | Treatment or prevention of bleeding in patients with hemophilia A |
| Anti‐inhibitor coagulant | Treatment of bleeding episodes in the presence of complex factor VIII inhibitor |
| von Willebrand factor/factor VIII concentrate | Treatment or prevention of bleeding in patients with von Willebrand factor |
| Unactivated prothrombin complex concentrate (PCC): | |
| 4‐Factor PCC includes vitamin K–dependent factors (factors II, VII, IX, X) 3‐Factor PCC includes factors II, IX,and X | Urgent reversal of acquired coagulation factor deficiency induced by vitamin K antagonists therapy in patients with acute major bleeding or need for an urgent surgery/invasive procedure |
| Activated PCC: 4‐Factor PCC includes factors II, VII,IX, and X; only factor VII is mostly the activated form | Prevention or treatment of bleeding in patients with hemophilia A and B complicated by an inhibitor, acquired hemophilia A, or bleeding associated with certain anticoagulants |
| Factor IX | Prophylaxis and treatment of patients with factor IX deficiency |
| Factor X | Prophylaxis and treatment of patients with factor X deficiency |
| Factor XI | Prevention and treatment of bleeding associated with factor XI deficiency |
| Factor XIII | Treatment of bleeding and disorders of wound healing due to factor XIII deficiency |
| Fibrinogen | Treatment of hemorrhagic diathesis in hypofibrinogenemia, dysfibrinogenemia, and afibrinogenemia |
| Fibrinolysin | Dissolution of intravascular clots |
| Other proteins | |
| Haptoglobin | Supportive therapy in viral hepatitis and pernicious anemia |
| Serum cholinesterase | Treatment of prolonged apnea after administration of succinyl choline chloride |
Each of these methods uses a different strategy of viral inactivation. There are differing amounts of data about the effectiveness of these viral inactivation methods, because not all of their products have been subjected to randomized controlled trials. In general, it appears that the methods are effective in inactivating virus with a lipid envelope, but infections with nonlipid envelope viruses, such as parvovirus B19 [101] and hepatitis A [102], have been reported.
The first recombinant‐produced coagulation factor VIII concentrates became available in late 1992 and 1993 [103, 104]. It appears that these products transmit no diseases. The factor VIII is produced in murine cell lines, and both fetal calf serum and murine monoclonal antibodies are used in the production process. The products are subjected to viral inactivation steps, even though there should be no way that human viruses should contaminate the products.