Acquired hemophilia - The development of an inhibitor, usually to factor VIII, causing a low plasma factor VIII activity level in a person with otherwise normal blood clotting. These autoantibodies usually occur in the presence of another autoimmune disease, pregnancy, lymphoid malignancy, or age >60 years.
Activity level (for coagulation factors) - A laboratory test that measures the functional amount of a clotting factor in the plasma, expressed as a percent of the activity found in normal human plasma. The normal level of factors VIII and IX is usually 50 IU/dL to 150 IU/dL.
Agammaglobulinemia - A total or near-total deficiency of gamma globulin which results in a tendency to develop infection. (See also hypogammaglobulinemia.)
Albumin, human serum - A protein that comprises a large proportion of the total protein in normal human plasma. It serves several functions including the maintenance of the volume of blood within blood vessels, and the balance of fluids and salts in the plasma. Albumin is added to some drugs and biological products to help stabilize their potency in manufacturing, shipping, and storage.
Alburex® - A brand of human albumin, available in two strengths 5% (Alburex® 5) and 25% (Alburex® 25), manufactured and marketed by CSL Behring.
Allele - A copy of a gene; the unit of DNA that specifies the sequence of a given protein. For most genes, an individual has two alleles, one inherited from the mother and one from the father. For genes on the X chromosome, such as factors VIII and IX, males only have one allele, whereas females have two alleles. This is why males are much more likely to express hemophilia A or B.
Alloantibody - An antibody (immunoglobulin) made by the body against a foreign substance, distinct from an autoantibody.
Antibodies - Or immunoglobulins, are derived from B cells. The primary function is to fight bacteria, viruses, toxins and other substances foreign to the body.
Antibody-antigen binding - The antibody molecules are Y-shaped molecules with two identical antigen binding sites—one at the tip of each arm of the Y. Because of their two antigen-binding sites, they are said to be bivalent. Such antibody molecules can crosslink antigen molecules into a large lattice, as long as the antigen molecules each have three or more antigenic determinants.
Antihemophilic factor (AHF) - The glycoprotein in plasma with factor VIII:C activity; also, the generic name of factor VIII products for replacement therapy in hemophilia A.
Autoantibody - An antibody directed against normal body components that is produced in some disease states.
Biologic - Products, such as coagulation factors, albumin, and immunoglobulin, that are derived from a biological source (human plasma or cell culture) rather than being synthesized from a chemical source.
Biologic recovery - The amount of a drug in the plasma after a dose is given. The biologic recovery of clotting factors may be decreased if an inhibitor is present.
Bolus - In infusion practice, the procedure of giving a concentrated dose of an approved therapeutic product over a short period of time.
Calcium - A mineral with several functions in the human body. In an insoluble form, it is a major component of bone. An ionized form circulates in plasma and is necessary for several processes, including coagulation.
Carrier - In genetics, an individual with one allele for a recessive trait. The trait is usually not evident in the carrier, but is likely to be passed to half of the carrier's children. Women may be carriers of hemophilia A or B.
Cell line - Cells used in the production of recombinant proteins, including coagulation factors.
Christmas disease - Another name for hemophilia B, the inherited factor IX deficiency.
Chromatography - A process to separate the components of a mixture, based on size, charge, or other chemical properties.
Cohn fractionation - A method of separating and purifying plasma into its component parts, based on the solubility under cold temperatures and in ethanol.
Cold ethanol fractionation - This method was originally developed by Cohn and was modified by Swiss scientists Kistler and Nitschmann to make it more efficient. The process depends on the fact that the different proteins in the plasma have different solubilities under different conditions of temperature, pH, ionic strength, and ethanol concentration.
Cryoprecipitate - The portion of plasma proteins that are insoluble after plasma is frozen, then thawed at 4°C. Cryoprecipitate contains large quantities of factor VIII, von Willebrand factor, fibrinogen, fibronectin, and factor XIII, among other proteins. Cryoprecipitate is made from individual units of human plasma. It is stored frozen, usually in a hospital blood bank.
ddavp/desmopressin challenge - The administration of desmospressin acetate to patients with hemophilia A or von Willebrand disease, to determine whether or not an individual patient responds with an appropriate increase of the plasma level of the deficient factor.
Desmospressin acetate - The acetate salt of 1-deamino, 8-D-arginine vasopressin, a synthetic analog of vasopressin.
ELISA - An acronym that means enzyme-linked immunosorbent assay; a test to measure very small quantities of a substance.
Enveloped virus - Infectious particle consisting of a nucleocapsid composed of nucleic acid that is packed into a protein shell and surrounded by a membrane made of lipids and proteins.
Excipient - An inactive ingredient added to the formulation of a drug or biologic.
Factor assay - A test to determine the functional amount of a specific clotting factor in the plasma. (See also activity level.)
Factor IX - A protein in the plasma that functions in the clotting cascade to activate factor X. Factor IX circulates as a zymogen, or inactive enzyme. When activated, it is designated factor IXa. Factor IXa works together with factor VIIIa for normal clotting activity.
Factor IX deficiency - Hemophilia B, an inherited X-linked coagulation disorder. (See also Christmas disease.)
Factor VIII - A protein in the plasma that functions with factor IXa in the clotting cascade to activate factor X. Factor VIII is a "cofactor" that facilitates the enzyme activity of factor IXa. Factor VIII circulates in an inactive form, attached to von Willebrand factor. When activated, it is designated factor VIIIa.
Factor VIII deficiency - Hemophilia A, an inherited X-linked coagulation disorder. A mild deficiency of factor VIII may also be due to von Willebrand disease.
Factor XIII - A plasma protein, also contained within fibrin sealant preparations, that cross links fibrin, resulting in the formation of a stable fibrin clot.
Fibrinogen - A plasma protein that, when activated by thrombin, becomes fibrin, the principle component of a blood clot.
Fractionation - The process of separating plasma into its component parts, such as clotting factors, albumin, and immunoglobulin, and purifying them.
FVIII:C - An abbreviation for factor VIII coagulant activity.
Gel filtration - A type of chromatography in which the components of a mixture are separated according to molecular size.
Half-life - The time required for half of a drug or biologic to be eliminated from the body.
FS Antihemophilic Factor (Recombinant) Formulated with Sucrose - The brand of recombinant antihemophilic factor VIII (human) manufactured by Bayer Corporation and distributed by CSL Behring.
Hemarthrosis - The condition of bleeding into a joint cavity. It is a frequent complication of bleeding disorders such as hemophilia A or B, and may cause intense pain. Over time, repeated hemarthroses can cause damage to the joint structures, chronic arthritis, or the need for prosthetic joint replacement.
Hemophilia A - See factor VIII deficiency.
Hemophilia B - See factor IX deficiency; see also Christmas disease.
Heterozygote - An individual with different alleles of a specified gene.
Homozygote - An individual processing identical alleles of a gene.
Humate-P®Antihemophilic Factor/von Willebrand Factor Complex (Human), Dried, Pasteurized - A brand of antihemophilic factor and von Willebrand factor manufactured and distributed by CSL Behring.
Hypogammaglobulinemia - A condition with abnormally low levels of immune globulin, a type of primary immune deficiency.
Hypovolemia - A decrease in the volume of circulating blood.
IGIV - Immune globulin, intravenous. A purified fraction of plasma, consisting largely of IgG antibodies.
Immune tolerance - The process of manipulating the immune system to recognize a substance as "self" (i.e., not foreign) to reduce or eliminate a reaction to that substance. Immune tolerance is usually achieved by administering frequent doses of the substance in question. Often, but not always, after a period of several months, the immune reaction against the substance abates. Immune tolerance also refers to the natural mechanism during development by which the body recognizes the normal elements and suppresses any immune reaction against itself.
Immunoaffinity chromatography - A method of purifying plasma proteins using monoclonal antibodies. (See also monoclonal antibody purification.)
Immunodeficiency - A decreased ability to fight infection caused by a decrease in the function or amount of immune globulins, or certain white blood cells.
Immunoglobulin - A group of plasma proteins, also known as antibodies, synthesized by a subset of B-lymphocytes called plasma cells. These proteins help to protect the body against infections. There are five major classes IgA, IgD, IgG, IgM, and IgE.
Inhibitor - An antibody against a coagulation factor that interferes with coagulation factor function and complicates replacement therapy. See also immune tolerance, alloantibody, autoantibody.
International unit (IU) - A standardized measure of the activity of a substance. The IU is the measurement that determines the potency of the product.
Intravenous (IV) administration - Administration of drugs or fluids directly into the veins.
Ion-exchange chromatography - A method of purifying plasma proteins using opposite-charge attraction. (See also chromatography.)
ITP: idiopathic thrombocytopenic purpura - An autoimmune disorder in which individuals develop antibodies directed against their own platelets, resulting in a low blood platelet count and a potential bleeding situtation.
IVIG - A common abbreviation used for human normal immunoglobulin for intravenous use.
Lipid-enveloped viruses - A subset of viruses that require a coat comprised of molecules related to fats or oils to be infectious. Examples include HIV and hepatitis C.
Loading dose - The initial dose in a series of doses of a therapeutic product, given for the purpose of attaining an effective plasma level in a short period of time.
Logarithmic, or log, reduction factor (LRF) - The LRF value represents the difference of the logarithms of the viral loads before and after the production step under evaluation. The virus inactivation/removal is indicated in decimal logarithm (log10) of the reduction factors.
Log kill (log reduction) - A measure of effectiveness of a particular process to remove certain viruses or bacteria from a biologic substance. One log reduction reduces the number of infectious units (i.e., certain viruses or bacteria) by 90%, two log reduction by 99%, three by 99.9%, four by 99.99%, and so on.
Lyophilization - The process of rapid freezing and dehydration under vacuum to produce a dried, stable biological product or drug.
Model viruses - Laboratory viruses that are used as substitutes for human pathogens.
Monoclonal antibody purification - A process used in the manufacture of protein products in which monoclonal antibodies are used to separate specific proteins such as factor VIII or factor IX from other proteins
Mononine®Coagulation Factor IX (Human) Monoclonal Antibody Purified - A brand of factor IX manufactured and marketed by CSL Behring.
Nanofiltration - A form of filtration that uses filters with small pores capable of removing many viruses and virus-antibody complexes for further enhancement of viral safety; nanofiltration removes many enveloped and non-enveloped viruses.
Neo-antigen - Novel antigen.
Non-lipid-enveloped viruses - Viruses that do not require a lipid coat in order to be infectious. Examples include hepatitis A and parvovirus B19.
On-demand therapy - The practice of administering coagulation factor in response to a bleeding episode.
Partitioning - A mechanism of virus removal by precipitation and filtration during the manufacturing process.
Pasteurization - Process of heating liquids to destroy harmful or undesirable microorganisms.
Pathogens - Causative agents such as viruses, bacteria, parasites, and others, associated with pathophysiological effects on a given host organism.
PCR - An acronym for polymerase chain reaction, a highly sensitive method of detecting minute amounts of genetic material such as viral DNA or RNA.
PCR testing - One of the highly sophisticated techniques utilized in the manufacture of plasma-derived products. PCR testing may identify the specific viral nucleic acid while traditional serological testing methods rely on a response, or antibody development, to virus presence. Because PCR testing can detect low levels of virus directly, it may dramatically reduce the "diagnostic window" period.
Peak (level) - The maximum plasma level of a therapeutic product attained, particularly after a bolus dose.
Pepsin - An enzyme used to digest proteins.
Pharmacokinetics - A pharmacological discipline that describes changes in the concentration of drugs in the organism over time. In particular, questions related to adsorption, distribution, metabolism, and elimination of a given drug are addressed.
PID - See Primary immune deficiency
Plasma - The fluid part of blood, consisting of water, salts (electrolytes), and proteins including coagulation factors, albumin, and immune globulins.
Plasma derived - Referring to biologic products made from human plasma.
Plasma expansion - The method of treatment in which proteins such as albumin (also known as colloid) or salt and water (known as crystalloid) are injected intravenously.
Plasmapheresis - A technique for collecting plasma from a donor by which the blood is taken from the vein and separated into plasma and blood cells. The plasma is retained and the blood cells are returned to the donor. It is performed in a sterile manner in a closed system. Plasmaphersis allows the donor to give plasma more frequently and in larger amounts than whole blood donations.
Primary immune deficiency (PID) - Represents a class of disorders in which there is an intrinsic defect in the immune system. There are more than 80 different primary immune deficiency diseases currently recognized by the World Health Organization. (see also Immunodeficiency)
Prophylaxis, prophylactic therapy - The practice of administering a therapeutic product in the anticipation of its need, rather than in response to a specific challenge.
Radioactive synovectomy - A procedure in which a dose of radioactive material is injected into a joint cavity to reduce the inflammation associated with chronic arthritis.
Recombinant - The process of manufacturing proteins by genetic engineering.
Recombinant antihemophilic factor (rAHF) - Factor VIII manufactured by recombinant techniques.
Recovery - See biologic recovery, survival study, half-life.
Ristocetin cofactor activity (VWF RCo) - A measure of the activity of von Willebrand factor based on an assay using the antibiotic ristocetin. Normal human plasma contains 0.5 to 1.5 RCo units per milliliter, sometimes expressed as 50 to 150. 2
SCIg - A common abbreviation used for human normal immunoglobulin for subcutaneous use. Also abbreviated IGSC.
Shock - Circulatory collapse that may be due to an allergic reaction, severe infection, blood loss, trauma, or burns. (See also hypovolemia.)
Sodium thiocyanate - A chemical used to inactivate certain viruses in the manufacture of some biologics.
Solvent/detergent process - Virus inactivation procedure using a combination of an organic solvent and a nonionic detergent. Enveloped viruses such as HIV-1, HIV-2, HBV, HCV, and others are effectively inactivated.
Specific activity - The amount of function of a protein, compared to the amount of total protein present. This is a measure of the purity of a protein; ultrahigh-purity factors have a high specific activity.
Steady state - The level of drug accumulation in the blood when input and output are equal.
Subcutaneous (SC) administration - Administration of drugs or fluids into the subcutaneous tissue, which is located just beneath the skin.
Survival study - A procedure in which a dose of factor is administered, and blood factor activity levels are determined several times over the subsequent 24 (or more) hours. A survival study is frequently performed prior to an elective surgical procedure in patients with bleeding disorders, in order to assist in determining the quantity and frequency of dosing required for the replacement factor at the time of surgery. (See also biologic recovery, half-life.)
Synovectomy - The process of removing excess synovium, or lining of a joint cavity, that has become inflamed and painful as a consequence of chronic arthritis. Sometimes this is done surgically, either open or through an arthroscope, or by the injection of a radioisotope. (See also hemarthrosis, radioactive synovectomy.)
Target joint - A joint that is a frequent site of spontaneous bleeding in an individual with a bleeding disorder. (See also hemarthrosis.)
Thrombin - The enzyme that converts fibrinogen to fibrin to form a blood clot. Thrombin circulates in the inactive form, prothrombin.
Trough (level) - The minimum plasma level of a drug attained prior to the next dose.
Ultra-high purity - A term used to designate a very high degree of purification of coagulation factors, indicating the removal of virtually all other plasma proteins.
Validation studies - Assessment of the ability of each significant production step to decrease the infective viral load.
Viral elimination - The process of physically removing or reducing certain viruses from biologics to non-detectable levels.
Viral inactivation - The process of rendering certain viruses non-infectious, without necessarily removing them from the product.
Viral-retentive ultrafiltration - See nanofiltration.
Virus-antibody complex - The complex formed by the binding of antibodies to viruses.
Virus removal - The process of physically removing certain viruses from biologics to non-detectable levels.
Vivaglobin® Immune Globulin Subcutaneous (Human) - The brand name for subcutaneous immunoglobulin, IgG, manufactured and distributed by CSL Behring.
von Willebrand disease (VWD) - The partial or complete deficiency of von Willebrand factor, or in some circumstances, the presence of abnormal von Willebrand factor that is not completely functional. Symptoms include mucosal bleeding such as epistaxis (nose bleeds) or menorrhagia (heavy uterine bleeding), easy bruising, or bleeding after surgery or trauma.
von Willebrand factor - A protein in plasma, platelets, and endothelial cells that serves to anchor platelets to a damaged blood vessel, and to carry coagulation factor VIII in the plasma.
X chromosome - One of the two "sex chromosomes" in humans, and the location of the factor VIII and IX genes. Females have two X chromosomes, and males have one X and one Y chromosome.
ZLB Plasma - An integrated network of plasma collection centers and a central testing laboratory that supply qualified plasma for CSL Behring's plasma-based therapies