Name: Factor IX Concentrate
Factor IX Complex

Factor IX (Recombinant)
BeneFIX - Genetics Institute, Inc., Cambridge, MA

Factor IX (Human)
AlphaNine SD - Alpha Therapeutic Corp., Los Angeles, CA
Mononine - Aventis Behring, LLC., Kankakee, IL

Factor IX Complex (prothrombin complex)
Bebulin VH - Baxter Healthcare, Vienna, Austria
Konyne 80 - Bayer Corp., Eikhart, IN
Profilnine SD - Alpha Therapeutic Corp., Los Angeles, CA
Proplex T - Baxter Healthcare, Glendale, CA.

Description/Contents: Recombinant Coagulation Factor IX (rFIX) is produced in a Chinese hamster ovary tissue cell-line under serum-free conditions and is extensively purified prior to storage as a lyophilized powder. It is inherently free of risk of transmission of human disease.

Human-derived Coagulation Factor IX is highly purified through chromatography (AlphaNine) or monoclonal antibody affinity columns (Mononine), but may contain non-therapeutic traces of Factors II, VII, and X.

Factor IX Complex is a less pure preparation from human plasma that also contains some Factors II, VII, and X, as well as proteins C and S. Some products also contain small amounts of heparin.

Human-derived Factor IX concentrates and complex are treated with heat, nanofiltration and/or solvent/detergent to reduce the risk of viral transmission. None of the currently available formulations have been known to transmit HIV or HCV; however there remains a theoretical risk of non-enveloped virus and/or prion disease transmission.

• Coagulation Factor IX and Factor IX Complex are indicated for the treatment of Factor IX deficiency (hemophilia B, Christmas disease).

• rFIX has become the treatment of choice for new patients with hemophilia B and for those with limited exposure to human-derived Factor IX products.

Dosage and Administration: Factor IX preparations are generally stored at 2-8oC as lyophilized powders. Activity units are stated on the product label on each bottle. One unit of Factor IX activity is equivalent to that found in 1 mL of normal human plasma. Each unit of Factor IX concentrate or complex infused per kilogram of body weight will yield approximately a 1% rise in the circulating Factor IX level, while each unit of rFIX will cause a 0.8 IU/ml rise. Factor IX concentrates are reconstituted with the sterile diluent provided with the product, filtered before use, and infused intravenously over several minutes as soon as possible after reconstitution, within an established time limit (usually 3 hours). Factor IX can also be administered by continuous infusion. Once administered, the half-life ranges from 18 to 32 hours.

The dose administered depends on the needs of each patient. For most situations, a dose should be calculated to raise the circulating Factor IX level to 20-30%; however, levels of 50-100% may be needed for major surgery or for treatment of life threatening bleeding episodes. Repeat doses should be half of the loading dose administered every 12 to 24 hours, but attempts to maintain levels >75-100% are not advisable due to concerns of thrombogenicity of some products. Some experts recommend prophylactic administration of 25-40 IU/kg twice weekly for patients with Factor IX levels less than 0.01 IU/mL in order to prevent spontaneous bleeding.

Adverse Reactions: Allergic type hypersensitivity reactions, including anaphylaxis, have been reported for all factor IX products. Frequently these events have occurred in close temporal association with the development of factor IX inhibitors. Patients should be informed of the early symptoms and signs of hypersensitivity reactions, including hives, generalized urticaria, angioedema, chest tightness, dyspnea, wheezing, faintness, hypotension, tachycardia and anaphylaxis. Patients should be advised to discontinue use of the product and contact physician and/or seek immediate emergency care, depending on the severity of the reactions, if any of these symptoms occur.

In Previously Untreated Patients (PUPs), it is possible that anaphylaxis may occur after a median exposure of eleven (11) days. It is recommended that these patients be monitored closely.

Rapid infusion of Factor IX Complex may cause chills, fever, headache, nausea, and flushing. Rapid administration of Coagulation Factor IX may also produce vasomotor reactions.

Factor IX Complex should be used with caution in certain patients due to the risk of thrombosis and disseminated intravascular coagulation. Deficiencies of antithrombin, as seen in patients with liver disease, may cause an accumulation of activated factors due to decreased hepatic clearance. Patients with crush injuries, extensive soft tissue injuries, and immobile orthopedic surgery patients are also at risk due to release of thromboplastic materials into the blood. Coagulation Factor IX is less thrombogenic than Factor IX Complex.

Nephrotic syndrome has been reported following attempted immune tolerance induction with factor IX products in hemophilia B patients with factor IX inhibitors and a history of severe allergic reactions to Factor IX.

Alternative Therapy: Recombinant Factor VIIa may be used to treat patients who have developed inhibitors to FIX therapy.

Recombinant Factor VIIa is also the current treatment of choice for hemophilia B patients who have had severe allergic reactions to products containing Factor IX.

Fresh frozen plasma may be used in an emergency when appropriate Factor IX concentrates are not available. Cryoprecipitated Antihemophilic Factor should not be used as it is devoid of Factor IX.

Triulzi DJ (ed.) Blood Transfusion Therapy; A Physician’s Handbook, 7th ed. American Association of Blood Banks. Bethesda, MD, 2002.

Furie B, Limentani SA, Rosenfield CG. A practical guide to the evaluation and treatment of hemophilia. Blood 1994;84:3-9.

Lusher JM. Congenital disorders of clotting proteins and their management. In: Simon TL, Dzik WH, Snyder EL, Stowell CP, Strauss RG, eds. Rossi’s principles of transfusion medicine, 3rd ed. Philadelphia: Lippincott, Williams & Wilkins, 2002:448-462.

Brecher ME (ed.) Technical Manual, 14th ed. American Association of Blood Banks. Bethesda, MD, 2002.

Physicians’ Desk Reference, 56th ed. Montvale: Medical Economics Company, 2002.

Transfusion Guidelines

Plasma Guidelines	Antithrombin III Guidelines
Platelet Guidelines	Activated Protein Guidelines
Red Cell Guidelines	Factor IX Guidelines
Cryoprecipitate Guidelines	Factor VIII Guidelines
AICC/Porcine Factor VIII Guidelines	IVIG Guidelines Coagulation Factor VII Guidelines

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