Transfusion medicine handbook

5. Fractionated Products

5.1.1 BIOSTATE (Factor VIII)

Biostate is a freeze-dried powder containing purified human coagulation factor VIII (FVIII) and human von Willebrand factor (vWF) complex. Biostate is available as vials of 1,000 IU factor VIII (when reconstituted to 10 mL the concentration is 100 IU/mL). The reconstituted product has a vWF to FVIII ratio of 2:1 so the vWF.RCo is 2000 IU (200 IU/mL). Biostate contains human albumin as a stabiliser.

The FVIII/vWF complex in Biostate is purified from cryoprecipitate using selective precipitation and chromatography steps. The manufacturing process of Biostate includes solvent detergent, dry heat treatment, and partitioning steps for inactivation/removal of HIV, hepatitis A, hepatitis B, and hepatitis C and also have some effect on parvovirus B19.

Indications for Use

Biostate is indicated for:

• Prophylaxis and treatment of non-surgical and surgical bleeding in patients with von Willebrand disease when desmopressin (DDAVP) treatment is ineffective or contraindicated
• Prophylaxis and treatment of non-surgical and surgical bleeding associated with FVIII deficiency due to haemophilia A

The number of vials of Biostate to be reconstituted is determined by dividing the total dose of FVIII or vWF:RCo required by the number of IU of that ingredient in the selected vial size. This should be rounded up to the nearest whole number of vials. Tables 5.1 and 5.2 provide guidance for dosing.

Table 5.1: Biostate Dosage Guidelines for Haemophilia A

Table 5.2: Biostate Dosage Guidelines for Von Willebrand Disease¹

¹ https://www.haemophilia.org.nz/files/docs/nz_national_guidelines_for_the_management_of_haemophilia.pdf

² Factor VIII activity level (not von Willebrand factor level) is used in dosage schedules and to monitor treatment because factor VIII is a major determinant of operative bleeding and the factor VIII assay is relatively easy to do. In major surgery it may be necessary to monitor vWF levels but this will need discussion with the specialised coagulation laboratory pre-operatively.

Precautions

• Allergic reactions
  Allergic reactions or fever are rarely observed. Depending on the nature of an adverse reaction, the rate of injection should be slowed or stopped to alleviate symptoms.
• Antibodies to factor VIII
  Patients with congenital factor VIII deficiency may develop neutralising alloantibodies (inhibitors) to factor VIII after treatment. If this occurs specialist advice must be sought.
• Antibodies to von Willebrand factor
  Patients with von Willebrand disease, especially type 3 patients, may very rarely develop neutralising alloantibodies (inhibitors) to von Willebrand factor. Such antibodies may occur in close association with anaphylactic reactions. Therefore, patients experiencing anaphylactic reactions should be evaluated for the presence of an inhibitor.
• Thrombosis
  Thromboembolic events have rarely been reported in vWD patients receiving coagulation factor replacement therapy, especially in the setting of known risk factors for thrombosis and may be related to the generation of supranormal FVIII levels. Those with aquired vWD are also potentially at risk.