• General Information
• Factor VIII (8)
• von Willebrand Factor
• Factor IX (9)
• Activated Factor VII (7) Novoseven^TM
• FEIBA-NF (Factor Eight Inhibitor Bypass Agent)
  
• Factor XIII (13) Fibrogammin^TM
• Prothrombinex^TM
• Factor XI (Eleven) BPL^TM
• Fibrinogen Concentrate (RiaSTAP^®)

General Information

• Clotting factor concentrates are stored in blood bank between 2⁰C & 8⁰C and should not be stored in ward fridges.
• A Blood Bank Release Order is required to pick up Clotting Factor Concentrates from Blood Bank (they cannot be sent via pneumatic tube)
  
• Clotting factor concentrates are ordered and documented on the EMR Medication Administration Record (MAR)
• Refer to Clotting Factor EMR tip sheets (Inpatient, Emergency Department, Anaesthesia, Outpatient) for further information, including how to print the Blood Bank Release Order
  
• Occasionally there are slightly more/less units in the vial e.g. a 500 unit vial may have 513 units or 489 units. Treat the vial as 500 units and give total content. Do not discard any product. 
• Plasma derived clotting factor concentrates are derived from the blood supply and require transfusion consent MR634/A
• Recombinant clotting factor concentrates are synthetic and do not require transfusion consent

Factor VIII (8)

Dosage

• Calculated on the basis that 1 unit/kg of factor VIII leads to a rise in plasma factor VIII of approximately 2%.
• EXAMPLE: 50 units/kg will increase factor VIII level by ~100%.
• Doses are rounded UP to the nearest vial size.
• There are standard and extended half life products
• Standard half life factor VIII products have a half life of approximately 8-12 hours 
• Extended half life factor VIII products have an increase in half life between 1.4 to 1.6 times that of standard half life FVIII products.
• Refer also to  RCH Clinical Practice Guideline Haemophilia

Administration

Factor VIII is generally administered as a slow IV push (bolus injection).

Continuous infusion of Factor VIII is indicated for patients requiring admission for severe bleeds or surgical procedures.  Factor VIII replacement for such patients should be managed in consultation with Clinical Haematology.  A continuous infusion of 3 units/kg/hour via syringe pump is commenced after a bolus loading dose. 

EXAMPLE: 18 kg child on Recombinant Factor VIII/Advate:

• Bolus loading dose 50 units per kg = 1000 units (round UP to nearest vial size)
• Continuous infusion
  • ~ 50 units per kg made up to total volume of 50ml Sodium Chloride 0.9%
    
  • 1000 units Advate in 50ml = 20 Factor VIII units/ml
  • commence at 3 units/kg/hour = 54 units per hour = 2.7 mls/hr

As Factor VIII does not contain any antimicrobial agent, syringes for continuous infusion should be prepared so that the contents of the syringe will be infused in less than 24 hours (as in example above).

If a plasma Factor VIII level is clinically indicated, the sample should not be taken from the same intravenous line as the continuous infusion. Notify the laboratory to expect the sample.

Recombinant Factor VIII

• Genetically engineered Factor VIII.
• The product of choice for the prevention and treatment of bleeding associated with Haemophilia A (Factor VIII deficiency).
• Does NOT contain von Willebrand Factor and is not indicated for the treatment of bleeding in von Willebrand's disease.

There are four Recombinant Factor VIII products available in Australia, see table below.
Standard Half Life Factor VIII products are available from RCH blood bank. 
Extended Half Life Factor VIII products are used by patients on home treatment and are not available from RCH blood bank.

Plasma derived Factor VIII and von Willebrand Factor (Biostate^TM)

• Derived from donated human plasma and contains Factor VIII (FVIII) and von Willebrand Factor (vWF).
• Used to treat bleeding episodes and prevent surgical bleeding in patients with von Willebrands disease. Refer also to  RCH Clinical Practice Guideline von Willebrand's Disease.
• Rarely used for patients with Haemophilia A (recombinant FVIII is the product of choice). 
• May be used in Haemophilia A patients with FVIII inhibitors
• Please note that the Biostate vial will state both Factor VIII and von Willebrand Factor units and the ratio of FVIII to vWF is 1:2.4
• Make sure Biostate dosage is ordered in FVIII units e.g. 'Biostate 1000 FVIII units' (=2400 vWF units)
• Administered as a slow IV push (bolus injection). 
  

Factor IX (9)

Dosage

• Calculated on the basis that 1 unit/kg of factor IX leads to a rise in plasma factor IX of approximately 0.7 - 1%.
• EXAMPLE 50 units/kg will increase factor IX level by ~35-50%
• Doses are rounded UP to the nearest vial size.
• There are standard and extended half life products
• Standard half life factor IX products have a half life of approximately 18-24 hours 
• Extended half life factor IX products have an increase in half life between 3 to 5 times that of standard half life FIX products.
• Refer also to  RCH Clinical Practice Guideline Haemophilia.

Administration

Factor IX is generally administered as a slow IV push (bolus injection).

Continuous infusion of Factor IX is indicated for patients requiring admission for severe bleeds or surgical procedures.  Factor IX replacement for such patients should be managed in consultation with Clinical Haematology.  A continuous infusion of 3 units/kg/hour via syringe pump is commenced after a bolus loading dose.

EXAMPLE: 18 kg child on Recombinant Factor IX / Benefix:

• Bolus loading dose 100 units per kg = 2000 units (round UP to nearest vial size)
• Continuous infusion
  
  • ~ 50 units per kg made up to total volume of 50ml Sodium Chloride 0.9%
    
  • 1000 units Benefix in 50ml = 20 Factor VIII units/ml
  • commence at 3 units/kg/hour = 54 units per hour = 2.7 mls/hr

As Factor IX does not contain any antimicrobial agent, syringes for continuous infusion should be prepared so that the contents of the syringe will be infused in less than 24 hours (as in example above).

If a plasma Factor IX level is clinically indicated, the sample should not be taken from the same intravenous line as the continuous infusion. Notify the laboratory to expect the sample.

Precaution: Haemophilia B patients with inhibitors (antibodies to Factor IX) are at risk of severe allergic reactions, including  anaphylaxis, to Factor IX.  Haemophilia patients are monitored for the development of inhibitors and inhibitors to Factor IX are rare.

Recombinant Factor IX

• Genetically engineered Factor IX.
• The product of choice for the prevention and treatment of bleeding associated with Haemophilia B (Factor IX deficiency).

There are two Recombinant Factor IX products available in Australia, see table below. 
Standard Half Life Factor IX is available from RCH blood bank. 
Extended Half Life Factor IX is used by patients on home treatment and is not available from RCH blood bank. 

Plasma derived Factor IX (Monofix^TM)

• Derived from donated human plasma and contains Factor IX.
• Rarely used for the treatment of Haemophilia B (recombinant Factor IX is the product of choice).
• May be used in Haemophilia B patients with FIX inhibitors.

Activated Factor VII (7) Novoseven^®RT

• Recombinant activated factor VII (7).
• Indicated and licensed for the treatment of bleeding episodes in haemophilia patients with inhibitors (antibodies) to factors VIII or IX.
• Has been used 'off label' in the management of intractable bleeding post trauma or surgery, which has not been controlled by surgery or conventional transfusion replacement therapy
• Clinical Haematology Department/Haematologist on call must be consulted prior to use of this product

Dosage

• According to individual treatment plan for haemophilia patients with Factor VIII or IX inhibitors (usually multiple doses of 90 microgram/kg).
• 90 micrograms/kg for intractable bleeding not responsive to surgical or transfusion replacement therapy (larger doses, up to 180 micrograms/kg may be appropriate in neonatal patients)
• 10 micrograms/kg for treatment of bleeding episodes in patients with factor VII deficiency (rare).
• The half life of activated Factor VII is 2 hours.
• After reconstitution with the supplied diluent each vial contains 1.0mg/ml Factor VIIa.

Administration

• Novoseven^®RT is stable for 24 hours after reconstitution but should be administered as soon as possible to avoid microbial contamination
• If not used immediately after reconstitution, Novoseven^®RT should be stored in the vial (not in the syringe) in a refrigerator at 2⁰C-8⁰C for no longer than 24 hours
• Administer as a slow IV push (bolus injection).
  
• Do not mix with other intravenous solutions or medications.
• Administer as close to the IV cannula as possible.
• Flush with Sodium Chloride 0.9% pre and post administration.

FEIBA-NF™ (Factor Eight Inhibitor Bypass Agent)

• Plasma derived factor 2 (prothrombin) and factor Xa
• Indicated and licensed for the treatment and prevention of bleeding episodes in haemophilia patients with inhibitors (antibodies) to factors VIII or IX
• Use of FEIBA-NF, particularly in high doses, has been associated with thrombosis
• The use of antifibrinolytic agents (e.g. Tranexamic acid) in combination with FEIBA-NF is not recommended
• Consult with Clinical Haematology prior to ordering this product.

Dosage

• According to individual treatment plan for haemophilia patients with Factor VIII or IX inhibitors. (Usually 50-100 units/kg every 12 hours for bleeding episodes).
• Maximum single dose 100 units/kg
• Maximum daily dose 200 units/kg

Reconstitution and Administration

• To reduce frothing, allow FEIBA-NF to come to room temperature prior to reconstitution. Do not shake, draw into syringe slowly.
• Administer via syringe pump. Maximum infusion rate 2 units/kg/minute.
• Flush with Sodium Chloride 0.9% post administration.
• If CVAD to be disconnected post FEIBA-NF administration: flush with 20 mls Sodium Chloride 0.9% using pulsatile action, then lock with 5mls heparin (50 units/5ml). Note that maximum frequency of heparin lock is daily.

Factor XIII (13) Fibrogammin^TM

• Plasma derived factor XIII.
• Used primarily for prevention and treatment of bleeding in Factor XIII deficiency (rare).
• Administered as a slow IV push (bolus injection).
  
• The half life of factor XIII is 8 to 10 days.

Prothrombinex^TM

• A plasma derived prothrombin complex concentrate which contains factors II, IX and X.
• NOT used in patients with Haemophilia B (Factor IX deficiency) as purified Factor IX concentrates are superior.
• Used for the prevention and treatment of bleeding in patients with low levels of factor II or factor X (rare) and in some patients who require reversal of anticoagulant therapy.
• The use of Prothrombinex with antifibrinolytics (tranexamic acid) is not recommended due to the theoretical increase in risk of thrombosis.
• Administered as a slow IV push (bolus injection).
  

Factor XI (Eleven) BPL^TM

• Plasma derived factor XI (Eleven)
• The half life of factor XI is approximately 2 days.
• Use of factor XI concentrates, particularly in high doses, has been associated with thrombosis
• Dosage should be determined in consultation with Clinical Haematology
• Administered as a slow IV push (bolus injection).
  
• Used primarily for prevention and treatment of bleeding in Factor XI deficiency (rare)

Fibrinogen Concentrate (RiaSTAP^®)

• Plasma derived fibrinogen (Factor I) concentrate
• The half life of fibrinogen is approximately 2 - 4 days
•  Available for the prevention and treatment of bleeding in patients with congenital fibrinogen deficiency only (this condition is  rare)
•  Use of RiaSTAP^® and dosage should be determined in consultation with Clinical Haematology
•  Administered by slow intravenous injection at a rate not exceeding 300ml per hour.