Prothrombinex-VF

Aka. 3-Factor Prothrombin Complex

Please note in 2024 in Australia, Prothrombinex will be replaced by Beriplex P/N and eventually (by 2025) Beriplex AU, a FOUR Factor concentrate. Please see the appropriate page.

DESCRIPTION

• Concentrated human factor II, IX and X (prothrombin complex)

INDICATIONS

1. Congenital factor II, IX or X (Haemophilia B) deficiency when a concentrated single-factor product is not available
2. Treatment or perioperative prophylaxis of bleeding for patients on vitamin K (e.g. warfarin) antagonist or vitamin K antagonist overdose
3. Because my ROTEM algorithm told me to, where the EXTEM CT>90s and FIBTEM A5>10mm or the EXTEM CT >140s and FIBTEM A5<10mm (please refer to your local guidelines)

ADMINISTRATION / DOSING

• Intravenous (IV)
• Dosing:
  • Generally starting dose for active haemorrhage: 10-20 IU/kg (suggested by institutional ROTEM/TEG algorithms)
  • Warfarin reversal for bleeding or surgery: 25-50 IU/kg
    • If INR >10, may require repeat dosing
    • Please refer to dosing table below for breakdown of dosing
  • For congenital deficiency of Factor IX (Haemophilia B):
    • Please see dosing table below
    • NOTE: concentrated Factor IX is superior to prothrombinex for the same, only administer if Factor IX is not available
    • **If unsure, please speak to your local haematology department**
• Administration:
  • Administer as a slow IV push
  • Not compatible with any other fluid nor any other blood product
  • Reconstitution guideline below
  • Need to allow the vials to come to room temperature prior to reconstitution

PREPARATION

• Manufactured from human plasma (Prothrombinex-VF made from Australian blood donors with donations supplied through LifeBlood)
• Heat treated (+80^oC for 72 hours) for viral inactivation and nanofiltration for virus removal
• It is then lipophilised (aka. freeze-dried, or cryodesiccated)

PHARMACEUTICS

• Presentation:
  • Single-dose glass vial of Prothrombinex®-VF with a rubber stopper closed with an aluminium seal
  • One glass vial of 20 mL water for injection
  • One Mix2Vial^TM filter transfer set
• Contents:
  • 500 IU of Factor IX
  • ~500 IU of Factor II
  • ~500 IU of Factor X
• Excipients:
  • Human plasma proteins <500 mg
  • Antithrombin III 25 IU
  • Heparin Sodium 192 IU
  • Sodium 112 mg
  • Phosphate 65 mg
  • Citrate 180 mg
  • Chloride 27 mg
• Storage:
  • Temperatures of 2-8^oC and is stable for up to 36 months
  • Can be stored below 25^oC and is stable up to 6 months
  • Must be administered immediately after reconstitution

GROUP / CROSSMATCH

• Not required

ADVERSE EFFECTS

• Thromboembolic episodes including MI, PE, DVT and arterial thrombosis
• Allergic reaction: anaphylaxis, dyspnoea, rash
• Chills, nausea, vomiting
• Risk of infectious disease transmission such as: CJD, HIV, Hep B and C

LOCATION OF ACTION

MECHANISM OF ACTION

• Coagulation factors II, VII, IX and X are all synthesised within the liver and dependent on vitamin K, and are commonly referred to as prothrombin complex
• Factor VII is the zymogen of the active serine protease factor VIIa by which the extrinsic pathway of blood coagulation is initiated
• Tissue factor-factor VIIa complex activates factors X and IX –> Factor IXa and Xa –> prothrombin activated and transformed into thrombin. Thrombin + Fibrinogen –> Fibrin –> clot formation
• Onset:
  • Peak effect within 5 mins
• Elimination half-life of factors:
  • Factor II: 60 h
  • Factor VII: 4.2 h
  • Factor IX: 17 h
  • Factor X: 31 h

CONTRAINDICATIONS

• Known hypersensitivity / anaphylaxis reactions to this product or other concentrated fractionated plasma products

ADVANTAGES AND DISADVANTAGES TO FFP

Advantages

• Small volume (20 mL vs ~300 mL), equally, does not provide volume during resuscitation
• Readily available
• Reliable reversal
• Avoids complications of FFP such as immune reaction, TRALI, fever, infection risk
• No time delay for unit thawing
• No crossmatch required

Disadvantages

• Roughly double the cost of a unit of FFP (1 unit of FFP ~500 IU of PTx)
• Cost of 500 IU of PTx: AUD$305.98
• Cost of 1 unit of FFP: AUD$152.37

RECONSTITUTION TIPS

DO NOT shake when the water for injection has been added, otherwise you will end up with a foamy mess (like teicoplanin, you only ever do it once)

• You will need, in addition to the package contents, a 20 mL luer-lock syringe, and a sterile alcohol wipe (or equivalent)
• You will also need a decent amount of bench space if you are reconstituting more than 500 units

WARFARIN REVERSAL DOSING TABLE

PROTHROMBINEX IN HAEMOPHILIA B (Factor IX Deficiency)

References and Links

References

• CSL Behring. (2020, March 23). Product Information. Retrieved January 27, 2023, from https://prothrombinex.cslbehring.com.au/system/files/pdf/2021-07/ProthrombinexVF-AU-PI-1400.pdf
• CSL Behring. (2021, February). PROTHROMBINEX®-VF RECONSTITUTION. Retrieved January 27, 2023, from https://prothrombinex.cslbehring.com.au/system/files/pdf/2021-04/prothombinex-updates-2021-A5-2pp-Instruction-Card.pdf
• CSL Behring. (2019, June). Consensus Guidelines Update for Warfarin Reversal. Retrieved January 27, 2023, from https://prothrombinex.cslbehring.com.au/warfarin-reversal-guidelines
• D, J. (2007, April 22). File:coagulation full.svg. Retrieved January 17, 2023, from https://commons.wikimedia.org/wiki/File:Coagulation_full.svg
• National Blood Authority Australia. (2023, January 01). What blood products are supplied – national product price list. Retrieved January 18, 2023, from https://www.blood.gov.au/national-product-price-list