Prothrombinex-VF

Aka. 3-Factor Prothrombin Complex

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

CCC Transfusion Series
Blood Products	Cryoprecipitate, Fresh Frozen Plasma (FFP), Platelets, Red Cells (RBCs) Concentrates: Prothrombinex, Factor VIIa, Fibrinogen Concentrate
Reversal	Rivaroxaban / Apixaban / Enoxaparin: Andexanet Alfa, Rivaroxaban and Bleeding Dabigatran: Idarucuzimab, Dabigatran and bleeding Heparin: Protamine Warfarin: Vitamin K / FFP / PTx, Warfarin Reversal, Warfarin Toxicity
Testing	Coagulation Studies, TEG / ROTEM (Thromboelastography), Platelet function assays
General Topics	Acute Coagulopathy of Trauma, Blood Bank, Blood conservation strategies, Blood Product Compatibilities, Blood transfusion risks, Disseminated Intravascular Coagulation, Massive blood loss, Massive transfusion protocol (MTP), Modifications to blood components,Procedures and Coagulopathy, Storage Lesions, TRALI, Transfusion Literature Summaries, Transfusion Reactions

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

[cite]