Question 2

Compare and contrast prothrombin complex concentrate (PCC) and fresh frozen plasma (FFP) in the management of a warfarinised patient with major haemorrhage under the following headings:

a. Constituents and methods of administration (2 marks)

b. Advantages (4 marks)

c. Contraindications and potential adverse effects (4 marks)

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Discussion

Syllabus topic/section: 2.1.21 Applied Pharmacology in Intensive Care

This was a compare and contrast question. Candidates gained more marks if they highlighted the differences and explained how they might be significant. For example, FFP contains all the clotting factors allowing for correction of non-Vitamin K dependent factor deficiencies (eg haemophilia's, factor V deficiency) however, PCC contains small amounts of heparin and therefore not suitable in the setting of ADR/HIT etc.

Likewise, the better answer for advantages contained information about product storage, preparation and administrative differences and what that would mean clinically. The above standard answer would also include references to blood typing.

The rubric is provided to aid in the candidates’ future study.

Domain Below standard At standard Above standard

a) Constituents and administration

(2 marks)

Does not accurately list contents of PCC or FFP

OR

Provides incorrect information around administration

0-0.5 marks

Lists the contents of PCC (either Prothrombinex or Beriplex) and FFP with few inaccuracies/omissions.

Mentions most of the information about dosing and preparation of the 2 products.

1-1.5 marks

At standard PLUS

Lists the contents of PCC and FFP with no inaccuracies/omissions.

Provides comprehensive detail about the dosing and administration of the 2 products.

2 marks

b) Advantages

(4 marks)

No or a limited number of advantages provided

OR

Provides a narrow range of advantages from only some of the categories of storage preparation or administration

OR

Only mentions advantages for one product

0 - 1.5 marks

Includes a broad range of advantages for each product with some comparison of the advantages related to product storage, preparation and administration.

2 - 2.5 marks

At standard PLUS

A more comprehensive range of advantages that includes reference to blood typing for FFP with more detail provided around storage, preparation and administration of each product.

3 - 4 marks

c) Contraindications/Potential adverse effects

(4 marks)

No or limited number of contraindications/adverse events provided

OR

Only mentions contraindications/adverse events for one product

Does not mention anaphylaxis for FFP

0 - 1.5 marks

Includes a broad range of contraindications/adverse events for each product with some comparison between them.

Must provide some examples of contraindications/adverse events for each product and include anaphylaxis for FFP.

2 - 2.5 marks

At standard PLUS

A more comprehensive and wide range of contraindications/adverse events that includes most of the AE listed below.

May include reference to the need for blood typing with FFP (if not already mentioned above).

3 - 4 marks

Interpretation

a. Constituents and methods of administration (2 marks)

  • PCC:
    • Factors II,  XI and X (prothrombinex), plus Factor VII, protein C and Protein S (Beriplex), as well as a small amount of heparin. 
    • Lyophilised powder; reconstituted for administration
    • Low volume; dose is 50 IU/kg for severe bleeding, which translates to 3500 units or seven 20-ml vials 
    • Long shelf life (3 years)
  • FFP:
    • Contains all the clotting factors, plus non-clotting blood proteins
    • Thawed human plasma, ready for administration when 
    • high volume; a big dose is 15-20 ml/kg, or approximately 1-1.5L
    • Needs to be thawed (available within 20-30 min)
    • Shorter shelf life
    • Contains anti-A/B antibodies and therefore requires blood typing 
    • Presents in bags, ready to puncture and manually infuse (requires no additional work for reconstitution and preparation of infusion)

b. Advantages (4 marks)

  • PCC:
    • Specific reversal of warfarin-dependent factors
    • Low volume favours use in patients with fragile cardiopulmonary relationships, eg. those with a propensity to have flash pulmonary oedema
    • Does not require blood typing
    • Low volume and room temperature; does not need to be warmed for administration
  • FFP:
    • The larger volume favours resuscitation in haemorrhagic shock
    • Quick to administer
    • Cheaper ($261 for about 300ml, so probably ~$1000 for a full dose, vs. $347 for a single 500 IU vial of Beriplex) 

c. Contraindications and potential adverse effects (4 marks)

  • PCC:
    • Potential for HITS
    • Anaphylaxis
    • Thrombosis (when the pre-warfarin procoagulant state is restored)
    • Unlikely to carry viruses, but could get contaminated in the course of the complicated reconstitution process
  • FFP:
    • Transfusion reaction
    • Volume overload (TACO)
    • Alloimmunisation
    • TRALI 
    • Can theoretically be contaminated with bloodborne pathogens

References

Robinson, Danielle, James McFadyen, Eileen Merriman, Chee Wee Tan, Ross Baker, and Huyen Tran. "Updated recommendations for warfarin reversal in the setting of four-factor prothrombin complex concentrate." The Medical Journal of Australia 222.1 (2025): 49-51.

Anderson, Brian J., Steven R. Keeley, and Neil D. Johnson. "Prothrombinex‐induced thrombosis and its management with regional plasminogen activator in hepatic failure." Medical journal of Australia 153.6 (1990): 352-356.

Bruce, David, and Tim JC Nokes. "Prothrombin complex concentrate (Beriplex P/N) in severe bleeding: experience in a large tertiary hospital." Critical Care 12.4 (2008): R105.

Robinson, Danielle, et al. "Updated recommendations for warfarin reversal in the setting of four‐factor prothrombin complex concentrate." Medical Journal of Australia 222.1 (2025): 49-51.

Hanke, Alexander A., Christine Joch, and Klaus Görlinger. "Long-term safety and efficacy of a pasteurized nanofiltrated prothrombin complex concentrate (Beriplex P/N): a pharmacovigilance study." British journal of anaesthesia 110.5 (2013): 764-772.

Holland, Lorne L., and Jay P. Brooks. "Toward rational fresh frozen plasma transfusion: the effect of plasma transfusion on coagulation test results." American Journal of Clinical Pathology 126.1 (2006): 133-13