Comparison of 4-factor VS 3-factor Prothrombin Complex Concentrate (PCC)

Please be noted that currently our PCC, brand Prothrombinex-VF (From National Blood Centre, Malaysia), is 3-factor PCC, which contains very low (non-therapeutic levels) of factor VII.

For each 500 units vial :

Component	Kcentra / Beriplex P/N (Canada)	Prothrombinex-VF (From National Blood Centre, Malaysia)
Factor II	380-800 IU	500 IU
Factor VII	200-500 IU	Low level ( ≤ 500 mg ≈ ≤ 0.01 IU )
Factor IX	400-620 IU	~ 500 IU
Factor X	500-1020 IU	~ 500 IU
Factor V	No info	Low level ( ≤ 500 mg )
Protein C	420-820 IU	No info
Protein S	240-680 IU	No info

*Factor VII = 50,000 units/mg

Dosing Guide

The dose for the same indication may be different by brand. Kindly double check product leaflet

Indication	Kcentra / Beriplex P/N (Canada)	Prothrombinex-VF (From National Blood Centre, Malaysia)
Vitamin K antagonist (VKA) reversal		From product leaflet Initial (Pre-treatment) INR Dose ( IU/kg ) Complete reversal ( 0.9-1.3 ) Partial reversal ( 1.4-2.0 ) 1.5 - 2.5 30 - 2.6 - 3.5 35 25 3.6 - 10.0 50 30 >10.0 50 ** 40 **May not fully correct INR, higher or repeat doses NOT recommended.
Life-threatening hemorrhage associated with warfarin (off-label use)	Initial (Pre-treatment) INR Dose Recommendation Dose suggested Max Dose 2 - <4 25 IU/kg 2500 4 – 6 35 IU/kg 3500 > 6 50 IU/kg 5000 With the correction of vitamin K antagonist-induced impairment of hemostasis in patients who have been treated concomitantly with an appropriate vitamin K dose, repeat dosing with PCC is usually not necessary.	From UptoDate Products contain low or nontherapeutic levels of factor VII component; therefore, additional fresh frozen plasma (FFP) or factor VIIa may be considered When immediate INR reversal is required, concomitant use of 1 to 2 units of FFP should be considered to ensure acute INR reversal. Co-administer vitamin K (phytonadione) 5-10 mg by slow IV infusion; vitamin K may be repeated every 12 hours if INR is persistently elevated. INR Adjusted-dose regimen, weight based <2 20 IU/kg 2-4 30 IU/kg >4 50 IU/kg
Intracranial hemorrhage associated with warfarin (off-label use)	Oral direct factor Xa inhibitor-mediated (api/rivaro-xaban):  50 IU/kg if ICH occurred within 3-5 terminal half-lives of drug exposure or when liver failure co-exists. Direct thrombin inhibitor-mediated (dabigatran [if idarucizumab unavailable], bivalirudin): 50 IU/kg if direct thrombin inhibitor was administered within a period of 3-5 half-lives prior and there is no evidence of renal failure OR there is renal impairment leading to drug exposure beyond 3-5 half-lives.	From UptoDate Four-factor PCC is preferred. Administer with vitamin K IV Fixed-dose regimen, weight based: ·      INR ≥1.4: 50 units/kg; repeat INR within 15 to 60 minutes and serially every 6 to 8 hours for the next 24 to 48 hours. ·      If INR remains ≥1.4 within the first 24 to 48 hours after initial dose, use FFP (alone) for further correction. ·      For initial reversal, it is suggested to administer PCC alone rather than combined with FFP or recombinant factor VIIa
Life-threatening hemorrhage associated with NON-vitamin K antagonist anticoagulation (off-label use)		No recommendation as most studies use 4-factor PCC However, Eikelboom & Merli (2016) 3 suggested (for Rivaro/Api-xaban): PCC Dosage 3-factor 50 IU/kg, may repeat q12h 4-factor 50 IU/kg, one time dose

# From Ref 7

Dosage Guideline of Prothrombinex-VF for Hemophilia B (congenital deficiency of factor IX)

Indication	Desired plasma concentration of factor IX (IU/dL)	Dose (IU/kg)	Frequency of dosing (per day)	Duration of treatment (day)
Minor haemorrhage	20-30	20-30	1	1-2
Moderate-Severe haemorrhage	30-50	30-50	1-2	1-5
Minor surgery *Loading dose *Maintenance	40-60 20-50	40-60 15-40	- 1-2	- 7-10

References:

1.     Product leaflet: Prothrombinex-VF [ CSL Behring (Australia) / National Blood Centre (KL, Malaysia) ]. Revised on 05 March 2015.

2.     UptoDate: Drug information: Prothrombin complex concentrate, 4-factor, unactivated, from human plasma

3.     UptoDate: Drug information: Prothrombin complex concentrate, 3-factor, unactivated, from human plasma

4.     Eikelboom J. & Merli G.M. Bleeding with direct oral anticoagulants vs warfarin: clinical experience. American Journal of Emergency Medicine 34 (2016) 3–8. Accessed online at: https://www.ajemjournal.com/article/S0735-6757(16)30647-7/pdf

5.     Dabi A. & Koutrouvelis A.P. Reversal Strategies for Intracranial Hemorrhage Related to Direct Oral Anticoagulant Medications. Critical Care Research and Practice, vol. 2018, Article ID 4907164, 11 pages, 2018. Accessed online at: https://www.hindawi.com/journals/ccrp/2018/4907164/#B51

6.     Steiner T et al. Anticoagulant-Associated Intracranial Hemorrhage in the Era of Reversal Agents. Stroke. 2017;48:1432-1437. DOI: 10.1161/STROKEAHA.116.013343. Accessed online at: https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.116.013343

7.     Tomaselli GF et al. 2017 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol 2017;Dec 1:[Epub ahead of print]. Accessed online at: http://www.onlinejacc.org/content/early/2017/11/10/j.jacc.2017.09.1085?_ga=2.153937912.1348582126.1564395594-1295211746.1554257012

8.     Tomaselli GF et al. SUMMARY OF 2017 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol 2017;Dec 1:[Epub ahead of print]. Accessed online at: https://www.acc.org/latest-in-cardiology/ten-points-to-remember/2017/11/29/17/23/2017-acc-expert-consensus-of-bleeding-on-oacs

Updated by J.C.K. Ho on 29/07/2019