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Monday, July 29, 2019

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

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