Prothrombin complex concentrate

Prothrombin complex concentrate (PCC), also known as factor IX complex, is a medication made up of blood clotting factors II, IX, and X.[1] Some versions also contain factor VII.[2] It is used to treat and prevent bleeding in hemophilia B if pure factor IX is not available.[1][3] It may also be used in those with not enough of these factors due to other reasons such as warfarin therapy.[3] It is given by slow injection into a vein.[1]

Prothrombin complex concentrate
Combination of
Factor IIBlood clotting factor
Factor VIIBlood clotting factor
Factor IXBlood clotting factor
Factor XBlood clotting factor
Clinical data
Trade namesBeriplex, Octaplex, Kcentra, others
Other namesfactor IX complex
AHFS/Drugs.comMonograph
Routes of
administration		injection
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Identifiers
CAS Number

Common side effects include allergic reactions, headache, vomiting, and sleepiness.[1][4] Other serious side effects include blood clots which may result in a heart attack, stroke, pulmonary embolism, or deep vein thrombosis.[4] Antibodies may form after long term use such that future doses are less effective.[3]

Prothrombin complex concentrate came into medical use in the 1960s.[5] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[6][7] It is made from human plasma.[4] A version that is made by recombinant methods which only contains factor IX is also available.[8] In the United States a dose of PCC costs about US$900.[9] A number of different formulations are available globally.[10]

Medical uses

PCC reverses the effects of warfarin and other vitamin K antagonist anti-coagulants and is used in cases of significant bleeding in people with a coagulopathy. It is also used when such a person must undergo an emergency operation treatment.[11] Other uses include a deficiency of one of the included clotting factors, either congenital or due to liver disease, and hemophilia.[11] Several guidelines, including those from the American College of Chest Physicians, recommend PCC for warfarin reversal in people with serious bleeding.[12][13][14][15]

For rapid anticoagulation reversal for surgery, four-factor PCC reduces international normalized ratio (INR) decreases bleeding during surgery appears better than fresh frozen plasma. No differences in thromboembolic event was found.[16]

Contraindications
Platelet factor 4 can cause heparin-induced thrombocytopenia.

The package insert states that PCC is contraindicated in patients with disseminated intravascular coagulation, a pathological activation of coagulation,[17] because giving clotting factors would only further fuel this process. However, if the PCC is given because factor levels are low, it can restore normal coagulation. As PCC products contain heparin, they are contraindicated in patients with heparin-induced thrombocytopenia.[17]

Chemistry

PCC contains a number of blood clotting factors. Typically this includes factor II, IX, and X.[1] Some versions also contain factor VII, protein C, and protein S.[2] Heparin may be added to stop early activation of the factors.[2]

History

The U.S. Food and Drug Administration (FDA) announced its approval in 2013. The FDA approved Kcentra's orphan drug status in December 2012.[18]

References
  1. WHO Model Formulary 2008 (PDF). World Health Organization. 2009. pp. 259–260. ISBN 9789241547659. Archived (PDF) from the original on 13 December 2016. Retrieved 8 December 2016.
  2. Perkins JC (2014). Hematology/Oncology Emergencies, An Issue of Emergency Medicine Clinics of North America. Elsevier Health Sciences. p. 720. ISBN 9780323320290. Archived from the original on 2017-01-05.
  3. British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 171. ISBN 9780857111562.
  4. "Factor IX (Human), Factor IX Complex (Human)". The American Society of Health-System Pharmacists. Archived from the original on 23 September 2017. Retrieved 8 December 2016.
  5. Besa EC (1992). Hematology. Lippincott Williams & Wilkins. p. 276. ISBN 9780683062229. Archived from the original on 2017-01-09.
  6. "19th WHO Model List of Essential Medicines (April 2015)" (PDF). WHO. April 2015. Archived (PDF) from the original on May 13, 2015. Retrieved May 10, 2015.
  7. The selection and use of essential medicines: Twentieth report of the WHO Expert Committee 2015 (including 19th WHO Model List of Essential Medicines and 5th WHO Model List of Essential Medicines for Children) (PDF). WHO. 2015. p. 510. ISBN 9789240694941. Archived (PDF) from the original on 20 December 2016. Retrieved 8 December 2016.
  8. "Factor IX (Recombinant)". The American Society of Health-System Pharmacists. Archived from the original on 23 September 2017. Retrieved 8 December 2016.
  9. Murray MJ, Rose SH, Wedel DJ, Wass CT, Harrison BA, Mueller JT (2014). Faust's Anesthesiology Review: Expert Consult (4th ed.). Elsevier Health Sciences. p. 543. ISBN 9781437703672. Archived from the original on 2017-01-09.
  10. Miller RD, Eriksson LI, Fleisher LA, Wiener-Kronish JP, Cohen NH, Young WL (2014). Miller's Anesthesia (8 ed.). Elsevier Health Sciences. p. 1892. ISBN 9780323280112. Archived from the original on 2017-01-09.
  11. Haberfeld, H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Cofact.
  12. "ACCP 2012 guidelines: 'Evidence-Based Management of Anticoagulant Therapy, Section 9.3 Treatment of Anticoagulant-Related Bleeding'". Chest Journal.
  13. Haemostasis and Thrombosis Task Force for the British Committee for Standards in Haematology. Guidelines on oral anticoagulation: 3rd edition. Br J Haematol. 1998;101:374-387.
  14. Baker RI, Coughlin PB, Gallus AS, Harper PL, Salem HH, Wood EM (November 2004). "Warfarin reversal: consensus guidelines, on behalf of the Australasian Society of Thrombosis and Haemostasis". The Medical Journal of Australia. 181 (9): 492–7. PMID 15516194.
  15. Palareti G (1998). "A guide to oral anticoagulant therapy. Italian Federation of Anticoagulation Clinics". Haemostasis. 28 Suppl 1: 1–46. doi:10.1159/000054103. PMID 9820837.
  16. Levy JH, Douketis J, Steiner T, Goldstein JN, Milling TJ (December 2018). "Prothrombin Complex Concentrates for Perioperative Vitamin K Antagonist and Non-vitamin K Anticoagulant Reversal". Anesthesiology. 129 (6): 1171–1184. doi:10.1097/ALN.0000000000002399. PMC 6234087. PMID 30157037.
  17. Kcentra Prescribing Information Archived 2013-10-26 at the Wayback Machine
  18. "Kcentra, from CSL Behring, Receives FDA Approval for Use in Warfarin Reversal in Patients Undergoing Surgery". CSL Behring. 13 December 2013. Archived from the original on 6 October 2016.

Further reading
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