Prothrombin complex concentrate explained

Type:combo
Component1:Factor II
Class1:Blood clotting factor
Component2:Factor VII
Class2:Blood clotting factor
Component3:Factor IX
Class3:Blood clotting factor
Component4:Factor X
Class4:Blood clotting factor
Tradename:Kcentra, others
Drugs.Com:
Dailymedid:Kcentra
Routes Of Administration:Intravenous
Atc Prefix:B02
Atc Suffix:BD01
Legal Ca:Rx-only
Legal Ca Comment:[1] [2]
Legal Uk:POM
Legal Uk Comment:[3]
Legal Us:Rx-only
Legal Us Comment:[4] [5] [6]
Legal Eu:Rx-only
Legal Eu Comment:[7]
Legal Status:Rx-only
Cas Number:37224-63-8
Drugbank:DB11330
Drugbank2:DB13152
Synonyms:factor IX complex

Prothrombin complex concentrate (PCC), also known as factor IX complex, sold under the brand name Kcentra among others, is a combination medication made up of blood clotting factors II, IX, and X(3-factor PCC) or, when also containing factor VII as does Kcentra, 4-factor PCC.[8] It is used to treat and prevent bleeding in hemophilia B if pure factor IX is not available. It may also be used for reversal of warfarin therapy.[9] It is given by slow injection into a vein.[10] Another product, activated prothrombin complex concentrate or FEIBA (Factor Eight Inhibitor Bypassing Agent), may be used for acquired hemophilia.[11]

Common side effects include allergic reactions, headache, vomiting, and sleepiness.[10] Other serious side effects include blood clots which may result in a heart attack, stroke, pulmonary embolism, or deep vein thrombosis. Antibodies may form after long term use such that future doses are less effective.[9]

Prothrombin complex concentrate came into medical use in the 1960s.[12] It is on the World Health Organization's List of Essential Medicines.[13] [14] It is made from human plasma.[15] Recombinant factor IX is also available in a stand-alone preparation.[16]

Medical uses

Prothrombin complex concentrate 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.[17] Other uses include a deficiency of one of the included clotting factors, either congenital or due to liver disease, and hemophilia. Several guidelines, including those from the American College of Chest Physicians, recommend prothrombin complex concentrate for warfarin reversal in people with serious bleeding.[18] [19] [20] [21]

For rapid anticoagulation reversal for surgery, four-factor prothrombin complex concentrate reduces international normalized ratio (INR) and decreases bleeding during surgery when compared with administration of fresh frozen plasma. No differences in thromboembolic event was found.[22]

Contraindications

The package insert states that prothrombin complex concentrate is contraindicated in patients with disseminated intravascular coagulation, a pathological activation of coagulation,[23] 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.

Chemistry

Prothrombin complex concentrate contains a number of blood clotting factors. Typically this includes factor II, IX, and X.[10] Some versions also contain factor VII, protein C, and protein S.[8] Heparin may be added to stop early activation of the factors.[8]

History

The US Food and Drug Administration (FDA) announced its approval in 2013.[24] The FDA approved Kcentra's orphan drug status in December 2012.[25]

Society and culture

Economics

In the United States a dose of prothrombin complex concentrate costs about US $3200[26] though one study described the cost as $11 650.[27] The Australian National Blood Authority sets Prothrombinex (500 IU) at around AUD$327. [28]

Brand names

A number of different formulations are available globally.[29]

Further reading

Notes and References

  1. Web site: Blood health (non-cancer) . . 11 May 2018 . 13 April 2024.
  2. Web site: Regulatory Decision Summary for Rebinyn . Drug and Health Products Portal . 29 November 2017 . 13 April 2024.
  3. Web site: Beriplex P/N 250 IU - Summary of Product Characteristics (SmPC) . (emc) . 27 January 2021 . 7 May 2023.
  4. Web site: Kcentra (Prothrombin Complex Concentrate, Human) . U.S. Food and Drug Administration (FDA) . 3 May 2023 . 7 May 2023.
  5. Web site: Balfaxar (prothrombin complex concentrate- human powder, for solution . DailyMed . U.S. National Library of Medicine . 21 July 2023 . 25 August 2023.
  6. Web site: Balfaxar . U.S. Food and Drug Administration (FDA) . 21 July 2023 . 25 August 2023.
  7. Web site: Active substance: human prothrombin complex . January 2017 . List of nationally authorised medicinal products . European Medicines Agency . EMA/45481/2017, PSUSA/00001638/201604 .
  8. Book: Wilson MD, Davis JE . Antithrombotic Reversal Agents . Perkins JC . Hematology/Oncology Emergencies . Emergency Medicine Clinics of North America . 3 . 3 . 893676529 . 2014. Elsevier . 978-0-323-32029-0. 720. .
  9. Book: British national formulary : BNF 69. 2015. British Medical Association. 978-0-85711-156-2. 171. 69th . 910448191.
  10. Book: WHO Model Formulary 2008 . 2009 . 978-92-4-154765-9 . ((World Health Organization)) . Stuart MC, Kouimtzi M, Hill SR . 10665/44053 . World Health Organization . World Health Organization . free . 259–60 . 609852935.
  11. Negrier C, Voisin S, Baghaei F, Numerof R, Novack A, Doralt JE, Romanov V, Gringeri A . Global Post-Authorization Safety Surveillance Study: real-world data on prophylaxis and on-demand treatment using FEIBA (an activated prothrombin complex concentrate) . Blood Coagul Fibrinolysis . 27 . 5 . 551–6 . July 2016 . 26829366 . 4935538 . 10.1097/MBC.0000000000000525 .
  12. Book: Besa EC . Clinical Aspects of Transfusion Therapy . Hematology . 1992 . Lippincott Williams & Wilkins . 978-0-683-06222-9 . 1175934487. 276. .
  13. Book: ((World Health Organization)) . World Health Organization model list of essential medicines: 21st list 2019 . 2019 . 10665/325771 . World Health Organization . World Health Organization . Geneva . WHO/MVP/EMP/IAU/2019.06 . free .
  14. Book: ((World Health Organization)) . 2015 . 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) . World Health Organization . Geneva . World Health Organization . 10665/189763 . WHO technical report series . 994 . free . 978-92-4-120994-6 . 0512-3054 . 510 .
  15. Web site: Factor IX (Human), Factor IX Complex (Human). The American Society of Health-System Pharmacists. 8 December 2016. live. https://web.archive.org/web/20170924045854/https://www.drugs.com/monograph/factor-ix-human-factor-ix-complex-human.html. 24 September 2017.
  16. Web site: Factor IX (Recombinant). The American Society of Health-System Pharmacists. 8 December 2016. live. https://web.archive.org/web/20170924093004/https://www.drugs.com/monograph/factor-ix-recombinant.html. 24 September 2017.
  17. Book: Austria-Codex. Cofact. Haberfeld, H. Österreichischer Apothekerverlag. Vienna. 2015. de.
  18. Web site: ACCP 2012 guidelines: 'Evidence-Based Management of Anticoagulant Therapy, Section 9.3 Treatment of Anticoagulant-Related Bleeding'. https://archive.today/20130703233657/http://journal.publications.chestnet.org/article.aspx?articleid=1159453. dead. 2013-07-03. Chest.
  19. ((Haemostasis and Thrombosis Task Force for the British Committee for Standards in Haematology)) . Guidelines on oral anticoagulation: 3rd edition . Br J Haematol . 101 . 2 . 374–387 . May 1998 . 10.1046/j.1365-2141.1998.00715.x . 9609538 .
  20. Baker RI, Coughlin PB, Gallus AS, Harper PL, Salem HH, Wood EM . Warfarin reversal: consensus guidelines, on behalf of the Australasian Society of Thrombosis and Haemostasis . The Medical Journal of Australia . 181 . 9 . 492–7 . November 2004 . 10.5694/j.1326-5377.2004.tb06407.x . 15516194 . 3035209 .
  21. Palareti G . A guide to oral anticoagulant therapy. Italian Federation of Anticoagulation Clinics . Haemostasis . 28 . 1–46 . 1998 . Suppl 1 . 9820837 . 10.1159/000054103 . 202659825 .
  22. Levy JH, Douketis J, Steiner T, Goldstein JN, Milling TJ . Prothrombin Complex Concentrates for Perioperative Vitamin K Antagonist and Non-vitamin K Anticoagulant Reversal . Anesthesiology . 129 . 6 . 1171–1184 . December 2018 . 30157037 . 6234087 . 10.1097/ALN.0000000000002399 .
  23. Web site: Kcentra- prothrombin, coagulation factor vii human, coagulation factor ix human, coagulation factor x human, protein c, protein s human, and water kit . DailyMed . U.S. National Library of Medicine . 22 October 2018 . 21 April 2020.
  24. CSL Behring Receives FDA Approval of Kcentra for Urgent Warfarin Reversal in Patients with Acute Major Bleeding . CSL Behring . 29 April 2013 . 7 May 2023.
  25. CSL Behring's Kcentra Receives FDA Approval For Use In Warfarin Reversal In Patients Undergoing Surgery . CSL Behring. 13 December 2013. live. https://web.archive.org/web/20161006060102/http://www.cslbehring.com/newsroom/Kcentra-Earns-FDA-Approval-for-Use-in-Patients-Undergoing-Surgery?tabSelections=1255923338766&currentPage=1. 6 October 2016. 5 October 2016 .
  26. Fasanya C, Arrillaga A, Caronia C, Rothburd L, Japhe T, Hahn Y, Joseph P, Reci D, Eckardt P . Use of Andexanet Alfa for Factor Xa Inhibitor Reversal in US Verified Trauma Centers: A National Survey . Clin Appl Thromb Hemost . 30 . 10760296241238013 . 2024 . 38494906 . 10946067 . 10.1177/10760296241238013 .
  27. Irizarry-Gatell VM, Bacchus MW, De Leo EK, Zhang Y, Lagasse CA, Khanna AY, Harris NS, Zumberg MS . The use of andexanet alfa vs. 4-factor prothrombin complex concentrates in the setting of life-threatening intracranial hemorrhage . Blood Coagul Fibrinolysis . 35 . 3 . 94–100 . April 2024 . 38358898 . 10.1097/MBC.0000000000001279 .
  28. Web site: What Blood Products are Supplied . National Product Price List . Australian National Blood Authority . 2024-01-18 .
  29. Book: Miller RD, Eriksson LI, Fleisher LA, Wiener-Kronish JP, Cohen NH, Young WL . Miller's Anesthesia. 2014. Elsevier . 978-0-323-28011-2. 1892. 8th . 63. Patient Blood Management: Autologous Blood Procurement, Recombinant Factor Vila Therapy, and Blood Utilization § Prothrombin Complex Concentrates . . 892338436.

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