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Semin Thromb Hemost
DOI: 10.1055/s-0043-1777301
Review Article

Dosing, Monitoring, Blood Product Utilization, and Thromboembolic Complications of Four-Factor Prothrombin Complex Concentrate as Part of an Institutional Protocol in Pediatric Cardiac Surgery: A Retrospective Cohort Study

Amy L. Kiskaddon
1   Department of Pharmacy, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
2   Division of Cardiology, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland
3   Institute for Clinical and Translational Research, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
4   Heart Institute, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
,
Neil A. Goldenberg
3   Institute for Clinical and Translational Research, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
5   Division of Hematology, Departments of Medicine and Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland
6   Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
,
Jamie L. Fierstein
7   Epidemiology and Biostatistics Shared Resource, Institute for Clinical and Translational Research, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
,
Alexandra Miller
7   Epidemiology and Biostatistics Shared Resource, Institute for Clinical and Translational Research, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
,
James A. Quintessenza
4   Heart Institute, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
,
Vyas M. Kartha
8   Department of Anesthesiology, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
9   Division of Anesthesiology and Critical Care Medicine, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland
› Author Affiliations Funding This work was supported by the JHACH Foundation.
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Abstract

Pediatric cardiac surgery patients are predisposed to blood loss. Blood product administration can lead to complications. Prothrombin complex concentrates (PCCs) offer potential advantages of factor composition, small volume, decreased immunogenicity/infectious risks, and accessibility. The objective of this study was to describe dosing, monitoring, blood product utilization, and thromboembolic complications of administering four-factor PCC (4F-PCC) in pediatric cardiac surgery. We performed a retrospective review of patients aged <18 years undergoing cardiac surgery from June 2020 to May 2022 (inclusive) who received 4F-PCC. Outcomes of interest included 4F-PCC dosing (units/kg) and number of doses administered, chest tube output, blood product administration, donor exposure, length of stay, and thromboembolic events. Eighty-six patients met eligibility criteria. The median (range) age and weight were 0.37 (0.01–16.3) years and 5.3 (1.6–98) kg, respectively. Median (range) total 4F-PCC dose per patient was 25 (9.2–50) units/kg, with 6 patients (7%) receiving a total of two doses. Median (range) 24-hour postoperative packed red blood cells, platelet, plasma, and cryoprecipitate administration volumes were 0 (0–2.57) mL/kg/24 h, 0 (0–1.09), 0 (0–2.64), and 0 (0–0.28 mL/kg/24 h), respectively. Median (range) length of stay and 24-hour postoperative chest tube output were 10 (6–26) days and 1.1 (0.1–4.2) mL/kg/h, respectively. Two (2%) patients experienced a thromboembolic event within 30 days of 4F-PCC administration. These retrospective findings suggest no worsening of hemostatic parameters, a mild median improvement in fibrinogen, low blood product utilization, and low thromboembolism rates following 4F-PCC use in pediatric cardiac surgery.

Keywords

4F-PCC - pediatric - cardiac surgery - bleeding - thrombosis

Author Contributions

A.L. Kiskaddon: study design, acquisition and interpretation of data, drafting manuscript, approval of final version, and ensuring integrity. N.A. Goldenberg: study design, manuscript revision, approval of final version, and ensuring integrity. J.L. Fierstein: data analysis, revising manuscript, approval of study, and ensuring integrity. A. Miller: data analysis, revising manuscript, approval of study, and ensuring integrity. J.A. Quintessenza: study design, manuscript revision, approval of final version, and ensuring integrity. V.M. Kartha: study design, acquisition and interpretation of data, approval of final version, and ensuring integrity.




Publication History

Article published online:
04 December 2023

© 2023. Thieme. All rights reserved.

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  • References

  • 1 Keung CY, Smith KR, Savoia HF, Davidson AJ. An audit of transfusion of red blood cell units in pediatric anesthesia. Paediatr Anaesth 2009; 19 (04) 320-328
    CrossrefPubMedGoogle Scholar
  • 2 Underwood W, Rogers CA, Plummer Z. et al. Detection of coagulopathy in paediatric heart surgery [DECISION study]: study protocol. BMC Hematol 2015; 15: 11
    CrossrefPubMedGoogle Scholar
  • 3 Key NS, Negrier C. Coagulation factor concentrates: past, present, and future. Lancet 2007; 370 (9585) 439-448
    CrossrefPubMedGoogle Scholar
  • 4 Sarode R, Milling Jr TJ, Refaai MA. et al. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study. Circulation 2013; 128 (11) 1234-1243
    CrossrefPubMedGoogle Scholar
  • 5 Makris M, van Veen JJ, Maclean R. Warfarin anticoagulation reversal: management of the asymptomatic and bleeding patient. J Thromb Thrombolysis 2010; 29 (02) 171-181
    CrossrefPubMedGoogle Scholar
  • 6 Tanaka KA, Mazzeffi M, Durila M. Role of prothrombin complex concentrate in perioperative coagulation therapy. J Intensive Care 2014; 2 (01) 60
    CrossrefPubMedGoogle Scholar
  • 7 Guzzetta NA, Miller BE. Principles of hemostasis in children: models and maturation. Paediatr Anaesth 2011; 21 (01) 3-9
    CrossrefPubMedGoogle Scholar
  • 8 Punzalan RC, Gottschall JL. Use and future investigations of recombinant and plasma-derived coagulation and anticoagulant products in the neonate. Transfus Med Rev 2016; 30 (04) 189-196
    CrossrefPubMedGoogle Scholar
  • 9 Kavarana M. Cardiopulmonary bypass and the coagulation system. Prog Pediatr Cardiol 2005; 21: 87-115
    CrossrefPubMedGoogle Scholar
  • 10 Kontras SB, Sirak HD, Newton Jr WA. Hematologic abnormalities in children with congenital heart disease. JAMA 1966; 195 (08) 611-615
    CrossrefPubMedGoogle Scholar
  • 11 Ware JA, Reaves WH, Horak JK, Solis RT. Defective platelet aggregation in patients undergoing surgical repair of cyanotic congenital heart disease. Ann Thorac Surg 1983; 36 (03) 289-294
    CrossrefPubMedGoogle Scholar
  • 12 Kipps AK, Wypij D, Thiagarajan RR, Bacha EA, Newburger JW. Blood transfusion is associated with prolonged duration of mechanical ventilation in infants undergoing reparative cardiac surgery. Pediatr Crit Care Med 2011; 12 (01) 52-56
    CrossrefPubMedGoogle Scholar
  • 13 Redlin M, Kukucka M, Boettcher W. et al. Blood transfusion determines postoperative morbidity in pediatric cardiac surgery applying a comprehensive blood-sparing approach. J Thorac Cardiovasc Surg 2013; 146 (03) 537-542
    CrossrefPubMedGoogle Scholar
  • 14 Iyengar A, Scipione CN, Sheth P. et al. Association of complications with blood transfusions in pediatric cardiac surgery patients. Ann Thorac Surg 2013; 96 (03) 910-916
    CrossrefPubMedGoogle Scholar
  • 15 Ghadimi K, Levy JH, Welsby IJ. Prothrombin complex concentrates for bleeding in the perioperative setting. Anesth Analg 2016; 122 (05) 1287-1300
    CrossrefPubMedGoogle Scholar
  • 16 Kcentra (prothrombin complex concentrate human) [prescribing information]. . Kankakee, IL: CSL Behring; October 2018 . Acce ssed December 2022 at: https://labeling.cslbehring.com/PI/US/Kcentra/EN/Kcentra-Prescribing-Information.pdf
    PubMedGoogle Scholar
  • 17 Sun GH, Patel V, Moreno-Duarte I. et al. Intraoperative administration of 4- factor prothrombin complex concentrate reduces blood requirements in cardiac transplantation. J Cardiothorac Vasc Anesth 2018; 32 (01) 161-167
    CrossrefPubMedGoogle Scholar
  • 18 Pratt Cleary J, Hodge L, Palmer B, Barreiro CJ, Ingemi A. 4-factor prothrombin complex concentrate (PCC4, Kcentra®) protocol reduces blood requirements for heart transplantation: a novel protocol. Ann Transplant 2016; 21: 531-537
    CrossrefPubMedGoogle Scholar
  • 19 Sisti DJ, Williams GD, Ding V. et al. The use of prothrombin complex concentrate as a warfarin reversal agent in pediatric patients undergoing orthotopic heart transplantation. Paediatr Anaesth 2020; 30 (05) 564-570
    CrossrefPubMedGoogle Scholar
  • 20 Kantorovich A, Fink JM, Militello MA. et al. Low-dose 3-factor prothrombin complex concentrate for warfarin reversal prior to heart transplant. Ann Pharmacother 2015; 49 (08) 876-882
    CrossrefPubMedGoogle Scholar
  • 21 Giorni C, Ricci Z, Iodice F. et al. Use of Confidex to control perioperative bleeding in pediatric heart surgery: prospective cohort study. Pediatr Cardiol 2014; 35 (02) 208-214
    CrossrefPubMedGoogle Scholar
  • 22 Dennhardt N, Sümpelmann R, Horke A. et al. Prevention of postoperative bleeding after complex pediatric cardiac surgery by early administration of fibrinogen, prothrombin complex and platelets: a prospective observational study. BMC Anesthesiol 2020; 20 (01) 302
    CrossrefPubMedGoogle Scholar
  • 23 Cruz-Suárez GA, Zamudio-Castilla L, Arango A. et al. Four-factor prothrombin complex concentrate in pediatric cardiac surgery for children under 8 kg: a short report. Paediatr Anaesth 2022; 32 (12) 1372-1373
    CrossrefPubMedGoogle Scholar
  • 24 Jooste EH, Machovec KA, Einhorn LM. et al. 3-Factor prothrombin complex concentrates in infants with refractory bleeding after cardiac surgery. J Cardiothorac Vasc Anesth 2016; 30 (06) 1627-1631
    CrossrefPubMedGoogle Scholar
  • 25 Guzzetta NA, Williams GD. Current use of factor concentrates in pediatric cardiac anesthesia. Paediatr Anaesth 2017; 27 (07) 678-687
    CrossrefPubMedGoogle Scholar
  • 26 R Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. 2021 . Accessed November 8, 2023 at: https://www.R-project.org/
    PubMedGoogle Scholar
  • 27 Fitzgerald J, Lenihan M, Callum J. et al. Use of prothrombin complex concentrate for management of coagulopathy after cardiac surgery: a propensity score matched comparison to plasma. Br J Anaesth 2018; 120 (05) 928-934
    CrossrefPubMedGoogle Scholar
  • 28 Ortmann E, Besser MW, Sharples LD. et al. An exploratory cohort study comparing prothrombin complex concentrate and fresh frozen plasma for the treatment of coagulopathy after complex cardiac surgery. Anesth Analg 2015; 121 (01) 26-33
    CrossrefPubMedGoogle Scholar
  • 29 Katz A, Ahuja T, Arnouk S. et al. A comparison of prothrombin complex concentrate and recombinant activated factor VII for the management of bleeding with cardiac surgery. J Intensive Care Med 2022; 37 (02) 231-239
    CrossrefPubMedGoogle Scholar
  • 30 Harper PC, Smith MM, Brinkman NJ. et al. Outcomes following three-factor inactive prothrombin complex concentrate versus recombinant activated factor VII administration during cardiac surgery. J Cardiothorac Vasc Anesth 2018; 32 (01) 151-157
    CrossrefPubMedGoogle Scholar
  • 31 Nellis ME, Tucci M, Lacroix J. et al; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network; and the Pediatric Critical Care Blood Research Network (BloodNet). Bleeding Assessment Scale in Critically Ill Children (BASIC): physician-driven diagnostic criteria for bleeding severity. Crit Care Med 2019; 47 (12) 1766-1772
    CrossrefPubMedGoogle Scholar
  • 32 Manlhiot C, Menjak IB, Brandão LR. et al. Risk, clinical features, and outcomes of thrombosis associated with pediatric cardiac surgery. Circulation 2011; 124 (14) 1511-1519
    CrossrefPubMedGoogle Scholar
  • 33 Mehringer SL, Klick Z, Bain J. et al. Activated factor 7 versus 4-factor prothrombin complex concentrate for critical bleeding post-cardiac surgery. Ann Pharmacother 2018; 52 (06) 533-537
    CrossrefPubMedGoogle Scholar
  • 34 Ashikhmina E, Said S, Smith MM. et al. Prothrombin complex concentrates in pediatric cardiac surgery: the current state and the future. Ann Thorac Surg 2017; 104 (04) 1423-1431
    CrossrefPubMedGoogle Scholar