Solvent/Detergent-Treated Plasma in the Management of Pediatric Patients Who Require Replacement of Multiple Coagulation Factors: An Open-Label, Multicenter, Post-marketing Study

Philip C Spinella, Santiago Borasino, Jeffrey Alten, Philip C Spinella, Santiago Borasino, Jeffrey Alten

Abstract

Background: Octaplas is a solvent/detergent-treated, pooled plasma used for the management of preoperative or bleeding patients who require replacement of single or multiple coagulation factors. The aim of this post-marketing study was to collect real-world data on octaplas treatment in pediatric patients, with the primary focus being safety. Methods: This was an open-label, multicenter, phase IV study conducted in patients <16 years old who required replacement of multiple coagulation factors due to liver dysfunction associated with coagulopathy and/or required cardiac surgery or liver surgery. Octaplas was administered intravenously based on ABO-group compatibility. The primary endpoints included the incidence of serious adverse events (SAEs), adverse drug reactions (ADRs), thrombotic events (TEs), thromboembolic events (TEEs) and hyperfibrinolytic events (HFEs). Results: A total of 50 patients were enrolled (≤2 years old, n = 37; >2 years old, n = 13; female, n = 24) and 49 patients completed the study. Indications for the use of octaplas included planned cardiac surgery (n = 40, 80.0%), liver transplant surgery (n = 5, 10.0%) and liver dysfunction (n = 5, 10.0%). No ADRs, HFEs or treatment-related TEs and TEEs occurred during the study. Five patients had SAEs, one of which was fatal (iatrogenic injury). Other SAEs included hemorrhage, hypotension, hemorrhagic shock, coronary artery hemorrhage, intracardiac thrombus, supraventricular tachycardia, portal vein thrombosis and respiratory failure (1 each). None of the SAEs were considered to be related to octaplas. Conclusions: Results of the present study support the use of octaplas in the management of preoperative or bleeding pediatric patients who require replacement of multiple plasma coagulation factors. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT02050841.

Keywords: bleeding; neonate; octaplas; pediatric; post-marketing; safety; surgery.

Copyright © 2020 Spinella, Borasino and Alten.

References

    1. Karam O, Demaret P, Shefler A, Leteurtre S, Spinella PC, Stanworth SJ, et al. . Indications and effects of plasma transfusions in critically ill children. Am J Respir Crit Care Med. (2015) 191:1395–402. 10.1164/rccm.201503-0450OC
    1. Labarinas S, Arni D, Karam O. Plasma in the PICU: why and when should we transfuse? Ann Intensive Care. (2013) 3:16. 10.1186/2110-5820-3-16
    1. New HV, Berryman J, Bolton-Maggs PH, Cantwell C, Chalmers EA, Davies T, et al. . Guidelines on transfusion for fetuses, neonates and older children. Br J Haematol. (2016) 175:784–828. 10.1111/bjh.14233
    1. Camazine MN, Karam O, Colvin R, Leteurtre S, Demaret P, Tucci M, et al. . Outcomes related to the use of frozen plasma or pooled solvent/detergent-treated plasma in critically ill children. Pediatr Crit Care Med. (2017) 18:e215–23. 10.1097/PCC.0000000000001149
    1. Lacroix J. Plasma transfusion in critically ill children. A magical mystery tour? Am J Respir Crit Care Med. (2015) 191:1347–9. 10.1164/rccm.201504-0810ED
    1. Spinella PC, Frazier E, Pidcoke HF, Dietzen DJ, Pati S, Gorkun O, et al. All plasma products are not created equal: characterizing differences between plasma products. J Trauma Acute Care Surg. (2015) 78:S18–25. 10.1097/TA.0000000000000629
    1. Theusinger OM, Baulig W, Seifert B, Emmert MY, Spahn DR, Asmis LM. Relative concentrations of haemostatic factors and cytokines in solvent/detergent-treated and fresh-frozen plasma. Br J Anaesth. (2011) 106:505–11. 10.1093/bja/aer003
    1. Heger A, Römisch J. Quality of octaplasLG® is independent on the plasma source. Transfus Med Hemother. (2012) 39:1–66. 10.1159/000170956
    1. Heger A, Romisch J, Svae TE. A biochemical comparison of a pharmaceutically licensed coagulation active plasma (octaplas) with a universally applicable development product (Uniplas) and single-donor FFPs subjected to methylene-blue dye and white-light treatment. Transfus Apher Sci. (2006) 35:223–33. 10.1016/j.transci.2006.08.008
    1. Horowitz B, Bonomo R, Prince AM, Chin SN, Brotman B, Shulman RW. Solvent/detergent-treated plasma: a virus-inactivated substitute for fresh frozen plasma. Blood. (1992) 79:826–31. 10.1182/blood.V79.3.826.bloodjournal793826
    1. Biesert L, Suhartono H. Solvent/detergent treatment of human plasma–a very robust method for virus inactivation. Validated virus safety of OCTAPLAS. Vox Sang 74 Suppl. (1998) 1:207–12. 10.1111/j.1423-0410.1998.tb05474.x
    1. Kuhnel D, Muller S, Pichotta A, Radomski KU, Volk A, Schmidt T. Inactivation of Zika virus by solvent/detergent treatment of human plasma and other plasma-derived products and pasteurization of human serum albumin. Transfusion. (2017) 57:802–10. 10.1111/trf.13964
    1. US Food and Drug Administration Octaplas, Pooled Plasma (human), Solvent/Detergent Treated: Solution for Intravenous Infusion. [US prescribing information]. Available online at: (accessed April 04, 2019).
    1. Leslie J, Brister N, Levy JH, Yared JP, Marty A, Martin H, et al. . Treatment of postoperative hypertension after coronary artery bypass surgery. Double-blind comparison of intravenous isradipine and sodium nitroprusside. Circulation. (1994) 90:II256–61.
    1. Chekrizova V, Murphy WG. Solvent-detergent plasma: use in neonatal patients, in adult and paediatric patients with liver disease and in obstetric and gynaecological emergencies. Transfus Med. (2006) 16:85–91. 10.1111/j.1365-3148.2006.00626.x
    1. Witt V, Pichler H, Beiglboeck E, Kursten F, Weidner L. Changes in hemostasis caused by different replacement fluids and outcome in therapeutic plasma exchange in pediatric patients in a retrospective single center study. Transfus Apher Sci. (2017) 56:59–65. 10.1016/j.transci.2017.01.001
    1. Hall S, Randall K, Cole R, Motwani J, Williams M. A paediatric tertiary referral centre experience of octaplasLG®. Br J Haematol. (2013) 161:66 10.1111/bjh.12263
    1. Kalsi AS, Al-Azzawi O, Gill R. Comparison of the coagulation effect achieved by octaplasLG versus fresh frozen plasma in pediatric cardiac surgical patients. Clin Appl Thromb Hemost. (2018) 24:1327–32. 10.1177/1076029618774145

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe