Independent role of interleukin-6 and interleukin-8 in the etiology of transfusion reactions to platelet concentrates in children

  • Olivera Miloš Šerbić Nonković Institute of Mother and Child Health Care of Serbia "Dr Vukan Cupic" Department of Blood Transfusion
  • Miloš Kuzmanović Institute of Mother and Child Health Care of Serbia "Dr Vukan Cupic" Department of Hematooncology Medical Faculty, University of Belgrade
  • Maja Životić Institute of Pathology, Belgrade, Serbia Medical Faculty, University of Belgrade
  • Svetlana Žunić Clinical Center of Serbia, The Center for Nuclear Medicine
  • Dragana Jovičić Gojkov Military Medical Academy, Serbia, Institute of Blood Transfusion and Hemobiology
  • Dragana Vujić Institute of Mother and Child Health Care of Serbia "Dr Vukan Cupic" Department of Bone Marrow Transplantation Medical Faculty, University of Belgrade
Keywords: platelet transfusion;, transfusion reaction;, interleukin-6;, interleukin-8;, child.

Abstract


Summary

Background/Aim. Transfusion reaction is an adverse event which manifests during or after administration of blood components to the patient. We aimed to show less known aspects of most common transfusion reactions (allergic and febrile non-hemolytic transfusion reactions – FNHTR) in the pediatric population at the platelet concentrates. The aim of this study was to determine the role of the accumulated cytokines interleukin-6 (IL-6), interlekin-8 (IL-8) and presence of anti-platelet antibodies in the etiology of transfusion reaction in children. Methods. The study included 239 pediatric patients, who received platelet concentrates. Data of reported transfusion reaction were collected and evaluated prospectively. The levels of IL-6 and IL-8 were determined using an immunoassay. Anti-human leukocyte antigen antibodies (anti-HLA) and anti-human platelet antigen antibodies (anti-HPA) were identified by Luminex flow cytometry. Results. Toral of 70 transfusion reactions were recorded 52 patients. Allergic reactions occurred in most of the cases (74.3%), followed by FNHTR (17.1%). Platelets derived from buffy coat caused the majority of reactions (73.5%). Patients with infection after platelet transfusion with FNHTR had the highest levels of IL-6, 483.30 ± 1,041.79 pg/mL (p = 0.020). Respectively, the febrile patients had IL-6, 302.52 ± 720.04 pg/mL (p = 0.004). The level of IL-8 in platelet units that caused transfusion reactions was 95.66 ± 319.10 pg/mL, which was significantly higher (p = 0.001) compared to the control platelet units. Conclusion. The predominant etiologic mechanism for FNHTR in our study was leukocyte derived cytokine accumulation during storage. Etiopathogenesis of FNHTR induced by IL-6 and IL-8 presented differently. We concluded that significant factors in the etiology of FNHTR by IL-6 were the factors related to the pediatric patient (infection, inflammation).

 

References

R E F E R E N C E S

Heddle NM, Blajchman MA, Meyer RM, Lipton JH, Walker IR, Sher GD, et al. A randomized controlled trial comparing the frequency of acute reactions to plasma-removed platelets and prestorage WBC-reduced platelets. Transfusion 2002; 42(5): 556–66.

Geiger TL, Howard SC. Acetaminophen and Diphenhydramine Premedication for Allergic and Febrile Nonhemolytic Transfu-sion Reactions: Good Prophylaxis or Bad Practice?. Transfus Med Rev 2007; 21(1): 1–12.

Lin JS, Tzeng CH, Hao TC, Hu HY, Ho YT, Lyou JY, et al. Cy-tokine release in febrile non-haemolytic red cell transfusion reactions. Vox Sang 2002; 82(3): 156–60.

Delaney M, Wendel S, Bercovitz RS, Cid J, Cohn C, Dunbar NM, et all. Transfusion reactions: Prevention, diagnosis, and treat-ment. Lancet 2016; doi: 10.1016/ S0140-6736(15)01313-6.

Oakley FD, Woods M, Arnold S, Young PP. Transfusion reactions in pediatric compared with adult patients: A look at rate, reaction type, and associated products. Transfusion 2015; 55(3): 563–70.

Li N, Williams L, Zhou Z, Wu Y. Incidence of acute transfusion reactions to platelets in hospitalized pediatric patients based on the US hemovigilance reporting system. Transfusion 2014; 54(6): 1666–72.

Gauvin F, Lacroix J, Robillard P, Lapointe H, Hume H. Acute transfusion reactions in the pediatric intensive care unit. Transfusion 2006; 46(11): 1899–908.

Karim F, Moiz B, Shamsuddin N, Naz S, Khurshid M.. Root cause analysis of non-infectious transfusion complications and the lessons learnt. Transfus Apher Sci 2014; 50(1): 111–7.

Kaufman RM, Assmann SF, Triulzi DJ, Strauss RG, Ness P, Granger S, et al. Transfusion-related adverse events in the Platelet Dose study. Transfusion 2015; 55(1): 144–53.

Seghatchian MJ, Wadhwa M, Thorpe R. Cytokines in platelet concentrates: a comparison of apheresis platelet (haemonetics) and filtered and unfiltered pooled buffy-coat derived platelet concentrates. Transfus Sci 1997; 18(1): 103–7.

Muylle L, Joos M, Wouters E, de Bock R, Peetermans ME. Increased tumor necrosis factor alpha (TNF alpha), interleukin 1, and interleukin 6 (IL-6) levels in the plasma of stored platelet concentrates: Relationship between TNF alpha and IL-6 levels and febrile transfusion reactions. Transfusion 1993; 33(3): 195–9.

Muylle L, Wouters E, Peetermans ME. Febrile reactions to platelet transfusion: The effect of increased interleukin 6 levels in concentrates prepared by the platelet-rich plasma method. Transfusion 1996; 36(10): 886–90.

Heddle NM, Klama L, Meyer R, Walker I, Boshkov L, Roberts R, et al. A randomized controlled trial comparing plasma removal with white cell reduction to prevent reactions to platelets. Transfusion 1999; 39(3): 231–8.

Schefold JC, Hasper D, von Haehling S, Meisel C, Reinke P, Schlosser HG. Interleukin-6 serum level assessment using a new qualitative point-of-care test in sepsis: A comparison with ELISA measurements. Clin Biochem 2008; 41(10–11): 893–8.

Costa EJ, Guimarães TM, de Almeida NC, de Toledo Vde P. Comparison of cytokine levels and metabolic parameters of stored platelet concentrates of the Fundação Hemominas, Belo Horizonte, Brazil. Rev Bras Hematol Hemoter 2012; 34(2): 94–9.

Shaiegan M, Pourfatollah AA, Namiri M, Babaee GR. Generation of IL-8 and TNF-alpha in platelet concentrates during storage. Arch Iran Med 2006; 9(1): 61–4.

Kjeldsen-Kragh J. Challenges in testing for platelet-related ad-verse events. ISBT Sci Series 2011; 6: 124–8.

Savage WJ, Hamilton RG, Tobian AA, Milne GL, Kaufman RM, Savage JH, et al. Defining risk factors and presentations of al-lergic reactions to platelet transfusion. J Allergy Clin Immunol 2014; 133(6): 1772–5.e9.

Savage WJ, Tobian AA, Savage JH, Hamilton RG, Borge PD, Kaufman RM, et al. Transfusion and component characteristics are not associated with allergic transfusion reactions to apheresis platelets. Transfusion 2015; 55(2): 296–300.

Kacker S, Ness PM, Savage WJ, Frick KD, McCullough J, King K, et al. The cost-effectiveness of platelet additive solution to prevent allergic transfusion reactions. Transfusion 2013; 53(11): 2609–18.

Shanwel A, Falker C, Gulliksson H. Storage of platelets in addi-tive solutions: The effects of magnesium and potassium on the release of RANTES, β-thromboglobulin, platelet factor 4 and interleukin-7, during storage. Vox Sang 2003; 85(3): 206–12.

Published
2020/12/01
Section
Original Paper