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International Journal of Hematology

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01-03-2023 | Platelet Transfusion | Original Article

A meta-analysis of risk factors associated with platelet transfusion refractoriness

Authors: Xiaofei Song, Jiaqian Qi, Kun Fang, Xueqian Li, Yue Han

Published in: International Journal of Hematology | Issue 6/2023

Abstract

Background

Platelet transfusion refractoriness (PTR) remains an intractable issue in clinical practice, and is common in hematological patients. At present, it is believed that both immune and non-immune factors play a role. We conducted a meta-analysis of various risk factors which may contribute to PTR.

Methods

PubMed, Embase, Cochrane library, and Web of Science were selected as research database platforms. Citations included were further assessed for quality and bias using the Newcastle–Ottawa Scale. All analyses were performed using Review Manager Version 5.4 and STATA 16.0.

Results

The preliminary search revealed 1069 publications, and 17 (5929 patients in total) were ultimately included in the quantitative analysis. The following variables were associated with the occurrence of PTR: fever (OR = 2.26, 95%CI 2.00–2.55, p < 0.00001), bleeding (OR = 2.10, 95%CI 1.36–3.24, p = 0.0008), female sex (OR = 2.06, 95%CI 1.13–3.75, p = 0.02), antibiotic use (OR = 2.94, 95%CI 1.54–5.59, p = 0.001), and infection (OR = 2.19, 95%CI 1.20–4.03, p = 0.01). Antibodies involved in immune activation were a higher risk factor (OR = 4.17, 95%CI 2.36–7.36, p < 0.00001), and splenomegaly was nearly significant (OR = 1.73, 95%CI 0.97–3.07, p = 0.06).

Conclusions

We identified some important risk factors for PTR, but further research is needed to identify the many other possible elements that may contribute to or mediate PTR.

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Forest SK, Hod EA. Management of the platelet refractory patient. Hematol Oncol Clin North Am. 2016;30(3):665–77. https://doi.org/10.1016/j.hoc.2016.01.008.CrossRefPubMed

Saris A, Pavenski K. Human leukocyte antigen alloimmunization and alloimmune platelet refractoriness. Transfus Med Rev. 2020;34(4):250–7. https://doi.org/10.1016/j.tmrv.2020.09.010.CrossRefPubMed

Slichter SJ, Davis K, Enright H, Braine H, Gernsheimer T, Kao KJ, et al. Factors affecting posttransfusion platelet increments, platelet refractoriness, and platelet transfusion intervals in thrombocytopenic patients. Blood. 2005;105(10):4106–14. https://doi.org/10.1182/blood-2003-08-2724.CrossRefPubMedPubMedCentral

Belizaire R, Makar RS. Non-alloimmune mechanisms of thrombocytopenia and refractoriness to platelet transfusion. Transfus Med Rev. 2020;34(4):242–9. https://doi.org/10.1016/j.tmrv.2020.09.002.CrossRefPubMedPubMedCentral

Juskewitch JE, Norgan AP, De Goey SR, Duellman PM, Wakefield LL, Gandhi MJ, et al. How do I … manage the platelet transfusion-refractory patient? Transfusion. 2017;57(12):2828–35. https://doi.org/10.1111/trf.14316.CrossRefPubMed

Arabi S, Almahayni AO, Alomair AA, Masuadi EM, Damlaj M, Al-Dorzi HM. Prevalence, Risk Factors, and Outcomes of Platelet Transfusion Refractoriness in Critically Ill Patients: A Retrospective Cohort Study. Crit Care Res Pract. 2021;2021:5589768. https://doi.org/10.1155/2021/5589768.CrossRefPubMedPubMedCentral

Balduini CL, Salvaneschi L, Klersy C, Noris P, Mazzucco M, Rizzuto F, et al. Factors influencing post-transfusional platelet increment in pediatric patients given hematopoietic stem cell transplantation. Leukemia. 2001;15(12):1885–91. https://doi.org/10.1038/sj.leu.2402307.CrossRefPubMed

Baron E, Charpentier J, François A, Ben Hadj Amor H, Habr B, Cariou A, et al. Post-transfusion platelet responses in critically ill cancer patients with hypoproliferative thrombocytopenia. Transfusion. 2020;60(2):275–84. https://doi.org/10.1111/trf.15596.CrossRefPubMed

Beligaswatte A, Tsiopelas E, Humphreys I, Bennett G, Robinson K, Davis K, et al. The mean fluorescence intensities of anti-HLA antibodies detected using micro-bead flow cytometry predict the risk of platelet transfusion refractoriness. Br J Haematol. 2013;162(3):409–12. https://doi.org/10.1111/bjh.12369.CrossRefPubMed

10.

Chenna D, Shastry S, Baliga P. Evaluation and monitoring of response to platelet transfusion therapy: experience from a tertiary care center. Acta Clin Belg. 2021;76(4):300–3. https://doi.org/10.1080/17843286.2020.1732568.CrossRefPubMed

11.

Cheok KPL, Chhetri R, Wee LYA, Friel O, Pham A, Salvi A, et al. The burden of immune-mediated refractoriness to platelet transfusions in myelodysplastic syndromes. Transfusion. 2020;60(10):2192–8. https://doi.org/10.1111/trf.16029.CrossRefPubMed

12.

Hu X, Cai H, Zheng L, Luo Y, Zhou J, Hui Y, et al. Clinical and immunological features of platelet transfusion refractoriness in young patients with de novo acute myeloid leukemia. Cancer Med. 2020;9(14):4941–8. https://doi.org/10.1002/cam4.3140.CrossRefPubMedPubMedCentral

13.

Kerkhoffs JL, Eikenboom JC, van de Watering LM, van Wordragen-Vlaswinkel RJ, Wijermans PW, Brand A. The clinical impact of platelet refractoriness: correlation with bleeding and survival. Transfusion. 2008;48(9):1959–65. https://doi.org/10.1111/j.1537-2995.2008.01799.x.CrossRefPubMed

14.

Kumawat V, Sharma RR, Malhotra P, Marwaha N. Prevalence of risk factors for platelet transfusion refractoriness in multitransfused hemato-oncological patients at tertiary care center in North India. Asian J Transfus Sci. 2015;9(1):61–4. https://doi.org/10.4103/0973-6247.150953.CrossRefPubMedPubMedCentral

15.

Mishima Y, Tsuno NH, Matsuhashi M, Yoshizato T, Sato T, Ikeda T, et al. Effects of universal vs bedside leukoreductions on the alloimmunization to platelets and the platelet transfusion refractoriness. Transfus Apher Sci. 2015;52(1):112–21. https://doi.org/10.1016/j.transci.2014.11.001.CrossRefPubMed

16.

Seftel MD, Growe GH, Petraszko T, Benny WB, Le A, Lee CY, et al. Universal prestorage leukoreduction in Canada decreases platelet alloimmunization and refractoriness. Blood. 2004;103(1):333–9. https://doi.org/10.1182/blood-2003-03-0940.CrossRefPubMed

17.

Shastry S, Chaudhary R. Clinical factors influencing corrected count increment. Transfus Apher Sci. 2012;47(3):327–30. https://doi.org/10.1016/j.transci.2012.04.006.CrossRefPubMed

18.

Solves P, Sanz J, Freiria C, Santiago M, Villalba A, Gómez I, et al. Factors influencing platelet transfusion refractoriness in patients undergoing allogeneic hematopoietic stem cell transplantation. Ann Hematol. 2018;97(1):161–7. https://doi.org/10.1007/s00277-017-3168-6.CrossRefPubMed

19.

Song T, Zhang Y, Huang J, Liu Z. Transfusion-induced platelet antibodies and regulatory T cells in multiply transfused patients. J Clin Lab Anal. 2021;35(7):e23864. https://doi.org/10.1002/jcla.23864.CrossRefPubMedPubMedCentral

20.

Tanoue S, Konuma T, Kato S, Oiwa-Monna M, Isobe M, Jimbo K, et al. Platelet transfusion refractoriness in single-unit cord blood transplantation for adults: risk factors and clinical outcomes. Biol Blood Marrow Transplant. 2018;24(9):1873–80. https://doi.org/10.1016/j.bbmt.2018.05.006.CrossRefPubMed

21.

Wong M, Narra R, Selim M, Zimmerman MA, Kim J, Padmanabhan A, et al. Human leukocyte antigen class I antibodies and response to platelet transfusion in patients undergoing liver transplantation. J Surg Res. 2020;255:99–105. https://doi.org/10.1016/j.jss.2020.05.029.CrossRefPubMed

22.

Zhou Z, Gao Y, Li X, Ren J, Liu Y, Li J. The clinical characteristics of patients with acute leukemia or stem cell transplantation exhibiting immune based platelet refractoriness. Transfus Apher Sci. 2020;59(3):102725. https://doi.org/10.1016/j.transci.2020.102725.CrossRefPubMed

23.

Liu Y, Zhang Y, Chen D, Fu Y. Current status of and global trends in platelet transfusion refractoriness from 2004 to 2021: a bibliometric analysis. Front Med. 2022;9:873500. https://doi.org/10.3389/fmed.2022.873500.CrossRef

24.

Schiffer CA, Bohlke K, Delaney M, Hume H, Magdalinski AJ, McCullough JJ, et al. Platelet transfusion for patients with cancer: American society of clinical oncology clinical practice guideline update. J Clin Oncol. 2018;36(3):283–99. https://doi.org/10.1200/jco.2017.76.1734.CrossRefPubMed

25.

Stanworth SJ, Navarrete C, Estcourt L, Marsh J. Platelet refractoriness–practical approaches and ongoing dilemmas in patient management. Br J Haematol. 2015;171(3):297–305. https://doi.org/10.1111/bjh.13597.CrossRefPubMed

26.

Legler TJ, Fischer I, Dittmann J, Simson G, Lynen R, Humpe A, et al. Frequency and causes of refractoriness in multiply transfused patients. Ann Hematol. 1997;74(4):185–9. https://doi.org/10.1007/s002770050280.CrossRefPubMed

27.

Ojha A, Nandi D, Batra H, Singhal R, Annarapu GK, Bhattacharyya S, et al. Platelet activation determines the severity of thrombocytopenia in dengue infection. Sci Rep. 2017;7:41697. https://doi.org/10.1038/srep41697.CrossRefPubMedPubMedCentral

28.

Bishop JF, McGrath K, Wolf MM, Matthews JP, De Luise T, Holdsworth R, et al. Clinical factors influencing the efficacy of pooled platelet transfusions. Blood. 1988;71(2):383–7.CrossRefPubMed

29.

Chu T, Tang Y, Wang H, Qi J, Zhao Y, Pan T, et al. Efficacy of recombinant factor VIIa for severe bleeding complicated by platelet transfusion refractoriness in patients with hematologic malignancies. Thromb Res. 2017;160:14–8. https://doi.org/10.1016/j.thromres.2017.10.015.CrossRefPubMed

30.

Aster RH. Pooling of platelets in the spleen: role in the pathogenesis of “hypersplenic” thrombocytopenia. J Clin Invest. 1966;45(5):645–57. https://doi.org/10.1172/jci105380.CrossRefPubMedPubMedCentral

31.

Hussein MA, Lee EJ, Schiffer CA. Platelet transfusions administered to patients with splenomegaly. Transfusion. 1990;30(6):508–10. https://doi.org/10.1046/j.1537-2995.1990.30690333480.x.CrossRefPubMed

32.

Mauro M, Camoglio F, Piccoli P, De Bortoli M, Balter R, Pegoraro A, et al. The use of splenectomy to manage platelet transfusion refractoriness due to anti-human leukocyte antibodies in allogeneic stem cell transplantation. Pediatr Rep. 2016;8(1):6159. https://doi.org/10.4081/pr.2016.6159.CrossRefPubMedPubMedCentral

33.

Trial to Reduce Alloimmunization to Platelets Study Group. Leukocyte reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet transfusions. N Engl J Med. 1997;337(26):1861–9. https://doi.org/10.1056/nejm199712253372601.CrossRef

34.

Ma N, Guo JP, Zhao XY, Xu LP, Zhang XH, Wang Y, et al. Prevalence and risk factors of antibodies to HLA according to different cut-off values of mean fluorescence intensity in haploidentical allograft candidates: A prospective study of 3805 subjects. Hla. 2022;100(4):312–24. https://doi.org/10.1111/tan.14704.CrossRefPubMed

35.

Ruggero MA, Abdelghany O, Topal JE. Vancomycin-induced thrombocytopenia without isolation of a drug-dependent antibody. Pharmacotherapy. 2012;32(11):e321–5. https://doi.org/10.1002/phar.1132.CrossRefPubMed

36.

Mohammadi M, Jahangard-Rafsanjani Z, Sarayani A, Hadjibabaei M, Taghizadeh-Ghehi M. Vancomycin-induced thrombocytopenia: a narrative review. Drug Saf. 2017;40(1):49–59. https://doi.org/10.1007/s40264-016-0469-y.CrossRefPubMed

37.

Chan CS, Tuazon CU, Lessin LS. Amphotericin-B-induced thrombocytopenia. Ann Intern Med. 1982;96(3):332–3. https://doi.org/10.7326/0003-4819-96-3-332.CrossRefPubMed

38.

Böck M, Muggenthaler KH, Schmidt U, Heim MU. Influence of antibiotics on posttransfusion platelet increment. Transfusion. 1996;36(11–12):952–4. https://doi.org/10.1046/j.1537-2995.1996.36111297091736.x.CrossRefPubMed

39.

McGrath K, Bertram JF, Houghton S, Boothman J, Manderson JA, Minchinton R. Amphotericin B-induced injury in stored human platelets. Transfusion. 1992;32(1):46–50. https://doi.org/10.1046/j.1537-2995.1992.32192116432.x.CrossRefPubMed

40.

Murphy S. Amphotericin B and platelet transfusion. Transfusion. 1992;32(1):7–8. https://doi.org/10.1046/j.1537-2995.1992.32192116437.x.CrossRefPubMed

41.

Li Y, Ryan J, Xu F, Vostal JG. Macrophage depletion mitigates platelet aggregate formation in splenic marginal zone and alleviates lps-associated thrombocytopenia in rats. Front Med. 2019;6:300. https://doi.org/10.3389/fmed.2019.00300.CrossRef

42.

Matics TJ, Sanchez-Pinto LN. Adaptation and validation of a pediatric sequential organ failure assessment score and evaluation of the sepsis-3 definitions in critically Ill children. JAMA Pediatr. 2017;171(10):e172352. https://doi.org/10.1001/jamapediatrics.2017.2352.CrossRefPubMedPubMedCentral

43.

Pavenski K, Freedman J, Semple JW. HLA alloimmunization against platelet transfusions: pathophysiology, significance, prevention and management. Tissue Antigens. 2012;79(4):237–45. https://doi.org/10.1111/j.1399-0039.2012.01852.x.CrossRefPubMed

44.

Wu KK, Thompson JS, Koepke JA, Hoak JC, Flink R. Heterogeneity of antibody response to human platelet transfusion. J Clin Invest. 1976;58(2):432–8. https://doi.org/10.1172/jci108487.CrossRefPubMedPubMedCentral

45.

Curtis BR, McFarland JG. Human platelet antigens-2013. Vox Sang. 2014;106(2):93–102. https://doi.org/10.1111/vox.12085.CrossRefPubMed

46.

Kurz M, Greinix H, Höcker P, Kalhs P, Knöbl P, Mayr WR, et al. Specificities of anti-platelet antibodies in multitransfused patients with haemato-oncological disorders. Br J Haematol. 1996;95(3):564–9. https://doi.org/10.1046/j.1365-2141.1996.d01-1936.x.CrossRefPubMed

47.

Cohn CS. Platelet transfusion refractoriness: how do I diagnose and manage? Hematol Am Soc Hematol Educ Program. 2020;2020(1):527–32. https://doi.org/10.1182/hematology.2020000137.CrossRef

48.

Vassallo RR. Recognition and management of antibodies to human platelet antigens in platelet transfusion-refractory patients. Immunohematology. 2009;25(3):119–24.CrossRefPubMed

49.

Saito K, Ichikawa S, Ohtomo R, Hatta S, Katsuoka Y, Harigae H, et al. Severe platelet transfusion refractoriness due to anti-HPA-5a antibody during induction chemotherapy for acute promyelocytic leukemia. Ann Hematol. 2022;101(9):2103–5. https://doi.org/10.1007/s00277-022-04875-y.CrossRefPubMed

50.

Inoue H, Sakamoto R, Nishimiya H, Sakamoto H, Terasu S, Aminaka R, et al. Minor impact of patient alloantibodies against human platelet antigen (HPA)-15 in the effectiveness of platelet transfusion: a pilot study. Transfusion. 2021;61(3):738–43. https://doi.org/10.1111/trf.16181.CrossRefPubMed

51.

Liu J, Shao Y, Ding H, Deng J, Xu X, Wang J, et al. Distribution of CD36 deficiency in different Chinese ethnic groups. Hum Immunol. 2020;81(7):366–71. https://doi.org/10.1016/j.humimm.2020.05.004.CrossRefPubMed

52.

Flesch BK, Scherer V, Opitz A, Ochmann O, Janson A, Steitz M, et al. Platelet CD36 deficiency is present in 2.6% of Arabian individuals and can cause NAIT and platelet refractoriness. Transfusion. 2021;61(6):1932–42. https://doi.org/10.1111/trf.16398.CrossRefPubMed

53.

Schmidt AE, Sahai T, Refaai MA, Sullivan M, Curtis BR. Severe platelet transfusion refractoriness in association with antibodies against CD36. Lab Med. 2020;51(5):540–4. https://doi.org/10.1093/labmed/lmz091.CrossRefPubMed

Title: A meta-analysis of risk factors associated with platelet transfusion refractoriness
Authors: Xiaofei Song
Jiaqian Qi
Kun Fang
Xueqian Li
Yue Han
Publication date: 01-03-2023
Publisher: Springer Nature Singapore
Keyword: Platelet Transfusion
Published in: International Journal of Hematology / Issue 6/2023
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-023-03557-3

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