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Immune and nonimmune causes of low recovery from leukodepleted platelet transfusions: a prospective study

Abstract

Alloantibodies against HLA antigens can be reduced by applying leukodepletion to transfusions. Because the importance of immunological and nonimmunological causes of poor platelet transfusion results using leukodepleted transfusions is not clear, we conducted a prospective study in an unselected patient population receiving leukodepleted transfusions. In 97 patients with hematological malignancies, 181 random leukodepleted platelet transfusions were studied for immunological causes of poor platelet transfusion results by calculating the odds ratio of four different screening tests for a low platelet recovery. Nonimmune causes were also studied by calculating the odds ratio of the most prevalent nonimmune causes for a low platelet recovery. No single screening test showed an association with recovery after 1 and 16 h following a platelet transfusion. The combination of a positive enzyme-linked immunosorbent assay (ELISA) and platelet immunofluorescence test (PIFT) or a combination of a positive lymphocyte immunofluorescence test (LIFT) and PIFT, demonstrating an association with a low platelet recovery after 16 h, was present in 2% of all platelet transfusions. Of nonimmune causes, splenomegaly and storage time of platelets for more than 3 days were associated with low platelet recovery after 1 h and 16 h of being present in 29% and 47% of all platelet transfusions, respectively. Immunological causes account for a small proportion of poor platelet transfusion results compared to nonimmunological causes in a nonselected patient population receiving leukodepleted transfusions.

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References

  1. Heckman KD, Weiner GJ, Davis CS, Strauss RG, Jones MP, Burns CP (1997) Randomized study of prophylactic platelet transfusion threshold during induction therapy for adult acute leukemia: 10,000/microL versus 20,000/microL. J Clin Oncol 15:1143–1149

    CAS  PubMed  Google Scholar 

  2. Rebulla P, Finazzi G, Marangoni F, Avvisati G, Gugliotta L, Tognoni G, Barbui T, Mandelli F, Sirchia G et al. (1997) The threshold for prophylactic platelet transfusions in adults with acute myeloid leukemia. N Engl J Med 337:1870–1875

    Article  CAS  PubMed  Google Scholar 

  3. Wandt H, Frank M, Ehninger G, et al. (1998) Safety and cost effectiveness of a 10×109/l trigger for prophylactic platelet transfusions compared with the traditional 20×109/l trigger: a prospective comparative trial in 105 patients with acute myeloid leukemia. Blood 91:3601–3606

    CAS  PubMed  Google Scholar 

  4. Safai-Kutti S, Zaroulis CG, Day NK, Good RA, Kutti J (1980) Platelet transfusion therapy and circulating immune complexes. Vox Sang 39:22–27

    CAS  PubMed  Google Scholar 

  5. Kutti J, Zaroulis CG, Safai-Kutti S, Dinsmore RE, Day NK, Good RA (1981) Evidence that circulating immune complexes remove transfused platelets from the circulation. Am J Hematol 11:255–259

    CAS  PubMed  Google Scholar 

  6. Hogge DE, Dutcher JP, Aisner J, Schiffer CA (1983) Lymphocytotoxic antibody is a predictor of response to random donor platelet transfusion. Am J Hematol 14:363–369

    CAS  PubMed  Google Scholar 

  7. Rosenfeld CS, Bodensteiner DC (1986) Detection of platelet alloantibodies by flowcytometry. Characterization and clinical significance. Am J Clin Pathol 85:207–212

    CAS  PubMed  Google Scholar 

  8. Klingemann H-G, Self S, Banaji M, Deeg HJ, Doney K, Slichter SJ, Thomas ED, Storb R (1987) Refractoriness to random donor platelet transfusions in patients with aplastic anaemia: a multivariate analysis of data from 264 cases. Br J Haematol 66:115–121

    CAS  PubMed  Google Scholar 

  9. Bishop JF, McGrath K, Wolf MM, Mathews JP, Luise De T, Holdsworth R, Yuen K, Veale M, Whiteside MG, Cooper IA, Szer J (1988) Clinical factors influencing the efficacy of pooled platelet transfusions. Blood 71:383–387

    CAS  PubMed  Google Scholar 

  10. Carr R, Hutton JL, Jenkins JA, Lucas GF, Amphlett NW (1990) Transfusion of AB0 mismatched platelets leads to early platelet refractoriness. Br J Haematol 75:408–413

    CAS  PubMed  Google Scholar 

  11. Bishop JF, Matthews JP, Mcgrath K, Yuen K, Wolf MM, Szer J (1991) Factors influencing 20-hour increments after platelet transfusions. Transfusion 31:392-396

    Article  CAS  PubMed  Google Scholar 

  12. Heal JM, Rowe JM, McMican A, Masel D, Finke C, Blumberg N (1993) The role of AB0 matching in platelet transfusion. Eur J Haematol 50:110–117

    CAS  PubMed  Google Scholar 

  13. Doughty HA, Murphy MF, Metcalfe P, Rohatiner AZS, Lister TA, Waters AH (1994) Relative importance of immune and non-immune causes of platelet refractoriness. Vox Sang 66:200–205

    CAS  PubMed  Google Scholar 

  14. Novotny VMJ, Doorn van R, Witvliet MD, Claas FHJ, Brand A (1995) Occurrence of allogeneic HLA and non-HLA antibodies after transfusion of prestorage filtered platelets and red blood cells: a prospective study. Blood 85:1736–1741

    CAS  PubMed  Google Scholar 

  15. Alcorta I, Pereira A, Ordinas A (1996) Clinical and laboratory factors associated with platelet transfusion refractoriness: a case-control study. Br J Haematol 93:220–224

    CAS  PubMed  Google Scholar 

  16. Legler TJ, Fischer I, Dittmann J, Simson G, Lynen R, Humpe A, Riggert J, Schleyer E, Kern W, Hiddemann W, Koehler M (1997) Frequency and causes of refractoriness in multiply transfused patients. Ann Hematol 74:185–189

    Article  CAS  PubMed  Google Scholar 

  17. Novotny VMJ (1999) Prevention and management of platelet transfusion refractoriness. Vox Sang 76:1-13

    Article  CAS  PubMed  Google Scholar 

  18. Fabris F, Soini B, Sartori R, Randi ML, Luzzatto G, Girolami A (2000) Clinical and laboratory factors that affect the post-transfusion platelet increment. Transfus Sci 23:63–68

    Article  CAS  PubMed  Google Scholar 

  19. Schiffer CA, Anderson KC, Bennett CL, Bernstein S, Elting LS, Goldsmith M, Goldstein M, Hume H, McCullough JJ, McIntyre RE, Powell BL, Rainey JM, Rowley SD, Rebulla P, Troner MB, Wagnon AH (2001) Platelet transfusion for patients with cancer: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 19:1519–1538

    CAS  PubMed  Google Scholar 

  20. Hussein MA, Lee EJ, Schiffer CA (1990) Platelet transfusions administered to patients with splenomegaly. Transfusion 30:508–510

    Article  CAS  PubMed  Google Scholar 

  21. Ishida A, Handa M, Wakui M, Okamoto S, Kamakura M, Ikeda Y (1998) Clinical factors influencing posttransfusion platelet increment in patients undergoing hematopoietic progenitor cell transplantation- a prospective analysis. Transfusion 38:839–847

    Article  CAS  PubMed  Google Scholar 

  22. Eernisse JG, Brand A (1981) Prevention of platelet refractoriness due to HLA antibodies by administration of leucocyte-poor blood components. Exp Haematol 9:77–83

    CAS  Google Scholar 

  23. Murphy MF, Metcalf P, Thomas H, Eve J, Ord J, Lister TA, Waters AH (1986) Use of leucocyte-poor blood components and HLA-matched platelet donors to prevent HLA alloimmunization. Br J Haematol 62:529–534

    CAS  PubMed  Google Scholar 

  24. Brand A, Claas FHJ, Voogt PJ, Wasser MNJM, Eernisse JG (1988) Alloimmunization after leucocyte-depleted multiple random donor platelet transfusions. Vox Sang 54:160–166

    CAS  PubMed  Google Scholar 

  25. Marwijk van-Kooy M, Prooyen van HC, Moes M, Bosma-Sants I, Akkerman JWN (1991) Use of leucocyte-depleted platelet concentrates for the prevention of refractoriness and primary HLA alloimmunization: a prospective, randomized trial. Blood 77:201–206

    PubMed  Google Scholar 

  26. Daly PA, Schiffer CA, Aisner J, Wiernik PH (1980) Platelet transfusion therapy. One-hour posttransfusion increments are valuable in predicting the need for HLA-matched preparations. JAMA 243:435–438

    Article  CAS  PubMed  Google Scholar 

  27. Velden van der KJ, Sintnicolaas K, Löwenberg B (1986) The value of a 51Cr platelet lysis assay as crossmatch test in patients with leukaemia on platelet transfusion therapy. Br J Haematol 62:635–640

    PubMed  Google Scholar 

  28. Lee EJ, Schiffer CA (1987) Serial measurement of lymphocytotoxic antibody and response to nonmatched platelet transfusions in alloimmunized patients. Blood 70:1727–1729

    CAS  PubMed  Google Scholar 

  29. Brubaker DB, Romine M (1987) Relationship of HLA and platelet-reactive antibodies in alloimmunized patients refractory to platelet therapy. Am J Hematol 26:341–352

    CAS  PubMed  Google Scholar 

  30. Freedman J, Garvey MB, Salomon de Friedberg Z, Hornstein A, Blanchette V (1988) Random donor platelet crossmatching: comparison of four platelet antibody detection methods. Am J Hematol 28:1-7

    CAS  PubMed  Google Scholar 

  31. Kickler T, Kennedy SD, Braine HG (1990) Alloimmunization to platelet-specific antigens on glycoproteins IIb-IIIa and Ib/IX in multiply transfused thrombocytopenic patients. Transfusion 30:622–625

    Article  CAS  PubMed  Google Scholar 

  32. Godeau B, Fromont P, Seror T, Duedari N, Bierling P (1992) Platelet alloimmunization after multiple transfusions: a prospective study of 50 patients. Br J Haematol 81:395–400

    CAS  PubMed  Google Scholar 

  33. Kurz M, Greinix H, Höcker P, Kahls P, Knoebl P, Mayr WR, Pober M, Panzer S (1996) Specificities of anti-platelet antibodies in multitransfused patients with haemato-oncological disorders. Br J Haematol 95:564–569

    CAS  PubMed  Google Scholar 

  34. Sanz C, Freire C, Alcorta I, Ordinas A, Pereira A (2001) Platelet-specific antibodies in HLA-immunized patients receiving chronic platelet support. Transfusion 41:762–765

    Article  CAS  PubMed  Google Scholar 

  35. Slichter SJ (1997) The 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 337:1861–1869

    Article  PubMed  Google Scholar 

  36. Davis KB, Slichter SJ, Corash L (1999) Corrected count increment and percent platelet recovery as measures of posttransfusion platelet response: problems and a solution. Transfusion 39:586–592

    Article  CAS  PubMed  Google Scholar 

  37. Levin M-D, Veld de JC, Holt van der B, Veer van 't MB (2003) Screening for allo antibodies in the serum of patients receiving platelet transfusions: a comparison of the ELISA, lymphocytotoxicity and the indirect immunofluorescence technique. Transfusion 43:72–77

    Article  PubMed  Google Scholar 

  38. Sintnicolaas K, Vries de W, Linden van der R, Gratama JW, Bolhuis RLH (1991) Simultaneous flow cytometric detection of antibodies against platelets, granulocytes and lymphocytes. J Immunol Methods 142:215–222

    Article  CAS  PubMed  Google Scholar 

  39. Gratama JW, Linden van der R, Vries de W, Veld de J, Levin M-D, Sintnicolaas K, Veer van 't MB, Bolhuis RLH (1998) Simultaneous detection of IgM and IgG antibodies against platelets, lymphocytes, and granulocytes by flow cytometry. Infus Ther Transf Med 25:317–324

    Article  Google Scholar 

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Acknowledgements

We thank Anneke Luijten and Marianne Beije for their help in collecting sera and data. We thank Nicole Bakker for her help on performing the tests and data collection and storing. We thank Dew Doekharan for his help with the data management.

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Correspondence to M.-D. Levin.

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Levin, MD., de Veld, J.C., van der Holt, B. et al. Immune and nonimmune causes of low recovery from leukodepleted platelet transfusions: a prospective study. Ann Hematol 82, 357–362 (2003). https://doi.org/10.1007/s00277-003-0648-7

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  • DOI: https://doi.org/10.1007/s00277-003-0648-7

Keywords

  • Alloantibody
  • Platelet transfusion
  • Leukodepletion
  • Recovery