TY - JOUR AU - Anderson, Kenneth C. AB - Abstract Platelet transfusions have long had an important role in the treatment of patients with thrombocytopenia due to disease or myelotoxic treatment or in patients with reduced platelet function. However, platelet transfusions are associated with numerous risks, both immunologic (e.g., transfusion reactions, alloimmunization, immunosuppression) and infectious (e.g., viral, bacterial). In addition, several laboratory and clinical factors can influence post-transfusion platelet recovery. Recent technological advances have introduced the potential for using alternatives to platelet transfusions, such as cytokines or platelet substitutes, which may avoid the risks of transfusion. Platelet development from megakaryocytes is a process that is highly regulated by cytokines and animal research suggests that selected cytokines involved in this process may be useful in the treatment of thrombocytopenia. Newer developments, including the utilization of recombinant cytokines with relatively selective stimulation of platelet production (e.g., interleukin 6 [IL-6]) and the recent discovery of a megakaryocyte colony stimulating factor (thrombopoietin), represent major therapeutic opportunities in the treatment of thrombocytopenia. Platelet substitutes, e.g., thromboerythrocytes, also show promise in the management of platelet deficiencies. Platelets, Cytokines, Interleukin 6, Thrombocytopenia, Thrombopoietin References 1 Duke WW . The relation of blood platelets to hemorrhagic disease . JAMA 1910 ; 55 : 1185 – 1192 . Google Scholar Crossref Search ADS WorldCat 2 Anderson KC . Hematologic complications. In: Holland IF, Frei E III, Bast RC et al., eds. Cancer Medicine . Philadelphia : Lea and Febiger , 1993 : 2294 – 2314 . Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC 3 Thompson CB , Jakubowski JA. The pathophysiology and clinical relevance of platelet heterogeneity . Blood 1988 ; 72 : 1 – 8 . Google Scholar Crossref Search ADS PubMed WorldCat 4 Lackner H . Hemostatic abnormalities associated with dysproteinemias . Semin Hematol 1973 ; 10 : 125 – 133 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 5 Cowan DH , Graham RC Jr, Baunach D. The platelet defect in leukemia: platelet ultrastructure, adenine nucleotide metabolism and the release reaction . J Clin Invest 1975 ; 56 : 188 – 200 . Google Scholar Crossref Search ADS PubMed WorldCat 6 Handin RJ . Clotting disorders: disorders of the platelet and vessel wall . In: Wilson JD, Braunwald E, Isselbacher KJ et al., eds. Harrison's Principles of Internal Medicine, 12th ed. 1991 : 1500 – 1505 . 7 Surgenor DM , Wallace EL, Hao SHS et al. Collection and transfusion of blood in the United States, 1982–1987 . N Engl J Med 1990 ; 322 : 1646 – 1651 . Google Scholar Crossref Search ADS PubMed WorldCat 8 Baer MR , Bloomfield CD, Kasprisin DO. Controversies in transfusion medicine: prophylactic platelet transfusion therapy: pro . Transfusion 1992 ; 32 : 377 – 380 . Google Scholar Crossref Search ADS PubMed WorldCat 9 Patten E , Kasprisin DO. Controversies in transfusion medicine: prophylactic platelet transfusion revisited after 25 years: con . Transfusion 1992 ; 32 : 381 – 385 . Google Scholar Crossref Search ADS PubMed WorldCat 10 Beutler E . Platelet transfusions: the 20,000/μL trigger . Blood 1993 ; 81 : 1411 – 1413 . Google Scholar Crossref Search ADS PubMed WorldCat 11 Gmür J , Burger J, Schanz U, Fehr J, Schnaffner A. Safety of stringent prophylactic platelet transfusion policy for patients with acute leukemia . Lancet 1991 ; 338 : 1223 – 1226 . Google Scholar Crossref Search ADS PubMed WorldCat 12 Office of Medical Applications Research, National Institutes of Health . Consensus conference: platelet transfusion therapy . JAMA 1987 ; 257 : 1777 – 1780 . Crossref Search ADS PubMed WorldCat 13 Daly PA , Schiffer CA, Aisner J et al. Platelet transfusion therapy: one-hour posttransfusion increments are valuable in predicting the need for HLA-matched preparations . JAMA 1980 ; 243 : 435 – 438 . Google Scholar Crossref Search ADS PubMed WorldCat 14 Harker LA , Slichter SJ. The bleeding time as a screening test for evaluation of platelet function . N Engl J Med 1972 ; 287 : 155 – 159 . Google Scholar Crossref Search ADS PubMed WorldCat 15 Anderson KC . Platelet transfusion. In: Transfusion Medicine . Boston, MA : Blackwell Scientific Publications , 1988 : 145 – 167 . Google Scholar Google Preview OpenURL Placeholder Text WorldCat COPAC 16 Bishop JF , McGrath K, Wolf MM et al. Clinical factors influencing the efficacy of pooled platelet transfusion . Blood 1988 ; 71 : 383 – 387 . Google Scholar Crossref Search ADS PubMed WorldCat 17 Flatow FA , Freireich EJ. Effect of splenectomy on the response to platelet transfusion in three patients with aplastic anemia . N Engl J Med 1966 ; 274 : 242 – 248 . Google Scholar Crossref Search ADS PubMed WorldCat 18 Chong BH , Du X, Berndt MC et al. Characterization of the binding domains on platelet glycoproteins Ib-IX and IIb/IIIa complexes for the quinine/quinidine-dependent antibodies . Blood 1991 ; 77 : 2190 – 2199 . Google Scholar Crossref Search ADS PubMed WorldCat 19 Fujisawa K , O'Toole TE, Tani P et al. Autoantibodies to the presumptive cytoplasmic domain of platelet glycoprotein IIIa in patients with chronic immune thrombocytopenic purpura . Blood 1991 ; 77 : 2207 – 2213 . Google Scholar Crossref Search ADS PubMed WorldCat 20 Kickler T , Kennedy SD, Braine HG. Alloimmunization to platelet-specific antigens on glycoproteins IIb-IIIa and Ib/IX in multiply transfused thrombocytopenic patients . Transfusion 1990 ; 30 : 622 – 625 . Google Scholar Crossref Search ADS PubMed WorldCat 21 Dutcher JP , Schiffer CA, Aisner J et al. Alloimmunization following platelet transfusion: the absence of a dose-response relationship . Blood 1981 ; 57 : 395 – 398 . Google Scholar Crossref Search ADS PubMed WorldCat 22 Halohan TV , Terasaki PI, Deisseroth AB. Suppression of transfusion-related alloimmunization in intensively treated cancer patients . Blood 1981 ; 58 : 122 – 128 . Google Scholar Crossref Search ADS PubMed WorldCat 23 Murphy MF , Riordan T, Minchinton RM et al. Demonstration of an immune-mediated mechanism of penicillin-induced neutropenia and thrombocytopenia . Br J Haematol 1983 ; 55 : 155 – 160 . Google Scholar Crossref Search ADS PubMed WorldCat 24 Stricker RB , Shuman MA. Quinidine purpura: evidence that glycoprotein V is a target platelet antigen . Blood 1986 ; 67 : 1377 – 1381 . Google Scholar Crossref Search ADS PubMed WorldCat 25 Herzig RH , Terasaki PI, Trapani J et al. The relationship between donor-recipient lymphocytotoxicity and the transfusion response using HLA-matched concentrates . Transfusion 1977 ; 17 : 657 – 661 . Google Scholar Crossref Search ADS PubMed WorldCat 26 Gmür J , von Felten A, Osterwalder B et al. Delayed alloimmunization using random single donor platelet transfusions: a prospective study in thrombocytopenic patients with acute leukemia . Blood 1983 ; 62 : 473 – 479 . Google Scholar Crossref Search ADS PubMed WorldCat 27 Howard JE , Perkins HA. The natural history of alloimmunization to platelets . Transfusion 1978 ; 18 : 496 – 503 . Google Scholar Crossref Search ADS PubMed WorldCat 28 Sintnicolaas K , Sizoo W, Haije WG et al. Delayed alloimmunization by random single donor platelet transfusions: a randomized study to compare single donor and multiple donor platelet transfusions in cancer patients with severe thrombocytopenia . Lancet 1981 ; 1 : 750 – 754 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 29 Dutcher JP , Schiffer CA, Aisner J et al. Longterm follow-up of patients with leukemia receiving platelet transfusions: identification of a large group of patients who do not become alloimmunized . Blood 1981 ; 58 : 1007 – 1011 . Google Scholar Crossref Search ADS PubMed WorldCat 30 Yankee RA , Grumet RC, Rogentine GN. Platelet transfusion therapy: the selection of compatible platelet donors for refractory patients by lymphocyte HLA-typing . N Engl J Med 1969 ; 281 : 1208 – 1212 . Google Scholar Crossref Search ADS PubMed WorldCat 31 Saarinen UM , Kekomäki R, Siimes MA et al. Effective prophylaxis against platelet refractoriness in multitransfused patients by use of leukocyte-free blood components . Blood 1990 ; 75 : 512 – 517 . Google Scholar Crossref Search ADS PubMed WorldCat 32 van Marwijk Kooy M , van Prooijen HC, Moes M et al. Use of leukocyte-depleted platelet concentrates for the prevention of refractoriness and primary HLA alloimmunization: a prospective, randomized trial . Blood 1991 ; 77 : 201 – 205 . Google Scholar Crossref Search ADS PubMed WorldCat 33 Schiffer CA . Prevention of alloimmunization against platelets . Blood 1991 ; 77 : 1 – 4 . Google Scholar Crossref Search ADS PubMed WorldCat 34 Schiffer CA , Patten E, Reilly J et al. Effective leukocyte removal from platelet preparations by centrifugation in a new pooling bag . Transfusion 1987 ; 27 : 162 – 164 . Google Scholar Crossref Search ADS PubMed WorldCat 35 Andreu G , Dewailly J, Leberre C et al. Prevention of HLA immunization with leukocyte-poor packed red cells and platelet concentrates obtained by filtration . Blood 1988 ; 72 : 964 – 969 . Google Scholar Crossref Search ADS PubMed WorldCat 36 Sniecinski I , O'Donnell MR, Nowicki B et al. Prevention of refractoriness and HLA-alloimmunization using filtered blood products . Blood 1988 ; 71 : 1402 – 1407 . Google Scholar Crossref Search ADS PubMed WorldCat 37 Sintnicolaas K , van Marwijk Kooy M, van Prooijen H et al. Leukocyte depletion of random single donor platelet transfusions does not prevent secondary human leukocyte antigen-alloimmunization and refractoriness: a randomized prospective study . Blood 1995 ; 85 : 824 – 828 . Google Scholar Crossref Search ADS PubMed WorldCat 38 Heddle NM , Blajchman MA. The leukodepletion of cellular blood products in the prevention of HLA-alloimmunyation and refractoriness to allogeneic platelet transfusions . Blood 1995 ; 85 : 603 – 606 . Google Scholar Crossref Search ADS PubMed WorldCat 39 Novotny VMJ , van Doorn R, Witvliet MD et al. Occurrence of allogeneic HLA and non-HLA antibodies after transfusion of pre-storage filtered platelets and red blood cells: a prospective study . Blood 1995 ; 85 : 1736 – 1741 . Google Scholar Crossref Search ADS PubMed WorldCat 40 Moroff G , Garratty G, Heal JM et al. Selection of platelets for refractory patients by HLA matching and prospective crossmatching . Transfusion 1992 ; 32 : 633 – 640 . Google Scholar Crossref Search ADS PubMed WorldCat 41 Lee EJ , Schiffer CA. ABO compatibility can influence the results of platelet transfusions . Transfusion 1989 ; 29 : 384 – 389 . Google Scholar Crossref Search ADS PubMed WorldCat 42 Murphy S . ABO blood groups and platelet transfusions . Transfusion 1988 ; 28 : 401 – 402 . Google Scholar Crossref Search ADS PubMed WorldCat 43 Muylle L , Joos M, Wouters E et al. Increased tumor necrosis factor α (TNFα), interleukin 1, and interleukin 6 (IL-6) levels in the plasma of stored platelet concentrates: relationship between TNFα and IL-6 levels and febrile transfusion reactions . Transfusion 1993 ; 33 : 195 – 199 . Google Scholar Crossref Search ADS PubMed WorldCat 44 Brunson ME , Alexander JW. Mechanisms of transfusion-induced immunosuppression . Transfusion 1990 ; 30 : 651 – 658 . Google Scholar Crossref Search ADS PubMed WorldCat 45 Anderson KC , Goodnough LT, Sayers M et al. Variation in blood component irradiation practice: implications for prevention of transfusion associated graft versus host disease . Blood 1991 ; 77 : 2096 – 2102 . Google Scholar Crossref Search ADS PubMed WorldCat 46 Heal JM , Jones ME, Forey JJ et al. Fatal Salmonella septicemia after platelet transfusion . Transfusion 1987 ; 27 : 2 – 5 . Google Scholar Crossref Search ADS PubMed WorldCat 47 Anderson KC , Lew MA, Gorgone BC et al. Transfusion-related sepsis after prolonged platelet storage . Am J Med 1986 ; 81 : 405 – 411 . Google Scholar Crossref Search ADS PubMed WorldCat 48 Hoofnagle JH . Posttransfusion hepatitis B . Transfusion 1990 ; 30 : 384 – 386 . Google Scholar Crossref Search ADS PubMed WorldCat 49 Barrett BB , Andersen JW, Anderson KC. Strategies for the avoidance of bacterial contamination of blood components . Transfusion 1993 ; 33 : 228 – 233 . Google Scholar Crossref Search ADS PubMed WorldCat 50 Kaplan J , Sarnaik S, Gitlin J et al. Diminished helper/suppressor lymphocyte ratios and natural killer activity in recipients of repeated blood transfusions . Blood 1984 ; 64 : 308 – 310 . Google Scholar Crossref Search ADS PubMed WorldCat 51 Blajchman MA , Bardossy L, Carmen R et al. Allogeneic blood transfusion-induced enhancement of tumor growth: two animal models showing amelioration by leukodepletion and passive transfer using spleen cells . Blood 1993 ; 81 : 1880 – 1882 . Google Scholar Crossref Search ADS PubMed WorldCat 52 Shivdasani RA , Haluska FG, Dock NL et al. Graft-versus-host disease associated with transfusion of blood from unrelated HLA homozygous donors . N Engl J Med 1993 ; 328 : 766 – 770 . Google Scholar Crossref Search ADS PubMed WorldCat 53 Stevens CE , Aach RD, Hollinger FB et al. Hepatitis B virus antibody in blood donors and the occurrence of non-A, non-B hepatitis in transfusion recipients: an analysis of the transfusion-transmitted viruses study . Ann Intern Med 1984 ; 101 : 733 – 738 . Google Scholar Crossref Search ADS PubMed WorldCat 54 Kline WE , Bowman RJ, McCurdy KK et al. Hepatitis B core antibody (anti-HBc) in blood donors in the United States: implications for surrogate testing programs . Transfusion 1987 ; 27 : 99 – 102 . Google Scholar Crossref Search ADS PubMed WorldCat 55 Kuo G , Choo QL, Alter HJ et al. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis . Science 1989 ; 244 : 362 – 364 . Google Scholar Crossref Search ADS PubMed WorldCat 56 Aach RD , Stevens CE, Hollinger FB et al. Hepatitis C virus infection in post-transfusion hepatitis . N Engl J Med 1991 ; 325 : 1325 – 1329 . Google Scholar Crossref Search ADS PubMed WorldCat 57 Kleinman S , Alter H, Busch M et al. Increased detection of hepatitis C virus (HCV)-infected blood donors by a multiple-antigen HCV enzyme immunoassay . Transfusion 1992 ; 32 : 805 – 813 . Google Scholar Crossref Search ADS PubMed WorldCat 58 Donahue JG , Muñoz A, Ness PM et al. The declining risk of post-transfusion hepatitis C virus infection . N Engl J Med 1992 ; 327 : 369 – 373 . Google Scholar Crossref Search ADS PubMed WorldCat 59 Winston DJ , Ho WG, Lin CH et al. Intravenous immunoglobulin for prevention of cytomegalovirus infection and interstitial pneumonia after bone marrow transplantation . Ann Intern Med 1987 ; 106 : 12 – 18 . Google Scholar Crossref Search ADS PubMed WorldCat 60 Bowden RA , Sayers M, Flourney N et al. Cytomegalovirus immune globulin and seronegative blood products to prevent primary cytomegalovirus infection after marrow transplantation . N Engl J Med 1986 ; 314 : 1006 – 1110 . Google Scholar Crossref Search ADS PubMed WorldCat 61 Sayers MH , Anderson KC, Goodnough LT et al. Reducing the risk for transfusion-transmitted cytomegalovirus infection . Ann Intern Med 1992 ; 116 : 55 – 62 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 62 Miller W , Flynn P, McCullough J et al. Cytomegalovirus infection after bone marrow transplantation and association with acute graft-versus-host disease . Blood 1986 ; 67 : 1162 – 1167 . Google Scholar Crossref Search ADS PubMed WorldCat 63 Peterson LR , Satten G, Dodd RY et al. Current estimates of the infectious window period and risk of HIV infections from seronegative blood donations . 5th National Forum on AIDS, Hepatitis, and Other Blood-Borne Diseases. Atlanta Georgia, 1994 : m-1.2a . 64 Erickson-Miller CL , Ji H, Murphy MI. Megakaryocytopoiesis and platelet production: does stem cell factor play a role? STEM CELLS 1993 ; 11 ( suppl 2 ): 163 – 169 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 65 Frenkel EP . Southwestern Medicine Conference: the clinical spectrum of thrombocytosis and thrombocythemia . Am J Med Sci 1991 ; 301 : 69 – 80 . Google Scholar Crossref Search ADS PubMed WorldCat 66 McDonald TP . The regulation of megakaryocyte and platelet production . Int J Cell Cloning 1989 ; 7 : 139 – 155 . Google Scholar Crossref Search ADS PubMed WorldCat 67 Mazur EM . Megakaryocytopoiesis and platelet production: areview . Exp Hematol 1987 ; 15 : 340 – 350 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 68 Hoffman R . Regulation of megakaryocytopoiesis . Blood 1989 ; 74 : 1196 – 1212 . Google Scholar Crossref Search ADS PubMed WorldCat 69 Gewirtz AM , Hoffman R. Human megakaryocyte production: cell biology and clinical considerations . Hematol Oncol Clin North Am 1990 ; 4 : 43 – 57 . Google Scholar Crossref Search ADS PubMed WorldCat 70 Peng I , Friese P, George JN et al. Alteration of platelet function in dogs mediated by interleukin-6 . Blood 1994 ; 83 : 398 – 403 . Google Scholar Crossref Search ADS PubMed WorldCat 71 Yonemura Y , Kawakita M, Masuda T et al. Effect of recombinant human interleukin-11 on rat megakaryopoiesis and thrombopoiesis in vivo: comparative study with interleukin-6 . Br J Haematol 1993 ; 84 : 16 – 23 . Google Scholar Crossref Search ADS PubMed WorldCat 72 Burstein SA , Downs T, Friese P et al. Thrombocytopoiesis in normal and sublethally irradiated dogs: response to human interleukin-6 . Blood 1992 ; 80 : 420 – 428 . Google Scholar Crossref Search ADS PubMed WorldCat 73 Takahashi T , Tsuyuoka R, Ueda Y et al. Megakaryocyte potentiating activity of IL-1, IL-6, and GM-CSF as evaluated by their action on in vitro human megakaryocytic colonies . Br I Haematol 1991 ; 78 : 480 – 487 . Google Scholar Crossref Search ADS WorldCat 74 Stahl CP , Zucker-Franklin D, Evatt BL et al. Effects of human interleukin-6 on megakaryocyte development and thrombocytopoiesis in primates . Blood 1991 ; 78 : 1467 – 1475 . Google Scholar Crossref Search ADS PubMed WorldCat 75 Neben TY , Loebelenz J, Hayes L et al. Recombinant human interleukin-11 stimulates megakaryocytopoiesis and increases peripheral platelets in normal and splenectomized mice . Blood 1993 ; 81 : 901 – 908 . Google Scholar Crossref Search ADS PubMed WorldCat 76 Monroy RL , Davis TA, Donahue RE et al. In vivo stimulation of platelet production in a primate model using IL-1 and IL-3 . Exp Hematol 1991 ; 19 : 629 – 635 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 77 Neben S , Turner K. The biology of interleukin 11 . Stem Cells 1993 ; 11 ( suppl 2 ): 156 – 162 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 78 Schwartz GN , Warren MK, Kessler SW et al. Insulin-like growth factor-II (IGF-II) enhanced cytokine-induced proliferation and differentiation of myeloid and megakaryocyte progenitor cells in serum-derived liquid cultures of CD34+ bone marrow cells . Annual Meeting of the American Society of Hematology 1993 ; 82 ( suppl 1 ): 103a . Google Scholar OpenURL Placeholder Text WorldCat 79 Ritch PS , Schiller J, Rinkin S et al. Phase I evaluation of recombinant human interleukin-6 . Blood 1993 ; 82 ( suppl l ): 367a . Google Scholar OpenURL Placeholder Text WorldCat 80 Gordon MS , Battiato L, Hoffman R et al. Subcutaneously (SC) administered recombinant human interleukin-11 (NeumegaTM rhIL-11 growth factor; rhIL-11) prevents thrombocytopenia following chemotherapy (CT) with cyclophosphamide (C) and doxorubicin (A) in women with breast cancer (BC) . Blood 1993 ; 82 ( suppl 1 ): 318a . Google Scholar OpenURL Placeholder Text WorldCat 81 Lok S , Kaushansky K, Holly RD et al. Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production in vivo . Nature 1994 ; 369 : 565 – 568 . Google Scholar Crossref Search ADS PubMed WorldCat 82 Kauschansky K , Lok S, Holly RD et al. Promotion of megakaryocyte progenitor expansion and differentiation by the c-Mpl ligand thrombopoietin . Nature 1994 ; 369 : 568 – 571 . Google Scholar Crossref Search ADS PubMed WorldCat 83 de Sauvage FI , Hass PE, Spencer SD et al. Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl ligand . Nature 1994 ; 369 : 533 – 538 . Google Scholar Crossref Search ADS PubMed WorldCat 84 Metcalf D . Thrombopoietin—at last . Nature 1994 ; 369 : 519 – 520 . Google Scholar Crossref Search ADS PubMed WorldCat 85 Coller BS , Kutok JL, Scudder LE et al. Studies of activated GPIIb/IIIa receptors on the luminal surface of adherent platelets. Paradoxical loss of luminal receptors when platelets adhere to high density fibrinogen . J Clin Invest 1993 ; 92 : 2796 – 2806 . Google Scholar Crossref Search ADS PubMed WorldCat 86 Coller BS , Springer KT, Beer JH et al. Thromboerythrocytes: in vitro studies of a potential autologous semi-artificial alternative to platelet transfusions . J Clin Invest 1992 ; 89 : 546 – 555 . Google Scholar Crossref Search ADS PubMed WorldCat This content is only available as a PDF. © 1995 AlphaMed Press This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) TI - Platelet transfusion and alternatives to transfusion in patients with malignancy JO - Stem Cells DO - 10.1002/stem.5530130603 DA - 1995-01-01 UR - https://www.deepdyve.com/lp/oxford-university-press/platelet-transfusion-and-alternatives-to-transfusion-in-patients-with-9SSE0Q3PFi SP - 588 EP - 596 VL - 13 IS - 6 DP - DeepDyve ER -