Platelet Transfusion Therapy: From 1973 to 2005
Introduction
We used to have an evening report, where the daily transfusion problems were discussed. It was 1973. We were Jon van Rood, chairman of the Department of ImmunoHaematology and Blood bank (IHB), and, opening the wine bottle to keep our attention, George Eernisse (the director of the Blood bank), Hans Bruning (chemist and validating our “Coombs” sera), several physicians doing HLA research, often as replacement for the military service, and me, just arrived fellow in transfusion medicine. Apart from an incidental autoimmune hemolytic anemia, which we proudly classified with the sera (antigamma and antinongamma) produced by our own rabbits in the cage at the back of the Blood bank, bleeding dominated the report: bleeding from all causes and requiring different solutions. For hemophilia patients the Blood bank prepared cryoprecipitate, which needed quick cooling of citrated plasma. Heart surgery for children had come of age, requiring fresh blood and platelet transfusions to prevent bleeding. A bone marrow transplant program for aplastic anemia had begun [1] and the preparation of on-demand platelets (platelets had no shelf life) did not comply with the other bleeding problems to be solved by our small Blood bank. Moreover, the multitransfused aplastic anemia patients soon developed chills, fever, and no increment on repeated platelet transfusions. We heavily relied on our few HLA-typed donors, who were subjected to manual plateletpheresis, and in emergency situations we always turned to our few donors homozygous for common HLA types [1]. It was shameful to call them so often. Jon used to have at least one brilliant problem-solving plan at every evening report, which we tried to forget, because most of us already had a plan. But this was a persistent plan, the Euro platelet plan, coming down to type as many donors as possible, select HLA-homozygous donors and freeze the platelets. As a newcomer, I did not yet have a plan and it became obviously my problem.
In 1973 we could not foretell that in 2005 the physician in charge of the hematology/transplant ward on the morning round orders platelet transfusions by just marking a cross on the transfusion request chart, choosing from random, HLA-matched, concentrated, washed, cytomegalovirus-sero-negative, irradiated platelets. The story is as follows.
Section snippets
Leukodepletion: 1974–1980
For patients with febrile transfusion reactions, the Central Laboratory of the Dutch Red Cross developed in 1972 a cotton-wool filter to remove leukocytes from fresh (less than 24 hours old) citrated blood or red cells [2]. In 1974 we attended a lecture on the clinical results with these filtered transfusions in dialysis patients, who not only suffered no febrile transfusion reactions but, remarkably, also developed fewer leukocyte antibodies despite the fact that 30% of the platelets were
Cryopreservation of Platelets: 1973–1977
This part of the Europlatelet project was the first to come to a dead end. Using a final dimethyl sulfoxide concentration of 5% we sequentially compared the 51Cr recovery and survival of fresh and cryopreserved platelets from the same HLA-matched donor in 20 thrombocytopenic patients. If we calculated the ratio of the recovery of frozen platelets compared to fresh platelets these varied between 14 and 93% (median 45%). Also in three volunteers we observed unexplained variation of the frozen to
Technical Innovations (Platelet Filters, Sterile Connecting Devices, and Storage Bags): 1980–1995
The technology of leukocyte removal from platelets lagged ten years behind filtration of red cells, but the first results became available in 1983 [9], followed by generations of ever-improving leukocyte removal filters manufactured by several companies. For filtration of cells, however, the closed bag system had to be opened, limiting the shelf life of fresh filtered red cells to 24 hours and that of platelets, stored at room temperature, to 6 hours. In the 1980s the FDA approved the sterile
HLA Typing of Donors: 1973–2005
From 1973 onward, simultaneous with every otherwise indicated HLA typing session, a few extra donors were HLA typed. We selected these donors by checking all the (paper) donor files. Donors who uneventfully gave blood at least three times, had not been involved in a hepatitis case, and had not a profession that according to our view could lead to noncompliance with frequent platelet apheresis were chosen. HLA-homozygous donors were asked to participate in plateletpheresis. Later we asked formal
Assays to Detect Platelet Antibodies: Never-Ending Story
Based on the results of more than 1500 platelet transfusions to alloimmunized patients, Duquesnoy validated HLA matching for platelet donor selection [21]. The matching could be distinguished in increasing degrees of mismatches. In case of an A degree match, in which the donor carries no HLA-A and -B antigens incompatible with the patient (four antigens compatible), a B1 match (three antigens matched, one blank/unknown (U) or (X) cross-reactive), or a B2 match (two antigens matched, two either
Platelet Transfusion Therapy: 2005 and Beyond
The story of platelet supportive care illustrates that future predictions are generally wrong and that progress comes by many small steps and from various sides. But there remain new and old questions to be solved. Looking back, the achievements are great, so great that we presumably use too many inappropriate platelet transfusions, and preventive versus therapeutic indication for platelet transfusions becomes a new future question. Although we have horrifying memories of bleeding patients back
References (35)
- et al.
Differential function of MHC antigens in T lymphocyte activation
Nature
(1976) - et al.
The leukodepletion of cellular blood products in the prevention of HLA-alloimmunization and refractoriness to allogeneic platelet transfusions
Blood
(1995) Meta-analysis of randomised controlled trials of the efficacy of white cell reduction in preventing HLA-alloimmunization and refractoriness to random donor platelet transfusions
Transfusion Med Rev
(1998)- et al.
Occurrence of allogenic HLA and non-HLA antibodies after transfusion of prestorage filtered plateets and red blood cellsa prospective study
Blood
(1995) - et al.
Platelet Transfusion therapy. Optimal donor selection with a combination of lymphocytotoxicity and platelet fluorescence test
Blood
(1978) - et al.
Selection of histocompatible apheresis platelet donors by cross-matching random donor platelet concentrates
Blood
(1992) - et al.
Leukocyte depletion of random single-donor platelet transfusions does not prevent secondary human leukocyte antigen-alloimmunization and refractorinessa randomized prospective study
Blood
(1995) - et al.
Allogeneic bone marrow transplantation in a patient with aplastic anemia using aphenotypically HLA-identical donor
Transplantation
(1973) - et al.
Removal of leukocytes from whole blood and erythrocyte suspensions by filtration through cotton wool
Vox Sang
(1972) - et al.
Prevention of platelet refractoriness due to HLA antibodies by administration of leukocyte-poor blood components
Exp Haematol
(1981)
Alloimmunization against the MHC antigens after platelet transfusions is due to contaminating leukocytes in the platelet suspension
Exp. Haematol.
Trial to Reduce Alloimmunization to Platelets study groupLeukocyte reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet transfusions
N Engl J Med
Preparation of leukocyte-free platelets for transfusion by filtration through cotton-wool
Vox Sang
Platelet storage for transfusion
Seminars in Hematology
Platelet quality after 15-day storage of plateletconcentrates prepared from buffy-coats and stored in a glucose-free crystalloid medium
Transfusion
Improvement of platelet storage conditions by using new polyofin containers
Transfusion
Transfusion results of filtered and subsequently stored random platelet suspensions prepared from buffy-coat
Vox Sang
Cited by (14)
Efficacy of anti-thymocyte globulin for platelet transfusion refractoriness in serious aplastic anemia patients
2022, Transfusion and Apheresis ScienceCitation Excerpt :PTR due to human leukocyte antigens antibody (HLA) alloimmunization is a common complication in patients receiving long-term packed red blood cell and platelet transfusions [2,3]. Following repeated platelet transfusions, antibodies to HLA are detected in a frequency between 7–55 % [4]. Pregnancy also can lead to the development of HLA antibodies [5].
Platelets: A more than a centenary old Odyssey and more to come
2018, Transfusion Clinique et BiologiqueBiomanufacture of human platelets for transfusion: Rationale and approaches
2014, Experimental HematologyCitation Excerpt :There is no single answer to this question, but it does provide a framework for considering the scale and complexity of the task. Recent reviews discuss in detail the issues of optimal timing and dosing of platelet transfusions [17,22–24]. Over the last 20 years, numerous randomized clinical trials have evaluated various aspects of platelet transfusion therapy and suggest that 3.0–6.0 x 1011 platelets is a clinically useful dose for most adults [25–27].
Approaches to synthetic platelet analogs
2013, BiomaterialsCitation Excerpt :As a result, evaluation of immunogenic potential is listed as one of the critical components for clinical translation of such products, as per FDA guidelines [121]. For donor blood-derived, natural platelet concentrates and products obtained there from, screening procedures (e.g. HLA tests) and leukoreduction techniques may reduce but not completely eliminate auto- or allo-immunogenicity risks [122]. Such residual risks may not only affect the activity of donor platelets (e.g. refractoriness and fever), but also compound into causing sepsis-like symptoms and life-threatening respiratory failure [123–127].