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Consensus Development Conference Statement October 6-8, 1986
This statement is more than five years old and is provided solely for historical purposes. Due to the cumulative nature of medical research, new knowledge has inevitably accumulated in this subject area in the time since the statement was initially prepared. Thus some of the material is likely to be out of date, and at worst simply wrong. For reliable, current information on this and other health topics, we recommend consulting the National Institutes of Health's MedlinePlus http://www.nlm.nih.gov/medlineplus/. This statement was originally published as: Platelet Transfusion Therapy. NIH Consens Statement 1986 Oct 6-8;6(7):1-6. For making bibliographic reference to the statement in the electronic form displayed here, it is recommended that the following format be used: Platelet Transfusion Therapy. NIH Consens Statement Online 1986 Oct 6-8 [cited year month day];6(7):1-6. IntroductionIn the past, patients with chronic thrombocytopenia died of hemorrhage with distressingly predictable frequency. The increased use of platelet transfusions during the past 15 years has prevented most such deaths. Furthermore, this therapy has made it possible to treat patients with drugs who have otherwise fatal disorders that temporarily suppress platelet production. With this great benefit, however, have come complex problems. Transfused platelets can transmit fatal diseases and can elicit an immune response in recipients, so that further transfusions are no longer effective. Although platelet therapy has contributed greatly to the management of patients with many diseases such as acute leukemia and aplastic anemia, serious questions have emerged regarding its use in patients undergoing cardiac surgery and in other circumstances. The prophylactic administration of platelets is also controversial, and there is uncertainty as to the platelet levels that predispose thrombocytopenic patients to hemorrhage and as to the effectiveness of modalities other than platelets in the prevention of bleeding. The relative merits of the various methods for obtaining and storing platelets remain unclear. The advantages and disadvantages of platelets obtained from multiple and single donors require evaluation. To resolve these issues, the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), the Center for Drugs and Biologics of the Food and Drug Administration, and the NIH Office of Medical Applications of Research convened a Consensus Development Conference on Platelet Transfusion Therapy on October 6-8, 1986. At a 1 1/2-day series of presentations by experts in the field, a consensus panel drawn from the medical professions, blood banking organizations, and the general public considered the evidence. The panel agreed on answers to the following key questions:
What Are the Appropriate Indications for Platelet Transfusion? Despite the obvious advantages of platelet transfusion therapy, there is concern that platelets are sometimes given to patients who do not really need them, are given too often to patients who do need them, and occasionally are given in insufficient quantities when treatment is urgently required. Clinical decisions regarding platelet transfusion are hampered by an insufficient number of properly controlled trials, by imprecise methods of evaluating clinical need, and by uncertain methods for measuring effects. The platelet levels that predispose thrombocytopenic patients to hemorrhage and the efficacy of therapeutic modalities other than transfusion are not well defined. It is apparent that factors other than the platelet count must also be considered in deciding when to transfuse. The efficacy of transfused platelets may be altered by other abnormalities in the recipient such as uremia, concomitant coagulation disorders, or medications. The rate and direction of change in platelet count must also be considered. Active BleedingPatients with thrombocytopenia or an abnormality of platelet function or both who have significant bleeding should receive platelets if the platelet disorder is likely to be causing or contributing to the bleeding. It is sometimes difficult to make this judgment clinically. It is unlikely that a patient with a platelet count of 50,000 per microliter or higher will benefit from a platelet transfusion if thrombocytopenia is the sole abnormality. If the disorder is one of function, reliance must be placed on some test of platelet function, such as the template bleeding time. A bleeding time of less than twice the upper limit of normal is usually not an indication for transfusion of platelets, unless there are other conditions that interfere with hemostasis. Patients with thrombocytopenia resulting from platelet destruction or splenic pooling may require more intensive transfusion therapy than those with marrow hypoplasia. ProphylaxisThe patient with severe thrombocytopenia may benefit from prophylactic administration of platelets. This is particularly true of patients with a temporary thrombocytopenia consequent to myelosuppressive therapy. It is common practice to use a preselected level of thrombocytopenia to decide when to transfuse platelets prophylactically. The value of 20,000 platelets per microliter is often used. This figure is based on older studies with potential defects as judged by current knowledge. Recent evidence suggests that this number might safely be lower for some patients based on clinical judgment and close observation. A problem with selecting specific concentrations is the lack of reproducibility and the variability of platelet counts at low levels. Patients with chronic thrombocytopenia caused by impaired platelet production (e.g., aplastic anemia, myelodysplastic disorders) generally do not require routine platelet transfusions. Patients with accelerated destruction but active production of platelets (e.g., idiopathic thrombocytopenic purpura) have relatively less bleeding at a given platelet count than patients with hypoplastic platelet disorders. Thus, platelet transfusions are rarely needed in these conditions. Other appropriate medical and surgical therapy is usually effective. Preparation for invasive procedures in thrombocytopenic or thrombocytopathic patients might include prophylactic administration of platelets. In many instances there are associated disorders of coagulation or platelet function that cannot be completely corrected, as is common in patients with advanced hepatic or renal insufficiency. In such patients, transfusion of platelets may be necessary, especially for procedures in which hemostasis cannot be assessed by direct observation. Transfusion of enough platelets to correct the bleeding time to the normal range is logical, but there are few, if any, pertinent studies. A similar approach may be justified for patients threatened with hemorrhage in the central nervous system or other sites in which a small amount of bleeding could be critical. Massive TransfusionDilutional thrombocytopenia occurs in patients receiving multiple tranfusions to replace blood lost through hemorrhage and may lead to generalized microvascular bleeding. The degree of dilution is usually predictable. Following replacement of one blood volume, 35 to 40 percent of the platelets usually remain. Thrombocytopenia is accentuated in the presence of accelerated platelet destruction, which sometimes occurs in such patients, mandating performance of platelet counts as a guide to platelet therapy. The majority of patients who receive rapid replacement of one to two blood volumes do not develop microvascular bleeding as a result of thrombocytopenia. Therefore, platelets should not be administered in the absence of documented thrombocytopenia and clinically abnormal bleeding. Cardiac SurgeryControlled prospective studies examining postoperative blood loss and outcome have demonstrated no correlation between platelet counts and bleeding following cardiopulmonary bypass and no detectable benefit from the prophylactic administration of platelets to such patients. The vast majority of such patients have some degree of thrombocytopenia, prolongation of the bleeding time, and continued slow bleeding. With an expected pattern of bleeding, thrombocytopenia alone is not an indication for platelet transfusion. There is no justification for prophylactic platelet administration in patients undergoing open heart surgery. NewbornsBecause of the special nature of neonatal
requirements for blood and blood products as well as dosages, these issues
were not addressed specifically in this report. Nonetheless, efforts
should be exerted to continue to avoid undue exposure to multiple donor
sources. What Products Are Available, and What Are Their Relative Merits?Platelets can be harvested from single donors by plateletapheresis or separated from whole blood, with pooling of cells from multiple donors to achieve a therapeutic dose. Single-donor platelets1 can be obtained from random donors or from donors selected on the basis of HLA compatibility. Local conditions and practices often influence the choice among these alternatives, but there are identifiable advantages and disadvantages of each product that should be considered. These include availability, potential for disease transmission, and potential for alloimmunization. 1 The term single-donor platelets is used to mean platelets obtained by apheresis from a single donor. The number of platelets obtained is approximately equal to the number of platelets obtained from five to eight whole-blood donations. ProductsSince each single-donor apheresis collection provides the equivalent of the platelets obtained from five to eight whole blood donations, this product exposes a patient to fewer donors and offers potential advantages over the multiple-donor product: less exposure to infectious agents and reduced likelihood of alloimmunization. However, there is no evidence that single-donor platelets are either more or less effective than multiple-donor concentrates in patients who have not become alloimmunized. A major advantage of multiple-donor platelets is that they are in relatively plentiful supply, having been derived from conventional whole-blood donations. Moreover, they can be stored for 5 days, assuring a stable community resource. Storage time for single-donor platelets depends on the method used for harvesting; in some cases, the product must be used within 24 hours. Certain organizational and logistical considerations influence the choice of platelets from random or HLA-matched single donors. Donation of platelets by apheresis requires a greater donor commitment than does whole-blood donation, as well as sophisticated equipment and highly trained personnel. Even where enough donors are available, the complexity of the procedure as currently employed can make its routine use infeasible. However, HLA-matched single-donor products are currently the most effective therapy for patients who have become refractory to unselected single-donor or multiple-donor platelets. StoragePlatelets are normally stored at 20° C to 24° C, with constant agitation for up to 5 days. Although platelets stored at 4° C are a licensed product, they are now rarely used because of their reduced survival and function after transfusion. Platelets can be frozen to extend their storage period. Since patients who have become refractory to platelet transfusions during one course of chemotherapy will usually be difficult to treat during subsequent periods of chemotherapy-induced hypoplasia, their anticipated need can be met by the cryopreservation of autologous platelets obtained by apheresis during a remission. The low yield and high cost of cryopreserved platelets have limited their use in other conditions. DosageThe therapeutic dose of platelets is affected by the patient's pretransfusion platelet count and blood volume, as well as by associated clinical conditions. The common practice of transfusing multiple-donor platelets at a dose of 1 unit per 10 kg body weight, or of transfusing a concentrate obtained from one apheresis donor, is a reasonable starting point for platelet therapy in the adult patient. The effect of a transfusion should be judged by the clinical result and the platelet count obtained 1 hour later. These measures plus later platelet counts as indicated can also provide guidance for further treatment. A standard 170 micron filter is recommended for the administration of platelets. Filters of smaller pore size are not indicated. Adjunctive TherapiesSeveral agents have been used in addition
to, or in place of, platelets in the treatment of thrombocytopenia
resulting from impaired production or platelet dysfunction. Epsilon-aminocaproic
acid (EACA) and prednisone have been considered useful for the treatment
of these conditions by some clinicians, but there are no satisfactory
studies that support their regular use. In uremia, bleeding responds in
many cases to treatment with cryoprecipitate or desmopressin (DDAVP), and
platelet transfusions can be avoided. What Are the Risks Associated With Platelet Transfusion Therapy?The major risks associated with platelet transfusion are alloimmunization and infection. Rarely, platelet transfusions cause graft-versus-host disease. Alloimmunization and the Refractory StateWhen platelet-reactive antibodies are induced by transfusion, platelets subsequently administered often fail to produce a therapeutic benefit. A poor response to transfused platelets also can be caused by splenomegaly, fever, sepsis, disseminated intravascular coagulation, nonviable platelets, and other conditions. Alloimmunization to platelet antigens is common in patients who have received repeated transfusions. However, an appreciable number of patients fail to form platelet-reactive antibodies for reasons that are not clear. There is no well-defined relationship between the number of donor exposures and the extent of antibody formation, although one study suggests a lower incidence of alloimmunization in patients exposed to platelets derived by apheresis from fewer donors. Alloimmunization to the HLA-A and HLA-B antigens is encountered most frequently. Evidence indicates that leukocytes, present in routinely prepared platelet concentrates, provoke HLA-antibody formation more readily than platelets. The failure of HLA-matched platelets to elevate the platelet count after transfusion to some alloimmunized patients suggests that antibodies reactive with non-HLA, platelet-specific antigens can cause destruction of transfused platelets. Circulating immune complexes have also been implicated. ABO compatibility between donor and recipient is of minor importance in platelet transfusion therapy in most adults. Administration of ABO incompatible platelets is an acceptable transfusion practice. The possibility of Rh immunization by red cells contained in platelet concentrates should be considered in female recipients. Various strategies have been proposed to cope with the therapeutic problems presented by alloimmunized, thrombocytopenic patients. Administration of leukocyte-poor blood products to patients likely to require continuing transfusion support has been advocated to reduce the frequency of alloimmunization, but the feasibility and effectiveness of this strategy have not been conclusively demonstrated. The same is true of the prospective use of platelets from single donors. New approaches to this problem, still in an experimental stage, are treatment of platelet concentrates with ultraviolet light to abolish the immunogenicity of contaminating leukocytes and the transfusion of soluble, class I HLA antigens to induce active tolerance. Various techniques have been used to improve the effectiveness of platelets in alloimmunized patients. The most feasible of these is the transfusion of HLA-matched platelets from family members or unrelated persons. If not available locally, matched platelets can sometimes be obtained from regional blood centers with access to large panels of HLA-typed donors. Only about two-thirds of HLA-matched platelet transfusions given to alloimmunized patients are effective. Newer immunologic techniques appear capable of predicting transfusion response in such patients with an 80 percent to 90 percent certainty. These assays are available in only a few centers and are not yet applicable to standard transfusion practice. High-dose intravenous immunoglobulin therapy, splenectomy, and removal of alloantibodies by plasmapheresis may be of marginal benefit but cannot be recommended for routine use. InfectionInfections transmitted by platelet transfusions are similar to those associated with other blood components. These are of special concern because platelet transfusions often are prepared by pooling concentrates from multiple donors and are given in large numbers to immunocompromised patients. With agents infrequently present in donated blood such as the human immunodeficiency virus (HIV), the risk of infection is roughly proportional to the number of donor exposures. As with other blood products, agents causing most of the serious infections are the non-A, non-B hepatitis virus(es), hepatitis B virus, cytomegalovirus, and HIV. The risk of disease transmission with blood transfusion varies geographically and among donor populations but appears to be decreasing nationally because of newly implemented test methods and donor screening policies. An unusual, but sometimes fatal, complication of platelet transfusion is infusion of bacteria that have proliferated in concentrates stored at 20° C to 24° C. Physicians should be aware of this complication and be prepared to administer antibiotics and supportive measures. Attempts should be made to identify the source of the contamination in all such cases. Graft-Versus-Host DiseaseGraft-versus-host disease is a rare
complication of platelet transfusions that can be prevented by gamma
irradiation of concentrates prior to transfusion to patients who have
undergone bone marrow transplantation or have other forms of
immunodeficiency. What Are the Most Important Directions for Future Research?Research should be directed toward the following2: 2 Priorities are not implied in this sequence. Recipient-Related Issues
Product-Related Issues
Donor-Related Issues
Platelet use is controlled locally and
determined largely by existing practice. Attempts to alter platelet use
frequently have been ineffective. The most successful attempts can be
attributed to a strong local proponent of appropriate transfusion
practices. Ongoing collaborative efforts, including component therapy
workshops involving clinicians, blood bank directors, and members of
hospital transfusion committees, can do much to alter existing practices.
Increased attention to the risks and benefits of component therapy in
medical schools and teaching hospitals also may change the use of platelet
concentrates. When appropriate, information regarding potential risks and
benefits of platelets and other blood products should be made available to
patients who receive those products. Monitoring the patterns of platelet
use on a continuing basis will provide a means for evaluating the impact
of those strategies and a basis for suggesting additional or alternative
approaches. ConclusionsIn this document, the panel has made a number of observations and recommendations based on information presented at this conference relating to the indications for platelet transfusion, products available, and associated risks. We believe platelets are overused in some conditions. An example is the prophylactic use of platelets in open heart surgery, a practice the panel believes is unwarranted. Some of the uncertainty surrounding platelet transfusion practices is related to the lack of methods for predicting which patients are at risk to bleed and the effectiveness of various platelet preparations. We recommend research initiatives to provide better guidelines for transfusion practice. More basic research to elucidate the role
of platelets in hemostasis is needed. In addition, better information on
current platelet transfusion practices, obtained through a surveillance
system at a national level, would be of great benefit as an educational
tool. Efforts to overcome the problems associated with alloimmunization to
platelets are imperative. A major step in this regard would be the
establishment of a national network to facilitate transfusion of HLA-matched
platelets to selected patients. Infections transmitted by platelet
transfusions remain a major concern. Elimination of bacterial growth in
platelet concentrates stored at room temperatures warrants special
attention. Consensus Development Panel
Panel Chairperson President Blood Center of Southeastern Wisconsin Clinical Professor of Medicine and Pathology Medical College of Wisconsin Milwaukee, Wisconsin
Professor and Chairman Department of Biostatistics and Biomathematics University of Alabama at Birmingham Birmingham, Alabama
Professor and Chairman Department of Surgery Stanford University School of Medicine Stanford University Medical Center Stanford, California
Professor of Public Health Boston University School of Public Health Boston, Massachusetts
Professor of Medicine Chief of Hematology Department of Medicine State University of New York Health Center at Syracuse Syracuse, New York
Director Hoxworth Blood Center Emeritus Professor of Internal Medicine and Pathology University of Cincinnati Cincinnati, Ohio
Associate Vice President Biomedical Research and Development American Red Cross Bethesda, Maryland
Director Weingart Center for Bone Marrow Transplantation Member, Department of Basic and Clinical Research Scripps Clinic and Research Foundation La Jolla, California
Professor and Director of Graduate Studies Department of Sociology University of Wisconsin Madison, Wisconsin
Deputy Director Quality Control Center Dana-Farber Cancer Institute Boston, Massachusetts
Chief Hemostasiology Laboratory Department of Clinical Pathology William Beaumont Hospital Royal Oak, Michigan and Clinical Professor of Medicine University of Michigan
Executive Vice President for Medical Affairs Blood Systems, Inc. Scottsdale, Arizona and Clinical Professor of Medicine University of New Mexico
Professor of Anesthesiology and Pediatrics State University of New York Health Center at Syracuse Syracuse, New York Speakers
"Prophylactic Platelet Transfusions" Chairman Department of Basic and Clinical Research Scripps Clinic and Research Foundation La Jolla, California
"Infectious Complications of Blood Transfusion" Professor of Laboratory Medicine Yale University School of Medicine Director Blood Bank Yale-New Haven Hospital New Haven, Connecticut
"Bacterial Contamination of Platelet Concentrates" Associate Professor of Oncology and Medicine Johns Hopkins Oncology Center Baltimore, Maryland
"Alloimmunization After Leukocyte-Depleted Multiple Random-Donor Platelet Concentrates" Department of Immunohematology and Blood Bank Academish Ziekenhuis Leiden Rijnsburgerweg NETHERLANDS
"Use and Avoidance of Platelet Transfusion in Idiopathic Thrombocytopenic Purpura" Assistant Professor of Pediatrics Division of Pediatric Hematology/Oncology New York Hospital-Cornell Medical Center New York, New York
"Platelet Transfusions in Massively Transfused Patients" Managing Director Puget Sound Blood Center Seattle, Washington
"Random Single-Donor Platelets Compared to Random Multiple-Donor Platelet Concentrates" Chief of Transfusion Medicine Department of Internal Medicine University Hospital of Zurich Zürich SWITZERLAND
"Prevention and Management of the Refractory State: Induction of Tolerance to Allogenic Platelet Transfusions" Associate Professor of Pathology Department of Pathology Stanford University Stanford Blood Center Palo Alto, California
"Refractoriness to Platelet Transfusions" Associate Professor of Medicine and Pathology Johns Hopkins University School of Medicine Baltimore, Maryland
"The Platelet as an Immunologic Target" Senior Investigator Blood Center of Southeastern Wisconsin Milwaukee, Wisconsin
"Use of Platelets in Open-Heart Surgery" Professor of Laboratory Medicine and Medicine Departments of Laboratory Medicine and Medicine University of California at San Francisco School of Medicine Chief Hematology Laboratory/Blood Bank Veterans Administration Medical Center Clinical Pathology Service San Francisco, California
"Graft-Versus-Host Disease as a Consequence of Transfusion of Platelets" Director Blood Bank and Hematology Children's Hospital National Medical Center George Washington University Medical Center Washington, D.C.
"Preparation and Storage of Platelet Concentrates" Professor of Medicine Thomas Jefferson University Philadelphia, Pennsylvania
"Role of Platelets in Hemostasis" Professor of Medicine Department of Medicine Cornell University Medical College New York, New York
"Transfusions of Platelets to Patients With Disorders of Platelet Functions" Associate Professor of Medicine and Thrombosis Research Deputy Director for Clinical Research Thrombosis Research Center Temple University School of Medicine Philadelphia, Pennsylvania
"Donor Selection in Platelet Transfusion" Professor of Medicine Florence McAlister Professor of Medicine Duke University Medical Center Durham, North Carolina
"Experience With Single-Donor Platelet Transfusion" Professor and Chief Division of Hematology University of Maryland Cancer Center University of Maryland School of Medicine Baltimore, Maryland
"Prevention and Management of the Refractory State" Chief Medical Services Missouri/Illinois Red Cross Regional Blood Services St. Louis, Missouri
"Historical Perspective" Medical Director Chief Clinical Hematology Branch National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Bethesda, Maryland
"Evaluation of the Effectiveness of Platelet Transfusion" Medical Director United Blood Services Associate Professor of Pathology and Medicine University of New Mexico School of Medicine Albuquerque, New Mexico
"Transfusion of Platelets to Patients With Hypoplastic States" Scientific Director Puget Sound Blood Center Professor of Medicine University of Washington School of Medicine Seattle, Washington
"Usage Patterns and Trends" President Center for Blood Research Visiting Professor of Pediatrics Harvard Medical School Boston, Massachusetts Planning Committee
Planning Committee Chairperson Chief Blood Resources Branch Division of Blood Diseases and Resources National Heart, Lung, and Blood Institute National Institutes of Health Bethesda, Maryland
President Blood Center of Southeastern Wisconsin Clinical Professor of Medicine and Pathology Medical College of Wisconsin Milwaukee, Wisconsin
Director of Communications Office of Medical Applications of Research National Institutes of Health Bethesda, Maryland
Social Science Analyst Office of Medical Applications of Research National Institutes of Health Bethesda, Maryland
Public Affairs Specialist National Heart, Lung, and Blood Institute National Institutes of Health Bethesda, Maryland
Chief Laboratory of Cellular Components and Transfusion Medicine Center for Drugs and Biologics Food and Drug Administration Bethesda, Maryland
Professor of Surgery Department of Surgery Harvard Medical School Beth Israel Hospital Boston, Massachusetts
Professor and Chief Division of Hematology University of Maryland Cancer Center University of Maryland School of Medicine Baltimore, Maryland
Scientific Director Puget Sound Blood Center Professor of Medicine University of Washington School of Medicine Seattle, Washington Conference Sponsors
Claude Lenfant, M.D. Director
Frank E. Young, M.D. Commissioner
Itzhak Jacoby, Ph.D. Acting Director Supplemental Information for NIH Consensus Statement on Platelet Transfusion TherapySince the NIH Consensus Statement on Platelet Transfusion Therapy was issued, additional information has become available that supplements the original statement. Recommendations included in the statement
continue to be valid. However, it should be noted that the current
frequencies of infectious virus transmission by single units of blood or
blood components are lower than reported in the statement. For more recent
information, see Schreiber GB. The risk of transfusion-transmitted viral
infections. NEJM 1996;334:1685-1690. Also, "non-A, non-B
hepatitis" is now known to be almost exclusively caused by hepatitis
C virus (HCV). A test for HCV antibodies was developed several years ago,
and a recently improved version is in universal use in the United States. |
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