Platelet refractoriness - practical approaches and ongoing dilemmas in patient management

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Abstract

Platelet refractoriness can represent a significant clinical problem that complicates the provision of platelet transfusions, is associated with adverse clinical outcomes and increases health care costs. Although it is most frequently due to non-immune platelet consumption, immunological factors are also often involved. Human leucocyte antigen (HLA) alloimmunization is the most important immune cause. Despite the fact that systematic reviews of the clinical studies evaluating different techniques for selecting HLA compatible platelets have not been powered to demonstrate improved clinical outcomes, platelet refractoriness is currently managed by the provision of HLA-matched or cross matched platelets. This review will address a practical approach to the diagnosis and management of platelet refractoriness while highlighting on-going dilemmas and knowledge gaps.

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Most cited references 65

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Leukocyte reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet transfusions. The Trial to Reduce Alloimmunization to Platelets Study Group.

(1997)

We conducted a multi-institutional, randomized, blinded trial to determine whether the use of platelets from which leukocytes had been removed by a filter or that had been treated with ultraviolet B irradiation would prevent the formation of antiplatelet alloantibodies and refractoriness to platelet transfusions. Patients who were receiving induction chemotherapy for acute myeloid leukemia were randomly assigned to receive one of four types of platelets transfusions: unmodified, pooled platelet concentrates from random donors (control); filtered, pooled platelet concentrates from random donors (F-PC); ultraviolet B-irradiated, pooled platelet concentrates from random donors (UVB-PC); or filtered platelets obtained by apheresis from single random donors (F-AP). All patients received transfusions of filtered, leukocyte-reduced red cells. Of 530 patients with no alloantibodies at base line, 13 percent of those in the control group produced lymphocytotoxic antibodies and their thrombocytopenia became refractory to platelet transfusions, as compared with 3 percent in the F-PC group, 5 percent in the UVB-PC group, and 4 percent in the F-AP group (P< or =0.03 for each treated group as compared with the controls; there were no significant differences among the treated groups). Lymphocytotoxic antibodies were found in 45 percent of the controls, as compared with 17 to 21 percent in the treated groups (P<0.001 for each treated group as compared with the controls; there were no significant differences among the treated groups). Antibodies against platelet glycoproteins developed in 6 to 11 percent of the patients, with no significant differences among the four groups. Reduction of leukocytes by filtration and ultraviolet B irradiation of platelets are equally effective in preventing alloantibody-mediated refractoriness to platelets during chemotherapy for acute myeloid leukemia. Platelets obtained by apheresis from single random donors provided no additional benefit as compared with pooled platelet concentrates from random donors.

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Platelet transfusion for patients with cancer: clinical practice guidelines of the American Society of Clinical Oncology.

Joann Powell, R. McIntyre, H Hume … (2001)

To determine the most effective, evidence-based approach to the use of platelet transfusions in patients with cancer. Outcomes of interest included prevention of morbidity and mortality from hemorrhage, effects on survival, quality of life, toxicity reduction, and cost-effectiveness. A complete MedLine search was performed of the past 20 years of the medical literature. Keywords included platelet transfusion, alloimmunization, hemorrhage, threshold and thrombocytopenia. The search was broadened by articles from the bibliographies of selected articles. Levels of evidence and guideline grades were rated by a standard process. More weight was given to studies that tested a hypothesis directly related to one of the primary outcomes in a randomized design. BENEFITS/HARMS/COST: The possible consequences of different approaches to the use of platelet transfusion were considered in evaluating a preference for one or another technique producing similar outcomes. Cost alone was not a determining factor. Appendix A summarizes the recommendations concerning the choice of particular platelet preparations, the use of prophylactic platelet transfusions, indications for transfusion in selected clinical situations, and the diagnosis, prevention, and management of refractoriness to platelet transfusion. Five outside reviewers, the ASCO Health Services Research Committee, and the ASCO Board reviewed this document. American Society of Clinical Oncology

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Platelet transfusion refractoriness.

Joseph Schwartz, Eldad Hod (2008)

The platelet, a fascinating anucleate cell, is critically important for haemostasis. Platelet transfusions have greatly reduced the incidence of major haemorrhagic complications associated with the management of haematological and oncological disorders. However, some patients fail to receive the full benefit of platelet transfusions because they do not achieve the appropriate platelet count increment following transfusion. This review will discuss the aetiology, diagnosis, and management of refractoriness to platelet transfusion, a complicated problem for both the treating physicians and the transfusion services supporting these patients. Although advances have been made in the diagnosis and treatment of immune-mediated platelet refractoriness, which is usually caused by anti-human leucocyte antigen antibodies, non-immune causes, such as sepsis, remain problematic.