Refractoriness to platelet transfusion in the presence of anti-HLA antibodies—reassessing the alloantibody hypothesis (original) (raw)
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Posttransfusion purpura associated with alloantibody specific for the platelet antigen, Pena
American Journal of Hematology, 1988
Post-transfusion purpura (PTP) with severe thrombocytopenia occurred eight days after transfusion in a 28-year-old woman and responded to treatment with prednisone and plasma exchange. In contrast to nearly all previously studied cases of PTP, the patient's platelets were PlA1-positive and anti-Pl*' antibody could not be detected in serum obtained during the thrombocytopenic episode. Her serum was found to contain an antibody specific for a recently described platelet-specific alloantigen, Baka, in addition to multiple HLA-specific antibodies. The patient's platelets, typed following recovery, were Baka-negative. These findings indicate that post-transfusion purpura can occur in association with alloimmunization to platelet-specific antigens other than In performing the serologic studies, a close relationship and possible identity between Baka and another recently reported platelet antigen, Leks, was observed. A method for analyzing mixtures of cytotoxic platelet-reactive antibodies without separating the individual antibodies is described.
Diseases, 2019
Alloimmunisation to platelet antigens is not uncommon; a large number of females, having had pregnancies, developed antibodies to Human Leukocyte Antigen (HLA) moieties harboured on their foetuses’ cells (inherited from the father(s)) that may conflict with further pregnancies and transfused Platelet Components occasionally. This is possible since platelets constitutionally express HLA class I molecules (though in copy numbers that consistently differ among individuals). Platelets also express HPA moieties that are variants of naturally expressed adhesion and aggregation molecules; HPA differences between mothers and foetuses and between donors and recipients explain alloimmune conflicts and consequences. Lastly, platelets express ABO blood group antigens, which are rarely immunising, however transfusion mismatches in ABO groups seem to be related to immunisation in other blood and tissue groups. Transfusion also brings residual leukocytes that may also immunise through their copiou...
…, 1995
The incidence and consequences of HLA and non-HLA immunization were evaluated in 229 patients with aplastic thrombocytopenia. All patients were transfused with prestorage filtered red blood cells and platelets. On admission, 29 patients presented with HLA antibodies due to prior immunization by pregnancy andlor blood transfusions. Of the 200 patients showing no detectable HLA antibodies on admission, 164 could be evaluated. HLA antibodies developed in 2.7% (3 of 112) of the patients with a negative risk history of prior immunization. The occurrence of HLA antibodies in patients with a history of previous pregnancies or prior nonleukocyte-depleted blood transfusions (risk history positive) was 3196 (16 of 52). Of the total of 48 patients who were or became alloimmunized, 92% (44 of 4 8 1 had a positive risk PROBLEM ASSOCIATED with long-term platelet supportive care in patients with aplastic thrombocytopenia is the development of a state of refractoriness resulting in poor platelet transfusion increments. Nonimmunologic factors are frequently associated with reduced platelet survival after transfusion. Platelet survival may also be impaired by the presence of circulating antibodies directed against antigens expressed on the platelet membrane. HLA antibodies are the most common cause of immunologic platelet transfusion refractoriness.
Transplant Immunology, 2002
In this review, we describe the platelet surface molecules with special focus on the polymorphic glycoproteins giving rise to the human platelet alloantigen (HPA) system. We list the platelet glycoprotein complexes GPIayIIa, GPIIbyIIIa, GPIbyVyIX and some other molecules, the corresponding genes that encode them and we describe their polymorphisms as well as their physiological function. Based on data obtained by serological and molecular methods, we explain how ancestral HPA alloepitopes have developed into the modern variants. We also describe the tissue distribution of these proteins, which seems to be wider than thought initially, and discuss the significance of the HPA encoding genes distribution in various populations. Methods for their determination are then described briefly. Since HPA alloepitopes can induce antibodies with resulting clinical conditions such as: post-transfusion refractoriness to platelets (PTR); post-transfusion thrombocytopenic purpura (PTTP); and fetomaternal alloimmune thrombocytopenia (FMAIT), the mechanism of this alloimmunization and its prevention is described. Although the humoral arm is more important from the clinical viewpoint, the activation of the cytotoxic arm by HPA alloepitopes is also possible. These polymorphisms also seem to have a role in certain other clinical circumstances, therefore their impact on cardiovascular diseases and haemostatic disorders as well as their role in the transplantation of solid organs and bone marrow is addressed. We conclude that during the last decades, the research of the platelet membrane molecules contributed considerably to the diagnostics, prevention and therapy of the blood coagulation and haemostatic disorders, to the management of the neonatal thrombocytopenias, transfusion-related thrombocytopenias, refractoriness to platelet transfusions and autoimmune disorders. It also changed our view on the role of HPA alloepitopes in bone marrow and solid organ transplantation. In the future, this accumulated knowledge will be useful for the development of the cell-based therapies and immune modulation of both acquired and hereditary diseases.
American Journal of Hematology, 1977
A critical factor limiting the availability of histocompatible platelet transfusions for alloimmunized, thrombocytopenic patients is the large pool of HLA-typed donors needed t o procure platelets perfectly matched for HLA antigens. We have, therefore, investigated the effectiveness of platelets obtained from donors having lesser degrees of histocompatibility. In 421 transfusions administered t o 59 alloimmunized patients who were refractory t o "random donor" platelets, it was found that platelets mismatched for 1 or 2 "cross-reactive" HLA antigens were in most instances as effective in increasing circulating platelet levels as perfectly matched platelets. A significant number of patients also responded t o platelets from donors selectively mismatched for non-cross-reactive HLA antigens. The latter group had a significantly reduced frequency of the antigen HLA-A2 (1 3%) in comparison t o the total patient population (49%). Use of donors whose HLA antigens are serologically cross-reactive with those of alloimmunized patients provides approximately 1 0 times as many prospective donors as does selection based on matching for HLA and simplifies the procurement of hemostatically effective platelets for such patients.
Asian Journal of Transfusion Science, 2015
Platelet transfusions have contributed to the revolutionary modern treatment of hypoproliferative thrombocytopenia. Despite the long-term application of platelet transfusion in therapeutics, all aspects of their optimal use (i.e., in cases of ABO and/or Rh (D incompatibility) have not been definitively determined yet. We reviewed the available data on transfusion practices and outcome in ABO and RhD incompatibility and platelet refractoriness due to anti-human leukocyte antigen (HLA) antibodies. Transfusion of platelets with major ABO-incompatibility is related to reduced posttransfusion platelet (PLT) count increments, compared to ABO-identical and minor, but still are equally effective in preventing clinical bleeding. ABO-minor incompatible transfusions pose the risk of an acute hemolytic reaction of the recipient that is not always related to high anti-A, B donor titers. ABO-identical PLT transfusion seems to be the most effective and safest therapeutic strategy. Exclusive ABO-identical platelet transfusion policy could be feasible, but alternative approaches could facilitate platelet inventory management. Transfusion of platelets from RhD positive donors to RhD negative patients is considered to be effective and safe though is associated with low rate of anti-D alloimmunization due to contaminating red blood cells. The prevention of D alloimmunization is recommended only for women of childbearing age. HLA alloimmunization is a major cause of platelet refractoriness. Managing patients with refractoriness with cross-matched or HLA-matched platelets is the current practice although data are still lacking for the efficacy of this practice in terms of clinical outcome. Leukoreduction contributes to the reduction of both HLA and anti-D alloimmunization.