The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform

Katerina Pavenski - One of the best experts on this subject based on the ideXlab platform.

  • human leukocyte antigen alloimmunization and alloimmune platelet Refractoriness
    Transfusion Medicine Reviews, 2020
    Co-Authors: Anno Saris, Katerina Pavenski
    Abstract:

    Despite significant advancements in the production of platelet products, storage, and transfusion, transfusion Refractoriness remains a significant clinical problem, affecting up to 14% of hematological patients receiving platelet transfusions. Human leukocyte antigen (HLA) alloimmunization is a major cause of immune platelet Refractoriness, and its rate can be significantly reduced by implementation of leukoreduction. Despite promising preclinical results, pathogen reduction does not reduce HLA alloimmunization. Patients with HLA alloimmune Refractoriness are usually managed with HLA-selected platelet transfusions. In this review, we describe the pathophysiology of HLA alloimmunization and alloimmune Refractoriness, as well as options to prevent and treat these transfusion complications. We discuss the evidence supporting these options and point out the outstanding gaps. Finally, we review the possible future directions for prevention and treatment of alloimmune Refractoriness.

  • hla alloimmunization against platelet transfusions pathophysiology significance prevention and management
    Tissue Antigens, 2012
    Co-Authors: Katerina Pavenski, John Freedman, John W Semple
    Abstract:

    Approximately five decades ago, alloimmunization to human leukocyte antigens (HLA) and platelet Refractoriness were recognized as potentially serious complications of platelet transfusions. The mechanisms that result in stimulating immunity against blood products are still incompletely understood but are related to both the composition of the donor product transfused and the immune status of the recipient. Based on murine studies of platelet immunity, platelets are inherently immunogenic and there are at least two independent levels of immunoregulation against platelet transfusions. The first level resides within the recipient and is related to antigen processing/presentation events and CD8+ T cell-mediated immunosuppression. The second level relates to the donor product and includes donor antigen presenting cells (APC) levels as well as age-induced changes in donor APC and/or platelets. Implementation of pre-storage leukoreduction of cellular blood components led to a marked reduction in platelet alloimmunization and its dreaded complication, platelet Refractoriness. Platelet Refractoriness is usually managed by transfusion of matched platelets, selected according to one of the many published methods. It is unclear which of these methods is superior, and given the difficulty of obtaining a perfectly matched product, perhaps the most logical approach is to use a combination of selection strategies. This review discusses the various aspects of platelet alloimmunization and the clinical consequences that may result. It highlights how animal studies have shed light on the immune mechanisms responsible for allogeneic platelet immunity and immunomodulation and reviews relevant literature on clinical and laboratory manifestations of immune platelet Refractoriness.

Sherrill J. Slichter - One of the best experts on this subject based on the ideXlab platform.

  • leukofiltration plus pathogen reduction prevents alloimmune platelet Refractoriness in a dog transfusion model
    Blood, 2017
    Co-Authors: Sherrill J. Slichter, Esther Pellham, Lawrence S Bailey, Todd Christoffel, Irena Gettinger, Lakshmi K Gaur, Yvette Latchman, Karen Nelson, Douglas Bolgiano
    Abstract:

    Human Lymphocyte Antigen (HLA) alloimmunization to filter leukoreduced (F-LR) platelets occurs in about 18% of immunosuppressed thrombocytopenic hematology/oncology patients and represents a significant challenge for effective chemotherapy. In a dog platelet transfusion model, we have evaluated other methods of preventing alloimmune platelet Refractoriness and demonstrated that successful methods in our dog model are transferable to man. In the present study, donor/recipient pairs were dog lymphocyte antigen (DLA) DR-B incompatible (88% of the pairs), and recipient dogs received up to 8 weekly treated transfusions from a single donor (a highly immunogenic stimulus), or until platelet Refractoriness. Continued acceptance of F-LR platelets occurred in 6/13 recipients (46%), but neither γ-irradiation (γ-I, 0/5) nor Mirasol™ pathogen reduction (MPR, 1/7) treatment of donor platelets prevented alloimmune platelet Refractoriness. Combining γ-I with F-LR was associated with only 2/10 (20%) recipients accepting the transfused platelets. Surprisingly, F-LR platelets that then underwent MPR were accepted by 21/22 (95%) recipients (p

  • clinical and laboratory correlates of platelet alloimmunization and Refractoriness in the plado trial
    Vox Sanguinis, 2016
    Co-Authors: John R Hess, R G Strauss, Sherrill J. Slichter, Suzanne Granger, Richard M Kaufman, Felicia L Trachtenberg, Susan F Assmann, Darrell J. Triulzi
    Abstract:

    Background and Objectives Platelet alloimmunization and Refractoriness to platelet transfusion are complications of platelet transfusion therapy. The platelet dose (PLADO) trial, as the largest prospective randomized trial of prophylactic platelet therapy to date, afforded an opportunity to analyse these two issues. Materials and Methods PLADO patient records were examined for evidence of platelet alloimmunization, defined as an increase in HLA Class I panel-reactive antibodies (PRA) to ≥20%, and clinical Refractoriness, defined as two consecutive ≤4 h posttransfusion corrected platelet count increments (CCI) of <5000. Multivariate logistic regression, restricted to platelet-transfused subjects who received exclusively either in-process leucoreduction apheresis or whole blood-derived (WBD) leucocyte-reduced platelets, compared the frequency of these outcomes by platelet unit and patient characteristics. Results Forty of 816 evaluable platelet-transfused patients (5%) became alloimmunized during the trial. Prior pregnancy, chemotherapy only compared to progenitor cell transplant, and low platelet dose – all were associated with significantly higher rates of alloimmunization. Among 35 alloimmunized patients evaluated for Refractoriness, 8 (23%) had two consecutive CCI < 5000/μl. Regardless of alloimmunization status, CCIs < 5000/μl were observed following 17% of platelet transfusions. Among 734 patients receiving at least two platelet transfusions, two consecutive CCIs of ≤5000 occurred in 102 (14%). Conclusions The incidence of new platelet alloimmunization was low in the PLADO study, but follow-up was at most 30 days. Alloimmunization was present in only 8 of 102 (8%) of observed cases of Refractoriness, suggesting that other causes of poor posttransfusion increments are frequent.

  • Regular Article TRANSFUSION MEDICINE CME Article
    2016
    Co-Authors: Sherrill J. Slichter, Philip J. Norris
    Abstract:

    • High, but not low to moderate, HLA antibody levels are associated with platelet Refractoriness. In the Trial to Reduce Alloimmunization to Platelets (TRAP) study, 101 of 530 par-ticipants became refractory to platelet transfusions without evidence of HLA or human platelet antigen (HPA) antibodies. We used a more sensitive bead-based assay to detect and quantify HLA antibodies and a qualitative solid-phase enzyme-linked immunosorbet assay for HPA to determine whether low-level antibodies could predict Refractoriness in longitudinal panels from 170 lymphocytotoxicity assay (LCA)2 and 20 LCA1 TRAP participants. All TRAP recipients who previously tested LCA1 were HLA antibody1, using the bead-based system. Levels of HLA or HPA antibodies did not predict Refractoriness among LCA2 recipients, although higher levels of HLA antibodies were associated with Refractoriness among LCA1 recipients. These data demonstrate that weak to moderate HLA antibody levels detectable by modern binding assays are not associated with platelet Refractoriness. (Blood. 2013

  • c1q binding hla antibodies do not predict platelet transfusion failure in trap study participant
    Blood, 2014
    Co-Authors: Rachael P Jackman, Mila Lebedeva, Sherrill J. Slichter, Douglas Bolgiano, Philip J. Norris
    Abstract:

    Introduction: In the Trial to Reduce Alloimmunization to Platelets (TRAP) study, 101 of the 530 subjects became clinically refractory (CR) to platelet transfusions in the absence of detectable antibodies against HLA as measured by the lymphocytotoxicity assay (LCA). Using more sensitive bead-based detection methods we have previously demonstrated that while many of these LCA- patients do have anti-HLA antibodies, that these low to moderate level antibodies do not predict Refractoriness. In addition to being less sensitive then bead based methods, the LCA screen only detects complement-binding antibodies. As these antibodies could be important for platelet rejection, we assessed if previously undetected complement-binding antibodies could account for some of the Refractoriness seen in LCA- patients. Methods: 169 LCA- (69 CR, 100 non-CR) and 20 LCA+ (10 CR, 10 non-CR) subjects were selected from the TRAP study. Anti-class I HLA IgG and C1q binding antibodies were measured in serum or plasma using two different multi-analyte, semi-quantitative, bead-based fluorescent antibody detection assays: the LabScreen mixed Luminex assay, and the LabScreen single antigen class I assay with or without added EDTA (One Lambda). Groups were compared using an unpaired t-test, a=0.05, and correlation between variables was also assessed. Results: New measurements of anti-class I HLA IgG antibodies reliably reproduced earlier data with a strong correlation between the old and new measurements (R2=0.9736, p<0.0001). While some of the LCA- subjects did have detectable C1q-binding anti-class I HLA antibodies, and some LCA+ subjects did not, levels of these antibodies were significantly higher among LCA+ subjects (p<0.0001). Levels of C1q-binding anti-class I HLA antibodies were not significantly different between CR and non-CR among either the LCA- or LCA+ subjects. Conclusions: While complement-binding anti-class I HLA antibody levels were higher in the LCA+ subjects, higher levels of these antibodies were not seen in CR LCA+ patients as compared with non-CR LCA+ patients. Complement-binding anti-class I HLA antibodies do not account for Refractoriness seen among the LCA- TRAP subjects. This work confirms that low to mid level anti-class I antibodies do not drive Refractoriness to platelets, and suggests that antibody-independent mechanisms cause Refractoriness in patients lacking higher levels of anti-HLA antibodies. Disclosures No relevant conflicts of interest to declare.

  • Factors affecting posttransfusion platelet increments, platelet Refractoriness, and platelet transfusion intervals in thrombocytopenic patients
    Blood, 2005
    Co-Authors: Sherrill J. Slichter, Thomas S. Kickler, Hayden G. Braine, Kathryn B. Davis, Janice G Mcfarland, Helen Enright, Terry Gernsheimer, Jeffrey Mccullough
    Abstract:

    A variety of patientand product-related factors influenced the outcome of 6379 transfusions given to 533 patients in the Trial to Reduce Alloimmunization to Platelets (TRAP). Responses measured were platelet increments, interval between platelet transfusions, and platelet Refractoriness. Patient factors that improved platelet responses were splenectomy and increasing patient age. In contrast, at least 2 prior pregnancies, male gender, splenomegaly, bleeding, fever, infection, disseminated intravascular coagulation, increasing height and weight, lymphocytotoxic antibody positivity, an increasing number of platelet transfusions, or receiving heparin or amphotericin were associated with decreased posttransfusion platelet responses. Platelet factors that were associated with improved platelet responses were giving ABO-compatible platelets, platelets stored for 48 hours or less, and giving large doses of platelets while ultraviolet B (UV-B) or gamma irradiation decreased platelet responses. However, in alloimmunized lymphocytoxic antibody-positive patients, the immediate increment to UV-B-irradiated platelets was well maintained, whereas all other products showed substantial reductions. Refractoriness to platelet transfusions developed in 27% of the patients. Platelet Refractoriness was associated with lymphocytotoxic antibody positivity, heparin administration, fever, bleeding, increasing number of platelet transfusions, increasing weight, at least 2 pregnancies, and male gender. The only factors that reduced platelet Refractoriness rates were increasing the dose of platelets transfused or transfusing filtered apheresis platelets.

Michael F Murphy - One of the best experts on this subject based on the ideXlab platform.

  • platelet transfusion alloimmunization and Refractoriness
    Seminars in Hematology, 2020
    Co-Authors: Catherine Prodger, Simon J Stanworth, Lise J Estcourt, Alexandros Rampotas, Michael F Murphy
    Abstract:

    The transfusion of platelets for both prophylaxis and treatment of bleeding is relevant to all areas of medicine and surgery. Historically, guidance regarding platelet transfusion has been limited by a lack of good quality clinical trials and so has been based largely on expert opinion. In recent years however there has been renewed interest in methods to prevent and treat hemorrhage, and the field has benefited from a number of large clinical trials. Some studies, such as platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH) and platelets for neonatal transfusion Study 2 (PLANET-2), have reported an increased risk of harm with platelet transfusion in specific patient groups. These studies suggest a wider role of platelets beyond hemostasis, and highlight the need for further clinical trials to better understand the risks and benefits of platelet transfusions. This review evaluates the indications for platelet transfusion, both prophylactic and therapeutic, in the light of recent studies and clinical trials. It highlights new developments in the fields of platelet storage and platelet substitutes, and novel ways to avoid complications associated with platelet transfusions. Lastly, it reviews initiatives designed to reduce inappropriate use of platelet transfusions and to preserve this valuable resource for situations where there is evidence for their beneficial effect.

Johnny C Hong - One of the best experts on this subject based on the ideXlab platform.

  • human leukocyte antigen class i antibodies and response to platelet transfusion in patients undergoing liver transplantation
    Journal of Surgical Research, 2020
    Co-Authors: Melissa Wong, Ravi Kishore Narra, Motaz Selim, Michael A Zimmerman, Joo Hyun Kim, Anand Padmanabhan, Johnny C Hong
    Abstract:

    Abstract Background Patients undergoing liver transplantation (LT) frequently receive platelet transfusion (PLT) to minimize their risk of hemorrhage. Alloimmunization to platelets may lead to Refractoriness to PLT. Data on the implications of platelet alloimmunization in patients undergoing LT remain limited. We examined the effect of human leukocyte antigen class I (HLA-I) antibodies on PLT Refractoriness and short-term outcomes after LT. Methods Peritransplant clinical and PLT factors were reviewed for all adult liver or simultaneous liver–kidney transplantations from 2012 to 2017. Sensitized patients (SE) with pretransplant HLA-I calculated panel-reactive antibody ≥20% were compared with unsensitized patients (US) with calculated panel-reactive antibody Results Alloimmunization was observed in 39% of the study cohort. SE (n = 28) received 272 PLTs, and US (n = 44) received 246 PLTs. History of pregnancy was higher among SE than US (P  Conclusions LT patients experienced high rates of HLA-I alloimmunization and PLT Refractoriness. SE had higher rates of Refractoriness and lower mean corrected count increment after transfusion compared with US. Our study suggests that further research to evaluate the utility of HLA-matched PLTs in HLA-I alloimmunized LT patients is warranted.

Francisco J Chorro - One of the best experts on this subject based on the ideXlab platform.

  • the training induced changes on automatism conduction and myocardial Refractoriness are not mediated by parasympathetic postganglionic neurons activity
    European Journal of Applied Physiology, 2012
    Co-Authors: Manuel Zarzoso, Luis Suchmiquel, German Parra, L Brinesferrando, L Such, Francisco J Chorro, Juan Guerrero, Antonio Guill, Joseenrique Oconnor, Antonio Alberola
    Abstract:

    The purpose of this study is to test the role that parasympathetic postganglionic neurons could play on the adaptive electrophysiological changes produced by physical training on intrinsic myocardial automatism, conduction and Refractoriness. Trained rabbits were submitted to a physical training protocol on treadmill during 6 weeks. The electrophysiological study was performed in an isolated heart preparation. The investigated myocardial properties were: (a) sinus automatism, (b) atrioventricular and ventriculoatrial conduction, (c) atrial, conduction system and ventricular Refractoriness. The parameters to study the Refractoriness were obtained by means of extrastimulus test at four different pacing cycle lengths (10% shorter than spontaneous sinus cycle length, 250, 200 and 150 ms) and (d) mean dominant frequency (DF) of the induced ventricular fibrillation (VF), using a spectral method. The electrophysiological protocol was performed before and during continuous atropine administration (1 μM), in order to block cholinergic receptors. Cholinergic receptor blockade did not modify either the increase in sinus cycle length, atrioventricular conduction and Refractoriness (left ventricular and atrioventricular conduction system functional refractory periods) or the decrease of DF of VF. These findings reveal that the myocardial electrophysiological modifications produced by physical training are not mediated by intrinsic cardiac parasympathetic activity.

  • intrinsic changes on automatism conduction and Refractoriness by exercise in isolated rabbit heart
    Journal of Applied Physiology, 2002
    Co-Authors: L Such, Antonio Alberola, A Rodriguez, L Lopez, R Ruiz, L Artal, I Pons, M L Pons, C Garcia, Francisco J Chorro
    Abstract:

    We have studied the intrinsic modifications on myocardial automatism, conduction, and Refractoriness produced by chronic exercise. Experiments were performed on isolated rabbit hearts. Trained anim...