http://cybernephrology.ualberta.ca/Banff/2015/Publications/banff09.pdf

Banff '09 meeting report: Antibody mediated graft deterioration and implementation of Banff working groups

Blood platelets have long been recognised to bring about primary haemostasis with deficiencies in platelet production and function manifesting in bleeding while upregulated function favourises arterial thrombosis. Yet increasing evidence indicates that platelets fulfil a much wider role in health and disease. First, they store and release a wide range of biologically active substances including the panoply of growth factors, chemokines and cytokines released from a-granules. Membrane budding gives rise to microparticles (MPs), another active participant within the blood stream. Platelets are essential for the innate immune response and combat infection (viruses, bacteria, micro-organisms). They help maintain and modulate inflammation and are a major source of pro-inflammatory molecules (e.g. P-selectin, tissue factor, CD40L, metalloproteinases). As well as promoting coagulation, they are active in fibrinolysis; wound healing, angiogenesis and bone formation as well as in maternal tissue and foetal vascular remodelling. Activated platelets and MPs intervene in the propagation of major diseases. They are major players in atherosclerosis and related diseases, pathologies of the central nervous system (Alzheimers disease, multiple sclerosis), cancer and tumour growth. They participate in other tissue-related acquired pathologies such as skin diseases and allergy, rheumatoid arthritis, liver disease; while, paradoxically, autologous platelet-rich plasma and platelet releasate are being used as an aid to promote tissue repair and cellular growth. The above mentioned roles of platelets are now discussed.

Platelets, inflammation and tissue regeneration

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1538-7836.2009.03586.x

Platelet functions beyond hemostasis

Background The problem of AMR remains unsolved because standardized schemes for diagnosis and treatment remains contentious. Therefore, a consensus conference was organized to discuss the current status of antibody-mediated rejection (AMR) in heart transplantation. Methods The conference included 83 participants (transplant cardiologists, surgeons, immunologists and pathologists) representing 67 heart transplant centers from North America, Europe, and Asia who all participated in smaller break-out sessions to discuss the various topics of AMR and attempt to achieve consensus. Results A tentative pathology diagnosis of AMR was established, however, the pathologist felt that further discussion was needed prior to a formal recommendation for AMR diagnosis. One of the most important outcomes of this conference was that a clinical definition for AMR (cardiac dysfunction and/or circulating donor-specific antibody) was no longer believed to be required due to recent publications demonstrating that asymptomatic (no cardiac dysfunction) biopsy-proven AMR is associated with subsequent greater mortality and greater development of cardiac allograft vasculopathy. It was also noted that donor-specific antibody is not always detected during AMR episodes as the antibody may be adhered to the donor heart. Finally, recommendations were made for the timing for specific staining of endomyocardial biopsy specimens and the frequency by which circulating antibodies should be assessed. Recommendations for management and future clinical trials were also provided. Conclusions The AMR Consensus Conference brought together clinicians, pathologists and immunologists to further the understanding of AMR. Progress was made toward a pathology AMR grading scale and consensus was accomplished regarding several clinical issues.

/pdf/report-from-a-consensus-conference-on-antibody-mediated-50d0scuw4i.pdf

Report from a consensus conference on antibody-mediated rejection in heart transplantation

Platelets are chief effector cells in hemostasis. In addition, they are multifaceted inflammatory cells with functions that span the continuum from innate immune responses to adaptive immunity. Activated platelets have key thromboinflammatory activities in a variety of vascular disorders and vasculopathies. Recently identified inflammatory and immune activities provide insights into the biology of these versatile blood cells that are directly relevant to human vascular diseases.

Platelets as Cellular Effectors of Inflammation in Vascular Diseases

Glutamate is an excitatory neurotransmitter that binds to the kainate receptor, the N-methyl-D-aspartate (NMDA) receptor, and the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR). Each receptor was first characterized and cloned in the central nervous system (CNS). Glutamate is also present in the periphery, and glutamate receptors have been identified in nonneuronal tissues, including bone, heart, kidney, pancreas, and platelets. Platelets play a central role in normal thrombosis and hemostasis, as well as contributing greatly to diseases such as stroke and myocardial infarction. Despite the presence of glutamate in platelet granules, the role of glutamate during hemostasis is unknown. We now show that activated platelets release glutamate, that platelets express AMPAR subunits, and that glutamate increases agonist-induced platelet activation. Furthermore, we demonstrate that glutamate binding to the AMPAR increases intracellular sodium concentration and depolarizes platelets, which are important steps in platelet activation. In contrast, platelets treated with the AMPAR antagonist CNQX or platelets derived from GluR1 knockout mice are resistant to AMPA effects. Importantly, mice lacking GluR1 have a prolonged time to thrombosis in vivo. Our data identify glutamate as a regulator of platelet activation, and suggest that the AMPA receptor is a novel antithrombotic target.

https://rupress.org/jem/article-pdf/205/3/575/1195982/jem_20071474.pdf

Glutamate mediates platelet activation through the AMPA receptor

Platelets recruit leukocytes and mediate interactions between leukocytes and endothelial cells. Most studies examining this important platelet immune function have focused on the development of atherosclerosis, but similar mechanisms may contribute to acute and chronic vascular lesions in transplants. Platelets have been described as markers of transplant rejection, but little investigation has critically examined a role for platelets in transplant vasculopathy and, in particular, alloantibody-mediated transplant rejection. We now demonstrate using a skin transplant model that alloantibody indirectly induces platelet activation and rolling in vivo. Repeated IgG2a alloantibody injections result in sustained platelet-endothelial interactions and vascular pathology, including von Willebrand factor release, small platelet thrombi, and complement deposition. Maintenance of continued platelet-endothelial interactions are dependent on complement activation. Furthermore, we demonstrate that platelets recruit leukocytes to sites of alloantibody deposition and sustain leukocyte-endothelial cell interactions in vivo. Taken together, our model demonstrates an important role for platelets in alloantibody induced transplant rejection.

In Vivo Platelet–Endothelial Cell Interactions in Response to Major Histocompatibility Complex Alloantibody

Factors Affecting Low Hematopoietic Cell Transplantation Rates in TP53-Mutated MDS/AML and Predictors of Overall Survival

Chromoanasynthesis involves massive chromosomal rearrangements arising during single chaotic cellular events. Reconstitution of the extensive abnormalities may result in focused duplication, triplication and deletions, gene fusions, amplification, loss of tumor suppressor genes and marker chromosomes. We report a case of a 27-year-old male with a prior history of relapsed Hodgkin lymphoma (in 2010), treated with chemoradiotherapy and autologous stem cell transplant, who presented in February 2021 with diffuse large B cell lymphoma (DLBCL), germinal center type, involving bone, bone marrow, lymph nodes, nasopharynx, kidney, and spleen. Chromosome analysis of the biopsy was highly complex with multiple structural and numerical abnormalities and marker chromosomes. 

27. Deregulation and shattering of chromosomal segments containing multiple oncogenic targets in the pathogenesis of diffuse large B cell lymphoma (DLBCL)

Emily Mason

Papers

Glutamate mediates platelet activation through the AMPA receptor

In Vivo Platelet–Endothelial Cell Interactions in Response to Major Histocompatibility Complex Alloantibody

Factors Affecting Low Hematopoietic Cell Transplantation Rates in TP53-Mutated MDS/AML and Predictors of Overall Survival

27. Deregulation and shattering of chromosomal segments containing multiple oncogenic targets in the pathogenesis of diffuse large B cell lymphoma (DLBCL)