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A comprehensive study of ovine haemostasis to assess suitability to model human coagulation

INTRODUCTION: Similarities in size, anatomy and physiology have supported the use of sheep to model a wide range of human diseases, including coagulopathy. However, coagulation studies involving sheep are limited by the absence of high quality data defining normal ovine coagulation and fibrinolysis.MATERIALS AND METHODS: Full blood examination, routine and specialised coagulation tests, rotational

A comparative study of different burning time models for the combustion of aluminum dust particles

In the present paper combustion of micron-sized aluminum dust cloud has been studied in a quiescent reaction medium with spatially discrete sources. A new thermal model is generated to estimate the flame front speed in a lean reaction environment in different oxidizer concentrations. Different burning time models for aluminum are utilized in the generated thermal model to compare their applicabili

Peripheral blood monocyte-derived chemokine blockade prevents murine transfusion-related acute lung injury (TRALI)

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality and can occur with any type of transfusion. TRALI is thought to be primarily mediated by donor antibodies activating recipient neutrophils resulting in pulmonary endothelial damage. Nonetheless, details regarding the interactions between donor antibodies and recipient factors are unknown. A murine a

Pathogenesis of immune thrombocytopenia

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by antibody-mediated platelet destruction. The platelet, as an accessible target, has made ITP an attractive disorder in the study of autoimmunity. However, the pathogenesis of ITP has proven complex with diverse pre-existing challenges to the immune system in the form of infection, genetic predisposition, underlying autoimmune

Allogeneic platelet transfusions prevent murine T-cell-mediated immune thrombocytopenia

Platelet transfusions are life-saving treatments for many patients with thrombocytopenia; however, their use is generally discouraged in the autoimmune disorder known as immune thrombocytopenia (ITP). We examined whether allogeneic platelet major histocompatibility complex (MHC) class I transfusions affected antiplatelet CD61-induced ITP. BALB/c CD61 knockout mice (CD61(-)/H-2(d)) were immunized a

Cellular immune dysfunction in immune thrombocytopenia (ITP)

Over the past decades, a wealth of information has been reported about the pathogenic features of immune thrombocytopenia (ITP). To this day, however, it is unclear whether the immune abnormalities associated with ITP play causative roles in the disease or are secondary epiphenomena brought on by the inflammatory processes that are associated with the disorder. Like the majority of all autoimmune

Platelets deliver small packages of genetic function

In this issue of Blood, Laffont et al have identified a type of delivery system by platelets in the form of platelet microparticles delivering functional microRNA to endothelial cells. The delivery, it appears, may be a relatively novel process of regulation of gene expression in endothelial cells and potentially other nucleated cells of the body.

Innate and adaptive immunity in immune thrombocytopenia

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by both accelerated clearance of autoantibody-sensitized platelets and suboptimal platelet production. A number of studies have provided evidence of disturbed innate and adaptive immune responses in patients with ITP. This brief review will highlight some of the more recent work in this field and highlight other findings that pr

T granules in human platelets function in TLR9 organization and signaling

Human and murine platelets (PLTs) variably express toll-like receptors (TLRs), which link the innate and adaptive immune responses during infectious inflammation and atherosclerotic vascular disease. In this paper, we show that the TLR9 transcript is specifically up-regulated during pro-PLT production and is distributed to a novel electron-dense tubular system-related compartment we have named the

Thymic retention of CD4+CD25+FoxP3+ T regulatory cells is associated with their peripheral deficiency and thrombocytopenia in a murine model of immune thrombocytopenia

Immune thrombocytopenia (ITP) is a bleeding disorder in which antibodies and/or T cells lead to enhanced peripheral platelet destruction and reduced bone marrow platelet production. Several reports have observed that ITP is associated with a peripheral deficiency of tolerance-inducing CD4+CD25+FoxP3+ T regulatory cells (Tregs). Using a murine model of ITP, we analyzed Tregs in the spleen and thymu

The immunopathogenesis of immune thrombocytopenia : T cells still take center-stage

PURPOSE OF REVIEW: Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder in which T and B cells recognize platelet antigens and initiate antiplatelet destructive mechanisms such as peripheral Fc receptor-mediated phagocytosis in the spleen or megakaryocyte destruction/inhibition within the bone marrow. The purpose of this review is to report on the ITP pathophysiology literature publish

HLA alloimmunization against platelet transfusions : pathophysiology, significance, prevention and management

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 r

Intravenous immunoglobulin prevents murine antibody-mediated acute lung injury at the level of neutrophil reactive oxygen species (ROS) production

Transfusion-related acute lung injury (TRALI) is a leading cause of transfusion-associated mortality that can occur with any type of transfusion and is thought to be primarily due to donor antibodies activating pulmonary neutrophils in recipients. Recently, a large prospective case controlled clinical study of cardiac surgery patients demonstrated that despite implementation of male donors, a high

Single nucleotide polymorphism (SNP) analysis demonstrates a significant association of tumour necrosis factor-alpha (TNFA) with primary immune thrombocytopenia among Caucasian adults

T-helper 1 polarization in patients with primary immune thrombocytopenia (ITP) is well documented. However, the genetic contribution to this imbalance remains unclear. To address this question, we selected six candidate single nucleotide polymorphisms within cytokine or cytokine receptor genes for association testing among Caucasian adults. Patients from the United Kingdom Adult ITP Registry were

Management of immune thrombocytopenic purpura in children : potential role of novel agents

The treatment of immune thrombocytopenic purpura (ITP) in children is controversial, requiring individualized assessment of the patient and consideration of treatment options. If the platelet count is >10 000/μL and the patient is asymptomatic, a 'watch and wait' strategy is appropriate since most children with ITP will recover completely without pharmacotherapy. If therapy is indicated because of

Platelets and the immune continuum

Platelets are anucleate cells that are crucial mediators of haemostasis. Most immunologists probably don't think about platelets every day, and may even consider these cells to be 'nuisances' in certain in vitro studies. However, it is becoming increasingly clear that platelets have inflammatory functions and can influence both innate and adaptive immune responses. Here, we discuss the mechanisms

Current problems and future directions of transfusion-induced alloimmunization : summary of an NHLBI working group

In April 2010, a working group sponsored by the National Heart, Lung, and Blood Institute was assembled to identify research strategies to improve our understanding of alloimmunization caused by the transfusion of allogeneic blood components and to evaluate potential approaches to both reduce its occurrence and manage its effects. Significant sequelae of alloimmunization were discussed and identif

Recent progress in understanding the pathogenesis of immune thrombocytopenia

PURPOSE OF REVIEW: Immune thrombocytopenia (ITP) is a bleeding disorder in which both antibody and cell-mediated autoimmune responses are directed against an individual's own platelets and/or megakaryocytes, leading to either enhanced platelet destruction and/or reduced platelet production, respectively. The cause of this platelet-specific autoimmunity remains unknown, but there has been a constan