Presenting ADAMTS13 on a TTP-associated MHC.

In this issue of Blood, Sorvillo et al investigate possible molecular triggers leading to idiopathic, autoimmune thrombotic thrombocytopenic purpura (TTP) by identifying naturally processed A Disintegrin And Metalloprotease with ThromboSpondin type 1 motif 13 (ADAMTS13)-derived peptides presented on human dendritic cells.

Cocaine and specific cocaine metabolites induce von Willebrand factor release from endothelial cells in a tissue-specific manner.

Objective: Cocaine use is associated with arterial thrombosis, including myocardial infarction and stroke. Cocaine use results in increased plasma von Willebrand factor (VWF), accelerated atherosclerosis, and platelet-rich arterial thrombi, suggesting that cocaine activates the endothelium, promoting platelet-VWF interactions.

Approach And Results: Human umbilical vein endothelial cells, brain microvasculature endothelial cells, or coronary artery endothelial cells were treated with cocaine or metabolites benzoylecgonine, cocaethylene, norcocaine, or ecgonine methylester.

Effect of storage of red blood cells on alloimmunization.

Background: Red blood cells (RBCs) undergo changes during storage. Various studies have suggested a higher risk of adverse and often multifactorial clinical outcomes associated with older-stored RBCs. Our aim therefore was to examine if storage of transfused RBCs is also associated with the risk of RBC-specific alloantibody formation.

Addition of ascorbic acid solution to stored murine red blood cells increases posttransfusion recovery and decreases microparticles and alloimmunization.

Background: The storage of red blood cells (RBCs) results in numerous changes, which over time result in decreased recovery of transfused RBCs. In addition (at least in animal models), stored RBCs can be more immunogenic and also stimulate the systemic release of inflammatory cytokines in transfusion recipients. One component of the RBC storage lesion is the accumulation of oxidative damage.

Pathogenesis in immune thrombocytopenia: new insights.

Idiopathic (immune) thrombocytopenic purpura (ITP) is a common autoimmune disorder resulting in isolated thrombocytopenia. ITP can present either alone (primary) or in the setting of other conditions (secondary) such as infections or altered immune states. ITP is associated with a loss of tolerance to platelet antigens and a phenotype of accelerated platelet destruction and impaired platelet production.

Inhibitory antibodies in hemophilia A.

Purpose Of Review: The review describes recent advances in our understanding of mechanisms leading to development of neutralizing antibodies following factor VIII (FVIII) replacement therapy for hemophilia A. Novel interventions with translational potential to lessen the incidence of these deleterious immune responses are discussed.

Recent Findings: Genetic and environmental risk factors for inhibitor development, and cellular mechanisms leading to antibody production versus immune tolerance to FVIII, are increasingly coming into focus.

Effects of genetic, epigenetic, and environmental factors on alloimmunization to transfused antigens: Current paradigms and future considerations.

Transfused red blood cells, platelets, or coagulation factors have the capacity to induce alloantibodies, which once formed, can be a clinical barrier to future transfusion therapy and/or transplantation. Large observational studies over the last 50 years have characterized some of the general properties of transfusion induced alloimmunization, which appear to vary to a considerable extent from what is generally observed for human responses to other immunogens, such as microbial pathogens and vaccines. Transfused cells and factor only induce immune responses in the minority of recipients.