Complement activation as a biomarker for platelet activating antibodies in heparin-induced thrombocytopenia (HIT).

Background: IgG antibodies (Abs) to platelet factor 4 complexed to heparin (PF4/H) commonly occur after heparin exposure but cause life-threatening complications of heparin-induced thrombocytopenia (HIT) in only a few patients. Presently, only platelet activation assays reliably distinguish anti-PF4/H Abs that cause disease (HIT Abs) from those likely to be asymptomatic (AAbs).

Objectives: Recent studies indicate that complement activation is an important serologic property of HIT Abs and is essential for FcγRIIA-mediated cellular activation.

Marginated Neutrophils in the Lungs Effectively Compete for Nanoparticles Targeted to the Endothelium, Serving as a Part of the Reticuloendothelial System.

Nanomedicine has long pursued the goal of targeted delivery to specific organs and cell types but has yet to achieve this goal with the vast majority of targets. One rare example of success in this pursuit has been the 25+ years of studies targeting the lung endothelium using nanoparticles conjugated to antibodies against endothelial surface molecules. However, here we show that such "endothelial-targeted" nanocarriers also effectively target the lungs' numerous marginated neutrophils, which reside in the pulmonary capillaries and patrol for pathogens.

Thioredoxin-related transmembrane protein 1 negatively regulates coagulation and phosphatidylserine exposure.

Background: Five secreted platelet protein disulfide isomerases (PDIs) and 1 transmembrane PDI regulate platelet function and thrombosis. Thioredoxin-related transmembrane protein 1 (TMX1) was the first member of the PDI family found to negatively regulate platelet aggregation and platelet accumulation . The effect of TMX1 on coagulation is unknown.

Studies of infused megakaryocytes into mice support a "catch-and-release" model of pulmonary-centric thrombopoiesis.

Unlabelled: Many aspects of thrombopoiesis, the release of platelets from megakaryocytes (Mks), remain under debate, including where this process occurs. Murine lung -microscopy studies suggested that a significant fraction of circulating platelets were released from lung-entrapped, marrow-derived Mks. We now confirm these studies that endogenous mMks are entrapped in the lungs and show that intravenously infused -differentiated, mature murine (m) and human (h) Mks are similarly entrapped followed by shedding of their cytoplasm over ∼30 minutes with a peak number of released platelets occurring 1.

G6b-B antibody-based cis-acting platelet receptor inhibitors (CAPRIs) as a new family of anti-thrombotic therapeutics.

Platelets are highly reactive fragments of megakaryocytes that play a fundamental role in thrombosis and hemostasis. Predictably, all conventional anti-platelet therapies elicit bleeding, raising the question whether the thrombotic activity of platelets can be targeted separately. In this study, we describe a novel approach of inhibiting platelet activation through the use of bispecific single-chain variable fragments (bi-scFvs), termed cis-acting platelet receptor inhibitors (CAPRIs) that harness the immunoreceptor tyrosine-based inhibition motif (ITIM)-containing co-inhibitory receptor G6b-B (G6B) to suppress immunoreceptor tyrosine-based (ITAM)-containing receptor-mediated platelet activation.