Transcription Factor RUNX1 Regulates Coagulation Factor XIII-A ( ): Decreased Platelet-Megakaryocyte Expression and Clot Contraction in Haplodeficiency.

Background: Germline haplodeficiency (RHD) is associated with thrombocytopenia, platelet dysfunction and predisposition to myeloid malignancies. Platelet expression profiling of a RHD patient showed decreased encoding for the A subunit of factor XIII, a transglutaminase that cross-links fibrin and induces clot stabilization. FXIII-A is synthesized by hematopoietic cells, megakaryocytes and monocytes.

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.