PFA-100 System: A New Method for Assessment of Platelet Dysfunction.

This is a celebratory reprint of a historical paper published in STH in 1998. The original Abstract follows.The PFA-100 system is a platelet function analyzer designed to measure platelet-related primary hemostasis.

S-Nitrosylation of Tissue Transglutaminase in Modulating Glycolysis, Oxidative Stress, and Inflammatory Responses in Normal and Indoxyl-Sulfate-Induced Endothelial Cells.

Circulating uremic toxin indoxyl sulfate (IS), endothelial cell (EC) dysfunction, and decreased nitric oxide (NO) bioavailability are found in chronic kidney disease patients. NO nitrosylates/denitrosylates a specific protein's cysteine residue(s), forming S-nitrosothios (SNOs), and the decreased NO bioavailability could interfere with NO-mediated signaling events. We were interested in investigating the underlying mechanism(s) of the reduced NO and how it would regulate the S-nitrosylation of tissue transglutaminase (TG2) and its substrates on glycolytic, redox and inflammatory responses in normal and IS-induced EC injury.

Association of Sickle Cell Trait With Incidence of Coronary Heart Disease Among African American Individuals.

Importance: The incidence of and mortality from coronary heart disease (CHD) are substantially higher among African American individuals compared with non-Hispanic White individuals, even after adjusting for traditional factors associated with CHD. The unexplained excess risk might be due to genetic factors related to African ancestry that are associated with a higher risk of CHD, such as the heterozygous state for the sickle cell variant or sickle cell trait (SCT).

Objective: To evaluate whether there is an association between SCT and the incidence of myocardial infarction (MI) or composite CHD outcomes in African American individuals.

The impact of prepartum factor XIII activity on postpartum blood loss.

Background: Postpartum hemorrhage (PPH), a major cause of maternal mortality, has several known risk factors but frequently occurs unexpectedly. PPH incidence and related maternal morbidity and mortality are rising worldwide.

Objective: To evaluate the impact of defined prepartum blood coagulation parameters on postpartum blood loss.

Successful Management of Thrombotic Thrombocytopenic Purpura in a Jehovah's Witness: An Individualized Approach With Joint Decision-Making.

The management of thrombotic thrombocytopenic purpura (TTP) presents a unique challenge in individuals who are unable to accept plasma due to religious beliefs, given that therapeutic plasma exchange (TPE) is the standard of care. A 61-year-old Jehovah's Witness woman presented to our hospital with neurological symptoms and laboratory findings suggestive of TTP. On admission, she refused transfusion of blood products, specifically red blood cells, platelets, and plasma but accepted albumin and intravenous immunoglobulin (IVIG); fractions of plasma.

Multicenter Evaluation of the Quantra QPlus System in Adult Patients Undergoing Major Surgical Procedures.

Background: The management of perioperative bleeding and the optimization of the available therapies are subjects of significant clinical interest. Clinical guidelines recommend the use of whole blood viscoelastic testing devices to target the utilization of blood products during major surgical procedures. The Quantra QPlus System is a new cartridge-based viscoelastic testing device based on an innovative ultrasound technology.

Modeling Biological Complexes Using Integrative Modeling Platform.

Integrative structure modeling provides 3D models of macromolecular systems that are based on information from multiple types of experiments, physical principles, statistical inferences, and prior structural models. Here, we provide a hands-on realistic example of integrative structure modeling of the quaternary structure of the actin, tropomyosin, and gelsolin protein assembly based on electron microscopy, solution X-ray scattering, and chemical crosslinking data for the complex as well as excluded volume, sequence connectivity, and rigid atomic X-ray structures of the individual subunits. We follow the general four-stage process for integrative modeling, including gathering the input information, converting the input information into a representation of the system and a scoring function, sampling alternative model configurations guided by the scoring function, and analyzing the results.

AGA Clinical Practice Update: Coagulation in Cirrhosis.

Description: This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership. The intent is to evaluate the current data on mechanism of altered coagulation in patients with cirrhosis, provide guidance on the use of currently available testing of the coagulation cascade, and help practitioners use anticoagulation and pro-coagulants appropriately in patients with cirrhosis.

Methods: This review is framed around the best practice points, which were derived from the most impactful publications in the area of coagulation in cirrhosis and agreed to by all authors.

Acute kidney injury is associated with low factor XIII in decompensated cirrhosis.

Background/aims: The coagulation system is known to be rebalanced but fragile in stable cirrhosis. Acute kidney injury (AKI) is common in these patients and associated with an increased bleeding risk. We aimed to assess coagulation parameters in this population.

Impact of Benign Hematology Didactic Lectures on In-service Exam in a Hematology-Oncology Fellowship Program: a Cross-sectional Longitudinal Study.

It remains unclear on whether the traditional formal didactic lecture sessions improve knowledge acquisition with conflicting data in the literature. This study evaluates the impact of an additional benign hematology didactic curriculum on the American Society of Hematology In-Service Exam (ASHISE). During the first 5 years of the study (2012-2016), formal didactic lectures consisted of medical oncology and malignant hematology topics only.

Limited impact of clinician education on reducing inappropriate PF4 testing for heparin-induced thrombocytopenia.

A high frequency of PF4-ELISA testing in patients suspected to have heparin-induced thrombocytopenia (HIT) despite low 4T scores has been observed in multiple medical centers. Education of clinicians has been suggested to reduce inappropriate testing. We determined trends of PF4-ELISA testing in our institution after the introduction of a HIT education program for clinicians.

Bayesian Weighing of Electron Cryo-Microscopy Data for Integrative Structural Modeling.

Cryo-electron microscopy (cryo-EM) has become a mainstream technique for determining the structures of complex biological systems. However, accurate integrative structural modeling has been hampered by the challenges in objectively weighing cryo-EM data against other sources of information due to the presence of random and systematic errors, as well as correlations, in the data. To address these challenges, we introduce a Bayesian scoring function that efficiently and accurately ranks alternative structural models of a macromolecular system based on their consistency with a cryo-EM density map as well as other experimental and prior information.

Analyzing the impact of systems-based hematologist in the healthcare system at an academic medical center.

Over the next decade, there is a predicted shortage of nonmalignant hematologist to maintain the workforce in the United States. To address this, the American Society of Hematology described the creation of the healthcare systems-based hematologist (SBH). The role of SBH has the potential to provide high-value, cost-conscious care to the healthcare system.

Practice Patterns of Inferior Vena Cava Filter Placement and Factors That Predict Retrieval Rates: A Single-Center Institution and Review of the Literature.

Background: There is a wide variability in practice patterns on the use of inferior vena cava filters (IVCFs) among institutions, which is likely due to contrasting indication guidelines published by different professional societies. The aim of the present study is to report our healthcare system use of IVCF to: 1) determine practice patterns, 2) determine factors that may predict IVCF retrieval and 3) identify areas for improvement.

Methods: A retrospective review of 180 consecutive IVCF placement performed between July 2014 and December 2015 was conducted.

Integrative structure and functional anatomy of a nuclear pore complex.

Nuclear pore complexes play central roles as gatekeepers of RNA and protein transport between the cytoplasm and nucleoplasm. However, their large size and dynamic nature have impeded a full structural and functional elucidation. Here we determined the structure of the entire 552-protein nuclear pore complex of the yeast Saccharomyces cerevisiae at sub-nanometre precision by satisfying a wide range of data relating to the molecular arrangement of its constituents.

Initial and long term impact of a multi-disciplinary task force in the diagnosis and management of heparin-induced thrombocytopenia.

Many medical centers are faced with a major challenge in making an accurate diagnosis of heparin-induced thrombocytopenia (HIT) and ensuring appropriate changes in management strategy in line with guideline recommendations. We report the initial and long-term impact and challenges of institution-wide changes in the diagnosis and management of HIT in the inpatient setting at an academic medical center. We established a HIT Task Force, consisting of a multidisciplinary team of non-malignant hematologists, nursing, pharmacist, pathology, blood bank and clinical lab informatics.

Endothelial cell-surface tissue transglutaminase inhibits neutrophil adhesion by binding and releasing nitric oxide.

Nitric oxide (NO) produced by endothelial cells in response to cytokines displays anti-inflammatory activity by preventing the adherence, migration and activation of neutrophils. The molecular mechanism by which NO operates at the blood-endothelium interface to exert anti-inflammatory properties is largely unknown. Here we show that on endothelial surfaces, NO is associated with the sulfhydryl-rich protein tissue transglutaminase (TG2), thereby endowing the membrane surfaces with anti-inflammatory properties.

Integrative structure modeling with the Integrative Modeling Platform.

Building models of a biological system that are consistent with the myriad data available is one of the key challenges in biology. Modeling the structure and dynamics of macromolecular assemblies, for example, can give insights into how biological systems work, evolved, might be controlled, and even designed. Integrative structure modeling casts the building of structural models as a computational optimization problem, for which information about the assembly is encoded into a scoring function that evaluates candidate models.

Molecular Details Underlying Dynamic Structures and Regulation of the Human 26S Proteasome.

The 26S proteasome is the macromolecular machine responsible for ATP/ubiquitin dependent degradation. As aberration in proteasomal degradation has been implicated in many human diseases, structural analysis of the human 26S proteasome complex is essential to advance our understanding of its action and regulation mechanisms. In recent years, cross-linking mass spectrometry (XL-MS) has emerged as a powerful tool for elucidating structural topologies of large protein assemblies, with its unique capability of studying protein complexes in cells.

Role of tissue transglutaminase-2 (TG2)-mediated aminylation in biological processes.

Post-translational modification (PTM) is an important mechanism in modulating a protein's structure and can lead to substantial diversity in biological function. Compared to other forms of PTMs such as phosphorylation, acetylation and glycosylation, the physiological significance of aminylation is limited. Aminylation refers to the covalent incorporation of biogenic/polyamines into target protein by calcium-dependent transglutaminases (TGs).

Structure of γ-tubulin small complex based on a cryo-EM map, chemical cross-links, and a remotely related structure.

Modeling protein complex structures based on distantly related homologues can be challenging due to poor sequence and structure conservation. Therefore, utilizing even low-resolution experimental data can significantly increase model precision and accuracy. Here, we present models of the two key functional states of the yeast γ-tubulin small complex (γTuSC): one for the low-activity "open" state and another for the higher-activity "closed" state.