Revisiting the full blood count: Circulating blood cells and their role in coagulation.

There has been an expansion in our understanding of the multifaceted roles of circulating blood cells in regulating haemostasis and contributing to thrombosis. Notably, there is greater recognition of the interplay between coagulation with inflammation and innate immune activation and the contribution of leucocytes. The full blood count (FBC) is a time-honoured test in medicine; however, its components are often viewed in isolation and without consideration of their haemostatic and thrombotic potential.

Identification of cross reactive T cell responses in adenovirus based COVID 19 vaccines.

Vaccination has proven to be a valuable tool to combat SARS-CoV-2. However, reports of rare adverse reactions such as thrombosis/thrombocytopenia syndrome after ChAdOx1 nCoV-19 vaccination have caused scientific, public and media concern. ChAdOx1 was vectorised from the Y25 chimpanzee adenovirus, which was selected due to low human seroprevalence to circumvent pre-existing immunity.

The convergent model of coagulation.

It is increasingly apparent that the pathologic interplay between coagulation and innate immunity, ie, immunothrombosis, forms the common basis of many challenges across the boundaries of specialized medicine and cannot be fully explained by the conventional concepts of cascade and cell-based coagulation. To improve our understanding of coagulation, we propose a model of coagulation that converges with inflammation and innate immune activation as a unified response toward vascular injury. Evolutionarily integral to the convergent response are damage-associated molecular patterns, which are released as a consequence of injury.

Fibrinogen binding to histones in circulation protects against adverse cellular and clinical outcomes.

Background: Circulating histones are released by extensive tissue injury or cell death and play important pathogenic roles in critical illnesses. Their interaction with circulating plasma components and the potential roles in the clinical setting are not fully understood.

Objectives: We aimed to characterize the interaction of histones with fibrinogen and explore its roles in vitro, in vivo, and in patient samples.

Microclots, as defined by amyloid-fibrinogen aggregates, predict risks of disseminated intravascular coagulation and mortality.

Microclots have been associated with various conditions, including postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection. They have been postulated to be amyloid-fibrin(ogen) aggregates, but their role as a prognostic biomarker remains unclear. To examine their possible clinical utility, blood samples were collected for the first 96 hours from critically ill patients (n = 104) admitted to the intensive care unit (ICU).

Shades of Grey-The brain in TTP.

In their paper, Hannan et al. suggest that new approaches to the management of the acute and remission phases of thrombotic thrombocytopenic purpura should be considered to address white matter changes seen in patients undergoing magnetic resonance imaging. Timely intervention may have significant implications for the long-term physical and mental health of patients.

Damage-associated cellular markers in the clinical and pathogenic profile of vaccine-induced immune thrombotic thrombocytopenia.

Background: Adenoviral vector-based COVID-19 vaccine-induced immune thrombotic thrombocytopenia (VITT) is rare but carries significant risks of mortality and long-term morbidity. The underlying pathophysiology of severe disease is still not fully understood. The objectives were to explore the pathophysiological profile and examine for clinically informative biomarkers in patients with severe VITT.

Rethinking coagulation: from enzymatic cascade and cell-based reactions to a convergent model involving innate immune activation.

Advancements in the conceptual thinking of hemostasis and thrombosis have been catalyzed by major developments within health research over several decades. The cascade model of coagulation was first described in the 1960s, when biochemistry gained prominence through innovative experimentation and technical developments. This was followed by the cell-based model, which integrated cellular coordination to the enzymology of clot formation and was conceptualized during the growth period in cell biology at the turn of the millennium.

Trauma-induced innate immune activation and disseminated intravascular coagulation.

Dysregulated innate immunity participates in the pathomechanisms of disseminated intravascular coagulation (DIC) in trauma-induced coagulopathy. Accidental and regulated cell deaths and neutrophil extracellular traps release damage-associated molecular patterns (DAMPs), such as histones, nuclear and mitochondrial DNA, and high-mobility group box 1, into circulation immediately after trauma. DAMP-induced inflammation activation releases tissue factor-bearing procoagulant extracellular vesicles through gasdermin D-mediated pore formation and plasma membrane rupture by regulated cell death.

Delivering trials in the NHS: more than worth it.

Randomised trials are the best method to determine the efficacy and safety of health technologies. A recent report by Lord O'Shaughnessy highlighted many of the current challenges to delivering trials in the UK and proposed potential solutions. Among these, making trials the business of all NHS institutions and a valued part of all doctors' work, while leveraging the potential of the data that the NHS collects routinely, offers an opportunity to improve NHS efficiency, doctors' job satisfaction and population health simultaneously.

A "Bundle of Care" to Improve Anticoagulation Control in Patients Receiving Warfarin in Uganda and South Africa: Protocol for an Implementation Study.

Background: The quality of warfarin anticoagulation among Sub-Saharan African patients is suboptimal. This is due to several factors, including a lack of standardized dosing algorithms, difficulty in providing timely international normalized ratio (INR) results, a lack of patient feedback on their experiences with treatment, a lack of education on adherence, and inadequate knowledge and training of health care workers. Low quality of warfarin anticoagulation, expressed as time in therapeutic range (TTR), is associated with higher adverse event rates, including bleeding and thrombosis, and ultimately, increased morbidity and mortality.

How to approach acute thrombosis and thrombocytopenia.

Acute thrombosis and thrombocytopenia pose challenges to the clinician. Thrombocytopenia is naturally viewed as a risk factor for bleeding, and an association with acute thrombosis appears paradoxical. It presents typically as a medical emergency and requires treatment to be started before having confirmatory results.

Cell-free histones and the cell-based model of coagulation.

The cell-based model of coagulation remains the basis of our current understanding of clinical hemostasis and thrombosis. Its advancement on the coagulation cascade model has enabled new prohemostatic and anticoagulant treatments to be developed. In the past decade, there has been increasing evidence of the procoagulant properties of extracellular, cell-free histones (CFHs).

The Importance of Pore-Forming Toxins in Multiple Organ Injury and Dysfunction.

Background: Multiple organ injury and dysfunction often occurs in acute critical illness and adversely affects survival. However, in patients who survive, organ function usually recovers without permanent damage. It is, therefore, likely that there are reversible mechanisms, but this is poorly understood in the pathogenesis of multiple organ dysfunction syndrome (MODS).

Tranexamic acid for safer surgery: the time is now.

Tranexamic acid reduces surgical bleeding. Consistent with previous research, the POISE-3 (Peri-Operative Ischemic Evaluation-3) trial found that tranexamic acid reduces major bleeding by 25% and with a low probability of any increase in thromboembolic events. Wider tranexamic acid use will improve surgical safety, avoid unnecessary blood use, reduce the risk of transfusion transmitted infections, and save healthcare funds.