Disparities in menstrual bleeding management during acute venous thromboembolism treatment: A review of UK practice and a call for clinical studies.

Background: Heavy menstrual bleeding (HMB) is a significant clinical burden for premenopausal individuals treated with anticoagulation for acute venous thromboembolism (VTE). Despite its prevalence, HMB management remains poorly studied, with wide variation in clinical practice.

Objectives: The current study aimed to explore current UK practices in managing HMB in anticoagulated individuals and identify areas requiring clinical research to address disparities.

The experience of patients undergoing aseptic, elective revision knee joint replacement surgery: a qualitative study.

Background: Around 6,000 revision knee replacement procedures are performed in the United Kingdom each year. Three-quarters of procedures are for aseptic, elective reasons, such as progressive osteoarthritis, prosthesis loosening/wear, or instability. Our understanding of how we can best support these patients undergoing revision knee replacement procedures is limited.

Use of IV immunoglobulin to treat steroid resistant, immune checkpoint inhibitor-induced pure red cell aplasia: A case report.

Pure red cell aplasia (PRCA) is characterised by normocytic normochromic anaemia, reticulocytopenia and reduced erythroid precursors in bone marrow. PRCA as an immune-related adverse event secondary to immune checkpoint inhibitor (ICI) therapy is rare. Steroids are usually used first line to treat ICI-induced PRCA.

Selective Btk inhibition by PRN1008/PRN473 blocks human CLEC-2, and PRN473 reduces venous thrombosis formation in mice.

Platelet C-type lectin-like receptor 2 (CLEC-2) is a hem-immunoreceptor tyrosine-based activation motif-containing receptor that has a critical role in venous thrombosis but minimal involvement in hemostasis. CLEC-2 can be blocked by Btk inhibitors. Treatment with ibrutinib is associated with increased bleeding due to off-target inhibition of Src family kinases (SFKs).

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.

Real-world use of thrombopoietin receptor agonists for the management of immune thrombocytopenia in adult patients in the United Kingdom: Results from the TRAIT study.

Few studies have reported the real-world use of both romiplostim and eltrombopag in immune thrombocytopenia (ITP). TRAIT was a retrospective observational study aimed to evaluate the platelet responses and adverse effects associated with the use of these thrombopoietin receptor agonists (TPO-RAs) in adult patients with ITP in the United Kingdom. Of 267 patients (median age at diagnosis, 48 years) with ITP (primary ITP [n = 218], secondary ITP [n = 49]) included in the study, 112 (42%) received eltrombopag and 155 (58%) received romiplostim as the first prescribed TPO-RA.

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.

PF4 activates the c-Mpl-Jak2 pathway in platelets.

Platelet factor 4 (PF4) is an abundant chemokine that is released from platelet α-granules on activation. PF4 is central to the pathophysiology of vaccine-induced immune thrombocytopenia and thrombosis (VITT) in which antibodies to PF4 form immune complexes with PF4, which activate platelets and neutrophils through Fc receptors. In this study, we show that PF4 binds and activates the thrombopoietin receptor, cellular myeloproliferative leukemia protein (c-Mpl), on platelets.

Epidemiology of revision hip replacement surgery in the UK over the past 15 years-an analysis from the National Joint Registry.

Objectives: To investigate trends in the incidence rate and main indication for revision hip replacement (rHR) over the past 15 years in the UK.

Design: Repeated national cross-sectional study from 2006 to 2020.

Setting/participants: rHR procedures were identified from the National Joint Registry for England, Wales, Northern Ireland, the Isle of Man and the States of Guernsey.

Novel therapeutics and emerging technology in haemostasis and thrombosis: highlights from the British society for haemostasis and thrombosis annual meeting.

The 2023 annual meeting of the British Society for Haemostasis and Thrombosis (BSHT) was held in Birmingham, United Kingdom. The theme of this year's meeting was novel therapeutics and emerging technology. Here, the exciting research presented at the meeting is discussed.

Lower limb muscle strength and balance in older adults with a distal radius fracture: a systematic review.

Background: Distal radius fractures are common fractures in older adults and associated with increased risk of future functional decline and hip fracture. Whether lower limb muscle strength and balance are impaired in this patient population is uncertain. To help inform rehabilitation requirements, this systematic review aimed to compare lower limb muscle strength and balance between older adults with a distal radius fracture with matched controls, and to synthesise lower limb muscle strength and balance outcomes in older adults with a distal radius fracture.

Amplified inhibition of atherosclerotic plaque-induced platelet activation by glenzocimab with dual antiplatelet therapy.

Background: Aspirin and platelet P2Y inhibitors, such as ticagrelor, suboptimally inhibit microvascular thrombosis during ST-elevation myocardial infarction. Glycoprotein (GP) IIb/IIIa inhibitors may further inhibit this but cause excessive bleeding.

Objectives: We investigated whether combination of glenzocimab, a GPVI inhibitor, with aspirin and ticagrelor provides additional antithrombotic effects, as GPVI has a critical role in atherothrombosis but minimal involvement in hemostasis.

Tailored exercise management (TEMPO) versus usual care for people aged 80 years or older with hip/knee osteoarthritis: study protocol for a feasibility randomised controlled trial.

Background: Exercise is recommended for all people with osteoarthritis. However, these recommendations are based on randomised clinical trials including people with an average age between 60 and 70 years, and these findings cannot reliably be generalised to people aged 80 years or older. Rapid loss of muscle occurs after 70 years of age, and older people are more likely to also have other health conditions that contribute to difficulties with daily activities and impact on their response to exercise.

UK media reporting of NICE recommendation of crizanlizumab for patients with sickle cell disease.

Crizanlizumab was recommended for use in patients with sickle cell disease in the UK in October 2021 and received widespread media coverage. Accuracy of reporting is paramount in building trust with this group of patients who are often wary of the medical profession. We carried out an analysis of internet-based news articles and applied a validated scoring system to assess quality.

Recent advances in understanding spleen tyrosine kinase (SYK) in human biology and disease, with a focus on fostamatinib.

Spleen tyrosine kinase (SYK) is an important regulatory molecule of signal transduction pathways involved in the pathogenesis of autoimmune diseases such as immune thrombocytopenia (ITP), and the SYK-signaling pathway has emerged as a potential target for the treatment of numerous diseases. The aim of this narrative review is to summarize the biological properties of SYK and its involvement in disease pathways, provide an update on SYK inhibitors in the treatment of ITP, and consider other potential applications. Fostamatinib, the only licensed SYK inhibitor to date, produces clinical response in ITP patients, including those who are refractory to other treatments.

Osteoarthritis year in review 2022: rehabilitation.

This year in review presents key highlights from research relating to osteoarthritis (OA) rehabilitation published from the 1 April 2021 to the 18 March 2022. To identify studies for inclusion in the review, an electronic database search was carried out in Medline, Embase and CINAHLplus. Following screening, included studies were grouped according to their predominant topic area, including core OA rehabilitation treatments (education, exercise, weight loss), adjunctive treatments, novel and emerging treatments or research methods, and translation of rehabilitation evidence into practice.

The Btk inhibitor AB-95-LH34 potently inhibits atherosclerotic plaque-induced thrombus formation and platelet procoagulant activity.

Background: New antithrombotic therapies with less effect on bleeding are needed for coronary artery disease. The Btk inhibitor ibrutinib blocks atherosclerotic plaque-mediated thrombus formation. However, it is associated with increased bleeding, possibly due to non-Btk-mediated effects.

Development and validation of a prediction model for self-reported mobility decline in community-dwelling older adults.

Objectives: The aim of this study is to develop and validate two models to predict 2-year risk of self-reported mobility decline among community-dwelling older adults.

Study Design And Setting: We used data from a prospective cohort study of people aged 65 years and over in England. Mobility status was assessed using the EQ-5D-5L mobility question.

S100A8/A9 drives the formation of procoagulant platelets through GPIbα.

S100A8/A9, also known as "calprotectin" or "MRP8/14," is an alarmin primarily secreted by activated myeloid cells with antimicrobial, proinflammatory, and prothrombotic properties. Increased plasma levels of S100A8/A9 in thrombo-inflammatory diseases are associated with thrombotic complications. We assessed the presence of S100A8/A9 in the plasma and lung autopsies from patients with COVID-19 and investigated the molecular mechanism by which S100A8/A9 affects platelet function and thrombosis.

Correlations between objective and self-reported step count adherence following total knee replacement: A longitudinal repeated-measures cohort study.

Objective: To determine how physically active individuals are following total knee replacement (TKR) and how accurately they self-report their step count adherence compared to objective measure following TKR.

Methods: Observational cohort study, nested within the PATHway randomised-clinical trial. Participants (n = 102) who had recently undergone TKR were recruited for the main trial.