Physiology of the Endometrium and Regulation of Menstruation.

The physiological functions of the uterine endometrium (uterine lining) are preparation for implantation, maintenance of pregnancy if implantation occurs, and menstruation in the absence of pregnancy. The endometrium thus plays a pivotal role in reproduction and continuation of our species. Menstruation is a steroid-regulated event, and there are alternatives for a progesterone-primed endometrium, i.e., pregnancy or menstruation. Progesterone withdrawal is the trigger for menstruation. The menstruating endometrium is a physiological example of an injured or "wounded" surface that is required to rapidly repair each month. The physiological events of menstruation and endometrial repair provide an accessible in vivo human model of inflammation and tissue repair. Progress in our understanding of endometrial pathophysiology has been facilitated by modern cellular and molecular discovery tools, along with animal models of simulated menses. Abnormal uterine bleeding (AUB), including heavy menstrual bleeding (HMB), imposes a massive burden on society, affecting one in four women of reproductive age. Understanding structural and nonstructural causes underpinning AUB is essential to optimize and provide precision in patient management. This is facilitated by careful classification of causes of bleeding. We highlight the crucial need for understanding mechanisms underpinning menstruation and its aberrations. The endometrium is a prime target tissue for selective progesterone receptor modulators (SPRMs). This class of compounds has therapeutic potential for the clinical unmet need of HMB. SPRMs reduce menstrual bleeding by mechanisms still largely unknown. Human menstruation remains a taboo topic, and many questions concerning endometrial physiology that pertain to menstrual bleeding are yet to be answered.

Oral Anticoagulants Beyond Warfarin.

Direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists, mostly warfarin, for the main indications for oral anticoagulation, prevention and treatment of venous thromboembolism, and prevention of embolic stroke in atrial fibrillation. While DOACs offer practical, fixed-dose anticoagulation in many patients, specific restrictions or contraindications may apply. DOACs are not sufficiently effective in high-thrombotic risk conditions such as antiphospholipid syndrome and mechanical heart valves. Patients with cancer-associated thrombosis may benefit from DOACs, but the bleeding risk, particularly in those with gastrointestinal or urogenital tumors, must be carefully weighed. In patients with frailty, excess body weight, and/or moderate-to-severe chronic kidney disease, DOACs must be cautiously administered and may require laboratory monitoring. Reversal agents have been developed and approved for life-threatening bleeding. In addition, the clinical testing of potentially safer anticoagulants such as factor XI(a) inhibitors is important to further optimize anticoagulant therapy in an increasingly elderly and frail population worldwide.

Standard of Care Versus Octreotide in Angiodysplasia-Related Bleeding (the OCEAN Study): A Multicenter Randomized Controlled Trial.

BACKGROUND & AIMS: Gastrointestinal angiodysplasias are vascular anomalies that may result in transfusion-dependent anemia despite endoscopic therapy. An individual patient data meta-analysis of cohort studies suggests that octreotide decreases rebleeding rates, but component studies possessed a high risk of bias. We investigated the efficacy of octreotide in reducing the transfusion requirements of patients with angiodysplasia-related anemia in a clinical trial setting. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Patients with angiodysplasia bleeding were required to have had at least 4 red blood cell (RBC) units or parental iron infusions, or both, in the year preceding randomization. Patients were allocated (1:1) to 40-mg octreotide long-acting release intramuscular every 28 days or standard of care, including endoscopic therapy. The treatment duration was 1 year. The primary outcome was the mean difference in the number of transfusion units (RBC + parental iron) between the octreotide and standard of care groups. Patients who received at least 1 octreotide injection or followed standard of care for at least 1 month were included in the intention-to-treat analyses. Analyses of covariance were used to adjust for baseline transfusion requirements and incomplete follow-up. RESULTS: We enrolled 62 patients (mean age, 72 years; 32 men) from 17 Dutch hospitals in the octreotide (n = 31) and standard of care (n = 31) groups. Patients required a mean number of 20.3 (standard deviation, 15.6) transfusion units and 2.4 (standard deviation, 2.0) endoscopic procedures in the year before enrollment. The total number of transfusions was lower with octreotide (11.0; 95% confidence interval [CI], 5.5-16.5) compared with standard of care (21.2; 95% CI, 15.7-26.7). Octreotide reduced the mean number of transfusion units by 10.2 (95% CI, 2.4-18.1; P = .012). Octreotide reduced the annual volume of endoscopic procedures by 0.9 (95% CI, 0.3-1.5). CONCLUSIONS: Octreotide effectively reduces transfusion requirements and the need for endoscopic therapy in patients with angiodysplasia-related anemia. CLINICALTRIALS: gov, NCT02384122.

Comparison of Vonoprazan Versus Intravenous Proton Pump Inhibitor for Prevention of High-Risk Peptic Ulcers Rebleeding After Successful Endoscopic Hemostasis: A Multicenter Randomized Noninferiority Trial.

BACKGROUND & AIMS: High-dose proton pump inhibitor (PPI) therapy has been recommended to prevent rebleeding of high-risk peptic ulcer (PU) after hemostasis. Vonoprazan has been proven to be noninferior to PPIs in various acid-related diseases. This study aimed to compare the efficacy of vonoprazan vs PPI for preventing high-risk PU rebleeding after hemostasis. METHODS: A multicenter, randomized, noninferiority study was conducted in 6 centers. Pre-endoscopic and endoscopic therapy were performed according to standard protocol. After successful hemostasis, patients with high-risk PU bleeding (Forrest class Ia/Ib, IIa/IIb) were randomized into 1:1 to receive vonoprazan (20 mg twice a day for 3 days, then 20 mg once a day for 28 days) or high-dose PPI (pantoprazole intravenous infusion 8 mg/h for 3 days, then omeprazole 20 mg twice a day for 28 days). The primary outcome was a 30-day rebleeding rate. Secondary outcomes included 3- and 7-day rebleeding rate, all-cause and bleeding-related mortality, rate of rescue therapy, blood transfusion, length of hospital stay, and safety. RESULTS: Of 194 patients, baseline characteristics, severity of bleeding, and stage of ulcers were comparable between the 2 groups. The 30-day rebleeding rates in vonoprazan and PPI groups were 7.1% (7 of 98) and 10.4% (10 of 96), respectively; noninferiority (within 10% margin) of vonoprazan to PPI was confirmed (%risk difference, -3.3; 95% confidence interval, -11.2 to 4.7; P < .001). The 3-day and 7-day rebleeding rates in the vonoprazan group remained noninferior to PPI (P < .001 by Farrington and Manning test). All secondary outcomes were also comparable between the 2 groups. CONCLUSION: In patients with high-risk PU bleeding, the efficacy of vonoprazan in preventing 30-day rebleeding was noninferior to intravenous PPI. (ClinicalTrials.gov, Number: NCT05005910).

Detection of Gastrointestinal Bleeding With Large Language Models to Aid Quality Improvement and Appropriate Reimbursement.

BACKGROUND & AIMS: Early identification and accurate characterization of overt gastrointestinal bleeding (GIB) enables opportunities to optimize patient management and ensures appropriately risk-adjusted coding for claims-based quality measures and reimbursement. Recent advancements in generative artificial intelligence, particularly large language models (LLMs), create opportunities to support accurate identification of clinical conditions. In this study, we present the first LLM-based pipeline for identification of overt GIB in the electronic health record (EHR). We demonstrate 2 clinically relevant applications: the automated detection of recurrent bleeding and appropriate reimbursement coding for patients with GIB. METHODS: Development of the LLM-based pipeline was performed on 17,712 nursing notes from 1108 patients who were hospitalized with acute GIB and underwent endoscopy in the hospital from 2014 to 2023. The pipeline was used to train an EHR-based machine learning model for detection of recurrent bleeding on 546 patients presenting to 2 hospitals and externally validated on 562 patients presenting to 4 different hospitals. The pipeline was used to develop an algorithm for appropriate reimbursement coding on 7956 patients who underwent endoscopy in the hospital from 2019 to 2023. RESULTS: The LLM-based pipeline accurately detected melena (positive predictive value, 0.972; sensitivity, 0.900), hematochezia (positive predictive value, 0.900; sensitivity, 0.908), and hematemesis (positive predictive value, 0.859; sensitivity, 0.932). The EHR-based machine learning model identified recurrent bleeding with area under the curve of 0.986, sensitivity of 98.4%, and specificity of 97.5%. The reimbursement coding algorithm resulted in an average per-patient reimbursement increase of $1299 to $3247 with a total difference of $697,460 to $1,743,649. CONCLUSIONS: An LLM-based pipeline can robustly detect overt GIB in the EHR with clinically relevant applications in detection of recurrent bleeding and appropriate reimbursement coding.

N-Acetyl Cysteine Prevents Arterial Thrombosis in a Dose-Dependent Manner In Vitro and in Mice.

BACKGROUND: Platelet-rich thrombi occlude arteries causing fatal infarcts like heart attacks and strokes. Prevention of thrombi by current antiplatelet agents can cause major bleeding. Instead, we propose using N-acetyl cysteine (NAC) to act against the protein VWF (von Willebrand factor), and not platelets, to prevent arterial thrombi from forming. METHODS: NAC was assessed for its ability to prevent arterial thrombosis by measuring platelet accumulation rate and occlusion time using a microfluidic model of arterial thrombosis with human blood. Acute clot formation, clot stability, and tail bleeding were measured in vivo with the murine modified Folts model. The effect of NAC in the murine model after 6 hours was also measured to determine any persistent effects of NAC after it has been cleared from the blood. RESULTS: We demonstrate reduction of thrombi formation following treatment with NAC in vitro and in vivo. Human whole blood treated with 3 or 5 mmol/L NAC showed delayed thrombus formation 2.0× and 3.7× longer than control, respectively (P<0.001). Blood treated with 10 mmol/L NAC did not form an occlusive clot, and no macroscopic platelet aggregation was visible (P<0.001). In vivo, a 400-mg/kg dose of NAC prevented occlusive clots from forming in mice without significantly affecting tail bleeding times. A lower dose of NAC significantly reduced clot stability. Mice given multiple injections showed that NAC has a lasting and cumulative effect on clot stability, even after being cleared from the blood (P<0.001). CONCLUSIONS: Both preclinical models demonstrate that NAC prevents thrombus formation in a dose-dependent manner without significantly affecting bleeding time. This work highlights a new pathway for preventing arterial thrombosis, different from antiplatelet agents, using an amino acid derivative as an antithrombotic therapeutic.

Prevalence and outcomes of upper gastrointestinal bleeding in COVID-19: A systematic review and meta-analysis.

Upper gastrointestinal bleeding (UGIB) in COVID-19 presents challenges in patient management. Existing studies lack comprehensive review due to varied designs, samples, and demographics. A meta-analysis can provide valuable insights into the incidence, features, and outcomes of UGIB in COVID-19. A comprehensive literature search was carried out using several databases. We considered all appropriate observational studies from all over the world. Mantel-Haenszel odds ratios and associated 95% confidence intervals (CIs) were produced to report the overall effect size using random effect models. Besides, Random effects models were used to calculate the overall pooled prevalence. Funnel plots, Egger regression tests, and Begg-Mazumdar's rank correlation test were used to appraise publication bias. Data from 21 articles consisting of 26,933 COVID-19 patients were considered. The pooled estimate of UGIB prevalence in patients admitted with COVID-19 across studies was 2.10% (95% CI, 1.23-3.13). Similarly, the overall pooled estimate for severity, mortality, and rebleeding in COVID-19 patients with UGIB was 55% (95% CI, 37.01-72.68), 29% (95% CI, 19.26-40.20) and 12.7% (95% CI, 7.88-18.42) respectively. Further, UGIB in COVID-19 patients was associated with increased odds of severity (OR = 3.52, 95% CI 1.80-6.88, P = 0.001) and mortality (OR = 2.16, 95% CI 1.33-3.51, P = 0.002) compared with patients without UGIB. No significant publication bias was evident in the meta-analysis. The results of our study indicate that UGIB in individuals with COVID-19 is linked to negative outcomes such as severe illness, higher mortality rates, and an increased risk of re-bleeding. These findings highlight the significance of identifying UGIB as a significant complication in COVID-19 cases and emphasise the importance of timely clinical assessment and proper treatment.

Bleeding risk prediction after acute myocardial infarction-integrating cancer data: the updated PRECISE-DAPT cancer score.

BACKGROUND AND AIMS: This study assessed the impact of incorporating cancer as a predictor on performance of the PRECISE-DAPT score. METHODS: A nationally linked cohort of ST-elevation myocardial infarction patients between 1 January 2005 and 31 March 2019 was derived from the UK Myocardial Ischaemia National Audit Project and the UK Hospital Episode Statistics Admitted Patient Care registries. The primary outcome was major bleeding at 1 year. A new modified score was generated by adding cancer as a binary variable to the PRECISE-DAPT score using a Cox regression model and compared its performance to the original PRECISE-DAPT score. RESULTS: A total of 216 709 ST-elevation myocardial infarction patients were included, of which 4569 had cancer. The original score showed moderate accuracy (C-statistic .60), and the modified score showed modestly higher discrimination (C-statistics .64; hazard ratio 1.03, 95% confidence interval 1.03-1.04) even in patients without cancer (C-statistics .63; hazard ratio 1.03, 95% confidence interval 1.03-1.04). The net reclassification index was .07. The bleeding rates of the modified score risk categories (high, moderate, low, and very low bleeding risk) were 6.3%, 3.8%, 2.9%, and 2.2%, respectively. According to the original score, 65.5% of cancer patients were classified as high bleeding risk (HBR) and 21.6% were low or very low bleeding risk. According to the modified score, 94.0% of cancer patients were HBR, 6.0% were moderate bleeding risk, and no cancer patient was classified as low or very low bleeding risk. CONCLUSIONS: Adding cancer to the PRECISE-DAPT score identifies the majority of patients with cancer as HBR and can improve its discrimination ability without undermining its performance in patients without cancer.

Long-term outcomes of high bleeding risk patients undergoing percutaneous coronary intervention: a Korean nationwide registry.

BACKGROUND AND AIMS: Patients with high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI) are at increased risk of not only bleeding, but also ischaemic events. This study aimed to determine the long-term relative risk of ischaemic and bleeding events in HBR patients. METHODS: This study was a nationwide cohort study, based on the Korean National Health Insurance Review and Assessment Service database. Patients diagnosed with stable angina or acute coronary syndrome and those who underwent PCI in Korea between 2009 and 2018 were included in the analysis. According to the Academic Research Consortium HBR criteria, the total population was divided into HBR and non-HBR groups. The co-primary outcomes were major bleeding events and ischaemic (composite of cardiac death, myocardial infarction, and ischaemic stroke) events. RESULTS: Among a total of 325 417 patients who underwent PCI, 66 426 patients (20.4%) had HBR. During the follow-up period, HBR patients had a higher risk for major bleeding events (23.9% vs. 8.9%, P < .001) and ischaemic events (33.8% vs. 14.4%, P < .001). However, the impact of HBR was significant for major bleeding events [hazard ratio (HR) 3.12, 95% confidence interval (CI) 3.04-3.21, P < .001] and for ischaemic events (HR 2.50, 95% CI 2.45-2.56, P < .001). The HBR group was also associated with a greater risk of all-cause mortality (HR 3.73, 95% CI 3.66-3.79, P < .001). The average annual rate of major bleeding events within the first year after PCI was 5.5% for a single major criterion, and 2.9% for a single minor criterion. CONCLUSIONS: Among patients undergoing PCI, those with HBR were at increased long-term risk for both bleeding and ischaemic events, with a greater risk of mortality compared to non-HBR patients.

Stroke and bleeding risk in atrial fibrillation with CHA2DS2-VASC risk score of one: the Norwegian AFNOR study.

BACKGROUND AND AIMS: The benefit of oral anticoagulant (OAC) therapy in atrial fibrillation (AF) and intermediate stroke risk is debated. In a nationwide Norwegian cohort with a non-sex CHA2DS2-VASc risk score of one, this study aimed to investigate (i) stroke and bleeding risk in AF patients with and without OAC treatment, and (ii) the risk of stroke in non-anticoagulated individuals with and without AF. METHODS: A total of 1 118 762 individuals including 34 460 AF patients were followed during 2011-18 until ischaemic stroke, intracranial haemorrhage, increased CHA2DS2-VASc score, or study end. One-year incidence rates (IRs) were calculated as events per 100 person-years (%/py). Cox regression models provided adjusted hazard ratios (aHRs [95% confidence intervals]). RESULTS: Among AF patients, the ischaemic stroke IR was 0.51%/py in OAC users and 1.05%/py in non-users (aHR 0.47 [0.37-0.59]). Intracranial haemorrhage IR was 0.28%/py in OAC users and 0.19%/py in non-users (aHR 1.23 [0.88-1.72]). Oral anticoagulant use was associated with an increased risk of major bleeding (aHR 1.37 [1.16-1.63]) but lower risk of the combined outcome of ischaemic stroke, major bleeding, and mortality (aHR 0.57 [0.51-0.63]). Non-anticoagulated individuals with AF had higher risk of ischaemic stroke compared to non-AF individuals with the same risk profile (aHR 2.47 [2.17-2.81]). CONCLUSIONS: In AF patients at intermediate risk of stroke, OAC use was associated with overall favourable clinical outcomes. Non-anticoagulated AF patients had higher risk of ischaemic stroke compared to the general population without AF with the same risk profile.

Low-dose aspirin for the prevention of atherosclerotic cardiovascular disease.

During the past 30 years, several developments have occurred in the antiplatelet field, including the role of aspirin in primary prevention of atherosclerotic cardiovascular disease. There have been several attempts to develop antiplatelet drugs more effective and safer than aspirin and a shift in emphasis from efficacy to safety, advocating aspirin-free antiplatelet regimens after percutaneous coronary intervention. Evidence supporting a chemopreventive effect of low-dose aspirin against colorectal (and other digestive tract) cancer has also strengthened. The aim of this article is to revisit the role of aspirin in the prevention of atherothrombosis across the cardiovascular risk continuum, in view of developments in the antiplatelet field. The review will offer a clinical perspective on aspirin's mechanism of action, pharmacokinetics, and pharmacodynamics. This will be followed by a detailed discussion of its clinical efficacy and safety.

Aspirin versus Clopidogrel Monotherapy After Percutaneous Coronary Intervention: 1-Year Follow-up of the STOPDAPT-3 Trial.

BACKGROUND AND AIMS: There was no previous trial comparing aspirin monotherapy with a P2Y12 inhibitor monotherapy following short dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). METHODS: In the STOPDAPT-3, patients with acute coronary syndrome (ACS) or high bleeding risk (HBR) were randomly assigned to either 1-month DAPT with aspirin and prasugrel followed by aspirin monotherapy (aspirin group) or 1-month prasugrel monotherapy followed by clopidogrel monotherapy (clopidogrel group). This secondary analysis compared aspirin monotherapy with clopidogrel monotherapy by the 30-day landmark analysis. The co-primary endpoints were the cardiovascular endpoint defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischaemic stroke, and the bleeding endpoint defined as Bleeding Academic Research Consortium 3 or 5. RESULTS: Of 6002 assigned patients, 5833 patients (aspirin group: N = 2920 and clopidogrel group: N = 2913) were included in the 30-day landmark analysis. Median age was 73 (interquartile range 64-80) years, women 23.4%, ACS 74.6%, and HBR 54.1%. The assigned monotherapy was continued at 1 year in 87.5% and 87.2% in the aspirin and clopidogrel groups, respectively. The incidence rates beyond 30 days and up to 1 year were similar between the aspirin and clopidogrel groups for both cardiovascular endpoint (4.5 and 4.5 per 100 person-year, hazard ratio [HR] 1.00 [95% confidence interval (CI) 0.77-1.30], P = .97), and bleeding endpoint (2.0 and 1.9, HR 1.02 [95% CI 0.69-1.52], P = .92). CONCLUSIONS: Aspirin monotherapy compared to clopidogrel monotherapy was associated with similar cardiovascular and bleeding outcomes beyond 1 month and up to 1 year after PCI with DES.

Engineered P2Y12-Overexpressing Cell-Membrane-Wrapped Nanoparticles for the Functional Reversal of Ticagrelor and Clopidogrel.

Antiplatelet agents, particularly P2Y12 receptor inhibitors, are critical medicines in the prevention and treatment of thrombotic diseases in the clinic. However, their long-term use introduces a significant risk of bleeding in patients with cardiovascular diseases. Whether the bleeding is caused by the drug itself or due to surgical procedures or trauma, the need to rapidly reverse the effects of antiplatelet agents in the circulation is essential; however, no such agents are currently available. To address this need, here we describe a strategy that uses cell-membrane-wrapped nanoparticles (CM-NPs) for the rapid reversal of P2Y12 inhibitors. CM-NPs are fabricated with membranes derived from 293T cells genetically engineered to overexpress the P2Y12 receptor. Our findings support the potential of CM-NPs as a strategy for managing bleeding complications associated with P2Y12 receptor inhibitors, offering an approach to improve the safety in the use of these drugs in clinical settings.

Genetics and Epigenetics in Acquired Hemophilia A: From Bench to Bedside.

Acquired hemophilia A (AHA) is a bleeding disorder characterized by the immunological inhibition of factor VIII (FVIII) of the hemostatic pathway leading to hemorrhagic events. Different domains of FVIII are the target of autoantibodies (mainly immunoglobulin (Ig) G) leading to the deficiency of FVIII. Several factors have been associated with the activation of the auto-immunity towards FVIII. Emerging evidence implicates CD4+ T cell activation in mediating this autoimmune response, with their involvement like that observed in congenital hemophilia A. Several genes such as HLA II DRB*16, DQB1*0502, and CTLA-4 + 49 are responsible for the pathogenesis of AHA. Epigenetic modifications and mainly long-coding RNAS (lncRNAs) are potentially contributing to the pathogenesis of AHA. The treatment approach of AHA includes the management of acute bleeding events and the administration of immunosuppressive medications. This review aimed to summarize the published data on the genetics and epigenetics of AHA. The severity and the mortality of this disease are creating an emerging need for further research in the field of the genetics and epigenetics of acquired hemorrhagic disorder.

A new clinical and prognostic characterization of the patterns of decompensation of cirrhosis.

BACKGROUND & AIMS: The prognostic impact of acute decompensation (AD), i.e. the development of complications that require hospitalization, has recently been assessed. However, complications of cirrhosis do not necessarily require hospitalization and can develop progressively, as in the recently defined non-acute decompensation (NAD). Nevertheless, there is no data regarding the incidence and prognostic impact of NAD. The aim of the study was to evaluate the incidence and the prognostic impact of NAD and AD in outpatients with cirrhosis. METHODS: A total of 617 outpatients with cirrhosis from two Italian tertiary centers (Padua and Milan) were enrolled from January 2003 to June 2021 and followed prospectively until the end of the study, death or liver transplantation. The complications registered during follow-up were considered as AD if they required hospitalization, or NAD if managed at the outpatient clinic. RESULTS: During follow-up, 154 patients (25.0% of total patients) developed complications, 69 patients (44.8%) developed NAD and 85 (55.2%) developed AD, while 29 patients with NAD (42.0%) developed a further episode of AD during follow-up. Sixty-month survival was significantly higher in patients with no decompensation than in patients with NAD or AD. On multivariable analysis, AD (hazard ratio [HR] 21.07, p <0.001), NAD (HR 7.13, p <0.001), the etiological cure of cirrhosis (HR 0.38, p <0.001) and model for end-stage liver disease score (HR 1.12, p = 0.003) were found to be independent predictors of mortality. CONCLUSIONS: The first decompensation is non-acute in almost 50% of outpatients, though such events are still associated with decreased survival compared to no decompensation. Patients who develop NAD must be treated with extreme care and monitored closely to prevent the development of AD. IMPACT AND IMPLICATIONS: This multicenter study is the first to investigate the role of non-acute decompensation (NAD) in patients with cirrhosis. In fact, while the unfavorable impact of acute decompensation is well known, there is currently a dearth of evidence on NAD, despite it being a common occurrence in clinical practice. Our data show that almost half of decompensations in patients with cirrhosis can be considered NAD and that such events are associated with a higher risk of mortality than no decompensation. This study has important clinical implications because it highlights the need to carefully consider patients who develop NAD, in order to prevent further decompensation and reduce mortality.

Could machine learning revolutionize how we treat immune thrombocytopenia?

The absence of reliable biomarkers in immune thrombocytopenia (ITP) complicates treatment choice, necessitating a trial-and-error approach. Machine learning (ML) holds promise for transforming ITP treatment by analysing complex data to identify predictive factors, as demonstrated by Xu et al.'s study which developed ML-based models to predict responses to corticosteroids, rituximab and thrombopoietin receptor agonists. However, these models require external validation before can be adopted in clinical practice. Commentary on: Xu et al. A novel scoring model for predicting efficacy and guiding individualised treatment in immune thrombocytopenia. Br J Haematol 2024; 205:1108-1120.

Pregnancy and childbirth in patients with Glanzmann Thrombasthenia.

Glanzmann thrombasthenia (GT) is a rare inherited platelet bleeding disorder caused by a quantitative and/or qualitative defect of the αIIbß3 integrin. Pregnancy and delivery pose special challenges as they entail increased risks of both maternal and foetal bleeding that may be life-threatening. Multidisciplinary management throughout the preconception, intrapartum and peripartum periods is vital to optimize pregnancy outcomes. This Nutshell review focuses on the challenging management of pregnancy and childbirth in patients with GT.

Thrombotic and bleeding complications in patients with AL amyloidosis.

Haemostatic abnormalities and deregulated coagulation are common complications in AL amyloidosis. The relevant risks of thromboembolic and haemorrhagic events have not been thoroughly evaluated. To describe clinically significant thrombotic/haemorrhagic events in 450 consecutive patients with AL amyloidosis. Venous thromboembolic events (VTEs) were reported in 6% and arterial embolic events (AEEs) in 5% of patients, respectively, during a 55-month median follow-up. Lower albumin, lower eGFR, higher BM infiltration, soft tissue involvement, IMiD-based therapy and prior thrombosis were associated with VTE risk. Prior thrombosis was the only independent prognostic variable (HR 9.3, p = 0.001). Coronary arterial disease, prior AEE, 24-h proteinuria and higher platelet counts were associated with AEE risk. Significant bleeding events were reported in 9%, and associated mortality was 19%. Liver involvement, higher serum creatinine and higher baseline VWF:Ag levels were linked to bleeding risk. Using competing risk analysis, the cumulative probability of thrombosis/bleeding was higher during the first year following diagnosis, but a stable lower risk for both events remained for the duration of follow-up. In AL amyloidosis patients, the risk of thrombotic/arterial embolic events is significant, but the bleeding risk is also high. A multiparametric assessment is required to initiate anti-thrombotic or anti-platelet therapy appropriately.

Quality of life in childhood immune thrombocytopenia: Revision of the Kids' ITP Tools (KIT).

The Kids ITP Tools (KIT) is a health-related quality of life (HRQoL) questionnaire that evaluates quality of life in children with immune thrombocytopenia (ITP). There are three formats: Child Self-Report, Parent Proxy-Report and Parent Impact-Report. This study aimed to develop a domain structure by grouping-related questions from the questionnaire into domains that independently reflect various aspects of HRQoL. The study was conducted in two phases. Phase 1 involved an online survey distributed to experts to identify conceptual domains for the KIT. Phase 2 utilized a statistical approach to analyse responses from patients with ITP and their families. A revised KIT 2.0 was ultimately developed to aid in treatment decision-making and monitoring of ITP.

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. Here, we review how the individual components of the FBC, that is, haemoglobin, platelets and leucocytes, engage with the haemostatic system and focus on both their quantitative and qualitative attributes. We also explore how this information can be harnessed into better management of people with multiple long-term conditions because of their higher risk of adverse clinical events.