Search Results (389)

Background: Early detection of joint damage in haemophilia is essential to prevent haemophilic arthropathy. This study longitudinally evaluated joint health in paediatric patients with haemophilia in Greece using the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) scoring system. Methods: Children aged 5–18 years with haemophilia of any severity, all receiving prophylaxis, were assessed at baseline and during longitudinal follow-up visits scheduled at 6, 12, 24, and 36 months. Evaluations included HEAD-US and Haemophilia Joint Health Score (HJHS), functional ability (PedHAL), health-related quality of life (HRQoL), and pain (BPI). Results: Forty-seven boys (mean age 11.5 ± 3.7 years) were included (severe 83%, moderate 11%, mild 6%). Baseline HEAD-US scores were low (mean ± SE: 0.22 ± 0.069). No significant overall change was observed over time, although left knee showed significant improvement (p < 0.05). Ankles consistently exhibited higher scores compared to other joints (p < 0.05). Synovitis was the most frequent abnormality, while cartilage damage was infrequent and subchondral bone changes were negligible. HEAD-US detected more abnormalities than HJHS. Conclusions: Joint health was well preserved under prophylaxis, with synovitis representing the earliest detectable change, although interpretation is limited by incomplete long-term follow-up. HEAD-US proved more sensitive than clinical assessment, supporting its role in routine longitudinal monitoring. Full article

Background: Early recognition of sepsis-related coagulation derangements may support timely risk stratification in emergency department (ED) patients with suspected infection. Evidence comparing coagulation-oriented scores in unselected “suspected sepsis” populations remains limited, particularly for predicting progression to sepsis, overt thrombotic/hemorrhagic events, and mortality. Methods: We conducted a single-center retrospective cohort study including consecutive ED patients evaluated for sepsis, suspected sepsis, or infection (January 2016–December 2024). Patients with overt disseminated intravascular coagulation (DIC) at admission were excluded. The Sepsis-Induced Coagulopathy (SIC), Japanese Association for Acute Medicine DIC (JAAM-DIC), International Society on Thrombosis and Haemostasis (ISTH) score, and Endothelial Activation and Stress Index (EASIX; and log2-EASIX) were calculated at admission. Outcomes were progression to confirmed sepsis (Sepsis-3), symptomatic coagulopathy (thrombotic and/or hemorrhagic events), and in-hospital mortality. Discrimination was assessed by ROC analysis (AUC with 95% CI) and clinical utility by decision curve analysis (DCA). Results: Among 11.274 patients without overt DIC, all scores showed moderate discrimination for mortality and sepsis progression. SIC performed best for in-hospital mortality (AUC 0.701, 95% CI 0.692–0.710) and for progression to confirmed sepsis (AUC 0.672, 95% CI 0.663–0.681). Prediction of overt thrombotic/hemorrhagic complications was poor across scores; ISTH yielded the highest (yet modest) AUCs for thrombotic events (0.614, 95% CI 0.604–0.623), hemorrhagic events (0.545, 95% CI 0.535–0.554), and combined coagulopathy (0.605, 95% CI 0.596–0.614). DCA suggested net benefit at low-to-intermediate threshold probabilities, particularly for SIC (and JAAM2) in early decision ranges. In the confirmed sepsis subgroup, discrimination attenuated overall; for combined coagulopathy, SIC showed the highest AUC (0.558, 95% CI 0.518–0.597). Conclusions: In ED patients with suspected sepsis and no overt DIC at presentation, SIC provides the strongest performance for early prognostic stratification (mortality and sepsis progression), whereas none of the evaluated scores reliably predict clinically overt thrombotic or hemorrhagic complications. Full article

Background: Femoral arteriotomy closure after peripheral angiography and intervention is commonly achieved using vascular closure devices (VCDs) or compression-based strategies; however, comparative randomised data in contemporary peripheral endovascular practice remain limited. Methods: In this prospective randomised trial, adults undergoing femoral-access diagnostic angiography or peripheral endovascular intervention were assigned in a 1:1 ratio to haemostasis with the FemoStop™ II Gold pneumatic compression system or a contemporary VCD strategy. The primary endpoint was a composite of major or minor groin-site complications immediately after sheath removal. Secondary endpoints included composite complications at recovery, discharge, and 30 days, with separate analyses of major and minor complications. Patient-reported pain was assessed using the Verbal Numerical Rating Scale (VNRS). Efficacy and safety analyses were performed according to the intention-to-treat and as-treated principles, respectively. Risk ratios were estimated using modified Poisson regression with robust variance, with prespecified adjustment for sex, systolic blood pressure before sheath removal, and sheath size. Results: A total of 130 participants underwent randomisation, including 66 assigned to FemoStop™ II Gold and 64 assigned to VCDs. The primary composite endpoint occurred in 23/66 participants (34.9%) in the FemoStop™ II Gold group and 16/64 (25.0%) in the VCD group (absolute difference, 9.9 percentage points; 95% confidence interval [CI], −6.1 to 25.7; p = 0.25), with the numerical difference driven predominantly by minor-only events (28.8% versus 15.6%; p = 0.09). At 30 days, the composite endpoint occurred in 17/66 participants (25.8%) and 12/64 participants (18.8%), respectively (absolute difference, 7.0 percentage points; 95% CI, −13.3 to 26.4; p = 0.40). Serious access-site events remained infrequent both immediately post-procedure (6.1% versus 9.4%; p = 0.53) and at 30 days (6.1% versus 4.7%; p = 0.72). The adjusted risk ratios were 1.28 (95% CI, 0.74 to 2.21) for the primary composite endpoint and 1.23 (95% CI, 0.63 to 2.40) for the 30-day composite endpoint. Ordinal VNRS pain distributions did not differ significantly at any timepoint, although “any pain” immediately post-procedure was less frequent with FemoStop™ II Gold (22.7% versus 40.6%; unadjusted risk ratio, 0.56; 95% CI, 0.33 to 0.93); this association was attenuated after adjustment (adjusted risk ratio, 0.63; 95% CI, 0.38 to 1.03). Prespecified interaction testing suggested that the effect of treatment on composite complications varied according to sheath size both immediately post-procedure and at 30 days (p < 0.001 for both interactions). Conclusions: In patients undergoing femoral-access diagnostic angiography or peripheral endovascular intervention, haemostasis with FemoStop™ II Gold resulted in 30-day groin-site complication rates that did not differ significantly from those observed with contemporary VCD strategies. Serious access-site events remained infrequent in both groups, and the apparent early reduction in patient-reported pain with FemoStop™ II Gold was not definitive after adjustment. Larger, adequately powered multicentre studies are warranted to clarify sheath size-dependent effects and uncommon clinically consequential vascular events. Full article

Introduction: Extended half-life (EHL) factor VIII (FVIII) products aim to reduce treatment burden and improve bleeding control in hemophilia A. Real-world evidence remains essential to complement clinical trials. Aim: To evaluate clinical outcomes following switching from standard half-life (SHL) rFVIII to efmoroctocog alfa in routine clinical practice in Greece. Methods: Multicenter observational pre–poststudy including patients with moderate to severe hemophilia A. Outcomes were assessed during the 12 months before and after switching. The primary endpoint was change in annualized bleeding rate (ABR). Secondary endpoints included annualized joint bleeding rate (AjBR), infusion frequency, joint health, pain, and FVIII consumption. Results: Sixty patients were included. Following switching, ABR decreased from 6.8 to 3.2 (53%), and AjBR from 6.4 to 2.9 (55%), p < 0.001. Reductions were more pronounced in patients switching from on-demand treatment, while more modest improvements were observed among patients already on prophylaxis. HJHS significantly decreased from 17.9 to 11.5 (p < 0.007), accompanied by a decrease in pain scores (p < 0.001), in available paired subsets. Weekly infusion frequency decreased (3.2 to 2.2; p < 0.001), while mean dose per infusion increased, resulting in no consistent reduction in total annual FVIII consumption. No inhibitor or treatment-related adverse events have been observed. Conclusions: Switching to efmoroctocog alfa in routine practice was associated with improved bleeding outcomes, reduced infusion frequency, and better joint-related parameters. These findings support the real world feasibility and clinical utility οf EHL FVIII therapy, while further controlled studies are needed to better define the independent effect of product switching from changes in treatment regimen and other potential confounders. Full article

Background/Objectives: Blood platelets exhibit substantial functional heterogeneity, yet no established principles exist for distinguishing their subpopulations. The present study proposes a methodology for the evaluation of platelet reactivity and inhibitor sensitivity, with the aim of facilitating the expeditious identification of platelet phenotypes under standard laboratory conditions. Methods: The phenotyping of healthy subjects was based on the study of platelet aggregation in response to agonists and inhibitors of P2Y₁₂, PAR-1 and GPVI receptors. The classification of variants was conducted on the basis of the similarities and differences in EC₅₀/IC₅₀ values obtained for individual ligands. Subsequently, the values were subjected to two- and six-variable cluster analyses. Results: Two major clusters (variants) were identified with consistent reliability across the range of analytical strategies employed. Cluster 1 comprised individuals with low EC₅₀ values and moderate to high IC₅₀ values, indicating high agonist responsiveness and relatively low inhibitor sensitivity. Conversely, cluster 2 exhibited the inverse pattern, characterised by moderate to high EC₅₀ values and moderate to low IC₅₀ values. Cluster 1 constituted a significant proportion of individuals (29–78%, depending on the analysis). The study did not identify a “low responder group”. Conclusions: The proposed methodology is distinguished by two features: its flexibility and its accessibility. These characteristics enable the identification of any platelet phenotype associated with selected signalling pathway(s). The application of this approach has the potential to facilitate the identification of individuals at elevated cardiovascular risk, thereby informing personalised antiplatelet therapy in the context of primary prevention. Full article

Background/Objectives: Surgical refinements in robot-assisted partial nephrectomy (RAPN) aim to reduce morbidity and optimize renal function preservation, particularly in patients with high-complexity renal tumours. This study describes the no-touch adaptive technique for RAPN and compares its perioperative outcomes, postoperative complications, and resulting early renal function with those of the conventional approach. Methods: A cohort of 72 consecutive patients with high-complexity renal tumours undergoing RAPN was evaluated. The study group included 38 patients treated with the no-touch adaptive technique, while 34 patients underwent the conventional approach. The no-touch adaptive technique consisted of sutureless, off-clamp, simple tumour enucleation with incremental haemostasis and the option to shift to arterial clamping, tumour enucleoresection, or renorrhaphy as needed. The conventional technique involved on-clamp minimal enucleoresection with double-layer renorrhaphy. Outcomes assessed included completion of a fully no-touch procedure, perioperative metrics, 90-day postoperative complications, and 3-month renal function change from baseline. Results: Baseline characteristics were comparable between groups. A fully no-touch RAPN was achieved in 30/38 (79%) patients. Adaptations were required in eight cases: shift to main arterial clamping (n = 2), renorrhaphy (n = 5), or both (n = 1), with one conversion to total nephrectomy due to intractable bleeding. Estimated blood loss was similar between groups (study: 150 mL [IQR 75–250] vs. control: 180 mL [IQR 100–400]). Length of stay was significantly shorter in the study group (3 days [IQR 3–4]) compared with controls (5 days [IQR 6–8]). Any-grade 90-day complications were significantly lower with the no-touch technique (21% vs. 56%, p < 0.01). Clinically significant 3-month eGFR decline occurred in 14% of controls versus 0% of study patients (p = 0.02). Conclusions: The no-touch adaptive RAPN technique is feasible in high-complexity renal tumours and provides reduced morbidity and superior early renal function preservation compared with the conventional approach. Full article

Dengue infection remains a major global health concern, with a subset of patients progressing from self-limited dengue fever to severe disease characterised by plasma leakage, shock, and organ dysfunction. The dengue non-structural protein 1 (NS1), a multifunctional glycoprotein expressed on infected cells and secreted into circulation, has emerged as a key mediator linking viral infection to immune-driven vascular pathology. This review synthesises experimental, animal, and human clinical evidence on NS1-driven immunopathogenesis, focusing on mechanisms leading to endothelial dysfunction and increased vascular permeability. NS1 modulates the complement system in a context-dependent manner, contributing to immune evasion by inhibiting terminal complement complex formation, while also promoting antibody-dependent complement activation associated with severe disease. Additionally, NS1 directly disrupts endothelial barrier integrity through disruption of adherens and tight junction architecture, Ang-2/Tie2 imbalance, activation of RhoA/ROCK (RhoA/Rho-associated coiled-coil-containing protein kinase) signalling, and enzymatic degradation of the endothelial glycocalyx, with further amplification through inflammatory mediators. In addition, evidence shows that NS1 activates innate immune signalling, perturbs platelet biology and haemostasis, and forms pro-inflammatory complexes with lipoproteins. Moreover, anti-NS1 antibodies may be both protective and pathogenic. Collectively, these data position NS1-linked pathways as rational targets for adjunctive therapies and next-generation vaccines aimed at preventing vascular leakage and severe dengue infection. Full article

Background/Objectives: Placental abruption remains one of the leading causes of maternal morbidity, and the development of disseminated intravascular coagulation (DIC) significantly worsens outcomes. We sought to develop and internally validate a prediction model—the Placental Abruption DIC (PAD) Score—using parameters routinely collected at presentation. Methods: We conducted a retrospective cohort study at a tertiary referral center in Istanbul, Turkey (January 2019–December 2024). Women with singleton pregnancies ≥22 weeks diagnosed with placental abruption were eligible. The primary outcome was overt disseminated intravascular coagulation (DIC) within 24 h of admission, adjudicated using the original International Society on Thrombosis and Haemostasis (ISTH) overt DIC scoring algorithm; a total score of ≥5 was considered compatible with overt DIC. We built a multivariable logistic regression model with bootstrap internal validation (1000 resamples). Robustness was evaluated through prespecified sensitivity analyses including complete-case analysis, single imputation, Firth-penalized logistic regression, exclusion of patients transferred from external facilities, a four-variable model excluding preeclampsia, and alternative score threshold grouping. Comparative discrimination against the admission ISTH overt DIC score, the Erez pregnancy-modified DIC score, and the Kobayashi obstetrical DIC score were evaluated using the area under the receiver operating characteristic curve and DeLong testing. Results: Of 237 women, 54 (22.8%) developed DIC. The final model retained five predictors: fibrinogen concentration, shock index, platelet count, placental separation percentage, and chronic hypertension/preeclampsia. The optimism-corrected area under the receiver operating characteristic curve (AUC) was 0.916, with calibration slope 0.96 and Brier score 0.12. DIC incidence was 2.9% in low-risk (0–4 points), 7.6% in moderate-risk (5–8 points), and 86.0% in high-risk (≥9 points) patients. Discrimination remained stable across complete-case (AUC 0.909), single-imputation (0.913), Firth-penalized (0.914), transfer-excluded (0.902), four-variable (0.892), reduced three-predictor (0.842, excluding fibrinogen and platelet count), pathology-confirmed subgroups (0.887) and composite clinical outcome (0.801) analyses, and exceeded that of the ISTH (0.812), Erez (0.848) and Kobayashi (0.793) comparator scores. Conclusions: The PAD Score offers a straightforward method for stratifying DIC risk in placental abruption. External validation in independent cohorts is needed before clinical implementation. Full article

The Cape cobra (Naja nivea), one of Africa’s most lethal snakes, can cause rapid, life-threatening paralysis. However, the impact of this venom on platelet function and blood coagulation remains poorly understood. To address this gap, we investigated the enzymatic profiles and the impacts of N. nivea venom on multiple aspects of haemostasis using human whole blood. Our results illustrate that Cape cobra venom significantly increases clotting time in rotational thromboelastometry without affecting other coagulation parameters. This venom significantly inhibits platelet aggregation and activation yet does not exert cytotoxic effects on platelets. The venom was subsequently fractionated using reverse-phase high-performance liquid chromatography, and the most potent purified fraction was identified as a cytotoxin (three-finger toxin) through mass spectrometry. This purified fraction showed an inhibitory effect on platelet activity. These findings highlight that N. nivea venom can induce haemotoxicity in addition to neurotoxicity. Moreover, three-finger toxins may be promising candidates for bioprospecting to develop novel antithrombotic agents. Full article

Chronic myeloid leukaemia (CML) is driven by the t(9;22) forming the BCR::ABL1 fusion gene, leading to the development of hyper-myeloid proliferation. This led to development of tyrosine kinase inhibitors (TKIs) such as Imatinib, Nilotinib, and Ponatinib. However, resistance or intolerance to ATP-competitive TKIs remains a challenge for some patients. asciminib (ABL001), a novel TKI, targets the myristoyl pocket of ABL1 instead of the ATP-binding site, reducing resistance to mutations. As asciminib is linked to thrombocytopenia, its effects on platelet activation, endothelial function, and inflammation must be studied to assess its potential to promote thrombosis. The main objective of this study is to determine the potential of asciminib as a monotherapy in inducing pathological responses to platelets and endothelium over time within the vasculature. This study assessed the effects of TKIs including asciminib on platelets and thrombotic biomarkers. Washed platelets were used to measure granule secretion, thrombus formation, surface expression of glycoproteins, apoptosis, and viability. Plasma from chronically Asciminib-treated CML patients was analysed using sandwich ELISA for inflammatory and platelet–endothelial biomarkers, and thrombin generation assays were performed to study coagulation. This approach combined in vitro and ex vivo methods to explore the impact of asciminib on platelet function and thrombotic potential. The study shows that acute treatment with asciminib does not promote platelet activation or thrombus formation. Instead, it exhibits an inhibitory effect on thrombus formation in vitro and is associated with reduced thrombo-inflammatory biomarkers ex vivo in chronically treated CML patients. Asciminib was associated with increased thrombin generation over time, suggesting an effect on secondary haemostasis. Asciminib does not appear to induce a prothrombotic or proinflammatory state under the conditions studied, which may be advantageous for CML patients. However, the observed increase in thrombin generation over time suggests a potential effect on secondary haemostasis that warrants further investigation in controlled studies. Full article

Background and Objectives: Venous thromboembolic disease (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a major cause of morbidity and mortality worldwide and imposes a substantial financial burden on health systems due to both the direct and indirect costs of acute management and long-term complications. This systematic review aimed to assess patient satisfaction with anticoagulation therapy for VTE and to highlight potential differences according to the type of anticoagulant. The review focused on factors influencing the patient experience, such as perceived efficacy, ease of use, adverse effects, and health-related quality of life. Materials and Methods: A systematic review, without quantitative meta-analysis, was conducted in accordance with PRISMA 2020 guidelines. Articles were identified through searches in major databases (PubMed, Scopus, Cochrane Library and others) using keywords including “patient satisfaction”, “anticoagulation”, “venous thromboembolic disease”, and “quality of life”. In total, 21 studies published between 2009 and 2025 met the inclusion criteria. The studies assessed patient satisfaction with different types of anticoagulation, including vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs), and low-molecular-weight heparin (LMWH) injections. Results: Across the included studies, patients generally reported higher levels of treatment satisfaction with DOACs compared with VKAs, mainly due to the absence of routine laboratory monitoring and fewer dietary restrictions. However, satisfaction varied according to age, sex, and clinical status. In specific patient populations, such as those with cancer-associated thrombosis, factors including fewer drug–drug interactions and perceptions of safety with LMWH appeared to influence treatment choice and satisfaction. Adverse effects, particularly bleeding, were identified as major drivers of dissatisfaction. Several studies suggested that higher treatment satisfaction was associated with better adherence, while quality of life appeared to improve in patients treated with DOACs in comparison with VKAs. Conclusions: Patient satisfaction is a critical component of successful VTE management. Overall, DOACs appear to be associated with higher treatment satisfaction than traditional therapies such as VKAs, although further high-quality research is needed to individualise anticoagulation strategies. Systematic incorporation of patient-reported satisfaction into clinical decision-making and into international guidelines may improve adherence, enhance quality of life, and ultimately increase the effectiveness of anticoagulation therapy. Full article

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent low-grade inflammation and a markedly increased risk of cardiovascular diseases (CVD). Leukocytes play an important role not only in host defense but are also increasingly recognized as key contributors to haemostasis and thromboinflammatory processes. In DM, chronic hyperglycaemia, oxidative stress and inflammation lead to leukocyte dysfunction, including enhanced cell activation, impaired mitochondrial function, and dysregulated interactions with platelets and endothelial cells. These alterations promote the thromboinflammatory state that contributes to vascular complications in DM. Thus, the modulation of oxidative stress and inflammation are important. Polyphenols are a class of plant secondary metabolites widely studied for their antioxidant and anti-inflammatory properties. This review comprehensively explores leukocyte dysfunction in DM, its contribution to thromboinflammation, and the mechanistic role of polyphenols in modulating these processes. The evidence presented suggests that polyphenols may contribute to the modulation of thromboinflammatory pathways. Further research in this area is required to enhance our understanding of thromboinflammation in DM and to translate these findings into effective adjunctive strategies, alongside standard pharmacological therapies to reduce CVD risk in individuals with DM. Full article

Objectives: The impact of renal ischemia during partial nephrectomy (PN) on postoperative renal function remains controversial. On-clamp PN provides improved surgical exposure and haemostasis but induces warm ischemia, which may impair renal function. Off-clamp PN avoids ischemia-related injury and may better preserve renal function, although concerns persist regarding blood loss and oncological safety. We systematically compared perioperative and functional outcomes, as well as surgical margin status between on-clamp and off-clamp PN. Methods: We performed a systematic search of PubMed, Embase, Cochrane, Web of Science, and Scopus to identify randomized controlled trials (RCTs) and observational studies comparing on-clamp versus off-clamp PN with no publication time limitations. Outcomes included estimated glomerular filtration rate (eGFR), percentage eGFR change, estimated blood loss (EBL), transfusion rates, positive surgical margins (PSMs), operative time, and complications. Results: Thirty-nine studies (four RCTs) including 10,154 patients were analysed. Off-clamp PN was associated with a smaller decline in eGFR (mean difference [MD] −4 mL/min/1.73 m², 95% CI −5.7 to −2.8) and lower percentage eGFR loss (MD −1.7%, 95% CI −2.8 to −0.7). On-clamp PN was associated with lower EBL (MD −48 mL, 95% CI −72 to −25). Transfusion rates favored on-clamp PN but were not statistically significant (OR 0.7, 95% CI 0.5–1.0). On-clamp PN was associated with a higher risk of PSM (OR 1.3, 95% CI 1.0–1.7) and postoperative complications (OR 1.3, 95% CI 1.1–1.6). Between-study heterogeneity and predominance of observational data were key limitations. Conclusions: Off-clamp PN provides superior renal functional preservation and lower risks of PSMs and complications, at the cost of increased blood loss. These findings support individualized surgical decision-making based on patient and tumor characteristics. What does the study add?: This study provides an extensive and detailed comparison of off-clamp versus on-clamp partial nephrectomy, encompassing more than 10,000 patients from 39 studies. By integrating the available evidence up to late 2024, it delivers comprehensive estimates of the renal functional benefits associated with ischemia-free surgery. Our findings delineate the trade-offs between renal preservation, blood loss, and surgical margin status, thereby informing individualised decision-making in nephron-sparing surgery and refining current understanding of when ischemia avoidance is most clinically advantageous. Patient summary: Our study suggests that performing partial nephrectomy without temporarily clamping the kidney blood vessels may better preserve kidney function and reduce cancer-related surgical risks, but can lead to increased blood loss during surgery. These findings indicate that the choice of surgical technique should be individualised, taking into account tumour features and patient-specific factors. Full article

The endothelial protein C receptor (EPCR) is an important component of the protein C (PC) system, recognised for its diverse roles in blood coagulation, inflammation, and stem cell regulation. Wound healing is a complex physiological process that can be divided into four distinct but overlapping phases: haemostasis, inflammation, proliferation and remodelling. Recently, EPCR has emerged as a key regulator in wound repair and regeneration. During haemostasis, EPCR enhances the conversion of PC to its activated form (APC) to optimise local and systemic anticoagulation. In the inflammatory phase, EPCR modulates immune cell activity, inhibits inflammatory factors, and maintains tissue barrier integrity. As the process transitions to the proliferative phase, EPCR promotes endothelial and epithelial cell proliferation, migration, neovascularisation and re-epithelization, and mediates the expression of matrix metalloproteinases to facilitate tissue reconstruction. Finally, during the remodelling phase, EPCR exerts a potential antifibrotic effect by regulating fibroblast activation and collagen deposition via the Transforming growth factor (TGF)-β1/Smad3 pathway, ensuring functional repair. While therapeutic potential has been shown in animal models, translating EPCR-mediated therapies to clinical application faces many challenges, including wound heterogeneity, dosage control, targeted delivery, and potential bleeding risks. Studies have shown that local drug delivery strategies, non-anticoagulant APC variants, and individualised treatment based on EPCR expression will be the key directions for future development. Additionally, EPCR may serve as a potential biomarker for assessing wound severity and guiding personalised interventions. Full article

Platelets are small circulating blood cells that mediate haemostasis and thrombosis. Platelets respond to vascular damage by adhesion, granule release, and aggregation. Healthy endothelial cells inhibit platelets through prostacyclin-induced cAMP signalling. Intracellular cAMP activates protein kinase A (PKA), a tetrameric kinase composed of two regulatory (R) and two catalytic (C) subunits. cAMP-binding triggers dissociation of C subunits from the PKA complex and phosphorylation of substrate proteins, which mediate platelet inhibition. The R subunits of PKA are known to be attached to A-kinase anchoring proteins (AKAPs), which enable subcellular compartmentalisation of cAMP signalling. Proteomics have identified 22 AKAPs in platelets, but only a few of these have been studied in detail. This review summarises current knowledge about platelet AKAPs, including studies done regarding other cells. Possible integration of AKAPs into platelet signalling is explored with a focus on subcellular localisation, interaction partners, and PKA-mediated substrate phosphorylation. As main platelet compartments, the plasma membrane, endosomes, mitochondria, the Golgi, the dense tubular system, and the cytoskeleton are considered. Potential roles of individual AKAPs in platelet inhibition are discussed, and open questions in the field are defined. Full article