Background/Objectives: The underlying molecular mechanisms of deep vein thrombosis (DVT), which continues to be a major global public health concern, remain unclear. A key component of anticoagulant therapy, heparin (HP) interacts with heparin-binding growth factors including pleiotrophin (PTN) and midkine (MK), both of which have basic amino acid-rich domains that have a strong affinity for HP. The purpose of this study was to determine if changes in the levels of circulating HP, MK, and PTN are linked to the onset of acute DVT. Methods: Thirty patients diagnosed with acute DVT by venous Doppler ultrasonography (VDU) and 28 healthy controls with normal VDU findings were enrolled. Serum HP, MK, and PTN concentrations were measured using ELISA. In DVT patients, blood samples were obtained before and after routine subcutaneous low-molecular-weight heparin treatment; controls provided a single blood sample. ROC curve analysis was used to assess diagnostic performance. Results: Prior to treatment, patients with acute DVT exhibited significantly lower serum HP levels (p < 0.05) and significantly higher MK and PTN levels compared with healthy controls (both p < 0.05). Following heparin administration, serum HP levels increased significantly (p < 0.05), while MK and PTN levels showed a decreasing trend that did not reach statistical significance (p > 0.05). ROC curve analysis demonstrated limited diagnostic performance for HP (sensitivity 10.3%, specificity 68.8%), PTN (62.1%, 54.2%), and MK (82.8%, 35.4%). Conclusions: Decreased circulating HP and increased MK and PTN levels are characteristics of acute DVT that may indicate endogenous HP sequestration through binding to these growth factors. This imbalance could lead to less free HP being available, which would encourage the formation of thrombus. Therapeutic approaches that target MK- and PTN-mediated HP interactions may constitute a unique approach for the therapy of acute DVT, as evidenced by the partial normalization seen after exogenous heparin delivery.

Background: The coronary slow flow phenomenon (CSFP) is delayed contrast progression through the epicardial coronary arteries in the absence of significant stenosis. The stress hyperglycemia ratio (SHR) normalizes admission glucose to the estimated average glucose derived from HbA1c, separating acute glycemic excursion from chronic hyperglycemia. Whether the SHR is independently associated with CSFP in patients with type 2 diabetes mellitus (T2DM) is not known. Methods: This retrospective case-control study enrolled 235 consecutive patients with T2DM who underwent coronary angiography between January 2022 and January 2025. Patients with epicardial stenosis exceeding 40% in any vessel, prior revascularization, or acute coronary syndrome within 30 days were excluded. Among the remaining patients, those with a corrected TIMI frame count (CTFC) above 27 in any epicardial vessel were classified as CSFP (n=112) and the rest as normal coronary flow (NCF) (n=123). The SHR was calculated as admission blood glucose (mmol/L) divided by (1.59 × HbA1c% − 2.59). Results: The SHR was higher in the CSFP group than in the NCF group (1.42 ± 0.31 vs. 1.08 ± 0.24, p<0.001). After multivariate adjustment, it remained independently associated with CSFP (odds ratio [OR] 2.84, 95% confidence interval [CI] 1.92–4.21, p<0.001). On receiver operating characteristic analysis the area under the curve (AUC) was 0.819 (95% CI 0.760–0.876); a cutoff of 1.21 gave 78.6% sensitivity and 74.0% specificity. The SHR correlated with mean CTFC (r=0.621, p<0.001) and outperformed admission glucose alone (AUC 0.724, p=0.003). Conclusion: In this cohort, the SHR was independently associated with CSFP and discriminated it better than admission glucose alone. Because it is calculated from two values routinely available at catheterization, admission glucose and HbA1c, the SHR is a practical candidate marker that warrants prospective validation for risk stratification in patients with T2DM undergoing coronary evaluation.

Early identification of anatomically significant coronary artery disease (CAD) remains a major clinical challenge despite advances in cardiovascular diagnostics. Novel circulating biomarkers may improve risk stratification and diagnostic discrimination beyond conventional parameters. We investigated the diagnostic utility of four emerging biomarkers—Phoenixin-14, Syntenin-1, Alamandine, and Cerebellin-1—for the assessment of CAD severity. In this prospective observational study, 90 participants undergoing coronary angiography were categorized into three groups: severe CAD (≥70% stenosis; n = 30), non-obstructive/non-critical CAD (<70% stenosis; n = 30), and angiographically normal controls (n = 30). Patients with acute coronary syndrome, diabetes mellitus, prior coronary revascularization, cardiomyopathy, or significant systemic disease were excluded. Circulating biomarker concentrations were quantified using the enzyme-linked immunosorbent assay. Comparative analyses, correlation testing, and receiver operating characteristic (ROC) analyses were performed to evaluate discriminatory performance. Circulating Phoenixin-14 concentrations progressively declined across the control, non-critical CAD, and severe CAD groups [40.1 (29.0–49.7) vs. 24.4 (18.5–30.1) vs. 16.7 (13.4–19.0) pg/mL, respectively; p < 0.001]. Phoenixin-14 demonstrated outstanding discrimination for severe CAD, achieving an area under the ROC curve (AUC) of 0.969 (95% CI, 0.888–0.997), with 86.7% sensitivity and 96.7% specificity at a threshold of ≤20.2 pg/mL. Diagnostic performance was substantially lower for Syntenin-1 (AUC, 0.795), Alamandine (AUC, 0.661), and Cerebellin-1 (AUC, 0.597). Phoenixin-14 also showed robust discrimination for non-critical CAD (AUC, 0.832). Biomarker concentrations exhibited correlations with metabolic indices while remaining largely independent of traditional cardiovascular risk factors. Among the evaluated novel circulating biomarkers, Phoenixin-14 demonstrated superior diagnostic performance for both obstructive and non-obstructive CAD, markedly outperforming Syntenin-1, Alamandine, and Cerebellin-1. These findings identify Phoenixin-14 as a promising candidate biomarker for CAD severity assessment and clinical risk stratification. Larger multicenter studies are warranted to validate these exploratory findings and determine their incremental value in contemporary cardiovascular practice.

Background: Acute superficial venous thrombosis (SVT) presenting with clinical features of thrombophlebitis is increasingly recognized as a thromboinflammatory disorder in which innate immunity and coagulation are closely interconnected. Nonetheless, the role of endogenous antimicrobial peptides and heparin-binding growth factors in its pathogenesis is still inadequately comprehended. We investigated circulating dermcidin (DCD), ghrelin (GHR), heparin (HP), midkine (MK), and pleiotrophin (PTN) to explore their potential involvement in the thromboinflammatory network underlying SVT. Methods: In this prospective case–control study, 30 individuals with SVT and 28 healthy controls matched for age and sex were recruited. DCD, GHR, HP, MK, and PTN concentrations were quantified using enzyme-linked immunosorbent assays. Results: Patients with SVT exhibited significantly higher circulating DCD, GHR, MK, and PTN concentrations and significantly lower the measured HP concentration than healthy controls (all p < 0.05). Following LMWH treatment, the measured HP concentration increased significantly (p < 0.05), whereas DCD, GHR, MK, and PTN showed downward trends. Conclusions: Acute superficial venous thrombosis is associated with coordinated alterations in circulating the measured heparin, dermcidin, ghrelin, midkine, and pleiotrophin, reflecting a systemic thromboinflammatory biomarker profile. These findings suggest potential interactions among heparin biology, heparin-binding growth factors, and innate immune mediators but do not establish direct molecular interactions, heparin sequestration, functional depletion, or causality. This biomarker profile establishes a foundation for creating hypotheses for forthcoming investigations that include direct biochemical validation, standardized longitudinal sampling, and independent cohorts.