Search Results (69)

Platelets have long been known to be critically involved in hemostasis and thrombosis. However, platelets are also recognized as metabolically active cells that require well-regulated mitochondrial function to support their multiple functions in hemostasis, thrombosis, and inflammation. Mitochondrial activity has also recently been shown to play a crucial role in determining platelet activation, survival, and pro-inflammatory potential. A key nexus in these processes is the mitochondrial permeability transition pore (mPTP), a high-conductance channel in the inner mitochondrial membrane. Sustained mPTP opening triggers mitochondrial depolarization, the cessation of ATP synthesis, osmotic swelling, and, finally, platelet dysfunction or clearance. However, its transient opening might play physiological signaling roles. This review summarizes the current understanding of the molecular components and regulatory factors governing the platelet mPTP, explores its physiological and pathological relevance, and evaluates its potential as a therapeutic target in cardiovascular disease, inflammation, cancer, and potentially neurodegenerative diseases. We also highlight the ongoing challenges and crucial future directions in deciphering the complexities of platelet mitochondrial dynamics and mPTP functions. Full article

Background/Objectives: Avatrombopag (AVA), a thrombopoietin receptor agonist used to treat thrombocytopenia in patients with chronic liver disease, exhibits significant pharmacokinetic (PK) variability, particularly under fasting conditions. This study investigates the combined influence of food intake and genetic polymorphisms in CYP2C9 and ABCB1 on the PK and pharmacodynamics (PD) of AVA, with the goal of informing individualized dosing strategies. Methods: A pharmacogenetic analysis was conducted in 92 healthy participants, who received 20 mg of AVA under both fasting and fed conditions. A population PK/PD model was developed to evaluate the covariates effects on the PK variability. Monte Carlo simulations were used to predict AVA exposure and platelet count profiles under diverse dosing scenarios. Results: Food intake significantly reduced PK variability, with approximately 50% reductions in clearance (CL/F) and volume of distribution (Vd/F) compared to fasting conditions. Under fed conditions, CYP2C9 intermediate metabolizers showed a 1.70-fold increase in exposure compared to normal metabolizers, but this difference was not observed under fasting conditions. ABCB1 polymorphisms showed minimal impact, with the exception of ABCB1 (C1236T) heterozygotes, which exhibited 1.37-fold increased exposure. Despite the observed PK variability, simulations demonstrated a consistent platelet count response across dosing regimens. Conclusions: While food intake and genetic polymorphisms in CYP2C9 and ABCB1 influenced AVA PK, these factors may not require dose adjustments, as platelet count responses remained consistent across genotypes and dosing conditions in the Chinese participants. These findings support simplified dosing strategies without the need for pharmacogenetic testing in Chinese individuals and may contribute to more individualized thrombocytopenia management. Full article

Background: Chronic kidney disease (CKD) and its advanced stage, end-stage renal disease (ESRD), affect millions worldwide and are associated with a paradoxical hemostatic imbalance—marked by both increased thrombotic and bleeding risks—which complicates anticoagulant use and demands clearer, evidence-based clinical guidance. Design: This study is a critical review synthesizing the current literature on anticoagulant therapy in CKD and ESRD, with emphasis on altered pharmacokinetics, clinical complications, and therapeutic adjustments. Data Sources: PubMed, Scopus, and Google Scholar were searched for articles discussing anticoagulation in CKD/ESRD, focusing on pharmacokinetics, clinical outcomes, and dosing recommendations. Study Selection: Studies examining the safety, efficacy, and pharmacokinetics of anticoagulants—including heparin, low-molecular-weight heparin (LMWH), warfarin, and direct oral anticoagulants (DOACs)—in CKD and ESRD populations were included. Data Extraction and Synthesis: Key findings were summarized to highlight the dose modifications, therapeutic considerations, and clinical challenges in managing anticoagulation in CKD/patients with ESRD. Emphasis was placed on balancing thrombotic and bleeding risks and identifying gaps in existing guidelines. Results: Patients with CKD and ESRD exhibit a paradoxical hypercoagulable state marked by platelet dysfunction, altered coagulation factors, and vascular endothelial damage. This condition increases the risk of thrombotic events, such as deep vein thrombosis (DVT) and pulmonary embolism (PE), while simultaneously elevating bleeding risks. Hemodialysis and CKD-associated variables further complicate the management of coagulation. Among anticoagulants, unfractionated heparin (UFH) is preferred due to its short half-life and adjustability based on activated partial thromboplastin time (aPTT). Low-molecular-weight heparins (LMWHs) offer predictable pharmacokinetics but require dose adjustments in CKD stages 4 and 5 due to reduced clearance. Warfarin necessitates careful dosing based on the estimated glomerular filtration rate (eGFR) to maintain an international normalized ratio (INR) ≤ 4, minimizing bleeding risks. Direct oral anticoagulants (DOACs), particularly Apixaban, are recommended for patients with eGFR < 15 mL/min or those on dialysis, although data on other DOACs in CKD remain limited. The lack of comprehensive guidelines for anticoagulant use in CKD and ESRD highlights the need for individualized, patient-centered approaches that account for comorbidities, genetics, and clinical context. Conclusions: Managing anticoagulation in CKD/ESRD is challenging due to complex coagulation profiles and altered pharmacokinetics. Judicious dosing, close monitoring, and patient-centered care are critical. High-quality randomized controlled trials are needed to establish clear guidelines and optimize therapy for this vulnerable population. Full article

Background: Transient tachypnea of the newborn (TTN) is traditionally viewed as a disorder of delayed lung fluid clearance, but emerging evidence suggests inflammatory involvement. Aim: This study investigated systemic inflammatory indices [(systemic immune-inflammation index (SII-i), systemic inflammation response index (SIR-i), neutrophil-to-lymphocyte ratio (NL-r), and platelet-to-lymphocyte ratio (PL-r)] and underlying mechanisms in TTN pathogenesis for the first time. Methods: This retrospective case–control study included 199 neonates (123 with TTN and 76 healthy controls) admitted between 2022 and 2025 to a tertiary care hospital. Complete blood count parameters were collected within the first two hours of life. Inflammatory indices were calculated and compared between groups. Subgroup analyses were conducted based on gestational age (late preterm vs. term) and mode of delivery (cesarean vs. vaginal). Results: Although not statistically significant, TTN infants showed a trend toward higher inflammatory indices with median NL-r (2.54 vs. 1.75, p = 0.197) and SII-i (729,307.83 vs. 373,593.50, p = 0.276). Term TTN infants had higher NL-r (3.08 vs. 2.04, p = 0.022) and SII-i (729,147.74 vs. 538,928.30, p = 0.133) than late preterm infants. SIR-i and NL-r values were higher in the full-term group than in the early-term and late-preterm groups (p = 0.014, p = 0.022, respectively). Cesarean births showed higher NL-r (3.20 vs. 2.33, p = 0.049) and SII-i (p = 0.040) than vaginal deliveries. Strong correlations existed between SII-I, NL-r (r = 0.886, p < 0.01), and SII-i, SIR-i (r = 0.817, p < 0.01). Conclusions: Elevated inflammatory indices in neonates with TTN, particularly in term infants and those delivered vaginally, suggest a supportive/potential role for systemic inflammation in TTN pathophysiology. These markers may serve as potential supplementary markers for risk stratification, though further prospective validation is required to confirm their clinical relevance. These findings suggest that the early assessment of systemic inflammatory indices may assist clinicians in identifying neonates at risk for TTN, thereby guiding initial respiratory support strategies. Full article

Current αIIbβ3 antagonists are potent antithrombotic agents, their clinical use is limited by the risk of life-threatening bleeding. Emerging evidence has highlighted key mechanistic differences between thrombosis and hemostasis, opening avenues for safer antithrombotic strategies. Targeting integrin αIIbβ3 outside-in signaling has been proposed to mitigate bleeding risk; however, the short half-life of peptide-based therapeutics remains a major challenge. In this study, we developed an optimized αIIbβ3 antagonist, KGDRR—a recombinant mutant protein derived from snake venom disintegrin, incorporating an Arg55 residue within the KGD loop—through systematic structure–activity relationship (SAR) analysis. Molecular docking revealed a critical cation–π interaction between Arg55 of KGDRR and Tyr122 of the β3 subunit, stabilizing integrin αIIbβ3 in an unliganded-closed conformation. Functionally, KGDRR selectively inhibited thrombus propagation by blocking ligand binding and downstream Gα13-mediated outside-in signaling while preserving initial thrombus core formation, which is a limitation of current αIIbβ3 inhibitors. Unlike conventional antagonists, KGDRR maintained αIIbβ3 in an unliganded-closed conformation without inducing the integrin activation and conformational change that lead to immune-mediated platelet clearance and thrombocytopenia. In animal models, KGDRR effectively suppressed thrombus growth without causing thrombocytopenia or prolonging bleeding time. Furthermore, intramuscular administration of KGDRR achieved a functional half-life 3.5 times longer than that of the clinically used antithrombotic eptifibatide at equivalent antithrombotic efficacy. In conclusion, KGDRR exhibits potent antithrombotic activity with a favorable safety profile and enhanced pharmacokinetic stability. These findings position KGDRR as a promising next generation αIIbβ3 antagonist with the potential to improve clinical outcomes in antithrombotic therapy. Full article

Graphene oxide (GO), owing to its extraordinary application prospects in biomedicine, is attracting growing research attention. However, the biosafety and blood compatibility of GO required for its clearance for use in clinical trials remain elusive. Therefore, we studied the mutagenic properties of GO as well as its cell toxicity and blood compatibility. Prior to biological experiments, we assessed the structural organization of GO using dynamic light scattering and microscopic visualization methods. The results of both the Ames mutagenicity test performed on Salmonella enterica serovar Typhimurium TA98 and TA102 strains and the cytotoxicity test on noncancerous, immortalized human keratinocytes revealed no mutagenic or toxic effects of GO. Simultaneously, GO reduced the viability of the MelJuSo human melanoma cell line. A blood compatibility assay revealed that a concentration of 10 μg/mL was critical for GO biosafety, as greater concentrations induced diverse side effects. Specifically, GO disrupts erythrocytes’ membranes in the dose-dependent manner. Moreover, GO at higher concentrations both inhibited the process of ADP (a physiological platelet agonist)-induced cell aggregation and affected their disaggregation process in platelet-rich plasma. However, in the blood clotting assessment, GO showed no effects on the activated partial thromboplastin time, prothrombin time, or thrombin time of the platelet-poor plasma. The obtained results clearly indicate that the relationship between the GO preparation method, its size, and concentration and biosafety must be cautiously monitored in the context of further possible biomedical applications. Full article

Background/Objectives: Palbociclib, an oral CDK 4/6 inhibitor, was evaluated in a Pediatric Brain Tumor Consortium (PBTC) phase 1 (NCT02255461; PBTC-042) study to treat children and young adults with recurrent, progressive, or refractory brain tumors. The objectives of this study were to characterize the palbociclib population pharmacokinetics in children enrolled on PBTC-042, to conduct a population pharmacodynamic analysis in this patient population, and to perform a simulation study to assess the role of palbociclib exposure on neutropenia and thrombocytopenia. Methods: The palbociclib population pharmacokinetics and pharmacodynamics were characterized in this patient population (n = 34 patients; 4.9–21.6 years old). Population pharmacokinetics were modeled using a one-compartment model with first-order absorption and elimination. Covariate analysis was performed, evaluating demographics, laboratory values, and concomitant medications. A pharmacodynamic model was used to describe the relation between palbociclib plasma exposure and changes in the ANC and platelet counts. Results: The population estimates for the apparent oral volume, apparent oral clearance, and absorption rate constant were 664.5 L/m², 36.8 L/h/m², and 0.48 h⁻¹, respectively. The palbociclib apparent oral clearance was decreased in patients with higher AST values (p = 0.0066). The ANC and platelet pharmacodynamic models estimated that the median (5th–95th percentile) time individuals had grade 3 or greater neutropenia was 4 (0, 21) days. Simulations showed that given 75 mg/m² palbociclib, 49% of the individuals were expected to have grade 3 or greater neutropenia. Conclusions: Palbociclib pharmacokinetics and pharmacodynamics were adequately characterized in this patient population, no unexpected adverse reactions were noted, and the drug was well tolerated. Full article

Background and Objectives: Patients with chronic kidney disease (CKD) are at increased risk of severe COVID-19 outcomes due to their compromised immune systems and chronic inflammatory state. This study aimed to evaluate and compare the inflammatory status of COVID-19 patients with CKD, stratified by creatinine clearance (CrCl) levels: CrCl < 30 mL/min, CrCl 30–60 mL/min, and CrCl > 60 mL/min. Multiple inflammatory scores combining laboratory parameters were assessed, including novel scores and established indices. Methods: In this retrospective cohort study, 223 patients admitted with confirmed COVID-19 were included and divided into three groups based on CrCl levels: CrCl < 30 (n = 41), CrCl 30–60 (n = 78), and CrCl > 60 (n = 104). Laboratory parameters including C-reactive protein (CRP), interleukin-6 (IL-6), neutrophil-to-lymphocyte ratio (NLR), ferritin, platelet count, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and serum albumin were collected. Multiple inflammatory scores were calculated, including inflammation scores (IS1–IS4), the systemic inflammatory index (SII), the C-reactive protein-to-albumin ratio (CAR), the lymphocyte-to-C-reactive protein ratio (LCR), and the prognostic nutritional index (PNI). Statistical analyses were performed to compare inflammatory scores among groups and assess correlations with clinical outcomes. Results: The CrCl < 30 group exhibited significantly higher levels of inflammatory markers and inflammatory scores compared with the other groups (p < 0.001). Among the additional scores, CAR and SII were significantly elevated in patients with lower CrCl levels, while LCR and PNI were decreased. CAR showed a strong positive correlation with COVID-19 severity (r = 0.65, p < 0.001), and PNI was inversely correlated with mortality (r = −0.58, p < 0.001). Multivariate regression analysis indicated that lower CrCl levels, higher IS3 and CAR, and lower PNI were independent predictors of severe COVID-19 outcomes. Conclusions: CKD patients with lower CrCl levels have an amplified inflammatory response during COVID-19 infection, as evidenced by elevated inflammatory scores. The additional inflammatory scores, particularly CAR and PNI, may serve as valuable tools for risk stratification and management of COVID-19 in CKD patients. Early identification of patients with high CAR and low PNI could improve clinical outcomes through timely therapeutic interventions. Full article

Introduction: Angiopoietin II (Ang-II) plays a pivotal role in the development of microcirculatory dysfunction as it provokes endothelial barrier disruption in patients with sepsis or septic shock. In particular, those with acute kidney injury show high Ang-II concentrations. So far, it is unclear which covariates influence Ang-II concentration in the early phase of sepsis, especially if extracorporeal therapies also do. Methods: Ang-II concentrations were measured in 171 patients with sepsis after the first day of antibiotic treatment between 03/2013 and 01/2015. Ang-II was correlated with potential influencing factors (Spearman correlation). A multivariate model was established including the significant correlating parameters. The Mann–Whitney U test and the Kruskal–Wallis test were used to detect significant differences in Ang-II concentration. Results: The median Ang-II concentration was 8015 pg/mL (interquartile range (IQR): 5024–14,185). A total of forty patients were treated with kidney replacement therapy (KRT) and 20 were supported by venovenous extracorporeal membrane oxygenation (vv-ECMO). Sequential organ failure assessment (SOFA) score (r = 0.541), creatinine clearance (r = −0.467), urinary output (r = −0.289), interleukin (IL)-6 (r = 0.529), C-reactive protein (CRP) (r = 0.241), platelet count (r = −0.419), bilirubin (r = 0.565), lactate (r = 0.322), KRT (r = 0.451), and fluid balance (r = 0.373) significantly correlated with Ang-II concentration and were included in the multivariate model. There, creatinine clearance (p < 0.01, b = −26.3, 95% confidence interval (CI) −41.8–−10.8), fluid balance (p = 0.002, b = 0.92, 95% CI 0.33–1.51), and CRP (p = 0.004, b = 127.6, 95% CI 41.6–213.7) were associated with Ang-II concentration. Furthermore, patients with KRT (median: 15,219 pg/mL, IQR: 10,548–20,270) had significantly (p < 0.01) higher Ang-II concentrations than those with vv-ECMO support (median: 6412 pg/mL, IQR: 5246–10,257) or those without extracorporeal therapy (median: 7156 pg/mL, IQR: 4409–12,741). Conclusion: Increased CRP, positive fluid balance, and impaired kidney function were associated with higher Ang-II concentrations in critically ill patients in the early stage of sepsis in this post hoc analysis. In particular, patients with KRT had very high Ang-II concentrations, whereas the use of vv-ECMO was not related to higher Ang-II concentrations. The significance for clinical practice should be clarified by a prospective study with standardized measurements. Full article

Background: 4-MDMB-BUTINACA, a next-generation synthetic cannabinoid, presents significant public health and forensic challenges due to its evolving nature and potential toxicity. Methods: This study evaluates the subacute toxic effects and pharmacokinetics of 4−Fluoro MDMB−BUTINACA (4F-MDMB-BUTINACA) in adult male albino rats, administered orally for seven days at doses of 1 mg/kg, 5 mg/kg, and 15 mg/kg. The hematological, biochemical, and histopathological parameters were assessed and compared to controls. Results: The pharmacokinetics were determined using GC–MS/MS with a positive chemical ionization and granisetron as an internal standard. A histological analysis revealed inflammatory cell aggregation, congestion, hemorrhage, edema, and fibrosis in various tissues, with renal examinations showing tubule degradation, glomerular atrophy, Bowman’s space expansion, edema, and hemorrhage. The liver exhibited cellular infiltration, while cardiac muscle fibers showed myocardial fiber degradation and inflammatory cell aggregation. Biochemical assays indicated significant alterations (p < 0.05) in the serum levels of AST, ALT, ALP, GGT, total protein, albumin, triglycerides, urea, MCHC, MCV, RDW, platelets, neutrophils, eosinophils, and basophils compared to the controls. Conclusions: The validated bioanalytical method revealed rapid absorption of 4F-MDMB-BUTINACA, with a plasma half-life of 2.371 h, a volume of distribution of 2272.85 L, and a plasma clearance rate of 664.241 L/h. In conclusion, 4F-MDMB-BUTINACA is a highly toxic synthetic cannabinoid, particularly affecting the liver, kidneys, and heart. Full article

(1) Background: There is a lack of knowledge about how a single dose of COX-2 selective non-steroidal anti-inflammatory drugs (NSAIDs) might affect the release of growth factors (GFs) and cytokines from canine platelet-rich gels (PRGs) and other hemocomponents. (2) Methods: A crossover study was conducted in six adult mongrel dogs. Animals were randomized to receive a single dose of either carprofen or firocoxib. PRG, temperature-induced platelet lysate (TIPL), chemically induced PL (CIPL), and plasma hemocomponents were obtained from each dog before (1 h) and after (6 h) the treatments. Platelet and leukocyte counts and determination of the concentrations of platelet-derived growth factor-BB, (PDGF-BB), transforming growth factor beta-1 (TGF-β₁), interleukin 1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-10 concentrations were assayed by ELISA in all hemocomponents. (3) Results: Both platelet and leukocyte counts and PDGF-BB concentrations were not affected by NSAIDs and time. Total TGF-β₁ concentrations were not affected by NSAIDs; however, the release of this GF was increased in PRG supernatants (PRGS) at 6 h. IL-1β and TNF-α concentrations were significantly (p < 0.001) lower in both firocoxib PRGS and plasma at 6 h, respectively. IL-10 concentrations were significantly (p < 0.001) lower at 6 h in all hemocomponents treated with both NSAIDs. (4) Conclusions: The clinical implications of our findings could indicate that these drugs should be withdrawn from patients to allow their clearance before the clinical use of PRP/PRG. On the other hand, the prophylactic use of NSAIDs to avoid the inflammatory reactions that some patients might have after PRP/PRG treatment should be performed only in those animals with severe reactive inflammation to the treatment. Full article

In this study, a mixed porcine–human bioengineered liver (MPH-BEL) was used in a preclinical setup of extracorporeal liver support devices as a treatment for a model of post-resection liver failure (PRLF). The potential for human clinical application is further illustrated by comparing the functional capacity of MPH-BEL grafts as assessed using this porcine PRLF model with fully human (FH-BEL) grafts which were perfused and assessed in vitro. BEL grafts were produced by reseeding liver scaffolds with HUVEC and primary porcine hepatocytes (MPH-BEL) or primary human hepatocytes (FH-BEL). PRLF was induced by performing an 85% liver resection in domestic white pigs and randomized into the following three groups 24 h after resection: standard medical therapy (SMT) alone, SMT + extracorporeal circuit (ECC), and SMT + MPH-BEL. The detoxification and metabolic functions of the MPH-BEL grafts were compared to FH-BEL grafts which were perfused in vitro. During the 24 h treatment interval, INR values normalized within 18 h in the MPH-BEL therapy group and urea synthesis increased as compared to the SMT and SMT + ECC control groups. The MPH-BEL treatment was associated with more rapid decline in hematocrit and platelet count compared to both control groups. Histological analysis demonstrated platelet sequestration in the MPH-BEL grafts, possibly related to immune activation. Significantly higher rates of ammonia clearance and metabolic function were observed in the FH-BEL grafts perfused in vitro than in the MPH-BEL grafts. The MPH-BEL treatment was associated with improved markers of liver function in PRLF. Further improvement in liver function in the BEL grafts was observed by seeding the biomatrix with human hepatocytes. Methods to reduce platelet sequestration within BEL grafts is an area of ongoing research. Full article

Aims: The pharmacokinetic (PK) profiles of voriconazole in intensive care unit (ICU) patients differ from that in other patients. We aimed to develop a population pharmacokinetic (PopPK) model to evaluate the effects of using extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) and those of various biological covariates on the voriconazole PK profile. Methods: Modeling analyses of the PK parameters were conducted using the nonlinear mixed-effects modeling method (NONMEM) with a two-compartment model. Monte Carlo simulations (MCSs) were performed to observe the probability of target attainment (PTA) when receiving CRRT or not under different dosage regimens, different stratifications of quick C-reactive protein (qCRP), and different minimum inhibitory concentration (MIC) ranges. Results: A total of 408 critically ill patients with 746 voriconazole concentration–time data points were included in this study. A two-compartment population PK model with qCRP, CRRT, creatinine clearance rate (CL_CR), platelets (PLT), and prothrombin time (PT) as fixed effects was developed using the NONMEM. Conclusions: We found that qCRP, CRRT, CL_CR, PLT, and PT affected the voriconazole clearance. The most commonly used clinical regimen of 200 mg q12h was sufficient for the most common sensitive pathogens (MIC ≤ 0.25 mg/L), regardless of whether CRRT was performed and the level of qCRP. When the MIC was 0.5 mg/L, 200 mg q12h was insufficient only when the qCRP was <40 mg/L and CRRT was performed. When the MIC was ≥2 mg/L, a dose of 300 mg q12h could not achieve ≥ 90% PTA, necessitating the evaluation of a higher dose. Full article

Hepatitis B virus (HBV) is a major driver of chronic hepatic inflammation, which regularly leads to liver cirrhosis or hepatocellular carcinoma. Immediate innate immune cell response is crucial for the rapid clearance of the infection. Here, natural killer (NK) cells play a pivotal role in direct cytotoxicity and the secretion of antiviral cytokines as well as regulatory function. The aim of this study was to further elucidate NK cell responses triggered by an HBV infection. Therefore, we optimized HBV in vitro models that reliably stimulate NK cells using hepatocyte-like HepG2 cells expressing the Na⁺-taurocholate co-transporting polypeptide (NTCP) and HepaRG cells. Immune cells were acquired from healthy platelet donors. Initially, HepG2-NTCP cells demonstrated higher viral replication compared to HepaRG cells. Co-cultures with immune cells revealed increased production of interferon-γ and tumor necrosis factor-α by NK cells, which was no longer evident in isolated NK cells. Likewise, the depletion of monocytes and spatial separation from target cells led to the absence of the antiviral cytokine production of NK cells. Eventually, the combined co-culture of isolated NK cells and monocytes led to a sufficient cytokine response of NK cells, which was also apparent when communication between the two immune cell subpopulations was restricted to soluble factors. In summary, our study demonstrates antiviral cytokine production by NK cells in response to HBV⁺ HepG2-NTCP cells, which is dependent on monocyte bystander activation. Full article

Background: Linezolid is used for Gram-positive bacterial infections. Thrombocytopenia is one of its main adverse effects resulting from myelosuppression. Several studies have assessed risk factors that may increase the risk of this adverse effect. However, most studies included patients with hemato-oncologic diseases, which may confound such assessments. This study aimed to investigate risk factors for linezolid-associated thrombocytopenia in patients without hemato-oncologic diseases. Methods: This was a multicenter retrospective case-control study of adult patients treated with linezolid twice daily for ≥3 days. Patients with hemato-oncologic diseases, active dengue fever, active COVID-19, baseline platelet count <100 × 10³/mm³, concurrent therapy with trimethoprim/sulfamethoxazole or valproic acid, and a recent platelet transfusion within 7 days were excluded. Thrombocytopenia was defined as a drop in platelet count below 100 × 10³/mm³. Results: Out of 158 evaluated patients, 33 developed thrombocytopenia, indicating an incidence rate of 20.9%. Of all the risk factors assessed, creatinine clearance of <60 mL/min and bacteremia/infective endocarditis were significantly associated with linezolid-associated thrombocytopenia (adjusted odds ratios, 3.25 and 5.95; 95% CI 1.12–9.45 and 1.23–28.66; p = 0.031 and 0.026, respectively). End of therapy platelet counts were significantly lower in the cases than in the controls (79 vs. 243 × 10³/mm³; p < 0.001). Similarly, the percentage of platelet count change was significantly different (−55.1% vs. −10.2%; p < 0.001). Conclusions: In our study, the incidence rate of linezolid-associated thrombocytopenia was 20.9%, and we found that patients with renal impairment and bacteremia may need close monitoring of platelet counts. Prospective studies are warranted to evaluate the potential need for renal dose adjustment. Full article