Kassar O, Mohamed RG, Sarhan K
… +6 more, Kashbour M, Abuhlaiga MA, Sabet H, Elawwad O, Yousef O, Abouelmagd ME
J Thromb Thrombolysis
· 2026 Mar · PMID 41206375
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Endovascular thrombectomy (EVT) is the standard of care in acute ischemic stroke (AIS), yet functional outcomes remain suboptimal. Normobaric hyperoxia (NBHO) is a potential neuroprotective strategy. This study is the fi...Endovascular thrombectomy (EVT) is the standard of care in acute ischemic stroke (AIS), yet functional outcomes remain suboptimal. Normobaric hyperoxia (NBHO) is a potential neuroprotective strategy. This study is the first systematic review and meta-analysis to assess NBHO as a potential neuroprotective adjunctive to improve outcomes in EVT-treated patients. A comprehensive search of electronic databases, including PubMed, Scopus, Cochrane, and Web of Science, was performed in February 2025. The inclusion criteria targeted randomized controlled trials (RCTs) comparing NBHO and EVT to EVT alone or with sham oxygen therapy. Statistical analyses were performed using RevMan software. Four RCTs comprising 648 patients with AIS due to large vessel occlusion in the anterior circulation were included in the study. For the primary efficacy endpoint of excellent functional outcome, defined as the number of patients who had a Modified Rankin Scale (mRS) score of ≤ 1 at 90 days, the overall odds ratio with a subgroup based on the oxygen delivery duration at 2, 4, and 6 h was in favor of the NBHO group compared to the control (OR = 1.66, 95% CI [1.13, 2.45], P = 0.01, I2 = 0%). The subgroup of 4-hour oxygen delivery duration was the only significant subgroup (OR = 1.6, 95% CI [1.01, 2.51], P = 0.04). Safety outcomes showed no significant differences between the NBHO group and the control group across all reported measures. NBHO as an adjunct to EVT appears to be effective and safe. A 4-hour duration was found to be the most effective. Further RCTs are needed to confirm our results and establish the optimal treatment protocol.
We aimed to investigate the effects of Xuebijing (XBJ) combined with levosimendan on the immune function and coagulation function in patients with sepsis complicated by myocardial injury. This double-blind, randomized co...We aimed to investigate the effects of Xuebijing (XBJ) combined with levosimendan on the immune function and coagulation function in patients with sepsis complicated by myocardial injury. This double-blind, randomized controlled trial involved 88 sepsis patients with myocardial injury, split into control (n = 44, levosimendan plus conventional therapy) and combination (n = 44, control group's treatment plus XBJ injection) groups. Primary outcomes: coagulation parameters [prothrombin time (PT), activated partial thromboplastin time (APTT), platelet count (PLT), fibrinogen (Fib), and D-dimer (D-D)], immune function indicators (peripheral blood T lymphocyte subsets: CD4+, CD8+, and the CD4+/CD8+ ratio). Secondary outcomes: inflammatory markers [procalcitonin (PCT), C-reactive protein (CRP), and tumor necrosis factor (TNF-α)], vascular endothelial function markers [endothelin-1 (ET-1), nitric oxide (NO), vascular endothelial growth factor (VEGF), von Willebrand factor (vWF), and soluble thrombomodulin (sTM)], myocardial function biomarkers [cardiac troponin I (cTnI), creatine kinase isoenzyme (CK-MB), and B-type brain natriuretic peptide (BNP)], and hemodynamic parameter [heart rate (HR), mean arterial pressure (MAP), and central venous pressure (CVP)]. Post-treatment, serum levels of PCT, CRP, TNF-α, ET-1, vWF, sTM, PT, APTT, D-D, CD8+, cTnI, CK-MB, BNP, and HR were lower in both groups, with further reductions in the combination group. Levels of NO, VEGF, PLT, Fib, CD4+, CD4+/CD8+ ratio, MAP and CVP were higher in the combination group than in the control group (all P < 0.05). The combination of XBJ and levosimendan improves coagulation function, regulates immune function, enhances vascular endothelial function and hemodynamics, reduces inflammation, and alleviates myocardial injury.
Platelet activation is a hallmark feature of coronary artery disease (CAD), characterized by a proaggregatory and proinflammatory state. However, the proadhesive phenotype, mediated by the collagen receptors GPVI and int...Platelet activation is a hallmark feature of coronary artery disease (CAD), characterized by a proaggregatory and proinflammatory state. However, the proadhesive phenotype, mediated by the collagen receptors GPVI and integrin α₂β₁, seems to be critically essential in the pathogenesis of disease yet underexplored in advanced CAD patients. Given the limited insight into this area, we aimed, for the first time, to comprehensively assess the expression of adhesion receptors, as well as the collagen-dependent adhesion of platelets, in CAD patients candidates for CABG (Advanced CAD) compared to healthy controls. Twenty CAD patients scheduled for CABG surgery, selected using strict exclusion criteria, and healthy controls were analyzed for expression of GPVI, integrin α₂β₁, and P-selectin via flow cytometry. Collagen-dependent platelet adhesion and spreading under static conditions were evaluated by immunofluorescence microscopy, which was correlated with GPVI expression and platelet indices. CAD patients exhibited higher levels of GPVI and P-selectin expression, but not α2β1, along with increased platelet adhesion and spreading on a collagen matrix. Platelet functional activity was strongly linked to GPVI expression and platelet indices, including MPV and PDW. The study presented here for the first time exhibited the higher proadhesive function in advanced CAD, which significantly correlates with platelet indices. These findings indicate that a sustained proadhesive state may increase the risk of prothrombotic complications before CABG, while the indices themselves may serve as indirect surrogate markers of platelet adhesive potential. Moreover, ROC curve analysis confirmed the high sensitivity and specificity of the adhesion profile in discriminating CAD patients from healthy controls.
Warfarin dosing guided by INR fails to account for pharmacokinetic/pharmacodynamic variability, leading to suboptimal outcomes; genetic and clinical factors, such as VKORC1 polymorphism and comorbidities, could refine do...Warfarin dosing guided by INR fails to account for pharmacokinetic/pharmacodynamic variability, leading to suboptimal outcomes; genetic and clinical factors, such as VKORC1 polymorphism and comorbidities, could refine dosing strategies and improve anticoagulation safety. The aim of this was to identify the main determinants of INR variability in Mexican patients under long-term anticoagulation therapy. For this purpose, patients undergoing warfarin treatment were included and a clinical data was retrieved from medical record. A bioanalytical HPLC method to quantify warfarin (CPW) and its primary metabolite, 7-OH warfarin (CP7OH), in plasma samples was standardized and validated. INR variability was assessed in relation to Charlson comorbidity index (CCI), warfarin dose, drug interactions, vitamin K intake, CPW, CP7OH, metabolic ratio, and VKORC1 1693 polymorphism using univariate and multivariate analysis. The results showed that among 22 patients (64% women) with atrial fibrillation and aortic-mitral valve replacement, warfarin dosing ranged from 8.75 to 55 mg/week (median: 22.5 mg/week). Over half (68.2%) did not achieve the therapeutic INR goal (2.0-3.5). VKORC1 1693 genotype frequencies were GG (36%), GA (50%), and AA (14%), with AA carriers requiring lower maintenance doses (p<0.01). Multivariate analysis incorporating CCI, CPW and CP7OH explained up to 70% of INR variability (p<0.01). Furthermore, currently reported dosing algorithms showed limited accuracy in predicting the appropriate warfarin dose in this cohort. Overall, INR variability depends on plasma warfarin levels, metabolite concentration, and key comorbidities. Therefore, tailored population models are essential to optimize anticoagulation therapy in Mexico. This research highlights the need for more inclusive studies incorporating genetic and clinical factors to refine warfarin dosing and improve outcomes.
Adachi K, Raymundo A, Sanchez A
… +4 more, Soliman Y, Fernando J, Sadeh M, Mehta AI
J Thromb Thrombolysis
· 2026 Mar · PMID 41177819
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Endovascular thrombectomy (EVT) is an effective treatment for acute ischemic stroke (AIS). Oral anticoagulants are used for stroke prevention in pro-embolic patients, but their impact on EVT outcomes, particularly sympto...Endovascular thrombectomy (EVT) is an effective treatment for acute ischemic stroke (AIS). Oral anticoagulants are used for stroke prevention in pro-embolic patients, but their impact on EVT outcomes, particularly symptomatic intracranial hemorrhage (sICH), remains uncertain. This study aims to evaluate the safety and efficacy of vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) on EVT outcomes. We searched PubMed, Cochrane, and Embase from 2015 to August 2024 for studies comparing anticoagulated and non-anticoagulated AIS patients undergoing EVT. Safety outcomes included sICH and 90 days mortality. Efficacy outcomes included successful reperfusion rate and 90 days functional outcome. Subgroup analyses evaluated the effect of therapeutic-dose anticoagulation. Fifteen studies with 62,328 AIS patients were included; 9,977 were anticoagulated (6,879 VKA, 3,098 DOAC). VKA patients had a significantly higher rate of sICH (OR = 1.32, 95% CI [1.05, 1.66]) and 90 days mortality (OR = 1.61, 95% CI [1.25, 2.08]) compared to non-anticoagulated patients. DOACs showed no significant difference in sICH risk (OR = 0.83, 95% CI [0.48, 1.44]) or mortality (OR = 1.20, 95% CI [0.89, 1.61]). Functional outcomes at 90 days were significantly worse in both anticoagulated groups, but only VKA patients demonstrated worsened outcomes in the therapeutic-dose subgroup analysis. EVT success rates were comparable between all groups. DOACs offer a safer EVT profile than VKAs, with lower sICH risk and mortality. These findings support DOACs as the preferred anticoagulant for stroke prevention. Further research should assess long-term outcomes and distinguish procedure-related mortality from secondary causes.
Atherosclerosis is the main cause of cardiovascular diseases. These diseases can lead to mortality and morbidity worldwide. Macrophage apoptosis plays an important role in the progression of atherosclerosis. ASA-X has an...Atherosclerosis is the main cause of cardiovascular diseases. These diseases can lead to mortality and morbidity worldwide. Macrophage apoptosis plays an important role in the progression of atherosclerosis. ASA-X has anticancer effects by inducing significant apoptosis in gastric cancer cells. We conducted a preliminary experiment and reported that ASA-X promotes macrophage apoptosis. Therefore, we hypothesize that ASA-X might play a role in anti-atherosclerosis by inducing macrophage apoptosis. The effects of ASA-X and ASA on RAW264.7 cells (in vitro) and mice (in vivo) were investigated. In vitro, RAW264.7 cell viability and apoptosis rates were assessed, and the levels of PARP, caspase-9, p-JNK, and p53 in cells treated with the two substances were compared. In vivo, Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) assays revealed macrophage apoptosis in mice treated with medium- or high-dose ASA-X or ASA. Aortic plaques in mice treated with either drug were examined using oil red O and H&E staining. Masson and collagen staining was performed on the aortic rings of mice treated with high-dose ASA-X or ASA. In vitro, unlike ASA, which had no effect, ASA-X markedly reduced RAW264.7 cell viability. ASA-X induced apoptosis at a rate about four times higher than ASA, with increased levels of PARP, caspase-9, phosphorylated JNK, and p53. In vivo, medium- and high-dose ASA-X significantly increased macrophage apoptosis in mice compared with ASA. In addition, ASA-X (at medium and high doses) reduced the number of aortic plaques, as shown by oil red O and H&E staining. Masson and collagen staining of aortic rings revealed similar results for the high-dose ASA-X and ASA treatments. ASA-X appeared to exhibit anti-atherosclerosis effects via a mechanism that involves the induction of macrophage apoptosis and the lowering of blood plasma lipid levels, eventually resulting in reduced aortic plaque. ASA-X could, therefore, be considered a promising candidate for the treatment of this cardiovascular disease.
Thromboembolic events (TE) cause significant morbidity and mortality in SLE patients. Comprehensive data on various types of thromboembolic events and their variation by gender, region, and hospital status are scant. To...Thromboembolic events (TE) cause significant morbidity and mortality in SLE patients. Comprehensive data on various types of thromboembolic events and their variation by gender, region, and hospital status are scant. To analyze the epidemiology, morbidity, mortality, and risk factors (e.g., obesity, smoking) of thromboembolic events in SLE. Data from the NIS (2003-2018) were analyzed using ICD-9 and ICD-10 codes to identify patients diagnosed with SLE. SAS-9.4 was used for data analysis. TE variables include DVT, PE, Cerebral venous sinus thrombosis (CVST), Splanchnic thrombosis (ST), and Arterial Thrombosis (AT). Among 513,904 SLE patients, PE, DVT, ST, CVST, and AT were identified in 7,070 (1.38%), 15,800 (3.07%), 6,868 (1.34%), 197 (0.04%), and 1,821 (0.35%) patients, respectively. The prevalence of PE, DVT, ST, and AT is higher in males with SLE. African Americans (29.55% of the cohort) demonstrated a higher prevalence of PE (2,188, 1.6%) and DVT (5,208, 3.46%). The prevalence of obesity was higher in SLE patients with all thrombotic events, except in AT, which had a significantly lower prevalence. A significantly higher all-cause in-hospital mortality, longer LOS, and cost of stay were seen in SLE with thrombotic events (except CVST). Arterial, venous, and atypical thrombosis exert significant morbidity and mortality in patients with SLE. The disparities in thrombotic events within the SLE population underscore the importance of targeted interventions to reduce substantial morbidity and healthcare expenditures.
Finger C, Emara G, Chiu GS
… +7 more, Li K, Sheth S, Tan C, Parekh M, Inam ME, Dongarwar D, Manwani B
J Thromb Thrombolysis
· 2026 Feb · PMID 41139137
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Identifying the underlying etiology of ischemic stroke is crucial for implementing effective stroke prevention measures. In the era of thrombectomy, ischemic stroke thrombus composition has gained considerable interest i...Identifying the underlying etiology of ischemic stroke is crucial for implementing effective stroke prevention measures. In the era of thrombectomy, ischemic stroke thrombus composition has gained considerable interest in the recent years. However, only a limited studies have analyzed the inflammatory milieu of the thrombus in association with stroke etiology. Atrial Fibrillation (AF), a common etiology of large strokes, is difficult to detect, but is known to be an inflammatory disease with a dominance of CD11b cell types (characterizes bone marrow derived myeloid cells such as monocytes, neutrophils, macrophages, and natural killer cells) in the atria. We hypothesized that thrombi from ischemic stroke patients with AF will have increased CD11b cell types as compared to other stroke etiologies. 51 ischemic stroke thrombi were stained for CD11b. The relationship between stroke etiology (TOAST - Trial of ORG 10172 in Acute Stroke Treatment) and number of CD11b positive cells was assessed. Cardioembolic thrombi contained significantly higher number of CD11b positive cells (248.2 ± 137.4, n = 27) as compared to strokes from large artery atherosclerosis (138.3 ± 92.1, n = 11, p = 0.01). Similarly, thrombi from patients with cryptogenic stroke had significantly higher number of CD11b positive cells, when compared to thrombi from patients with strokes from large artery atherosclerosis ((212.1 ± 104.8 vs. 138.3 ± 92.1, p = 0.04). Our study suggests that increased expression of CD11b in ischemic stroke thrombi characterizes strokes from cardioembolic etiology. It elucidates atrial substrate inflammation driven by CD11b positive leukocytes, which leads to thrombogenesis and ischemic stroke. The shared histology of cardioembolic and cryptogenic strokes suggests that many of the cryptogenic strokes may be due to occult AF.
Post-thrombotic syndrome (PTS) is the most frequent and disabling complication of deep vein thrombosis (DVT). Several studies have evaluated whether direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs) may...Post-thrombotic syndrome (PTS) is the most frequent and disabling complication of deep vein thrombosis (DVT). Several studies have evaluated whether direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs) may reduce the PTS risk over time. Data on patients with inherited thrombophilias (IT) remains scarce. To assess the long-term incidence and severity of PTS in a population of IT patients with proximal DVT of the lower extremity treated with DOACs vs. VKAs. Cases were consecutive IT patients prospectively diagnosed with a first DVT episode at Padova University Hospital, Italy between January 2014 and December 2021, and treated with DOACs. Controls were consecutive IT patients diagnosed with DVT between January 2004 and December 2019, and treated with VKAs. In both groups, the onset and grade of PTS - diagnosed using the Villalta score - was evaluated at 3, 6, 12, 24 and 36 months after DVT diagnosis. We diagnosed PTS in 71 (23.0%) DOACs and 121 (24.3%) VKAs. Crude and adjusted hazard ratios (95% Confidence Interval, CI) for the 3-year cumulative incidence of PTS in cases vs. controls were 0.93 (95% CI, 0.70-1.24) and 0.87 (95% CI, 0.61-1.23), respectively. Severe PTS was observed in 12 (16.9%) cases and 24 (10.8%) controls (p 0.62). The long-term incidence and severity of PTS was comparable between IT patients treated with DOACs or VKAs following a first DVT episode of the lower extremity. Larger more powerful studies are needed to ascertain how to mitigate the risk of developing PTS over time in this subset of patients.
Trauma-induced coagulopathy (TIC) is a dynamic process that contributes to early mortality following injury, with dysregulated fibrinolysis playing a central role in its pathophysiology. Tranexamic acid (TXA), a potent a...Trauma-induced coagulopathy (TIC) is a dynamic process that contributes to early mortality following injury, with dysregulated fibrinolysis playing a central role in its pathophysiology. Tranexamic acid (TXA), a potent antifibrinolytic agent, is widely used in trauma and surgical settings for hemorrhage management. Its effectiveness is dependent on appropriate timing and patient selection, as indiscriminate use may increase the risk of thromboembolic events. As a result, real-time monitoring of coagulation status is essential to guide TXA therapy. Conventional coagulation tests (CCTs), such as the International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (aPTT), are inadequate in trauma care, as they provide static snapshots of coagulation status. By contrast, viscoelastic testing (VET) platforms, including thromboelastography (TEG) and rotational thromboelastometry (ROTEM), allow for real-time assessments of coagulation status. More recently, tissue plasminogen activator-augmented VET (tPA-VET) has been developed to more effectively distinguish between fibrinolysis phenotypes. This review explores the pathophysiology of TIC, current approaches to hemorrhage management including the use of TXA, the role of VET in guiding TXA therapy, the diagnostic value of tPA-VET, and future directions in implementing VET-guided trauma resuscitation protocols.
This commentary explores the evolving landscape of United States healthcare policy and its global implications, specifically in cardiovascular and thrombosis associated conditions. Recent legislative and executive action...This commentary explores the evolving landscape of United States healthcare policy and its global implications, specifically in cardiovascular and thrombosis associated conditions. Recent legislative and executive actions have introduced sweeping reforms to federal programs such as Medicaid, Medicare, and drug pricing (Medicare Drug Price Negotiation, Medicaid Drug Rebate, Federal Supply Schedule) threatening access and affordability for millions of Americans-many already vulnerable and at risk for life threatening and life altering events. These changes reverberate internationally, influencing research collaborations, supply chains, accessibility, and the cost of care. This commentary advocates for evidence-based policy, multi-level collaboration, increased international education directives, and an unwavering commitment to broad-based healthcare access worldwide.
Szmit S, Kępski J, Lech-Marańda E
… +3 more, Kowalski DM, Krzakowski M, Zaborowska-Szmit M
J Thromb Thrombolysis
· 2025 Dec · PMID 41099929
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Cancer and its treatment predispose to thromboembolic complications and thrombocytopenia. Thrombocytopenia does not protect against thromboembolism, but increases the risk of bleeding. The prognosis in venous thromboembo...Cancer and its treatment predispose to thromboembolic complications and thrombocytopenia. Thrombocytopenia does not protect against thromboembolism, but increases the risk of bleeding. The prognosis in venous thromboembolism (VTE) strictly depends on the efficacy of anticoagulation. The choice of anticoagulation strategy will depend on the severity of thrombocytopenia and its expected duration. Thrombotic risk is also important, determining the risk of death related to pulmonary embolism and the risk of recurrence/progression of VTE. Possible strategies include full anticoagulation and possible platelet transfusions, modification of the anticoagulation dose or interruption of anticoagulation. The review focuses on the possibilities of VTE treatment in the aspect of clinically significant thrombocytopenia with a platelet count below 50 × 10/L (50 000/µl).
Ling L, Liu C, Huang X
… +3 more, Wang S, Yu Z, Zhou J
J Thromb Thrombolysis
· 2026 Feb · PMID 41071257
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It is generally accepted that higher phospholipid concentrations generate shorter clotting times. Phospholipid-dependent lupus anticoagulants (LA) assays such as dilute Russell's viper venom time (dRVVT) and silica clott...It is generally accepted that higher phospholipid concentrations generate shorter clotting times. Phospholipid-dependent lupus anticoagulants (LA) assays such as dilute Russell's viper venom time (dRVVT) and silica clotting time (SCT) have therefore been developed. However, cases have been observed where LA confirming tests (concentrated phospholipid) generates longer clotting times than screening tests (diluted phospholipid). This study investigates the underlying cause of this paradox and assess its implications. With different phospholipid concentrations, Russell's viper venom and/or silica-induced clotting times were assayed in normal pooled plasmas (NPPs), factor deficient plasmas, cirrhotic patients' plasmas (CPPs), LA positive plasmas (LPPs). Additionally, routine LA assays were performed in LPPs with or without factor deficiency. In NPPs and factor deficient plasmas, higher phospholipid concentrations resulted in shorter clotting times, however, this effect was more evident with low-middle phospholipid than with higher phospholipid (a U shape curve). In CPPs, clotting time was increasing along with increasing phospholipid from the beginning (right part of a U shape curve). In LPPs, clotting time was shortening along with increasing phospholipid at the beginning, but changeless thereafter (left part of a U shape curve). Compared to LPPs without factor deficiency, LPPs with factor deficiency demonstrated a smaller correction of screening by confirming (dRVVT, 25.9% versus 15.1%, SCT, 28.6% versus 4.1%), leading to a possibility of LA misdiagnosis. Increasing phospholipid could induce "hook effect" in coagulation assays, therefore, phospholipid-dependent clot-based coagulation assays such as LA assays need careful interpretation, especially among patients suffering coagulation factor deficiency.
Despite timely primary percutaneous coronary intervention (pPCI), the no-reflow phenomenon (NRP) continues to adversely affect myocardial perfusion and outcomes in ST-segment elevation myocardial infarction (STEMI). Whil...Despite timely primary percutaneous coronary intervention (pPCI), the no-reflow phenomenon (NRP) continues to adversely affect myocardial perfusion and outcomes in ST-segment elevation myocardial infarction (STEMI). While multiple mechanisms are implicated, reliable biomarkers for early prediction remain limited. Platelet-derived growth factor-BB (PDGF-BB), a cytokine involved in vascular inflammation and remodeling, is elevated in acute coronary syndromes. This study aimed to assess whether pre-procedural PDGF-BB levels could predict NRP in STEMI patients undergoing pPCI. In this prospective observational study, 80 STEMI patients undergoing pPCI were grouped by post-procedural TIMI flow: NRP(+) (TIMI ≤2; n=33) and NRP(−) (TIMI 3; n=47). Serum PDGF-BB levels were measured before angiography, and clinical, angiographic, and laboratory variables were compared. PDGF-BB levels were significantly higher in the NRP group (168.5 ± 177.3 vs. 65.5 ± 43.1 pg/mL; p=0.004), along with lower baseline TIMI flow (p=0.002), greater stent diameter (p=0.013), and more total occlusions (p=0.015). PDGF-BB remained an independent predictor in multivariate analysis (p=0.01). ROC analysis showed a cutoff of 89.99 pg/mL predicted NRP with 51.5% sensitivity and 87.2% specificity (AUC=0.688; p=0.004). Elevated pre-procedural PDGF-BB levels are independently associated with NRP in STEMI patients. Although its diagnostic performance is moderate, its high specificity may aid in identifying high-risk patients. Further validation and integration into risk models are warranted.
Following percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) is standard to reduce thrombotic complications. However, the optimal monotherapy after DAPT remains debated. Clopidogrel may offer bett...Following percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) is standard to reduce thrombotic complications. However, the optimal monotherapy after DAPT remains debated. Clopidogrel may offer better protection than aspirin. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing clopidogrel versus aspirin monotherapy after DAPT in PCI patients. Searches were performed in MEDLINE, Embase, Scopus, CENTRAL, and ClinicalTrials.gov up to April 12, 2025. Outcomes included stroke, myocardial infarction (MI), all-cause mortality, and cardiovascular (CV) death. Hazard ratios (HRs) were pooled using random-effects models. Four RCTs comprising 19,554 patients (clopidogrel: 9,846; aspirin: 9,708) were included. Clopidogrel was associated with a significantly lower risk of stroke (HR: 0.69; 95% CI: 0.51-0.94; p = 0.02; I² = 28%) and MI (HR: 0.71; 95% CI: 0.51-0.99; p = 0.05; I² = 48%) compared with aspirin. There was no significant difference between clopidogrel and aspirin in terms of all-cause mortality (HR: 0.99; 95% CI: 0.78-1.25; p = 0.92; I² = 55%), CV death (HR: 0.87; 95% CI: 0.70-1.08; p = 0.22; I² = 0%), coronary revascularization (HR: 0.95; 95% CI: 0.83-1.09; p = 0.44; I² = 0%), major bleeding (HR: 0.97; 95% CI: 0.70-1.35; p = 0.87; I² = 57%), or stent thrombosis (HR: 0.66; 95% CI: 0.38-1.15; p = 0.15; I² = 0%). Clopidogrel monotherapy post-DAPT after PCI reduces stroke and MI risk compared to aspirin, without increasing mortality or bleeding. These findings support clopidogrel as a favorable alternative for monotherapy.
Taghiyev ZT, Sadowski M, Beier LM
… +9 more, Leweling C, Gunkel S, Keschenau P, Kalder J, Arneth BM, Skevaki C, Sachs U, Müller J, Böning A
J Thromb Thrombolysis
· 2026 Feb · PMID 41071254
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Cardiac surgery is considered to be a hypercoagulable state with an increased incidence of thromboembolic events. To evaluate the connection between hypercoagulability and mesenteric ischemia (Me-Is), we investigated hem...Cardiac surgery is considered to be a hypercoagulable state with an increased incidence of thromboembolic events. To evaluate the connection between hypercoagulability and mesenteric ischemia (Me-Is), we investigated hemostatic parameters in patients with diagnosed Me-Is. Out of a cohort of 500 consecutive cardiac surgery patients, 25 patients with hyperinflammatory indicators (interleukin-6 > 600 ng/l) and metabolic acidosis (lactate > 4 mmol/l) were retrospectively matched 1:4 into Me-Is (n = 5) and control (n = 20) groups. Blood samples collected before surgery, on intensive care unit (ICU) admission, and 12 h after ICU admission were assessed for hemostatic parameters, including fibrinogen, D-dimer, thrombin-anti-thrombin complex (TAT), and prothrombin fragments 1 + 2 (F1.2). Thrombin generation assays were conducted on all samples, and intestinal fatty acid-binding protein (I-FABP) was assessed as a marker for Me-Is. Baseline levels of hemostatic markers were similar between the two groups. TAT levels were significantly higher in the Me-Is group 12 h after ICU admission (54.20 ± 10.49 vs. 22.18 ± 12.43 ng/ml, p = 0.010). In contrast, at ICU admission, absolute F1.2 values were higher in the control group (1.19 ± 0.04 vs. 0.49 ± 0.47 ng/ml, p = 0.047). However, increase of F1.2 values of the Me-Is group (394.2 ± 231.6%) vs. the control group (114.7 ± 144.9%) 12 h after ICU admission were 3.9- vs. 1.1-fold compared to baseline (p = 0.046). Postoperatively, higher levels of I-FABP and of D-dimers were observed in the Me-Is group at ICU admission (17116.2 ± 18185.4 vs. 2252.3 ± 1582.7 pg/ml; p = 0.006; and 5.3 ± 1.3 vs. 3.0 ± 2.1 µg/ml; p = 0.043; respectively) and 12 h after ICU admission (16998.2 ± 20346.3 vs. 1030.8 ± 1100.0 pg/ml; p = 0.030; and 3.7 ± 1.8 vs. 1.2 ± 0.8 µg/ml; p = 0.005; respectively) compared to the control group. No significant differences were observed for parameters of thrombin generation (TGA, peak value, ETP) between the two groups. Our findings suggest that TAT and F1.2 levels are promising candidates as markers of coagulability after cardiac surgery. High levels of activation markers suggest a temporary stage of hypercoagulability immediately after surgery in Me-Is patients. Nevertheless, the serial assessment of thrombotic profiles offers valuable mechanistic insights, although these exploratory findings require confirmation in larger cohorts.
During the alpha wave of SARS-CoV-2 (SCA), the number of ICU-hospitalized COVID-19 patients was high. In a dynamic co-evolution, the virulence of the virus changed during the Omicron wave (SCO). Initial findings of COVID...During the alpha wave of SARS-CoV-2 (SCA), the number of ICU-hospitalized COVID-19 patients was high. In a dynamic co-evolution, the virulence of the virus changed during the Omicron wave (SCO). Initial findings of COVID-19 indicate that infection with SARS-CoV-2 leads to endothelial dysfunction through inflammatory pathways, oxidative stress, and alterations in vascular homeostasis. Upregulation of adhesion molecules (ICAM-1 and VCAM-1) in response to pro-inflammatory cytokines helps immune cell migration and vascular inflammation. Furthermore, oxidative stress disrupts the balance between the oxidant and antioxidant systems. Excessive NOX2 activity promotes ROS production and Nrf2 suppression, leading to endothelial dysfunction. Also, alterations in vascular homeostasis and increased vWF secretion heightens the risk of thrombosis, while dysregulated iNOS contributes to further endothelial damage. Considering that endothelial cell dysfunction can promote various disease processes, including thrombosis and atherosclerosis, this study evaluates the main changes in the host lung endothelium in COVID-19 during this co-evolution. The direct effects of SCA and SCO on endothelial function were investigated in bronchoalveolar lavage fluid (BALF) samples obtained from leftover specimens of COVID-19 patients, which were compared to the control group. In the BALF samples of patients, key endothelial molecules involved in immune cell recruitment, such as iNOS, Nrf2, NOX2, vWF, ICAM-1, and VCAM-1, were evaluated using RT-qPCR and Western blotting. In severe COVID-19, ICAM-1 and VCAM-1 were upregulated compared to the control group. Furthermore, vWF expression was also upregulated. A significant increase in iNOS gene expression was observed during the Omicron wave. Although NOX2 expression increased during the SCA and SCO waves, Nrf2 expression was downregulated in both SARS-CoV-2 waves. Overall, during the co-evolution of the virus and host, disruption of endothelial cell function can affect selective immune cell recruitment and, in the late phase, lead to local vascular dysfunction and severe outcomes such as hospitalization. Targeting key endothelial molecules for therapy can not only alter immune cell recruitment but also prevent endothelial dysfunction throughout the body.
J Thromb Thrombolysis
· 2026 Feb · PMID 41047446
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Hereditary thrombophilia testing is frequently ordered after venous thromboembolism (VTE), despite little evidence of clinical utility and most guidelines cautioning against testing. We conducted a retrospective, observa...Hereditary thrombophilia testing is frequently ordered after venous thromboembolism (VTE), despite little evidence of clinical utility and most guidelines cautioning against testing. We conducted a retrospective, observational study of inpatient hereditary thrombophilia testing ordered during a hospital admission for acute VTE between 2019 and 2024. We aimed to characterize patterns of testing results, and costs, and to evaluate whether younger patients and those with unprovoked VTE were more likely to test positive for hereditary thrombophilia. A total of 835 hereditary thrombophilia tests - including those for factor V Leiden, prothrombin, deficiencies of protein S, protein C, and antithrombin, hyperhomocysteinemia, and plasminogen activator inhibitor-1 excess - were ordered in 220 patients. Overall, 19.6% of results were abnormal, and 45.0% of patients had at least one abnormal result. There was no difference in the rate of positive results among patients with provoked vs. unprovoked VTE (30.7% vs. 34.5%, p = .554) nor patients < 50 vs. ≥ 50 years of age (33.1% vs. 32.4%, p = .912). Only 4/99 (4.0%) patients with an abnormal result had their clinical management clearly changed due to the result. The tests totaled $385,161 USD in institutional charges and $26,029 USD in Medicare fees. Inpatient hereditary thrombophilia testing during admission for acute VTE is low yield, with frequent abnormal results, many of which likely represented false positives, and minimal impact on clinical management with high costs.