Risk Of Thrombosis Research Articles

Abstract 4140192: Time Trends in Outcomes of Trans-Catheter Aortic Valve Replacement with Balloon-expanding Versus Self-expanding Valves: A Meta-analysis of Randomized Controlled Trials

Background: The research on the outcomes of transcatheter aortic valve replacement with balloon-expandable valves (BEV) and self-expanding valves (SEV) are limited. Hypothesis: This study aims to compare the clinical and hemodynamic outcomes of BEV and SEV at short-term (30 days), mid-term (1 year), and long-term (>1 year) endpoints. Methods: PubMed, Embase, Scopus, and Cochrane Library databases were searched up to April 25, 2024, for randomized controlled trials (RCTs). Random-effect model (DerSimonian–Laird method) was used to pool the risk ratios (RR), mean differences (MD) and 95% confidence interval (CI) for binary and continuous outcomes, respectively. Results: A total of 11 RCTs comprising 4,325 patients (2,295 BEV, 2,030 SEV) were included. At short-term, the risk of cardiovascular (RR: 0.56, 95% CI: 0.36-0.87) and all-cause mortality (RR: 0.54, 95% CI: 0.35-0.81) were lower in the BEV group. However, no differences were noted between the two treatment modalities in longer follow-ups despite the lower risk of moderate to severe paravalvular leak (PVL) among BEV patients. The risk of stroke was comparable between two groups across all three follow-up endpoints, albeit a limited number of studies suggesting the BEV group showed a greater risk of clinical valve thrombosis in mid-term and long-term assessments. The need for permanent pacemaker implantation was lower in BEV arm in short-term (RR: 0.56, 95% CI: 0.37-0.87) and mid-term (RR: 0.78, 95% CI: 0.64-0.94). Yet, this difference was not observed in long-term follow-ups. Conversely, the SEV group had a larger effective orifice area with lower mean transvalvular pressure gradient from short-term (MD: 0.17, 95% CI: 0.07-0.26 and MD: 3.71, 95% CI: 2.64-4.78, respectively) to long-term (MD: 0.25, 95% CI: 0.17-0.32 and MD: 3.73, 95% CI: 3.19-4.27, respectively) periods. Conclusions: BEV is associated with reduced risk of clinical outcomes at short-term; however, most differences diminish in longer evaluations, except for moderate to severe PVL. Conversely, SEV is linked to better hemodynamic outcomes and a lower risk of clinical valve thrombosis across all follow-up durations.

Abstract 4137019: Paclitaxel-Coated Balloon vs Uncoated Balloon for Coronary In-Stent Restenosis: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Background: Despite the effectiveness of drug-eluting stents (DES) in preventing restenosis, many patients still experience DES restenosis. Neointimal hyperplasia and neoatherosclerosis can develop within these stents, leading to recurrent coronary syndromes. Hypothesis: Repeated stenting with DES is limited by additional metal layers, the need for prolonged dual antiplatelet therapy, and heightened risks of stent thrombosis. Locally acting drugs with sustained efficacy may prevent this progression. Paclitaxel delivery via contrast medium or drug-coated balloon catheters could exert antiproliferative effects, reducing neointimal proliferation. Aims: To synthesize existing evidence on the efficacy and safety of Paclitaxel-Coated Balloons versus Uncoated Balloons in coronary in-stent restenosis. Methods: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched five electronic databases (PubMed, EMBASE, Cochrane Library, Scopus, and Web of Science) to identify eligible studies reported up to March 23, 2024. Using R version 4.4.0, we reported outcomes as risk ratios (RRs) or mean differences (MD) and confidence intervals (CIs). This review has been registered and published in PROSPERO (CRD42024527412). Results: The meta-analysis included a total of six trials with 1,541 patients. PCB significantly reduced the incidence of myocardial infarction (RR 0.65, 95% CI [0.42, 1.00], p = 0.052), stent thrombosis (RR 0.26, 95% CI 0.08, to 0.83], p = 0.023), major adverse cardiac events (RR 0.32, 95% CI 0.25, to 0.42], P < 0.001), target lesion revascularization (RR 0.34, 95% CI [0.14, 0.84], p < 0.001). No significant differences were observed between PCB and UCB regarding cardiac-related mortality, target vessel revascularization, percutaneous coronary intervention, all-cause death, Q wave and non-Q wave myocardial infarction, coronary artery bypass grafting, and target vessel failure. Conclusion: PCB for ISR significantly reduced the incidence of myocardial infarction, MACE, and stent thrombosis compared to UCB.

Abstract 4137942: Comparing Outcomes in Low versus High Activated Partial Thromboplastin Time-guided Anticoagulation Monitoring during Extracorporeal Membrane Oxygenation

Introduction: Systemic anticoagulation in Extracorporeal Membrane Oxygenation (ECMO) aims to reduce the risk of patient and circuit thrombosis, but requires monitoring due to risk of bleeding. Activated partial thromboplastin time (aPTT) is one of many tests utilized for this purpose. However, it lacks validation in ECMO patients and its clinical utility necessitates further analysis. Aim: We aim to elucidate associations between low versus high aPTT-guided anticoagulation monitoring and total time, survival, bleeding, and thrombotic events during ECMO. Methods: A retrospective review was conducted on 93 patients requiring ECMO at our institution between January 2020 and March 2021. Study inclusion required more than 2 days on ECMO and maintenance on anticoagulation with aPTT targets predominantly greater (>) or less than (<) 60 seconds (s). Final cohort was 74 subjects; 30 subjects with majority aPTT targets <60s composed the control “low” aPTT group and 44 subjects with aPTT targets >60s composed the “high” aPTT group. Primary outcomes were survival to decannulation, survival to discharge, average time on ECMO, and incidence of bleeding and thrombotic events during ECMO. Bleeding and thrombotic events were classified into subtypes and incidence of each was recorded. Statistical analyses were performed with Fisher’s exact, Pearson’s chi-square, and Student’s t-tests with an alpha level of .05 on IBM SPSS software. Results: The high group required a longer average time on ECMO (29.5 days versus 14.3 days; p = .002; 95% CI [5.5; 24.7]). Chi-square tests did not show an association between the low versus high groups and survival to decannulation (22/30 and 35/44; p = .533), survival to hospital discharge (17/30 and 30/44; p = .312), or overall incidence of bleeding (18/30 and 20/44; p = .219) and thrombotic events (7/30 and 14/44; p = .427). Regarding subtypes of events, Fisher’s exact test showed an association between aPTT target >60s and severe epistaxis (1/30 in the low and 9/44 in the high group; two-tailed p = .042). Though not significant, a greater incidence of oxygenator failure and circuit thrombosis was recorded in the high group. Conclusions: Our findings did not establish a relationship between aPTT target <60s or >60s and survival, bleeding, or thrombotic events. However, aPTT target >60s was associated with longer average ECMO time and severe epistaxis. Further investigation of aPTT-guided anticoagulation monitoring in ECMO patients is needed.

Abstract 4127931: Chronic Steroid Use is Associated with Increased Readmission Rates in Patients Admitted with Acute Coronary Syndromes

Introduction: Acute coronary syndrome (ACS) is associated with significant morbidity and mortality. Management of ACS includes percutaneous coronary intervention (PCI) and requires the use of antithrombotic therapy, which increases bleeding risk. Chronic steroid use (CSU) is common for many diseases and is also associated with bleeding risk and impaired wound healing. However, data on outcomes of patients with CSU and AMI are sparse. Methods: Patients admitted for ACS and managed with PCI from 2014 to 2020 with and without CSU were identified using the National Readmissions Database (NRD). In-hospital outcomes include death, arterial thrombosis (composite of ischemic stroke and arterial thromboembolism), and major bleeding (composite of gastrointestinal, intracranial, or post-procedure bleeding or transfusion). Ninety-day readmission outcomes were cardiovascular (CV)-related, bleeding-related and all-cause. Multivariable logistic or Cox proportional hazards were utilized. Results: A total of 1,087,357 patients with ACS were included, of whom, 9,864 (0.9%) had CSU. After multivariable adjustment, there was no significant difference in in-hospital mortality (3.1% vs 3.2%; OR 1.09, 95% CI 0.93-1.26) or risk of arterial thrombosis (3.3% vs 2.8%; OR 0.91, 95% CI 0.81-1.02) between patients with and without CSU. CSU was associated with an increased risk of major bleeding events (8.3% vs 6.0%; OR 1.15, 95% CI 1.06-1.25). CSU was associated with a higher risk of CV-related (10.7% vs 7.5%; HR 1.10, 95% CI 1.02-1.18), bleeding-related (2.3% vs 1.2%; HR 1.28, 95% CI 1.09-1.51), and all-cause 90-day readmissions (23.9% vs 14.9%; HR 1.28, 95% CI, 1.22-1.34). Conclusion: Among patients admitted with ACS who underwent PCI, CSU was associated with increased risk of bleeding during index hospitalization and readmissions for bleeding. Furthermore, CSU was associated with increased risk of 90-day CV and all-cause readmission. Further studies are needed to better characterize this risk.

Abstract 4120966: Outcomes Following Balloon Angioplasty with Drug Coated Versus Uncoated Balloons in Patients with Coronary In-Stent Restenosis: A Systematic Review and Meta-Analysis

Background <div> </div> <div>The development of in-stent restenosis (ISR) has emerged as a substantial barrier to interventional treatment for coronary heart disease. Drug-coated balloon (DCB) is an efficacious interventional technique for the management of ISR. This meta-analysis compares the efficacy of DCB in the treatment of ISR with that of an uncoated balloon (UCB).</div> <div> </div> <div>Methods</div> <div> </div> <div>We comprehensively searched literature on MEDLINE, Embase, Cochrane, and clinicaltrials.gov using MeSH terms and relevant keywords for “Balloon Angioplasty” and “in-stent Restenosis” from inception to June 1, 2024, followed by a meta-analysis of all randomized controlled trials (RCTs) to assess both strategies for treatment of ISR. Random effects model was used to aggregate the risk ratios (RR) for dichotomous and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI).</div> <div> </div> <div>Results</div> <div> </div> <div>The search strategy retrieved 2330 studies. Duplicates and irrelevant articles were removed and data from seven RCTs (1,408 patients) was extracted. The mean age ranged from 64 to 74 years. The mean clinical follow-up ranged from 1 to 10 years. DCB was found to be superior to UCB at latest follow up in terms of target lesion revascularization (TLR) (RR 0.34, 95% CI 0.19-0.58; p 0.0001; I2 79%), major adverse cardiovascular events (MACE) (RR 0.41, 95% CI 0.23-0.73; p 0.003; I2 84%), late lumen loss (LLL) (MD -0.46 mm, 95% CI -0.64- -0.28]; p <0.00001; I2 64%), and target vessel revascularization (TVR) (RR 0.45, 95% CI 0.29-0.70; p 0.0003; I2 67%). The two groups were comparable at latest follow up in terms of mortality (RR 0.87, 95% CI 0.65-1.16; p 0.35; I2 0%), cardiac death (RR 0.89, 95% CI 0.66-1.19; p 0.43; I2 0%), myocardial infarction (MI) (RR 0.70, 95% CI 0.39-1.24; p 0.22; I2 28%) and stent thrombosis (RR 0.22, 95% CI 0.04-1.10; p 0.06; I2 46%).</div> <div> </div> <div> </div> <div> </div> <div>Conclusion</div> <div> </div> <div>DCB showed promising results in the treatment of patients with coronary ISR. DCB outperformed UCB in significantly reducing TLR, MACE, LLL and TVR risks. The risk of mortality, cardiac death, MI, and stent thrombosis was similar between DCB and UCB.</div> <div> </div> <div> </div>

Abstract 4121530: Comparison of Drug-Coated Balloon Versus Drug-Eluting Stents in Acute Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis

Background: Percutaneous coronary intervention (PCI) is the preferred revascularization strategy for acute myocardial infarction (AMI). Drug-eluting stents (DES) are linked to higher risks of stent restenosis and stent thrombosis when implanted for AMI. Drug-coated balloons (DCB) provide a high concentration of anti-proliferative drugs over the target lesion without using the polymeric stent structures. The current literature comparing DCB to DES for AMI PCI is limited. Methods: A systematic literature search was performed on the major electronic databases for studies comparing DCB to DES for AMI PCI. Mean difference (MD) and odds ratio (OR) with their corresponding 95% confidence intervals were pooled using a random-effects model, and a p-value of <0.05 was considered statistically significant. Results: A total of 8 studies with 1401 AMI patients were included (545: DCB and 856: DES). The pooled analysis demonstrated that DCB was associated with significantly lower mean lumen diameter on follow-up [MD: -0.26; 95% CI: -0.47, -0.05; p=0.02] compared to DES. However, there was no statistically significant difference in mean in-stent late lumen loss [MD: 0.07; 95% CI: -0.03, 0.18], cardiovascular mortality [OR: 0.90; 95% CI: 0.35, 2.34], all-cause mortality [OR: 0.80; 95% CI: 0.25, 2.63], myocardial infarction [OR: 0.94; 95% CI: 0.36, 2.45], major adverse cardiovascular events [OR: 0.97; 95% CI: 0.47, 2.00], target lesion revascularization [OR: 1.59; 95% CI: 0.52, 4.87], and stent thrombosis [OR: 0.48; 95% CI: 0.05, 4.94]. Conclusion: In patients with AMI, PCI using DCB leads to a significant reduction in the minimum lumen diameter on follow-up compared to DES. No statistically significant difference was noted in mean in-stent late lumen loss, cardiovascular mortality, all-cause mortality, myocardial infarction, major adverse cardiovascular events, target vessel revascularization, and stent thrombosis. Further trials are warranted to confirm these findings.

Neutrophil‐to‐lymphocyte ratio (NLR) at diagnosis in essential thrombocythemia: A new promising predictor of thrombotic events

ABSTRACTBackgroundMyeloproliferative neoplasms represent a heterogeneous group of acquired hematopoietic stem cell diseases in which chronic inflammation is essential for both clonal evolution and thrombotic complications. The neutrophil‐to‐lymphocyte ratio (NLR), reflecting the imbalance between systemic inflammation and immunity, is emerging as a prognostic biomarker in several diseases, including hematological ones.MethodsA total of 473 patients with essential thrombocythemia (ET), the relationship between NLR value at diagnosis and the risk of thrombotic events in the follow‐up, in addition to conventional clinical and biological variables, were retrospectively analyzed.ResultsA total of 78 thrombotic events were reported for an incidence rate of 1.8 × 100 patients/year. In multivariate analysis, NLR value ≥4 at diagnosis was associated with higher cumulative thrombotic risk (hazard ratio [HR], 2.05; 95% CI, 1.29–2.28; p = .0001) as well International Prognostic Score for Thrombosis in Essential Thrombosis score intermediate‐high (HR, 2.69; 95% CI, 1.27–5.72; p = .01) and diabetes (HR, 2.49; 95% CI, 1.23–3.05; p = .010). Concerning arterial thrombotic events, in multivariate analysis, NLR value at diagnosis ≥4 was predictive for thrombosis (HR, 2.13; 95% CI, 1.31–4.04; p = .001 as well diabetes (HR, 2.44; 95% CI, 1.05–5.68; p = .04) and hypertension (HR, 2.46; 95% CI, 1.05–5.68; p = .01). About venous thrombotic events, NLR value ≥5 was a marker predictive for venous thrombosis (HR, 2.99; 95% CI, 2.45–6.48; p = .01) as well age >60 years old (HR, 2.26; 95% CI, 1.0–5.10; p = .05).ConclusionNLR value is a simple, cost‐effective, and easy‐to‐obtain inflammatory marker that can predict a diagnosis the risk of thrombosis in ET. Our results suggest that NLR value could be integrated into conventional cardiovascular risk scores, to better classify high‐risk patients who are candidates for cytoreductive therapy. Further larger and prospective studies are warranted.

Case report of varicose veins treatment in patient with a prosthetic mitral valve

This clinical case may be of interest in situations where a patient with varicose veins of the lower limbs and concomitant heart disease, who is on long-term anticoagulant therapy and is scheduled to undergo minor surgery, may present the possibility of endovenous laser ablation (EVLA) against the background of warfarin use. Patient, G., 68 years old, with rheumatic combined mitral valve disease (mitral valve replacement in 2019, permanent atrial fibrillation), also had varicose vein disease of the lower limbs. History included acute cerebrovascular accident (19.01.2023). Duplex Ultrasonography Screening (DUS) showed failure of the left great saphenous vein valve. Hypocoagulation was also observed in coagulogram and the risk of bleeding on HAS-BLED score was average. On Caprini score, the risk was very high. Endovenous laser ablation of the large saphenous vein on the left side was performed. During follow-up examinations, there were no signs of bleeding from puncture sites. The target trunk was obliterated in dynamics at DUS. Therefore, it is possible to carry out EVLA of a large subcutaneous vein while taking therapeutic doses of warfarin without switching to bridge therapy. Endovascular laser ablation allowed it to be done with less risk of bleeding and, against the background of taking warfarin, reduced the risk of thrombosis.

Observational Analyses of Ex Vivo Native American Platelet Responses

Platelet activation plays an essential role in clot formation to prevent blood loss following vascular damage. In pathologic conditions, platelet activation can lead to obstructive clots, disrupting blood flow and resulting in thrombosis. Native Americans suffer disproportionately from arterial disease and previous research has shown that Blacks are enriched in genetic polymorphisms that correlate with higher platelet reactivity contributing to an increased risk for thrombosis. Therefore, the current study sought to determine phenotypic variations in Native American platelet responses following stimulation with agonists, simulating vascular damage. Several donors from a small cohort of Native Americans showed atypical robust platelet aggregation when stimulated with submaximal concentrations of agonists. Further, when comparing α-granule secretion, a specific marker of platelet activation, Native Americans were more likely to have elevated responses to multiple agonist conditions of stimulation compared to Whites. Interestingly, there were no noticeable differences in integrin activation between Native Americans and Whites. Our study is the first to observe elevated Native American platelet responses compared to Whites, supporting further mechanistic studies and investigation of treatment approaches for the prevention of thrombosis.

Platelet-Function-Monitoring-Guided Therapy After Emergent Carotid Artery Stenting

Background/Objectives: Antiplatelet therapy after emergent carotid stenting (eCAS) represents a challenge in balancing the risk of intracerebral hemorrhages (ICHs) and in-stent thrombosis (IST). Post-procedural platelet function monitoring may guide antiplatelet therapy and could potentially improve outcomes due to fewer post-procedural complications. Methods: Consecutive eCAS patients (2019–2021) were included in a single-center retrospective observational study. Patients treated with eCAS received peri-procedural eptifibatide followed by dual antiplatelet treatment with aspirin and clopidogrel. The effect of platelet ADP inhibition by clopidogrel was monitored using the Multiplate® Analyzer (Roche). Clopidogrel non-responders were changed to ticagrelor treatment. The primary outcome was defined as a favorable outcome at 90 days using the modified Rankin Scale (mRS) of 0–2 versus 3–6. Safety outcomes included ICH, IST, and mortality. Data were analyzed and compared in clopidogrel- and ticagrelor-treated patients using Fischer’s exact test and multivariate logistic regression. Results: A total of 105 patients had eCAS, and 28 patients (27%) were clopidogrel non-responders and were changed to treatment with ticagrelor. The favorable outcome was more frequent in ticagrelor-treated patients, 23 (82%), than in clopidogrel-treated patients, 44 (57%), p = 0.036. Numerically, ICH, IST, and mortality were more frequent in clopidogrel-treated patients, but none of the differences were statistically significant. In multivariate analyses, ticagrelor treatment was significantly associated with the favorable outcome, OR = 3.89 (95% CI: 1.09–13.86), p = 0.036. Conclusions: One in four eCAS patients were clopidogrel non-responders. This study suggests that personalized antiplatelet treatment therapy was safe, and that changing treatment to ticagrelor in clopidogrel non-responders was associated with better outcomes in eCAS patients.

Stent thrombosis in the setting of ST-segment elevation acute myocardial infarction in the contemporary practice: results from the TOTAL randomized trial.

The aim was to know the risk and predictive factors of stent thrombosis (ST) in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) in the contemporary practice. The TOTAL [ThrOmbecTomy with percutaneous coronary intervention (PCI) versus PCI ALone] randomized trial, being the largest trial performed in the setting of STEMI with a general application of the recent recommendations, represents a unique opportunity to know the current real-world incidence of ST as well as its associated factors. A total of 10 064 patients that received ≥1 coronary stent in the TOTAL trial comprise the study population. The risk, predictive factors, and clinical implications of ST was studied. During 1-year follow-up, 155 patients (1.54%) suffered definitive or probable ST (59 acute, 67 subacute, and 29 late). Previous infarction, the number of stents, the previous use of clopidogrel, and the use of diuretics at discharge were independent predictors for ST, whereas the use of upfront glycoprotein IIb/IIIa inhibitors, radial access, and treatment with statins at discharge were independent protective factors. The number of stents, stent diameter, upfront treatment with IIb/IIIa inhibitors, previous treatment with clopidogrel, and treatment with statins at discharge were independently associated with the risk of early ST. Only previous infarction was associated with the risk of late ST. In the contemporary practice, ST still constitutes a frequent complication of primary PCI for STEMI, occurring in 1.5% of patients. Independent predictors are different depending on the time of ST.

Use of Affimer Technology for Inhibition of α2-antiplasmin and Enhancement of Fibrinolysis

Hypofibrinolysis is a documented abnormality in conditions with high risk of vascular occlusion. A key inhibitor of fibrinolysis is α2-antiplasmin (α2AP) and we hypothesise that the Affimer technology, comprising small conformational proteins with two nine amino acid variable regions, can be used to modulate α2AP activity and facilitate fibrinolysis.Using a phage display system, a library of Affimers was screened against α2AP. A total of 28 α2AP-specific Affimers were isolated of which one, termed Affimer A11, inhibited protein function and enhanced fibrinolysis. Affimer A11 displayed a monomeric form and consistently reduced lysis time of clots made from plasma samples of individuals with type 2 diabetes mellitus (n=15; from 150.8±100.9 to 109.8±104.8 mins) and those with cardiovascular disease (n=15; 117.6±40.6 to 79.7±33.3 mins); p<0.01 for both groups. The effects of A11 on fibrinolysis were maintained when clots were made from whole blood samples.Mechanistic studies demonstrated that A11 did not affect clot structure or interfere with incorporation of α2AP into fibrin networks but significantly enhanced plasmin activity and accelerated plasmin generation. Affimer A11 reduced α2AP binding to plasmin(ogen), while molecular modelling demonstrated interactions with α2AP in an area responsible for binding to plasminogen, explaining the effects on both plasmin activity and generation. Affimer A11, at 0.15-0.60 mg/ml, had the ability to bind 70-90% of plasma α2AP.In conclusion, we demonstrate that Affimers are viable tools for inhibiting α2AP function and facilitating fibrinolysis, making them potential future therapeutic agents to reduce thrombosis risk.

Investigating the Matrix of Factor V Leiden (G1691A), Factor II Prothrombin (G2021A), MTHFR C677T and A1298G Polymorphisms in Greek Population: A Preliminary Study

Background: Thrombophilia, characterized by an increased risk of thrombosis, can result from genetic polymorphisms in clotting factors. This study aims to investigate the prevalence of factor V Leiden (G1691A), factor II prothrombin (G20210A), and MTHFR (C677T and A1298C) polymorphisms in a Greek population, evaluating not only their association with thrombophilia, but also broader health implications. Methods: We conducted a cross-sectional study involving one hundred apparently healthy adults from Thessaloniki, Greece. After obtaining informed consent, DNA was isolated and analyzed using real-time PCR to detect the frequencies of the aforementioned polymorphisms. Results: The genetic distribution of the examined polymorphisms aligns closely with that observed in Northern Europe. Factor V Leiden (FVL) and prothrombin G20210A mutations were predominantly wild types, with a small percentage showing heterozygous mutations. The MTHFR C677T and A1298C polymorphisms showed a higher variation in allele frequency. Certain lifestyle factors such as smoking and high body mass index were significantly associated with the occurrence of combined MTHFR genotypes, suggesting an interaction between genetic and environmental risk factors. Family cancer and cardiovascular history was significantly associated with combined FVL and prothrombin G20210A and MTHFR polymorphism heterozygous carriers. Conclusions: Our findings indicate that these genetic polymorphisms are not only pivotal in understanding thrombophilia but also have broader implications for cardiovascular disease and cancer. This study highlights the need for further research into the combined effects of genetic and epigenetic factors on health, which could lead to improved screening and personalized preventive healthcare strategies.

Stent strategies: Endothelial progenitor cell coated stents vs sirolimus eluting stents in a pairwise meta-analysis

BackgroundEndothelial progenitor cells (EPCs) capturing stents were developed to enhance endothelial repair and reduce the risk of stent thrombosis, addressing limitations of Sirolimus-Eluting Stents (SES). This study aims to compare the safety and efficacy of EPC stents versus SES in patients undergoing percutaneous coronary intervention (PCI). MethodsWe performed a meta-analysis following PRISMA guidelines in patients undergoing PCI treated with Sirolimus eluting stent (SES) vs the use of EPC stents and recognized 8 clinical trials with patients undergoing PCI and reporting outcomes such as Target Lesion Failure (TLF), stent thrombosis, and revascularisation. Relative risks were calculated using a random effects model and heterogeneity was assessed with I^2 statistics. ResultsThe EPC group showed higher incidence of TLF (RR ​= ​1.28), MI(RR ​= ​1.10), and cardiac death (RR ​= ​1.19) compared to SES, though these differences were not statistically significant. Revascularisation rates were significantly higher in EPC group with TVR (RR ​= ​1.60) and TLR(RR ​= ​2.20) while stent thrombosis was lower (RR ​= ​0.93). ConclusionThe results of this EPC study reveals that while EPC stents show promise in revascularisation and lowering stent thrombosis, they are also associated with higher incidence of adverse events. The utility of EPC, especially vast reendothelialization, may have niche applications but their full potential can be realized with more rigorous trials as a clear advantage over SES remains lacking.

Association of thrombophilic genes (MTHFR, MTR and MTRR) polymorphisms and homocysteine level in relation to the increased risk of thrombosis among COVID-19 patients

BackgroundPatients with COVID-19 have an increased risk of thrombosis and coagulopathy. Homocysteine, an amino acid essential to coagulation, is thought to be involved in such conditions, as its level is mediated by the presence of some single nucleotide polymorphisms (SNPs) in certain genes including MTHFR, MTR and MTRR. AimThe current study aimed to assess the significant role of MTHFR (C677T and A1298C), MTR A2756G and MTRR A66G SNPs as risk factors for thrombosis among Egyptian COVID-19 patients and their effect on homocysteine level. Subjects and methodsThis case-control study was carried out on 90 Egyptian COVID-19 cases, divided into 45 non-complicated cases and 45 complicated cases with thrombosis, in addition to 80 healthy control individuals. DNA was isolated from blood samples of all the participants. The genotyping was performed using real-time PCR; in addition, serum homocysteine level was estimated. ResultsThe MTHFR (C677T and A1298C), MTR A2756G and MTRR A66G variants revealed a significant higher risk of thrombosis under different genetic models including the homozygous comparison of the co-dominant (20 % vs. 2.3 %, OR = 15.88, p = 0.007), the dominant (62.2 % vs. 33.3 % OR = 3.29, p = 0.006) and the allelic models (41.1 % vs. 17.8 %, OR = 3.2, p < 0.001) for MTHFR C677T and also the dominant (77.8 % vs. 51.1 %, OR = 3.3, p = 0.008) and the allelic models (52.2 % vs. 31.1 %, OR = 2.4, p = 0.004) for MTHFR A1298C. In addition, the heterozygous comparison of the co-dominant (60 vs. 11.1, OR = 12.7, p < 0.001), the dominant (62.2 % vs. 11.1 %, OR = 13.1, p < 0.001) and the allelic models (32.2 % vs. 5.6 %, OR = 8.08, p < 0.001) for MTR A2756G and the heterozygous and homozygous comparisons of the co-dominant model [(53.3 % vs. 31.1 %, OR = 3.4, p = 0.03) and (13.4 % vs. 2.2 %, OR = 12.0, p = 0.049), respectively], the dominant (66.4 % vs. 33.3 %, OR = 4.0, p = 0.001) and the allelic models (40 % vs. 17.8 %, OR = 3, p = 0.001) for MTRR A66G. Moreover, MTHFR (C677T and A1298C), MTR A2756G, and MTRR A66G variants were also associated with high levels of serum homocysteine (p = 0.045, 0.001, 0.005 and 0.039, respectively). The homocysteine level was related to the disease severity by its correlation with higher LDH (rs = 0.49, p < 0.001), CRP (rs = 0.44, p < 0.001), IL-6 (rs = 0.46, p < 0.001) and D-dimer (rs = 0.66, p < 0.001) levels. The multivariate regression analysis showed that homocysteine and the dominant models of MTHFR (C677T and A1298C), MTR A2756G and MTRR A66G were independent predictors of susceptibility to thrombosis among COVID-19 patients [(OR = 1.02, p = 0.007), (OR = 1.15, p = 0.043), (OR = 1.2, p = 0.024), (OR = 1.42, p < 0.001), (OR = 1.19, p = 0.021), respectively]. ConclusionMTHFR (C677T and A1298C), MTR A2756G, and MTRR A66G gene variants were associated with high homocysteine and D-dimer levels that carried a risk for thrombosis among COVID-19 patients and associated with the disease progression.

OA05 A case of VEXAS syndrome treated with hematopoietic stem cell transplantation

Abstract Introduction VEXAS is an acquired auto-inflammatory condition first described in 2020. It is linked to a somatic inactivating mutation in the X-linked UBA1 gene in haemopoietic progenitor cells. The UBA1 gene codes for UBA1 enzymes including E1 enzymes that catalyse the first steps of ubiquitination and lend an ‘E’ to the VEXAS acronym. Ubiquitination is a process whereby proteins are flagged for degradation, transported within the cell, or up or downregulated. We discuss the case of a 68-year-old male diagnosed with VEXAS syndrome and his response to treatments including glucocorticoids, biologic therapy, and stem cell transplantation. Case description The patient presented with coryza, cough, night sweats, fever, and testicular pain. Bloods showed normocytic anaemia (Hb 128 g/L), neutropenia (neutrophils 1.9x10^9/L) and raised CRP (98 mg/L). PET CT, autoantibody testing, complement, ACE, CK, myeloma and infection screening were unremarkable. Symptoms progressed to include auricular and nasal swelling in keeping with chondritis, sinusitis, headaches, and myalgias. A diagnosis of relapsing polychondritis was suspected. Treatment with prednisolone 40 mg once daily and methotrexate 15 mg once weekly commenced with dramatic biochemical (CRP 10 mg/L) and symptomatic improvement, though cytopenias persisted. Prednisolone was weaned gradually to 15 mg once daily, however, symptoms returned and remained uncontrolled despite reinstating higher steroid doses. A bone marrow biopsy was undertaken and UBA1 mutation c.122T&amp;gt;c, p.Met41Th was found, in keeping with VEXAS syndrome. Treatment was escalated to tocilizumab with initial partial symptomatic response, however, cell counts continued to drop with Hb, platelets, and neutrophils dipping as low as 63 g/L, 23x10^9/L, and 0.4x10^9/L respectively. He required regular blood transfusions, developed severe and recurrent infections, and had rash, paraesthesias, scleritis, breathlessness, episodic tongue and throat swelling, and injection site reactions. Following discussion about further treatment options, the patient went on to have a successful hematopoietic stem cell transplant (HSCT). Discussion The inflammatory and haematological manifestations of VEXAS syndrome are frequently resistant to DMARD and biologic treatment which is reflected in this case. Corticosteroid use has been shown to improve inflammatory symptoms at high doses, though is associated with significant toxicity and has not been effective in improving VEXAS associated cytopenias. Currently, medical therapeutic options for VEXAS syndrome include IL-1 inhibitors (e.g. Anakinra), IL-6 inhibitors (e.g. Tocilizumab), JAK inhibitors (e.g. Baricitinib), and corticosteroids. Available evidence suggests symptomatic response rates to IL-6 inhibitors and JAK inhibitors are around 50% but that they have no effect on bone marrow failure. Supportive measures include infection prevention through vaccination and prophylactic antibiotics, assessment of bleeding and thrombosis risk, thrombopoetin receptor agonists (e.g. Eltrombopag), erythropoetin, and blood products to optimise blood counts. For patients with bone marrow failure, HSCT is an option, though case series and case-reported outcomes have been variable. Some patients are reported to have had complete and sustained remission of symptoms and normalisation of cell counts without complication, while others developed significant complications including viral reactivation, graft vs host disease, and in some cases, mortality. In our case, HSCT was the preferred treatment choice as recurrent infections limited immunosuppression. The patient has been reviewed at day 50 post HSCT. There has been a near resolution of cell counts with Hb 115 g/L, platelets 143 x 10^9/L, WCC 6.1x10^9/L, neutrophils 4.7x10^9/L. Inflammatory symptoms have all but resolved, save persistent paraesthesia in the feet. Tocilizumab has been ceased and prednisolone has been reduced to 4 mg once daily. Key learning points • HSCT is an important management option for patients with VEXAS syndrome, however, is associated with significant morbidity and mortality. The nature of VEXAS syndrome means that those affected are more likely to be of more advanced age and frailty, and so at higher risk of post-transplant complications. Some data suggests better outcomes post HSCT in patients who had better controlled disease or less severe disease prior to HSCT and the benefit of early HSCT may be worth considering. • Further collation of data regarding outcomes of patients who receive HSCT will be beneficial in risk stratifying VEXAS syndrome patients who may be suitable for HSCT.

Rescue of COVID-19 Patient Complicated by Spontaneous Pneumothorax and Acute Pulmonary Thromboembolism

Abstract Pulmonary thromboembolism is a common cardiovascular disease, with high morbidity and mortality rates in hospitalized patients. Because of clotting disorders and hypoxemia caused by COVID-19, critically ill patients are highly susceptible to thrombotic complications. A study published in the Journal of the American Medical Association in 2022 showed that the incidence of venous thromboembolism (VTE) in critically ill COVID-19 patients was approximately 10% to 35%, whereas the incidence of VTE in autopsy cases was as high as 60% (JAMA Intern Med 182:1063-1070). Clinicians need increased awareness of VTE in COVID-19 patients, to reduce the risk of deep vein thrombosis and pulmonary thromboembolism and to be alert to life-threatening complications.

Role of Thrombosis in Neurodegenerative Diseases: An Intricate Mechanism of Neurovascular Complications.

Thrombosis, the formation of blood clots in arteries or veins, poses a significant health risk by disrupting the blood flow. It can potentially lead to major cardiovascular complications such as acute myocardial infarction or ischemic stroke (arterial thrombosis) and deep vein thrombosis or pulmonary embolism (venous thrombosis). Nevertheless, over the course of several decades, researchers have observed an association between different cardiovascular events and neurodegenerative diseases, which progressively harm and impair parts of the nervous system, particularly the brain. Furthermore, thrombotic complications have been identified in numerous clinical instances of neurodegenerative diseases, particularly Alzheimer's disease, Parkinson's disease, multiple sclerosis, and Huntington's disease. Substantial research indicates that endothelial dysfunction, vascular inflammation, coagulation abnormalities, and platelet hyperactivation are commonly observed in these conditions, collectively contributing to an increased risk of thrombosis. Thrombosis can, in turn, contribute to the onset, pathogenesis, and severity of these neurological disorders. Hence, this concise review comprehensively explores the correlation between cardiovascular diseases and neurodegenerative diseases, elucidating the cellular and molecular mechanisms of thrombosis in these neurodegenerative diseases. Additionally, a detailed discussion is provided on the commonly employed antithrombotic medications in the context of these neuronal diseases.

Incidence of venous thromboembolic disease and risk of bleeding in critically ill patients with hematologic malignancies: A retrospective study

ObjectiveOur objectives were to describe the use of thromboprophylaxis and the incidence of VTE/bleeding in critically ill patients with hematologic malignancies (HM). DesignRetrospective cohort study (2014–2022). SettingMedic-Surgical Intensive Care Unit (ICU) in a tertiary care academic center. PatientsAdult patients admitted to ICU with a concomitant diagnosis of a hematological malignancy. InterventionsNone. Main variables of interestWe analyzed demographic data, use of thromboprophylaxis and secondary outcomes that included incidence of VTE (venous thromboembolism), bleeding, mortality, severity scores and organ support. We applied a multivariable logistic regression model to examine the risk of thrombosis in the ICU. ResultsWe included 862 ICU admissions (813 unique patients). Thromboprophylaxis was given during 65% of admissions (LMWH 14%, UFH 8%, and SCDs 43%); in 21% it was contraindicated due to thrombocytopenia; 14% of cases lacked documentation on prophylaxis. There were 38 unique incident cases of VTE (27 DVT, 11 PE), constituting 4.4% of ICU episodes. Most of VTE cases happened in patients with various degrees of thrombocytopenia. In the multivariable analysis, SOFA score on the first ICU day was independently associated (OR 0.85, 95% CI 0.76−0.96) with the risk of VTE. Bleeding occurred in 7.2% (minor) and 14.4% (major) of episodes; most frequent sites being CNS, abdomen/GI and pulmonary. ConclusionsIn this cohort of critically ill patients with HM, there was considerable variability in the utilization of DVT prophylaxis, with predominant use of SCDs. The incidence of VTE was 4.4% and major bleeding 14%. Clinical Trial RegistrationNCT05396157. Venous Thromboembolism in Hematologic Malignancy and Hematopoietic Cell Transplant Patients: a Retrospective Study (https://clinicaltrials.gov/).

The Use of Pedicular Arteriovenous Fistula (PAVF) in Microvascular Reconstruction to Enhance Flow Across the Microvascular Anastomoses.

Free flap success rates have improved dramatically over the past three decades, setting a high standard for microvascular reconstruction. However, rates of arterial or venous thrombosis, and subsequent failure, remain high in burn and trauma reconstruction when compared to autologous breast reconstruction and other elective flaps. To address the higher failure rate, we use a novel vascular approach. We create a pedicular arteriovenous fistula (PAVF), allowing the flow to be enhanced across the microvascular anastomoses. We performed a retrospective review of 13 consecutive patients with 14 free flaps who underwent PAVF creation by the first author, AO. All patients who required free tissue transfer for trauma and burn reconstruction were indicated for PAVF during this study period. The flaps in this study included ALT, fibula, parascapular, and partial latissimus. The perforator and pedicle for the flaps were dissected in the usual manner. Distal to the takeoff of the perforator to the flap, the pedicular artery and the larger of the accompanying veins were anastomosed to create the PAVF. Patients were followed for a mean of 171 days Thrombosis was a rare complication in the group with one venous thrombosis (n = 1, 7.14%) and no arterial thrombosis. The most common complication was return to the operating room n = 4 (28.57%), two of which secondary to hematomas (14.29%), one wound dehiscence and one venous thrombosis. This latter patient eventually had partial flap loss. We did not observe flap ischemia due to vascular steal, nor any venous congestion from pressurizing the venous outflow. As opposed to anticoagulation, flow enhancement aims to decrease the risk of thrombosis by reducing stasis. While further data is needed to compare the outcomes of venous enhanced flaps when compared to flaps treated prophylactically with anticoagulation, our initial data suggests that PAVF is a safe procedure and does not result in vascular steal or flap congestion.