Rate Of Thrombosis Research Articles

Strategies to reduce rates of severe endothermal heat-induced thrombosis following radiofrequency ablation

ObjectiveEndothermal heat-induced thrombosis (EHIT) is a potential complication of radiofrequency ablation (RFA). Data on effective prophylaxis of EHIT are limited. In 2018, a high-volume, single institution implemented strategies to decrease the incidence of EHIT, including a single periprocedural prophylactic dose of low-molecular-weight heparin to patients with a great saphenous vein (GSV) diameter of ≥8 mm or saphenofemoral junction (SFJ) diameter of ≥10 mm and limiting treatment to one vein per procedure. The size threshold was derived from existing literature. The study objective was to evaluate the effects of these institutional changes on thrombotic complication rates after RFA. MethodsA retrospective cohort control study was conducted using the Vascular Quality Initiative database. Data were collected for patients who underwent RFA with a GSV diameter of ≥8 mm or SFJ diameter of ≥10 mm from January 2015 to July 2022. The clinical end points were thrombotic complications (ie, thrombophlebitis, EHIT, deep vein thrombosis) and bleeding complications. Patient demographic and procedural variables were included in the analysis, and significant variables after univariable logistic regression were included in a multivariable logistic regression. ResultsAfter the policy change, the overall vein center EHIT rate decreased from 2.6% to 1.5%, with a trend toward significance (P = .096). The inclusion criterion of a GSV diameter of ≥8 mm or an SFJ diameter of ≥10 mm yielded 845 patients, of whom 298 were treated before the policy change and 547 after. There was a significant reduction in the rate of EHIT classified as class ≥III (2.34 vs 0.366; P = .020) after the institutional changes. Treatment of two or more veins and an increased vein diameter were associated with an increased risk of EHIT (P = .049 and P < .001, respectively). No significant association was found between periprocedural anticoagulation and all-cause thrombotic complications or EHIT (P = .563 and P = .885, respectively). ConclusionsThe institutional policy changes have led to lower rates of EHIT, with a reduction in severe EHIT rates in patients with an ≥8-mm diameter GSV or a ≥10-mm diameter SFJ treated with RFA. Of the changes implemented, restricting treatment to one vein was associated with a reduction in severe EHIT. No association was found with periprocedural low-molecular-weight heparin, although a type 2 error might have occurred. Alternative strategies to prevent thrombotic complications should be explored, such as increasing the dosage and duration of periprocedural anticoagulation, antiplatelet use, and nonpharmacologic strategies.

Low recurrent thrombosis rates in single positive antiphospholipid syndrome regardless of type of anticoagulation

Thrombotic antiphospholipid syndrome (TAPS) is characterized by thrombosis and persistently positive tests for antiphospholipid antibodies or lupus anticoagulant (LAC). Triple-positive APS has the highest risk of recurrent thrombosis, but no studies have focused on recurrent thrombosis in patients with single-positive TAPS. We conducted a retrospective cohort study of patients with single-positive TAPS diagnosed at Lifespan Health System, Rhode Island, to determine the rates and risk factors for recurrent thrombosis. Between January 2001 and April 2022, 128 patients were assessed who had single-positive APS (LAC = 98, aCL = 21, aβ2GPI = 9) and who had been followed for a total of 1453.8 patient-years (median follow-up 3.04 years). The initial antithrombotic regimen was warfarin in 44 %, a direct oral anticoagulant (DOAC) in 34 %, enoxaparin in 2 %, and no antithrombotic therapy or antiplatelet therapy only in 20 %. Recurrent thrombosis occurred in 16 (12.5 %) with a recurrent thrombosis rate of 3.08 per 100 patient-years. Systemic lupus erythematosus was the only variable significantly associated with recurrent thrombosis in a model adjusted for age, sex, body mass index, and type of positive APS test. All 16 patients with recurrent thrombosis were initially treated with warfarin, and, at the time of recurrent thrombosis, 13 patients remained on warfarin and three were off anticoagulation. In conclusion, the recurrent thrombosis rate in single-positive APS is low, and not all patients with a single-positive test may need indefinite anticoagulation with warfarin. Larger prospective studies are required to confirm this finding and establish optimal anticoagulation regimens for low-risk TAPS.

Antithrombotic pharmacodynamics and metabolomics study in raw and processed products of Whitmania pigra Whitman

ObjectiveAs a traditional Chinese medicine, leech has obvious pharmacological activities in anticoagulantion and antithrombosis. Whitmania pigra Whitman (WP) is the most commonly used leech in the Chinese market. It is often used in clinical applications after high-temperature processing by talcum powder to remove the fishy taste and facilitate crushing. The anticoagulant and thrombolytic active ingredients are protein and polypeptide, which may denaturate and lose activity after high-temperature processing. The rationality of its processing has been questioned in recent years. This study aims to investigate the effect of talcum powder scalding on the antithrombotic activity of WP in vivo and to discuss its pharmacodynamic mechanism in vivo. MethodsRaw and talcum-powdered processed WP were administered intragastrically for 14 days, and carrageenan was injected intraperitoneally to prepare a mouse model of tail vein thrombosis. The incidence rate of tail vein thrombosis and the thrombus area under pathological tissue sections were calculated to evaluate the antithrombotic effect between raw and processed WP. Non-targeted metabolomics was conducted using UPLC-Q-TOF/MS technology to analyze the changes of small molecule metabolites in the body after administration of WP. ResultsAfter intragastric administration, both the raw product and the processed product of WP could inhibit the thrombosis induced by carrageenan, and the processed product had a more apparent antithrombotic effect than the raw product. The administration of WP could regulate the changes of some small molecular metabolites, such as amino acids, lipids, and steroids, in Sphingolipid metabolism and Glycerophospholipid metabolism. ConclusionsBased on the results of pharmacodynamics and metabolomics, processed WP will not reduce the antithrombotic activity of WP. This study provided a scientific basis for the rational use of leeches.

Autologous cell salvage in off-pump coronary artery bypass surgery reduces post-operative complications: a retrospective weighted-matching analysis.

Blood transfusion plays a crucial role in coronary artery bypass grafting (CABG). The choice between autologouscell saver (CS) and allogenic blood transfusion (ABT) has been a continuous debate in the medical community, especially within cardiac surgery. This study aimed to assess the outcomes of off-pump CABG (OPCAB) surgery in patients receiving blood solely via cell salvage compared to those receiving ABT or a combination of ABT and CS perioperatively. A total of 414 patients who underwent isolated OPCAB surgery at our cardiovascular clinic were analyzed. Among them, 250 patients (60.4%) received blood via CS alone, while 164 patients (39.6%) received either ABT or a mix of ABT and CS. Stabilized inverse probability treatment weighted (IPTW) matching technique ensured balance in baseline covariates. We found no significant differences in 30-day mortality rates between the CS and ABT groups. The CS group displayed significantly lower rates of overall complications, encompassing stroke, acute kidney injury, atrial fibrillation, and pulmonary complications. Rates of sepsis, readmission, gastrointestinal complications, heparin-induced thrombosis, and deep venous thrombosis were comparable between the two groups. However, in contrast to the ABT group,the CS group exhibited significantly shorter median lengths of hospital stay (LOHS), ICU stay, andventilation time, along with higher rates of discharge to homerather than acute care facilities. Our data suggest that autologous blood transfusion via CS results in fewer perioperative complications and faster recovery following OPCAB procedures as compared to ABT.

Efficacy and safety of durable versus biodegradable polymer drug-eluting stents in patients with acute myocardial infarction complicated by cardiogenic shock

The clinical impact of different polymer technologies in newer-generation drug-eluting stents (DESs) for patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) remains poorly understood. We investigated the efficacy and safety of durable polymer DESs (DP-DESs) compared with biodegradable polymer DESs (BP-DESs). A total of 620 patients who underwent percutaneous coronary intervention with newer-generation DESs for AMI complicated by CS was divided into two groups based on polymer technology: the DP-DES group (n = 374) and the BP-DES group (n = 246). The primary outcome was target vessel failure (TVF) during a 12-month follow-up, defined as a composite of cardiac death, myocardial infarction, or target vessel revascularization. Both the DP-DES and BP-DES groups exhibited low stent thrombosis rates (1.3% vs. 1.6%, p = 0.660). The risk of TVF did not significantly differ between the two groups (34.2% vs. 28.5%, hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.69–1.29, p = 0.721). This finding remained consistent after adjustment with inverse probability of treatment weighting (28.1% vs. 25.1%, HR 0.98, 95% CI 0.77–1.27, p = 0.899). In AMI patients complicated by CS, the risk of a composite of cardiac death, myocardial infarction, or target vessel revascularization was not significantly different between those treated with DP-DESs and those treated with BP-DESs.Trial registration: RESCUE registry, https://clinicaltrials.gov/ct2/show/NCT02985008, NCT02985008.

Quantitative Coronary Angiography vs Intravascular Ultrasonography to Guide Drug-Eluting Stent Implantation

Although intravascular ultrasonography (IVUS) guidance promotes favorable outcomes after percutaneous coronary intervention (PCI), many catheterization laboratories worldwide lack access. To investigate whether systematic implementation of quantitative coronary angiography (QCA) to assist angiography-guided PCI could be an alternative strategy to IVUS guidance during stent implantation. This randomized, open-label, noninferiority clinical trial enrolled adults (aged ≥18 years) with chronic or acute coronary syndrome and angiographically confirmed native coronary artery stenosis requiring PCI. Patients were enrolled in 6 cardiac centers in Korea from February 23, 2017, to August 23, 2021, and follow-up occurred through August 25, 2022. All principal analyses were performed according to the intention-to-treat principle. After successful guidewire crossing of the first target lesion, patients were randomized in a 1:1 ratio to receive either QCA- or IVUS-guided PCI. The primary outcome was target lesion failure at 12 months, defined as a composite of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization. The trial was designed assuming an event rate of 8%, with the upper limit of the 1-sided 97.5% CI of the absolute difference in 12-month target lesion failure (QCA-guided PCI minus IVUS-guided PCI) to be less than 3.5 percentage points for noninferiority. The trial included 1528 patients who underwent PCI with QCA guidance (763; mean [SD] age, 64.1 [9.9] years; 574 males [75.2%]) or IVUS guidance (765; mean [SD] age, 64.6 [9.5] years; 622 males [81.3%]). The post-PCI mean (SD) minimum lumen diameter was similar between the QCA- and IVUS-guided PCI groups (2.57 [0.55] vs 2.60 [0.58] mm, P = .26). Target lesion failure at 12 months occurred in 29 of 763 patients (3.81%) in the QCA-guided PCI group and 29 of 765 patients (3.80%) in the IVUS-guided PCI group (absolute risk difference, 0.01 percentage points [95% CI, -1.91 to 1.93 percentage points]; hazard ratio, 1.00 [95% CI, 0.60-1.68]; P = .99). There was no difference in the rates of stent edge dissection (1.2% vs 0.7%, P = .25), coronary perforation (0.2% vs 0.4%, P = .41), or stent thrombosis (0.53% vs 0.66%, P = .74) between the QCA- and IVUS-guided PCI groups. The risk of the primary end point was consistent regardless of subgroup, with no significant interaction. Findings of this randomized clinical trial indicate that QCA and IVUS guidance during PCI showed similar rates of target lesion failure at 12 months. However, due to the lower-than-expected rates of target lesion failure in this trial, the findings should be interpreted with caution. ClinicalTrials.gov Identifier: NCT02978456.

Bleeding complications, coagulation disorders, and their management in acute myocardial infarction-related cardiogenic shock rescued by veno-arterial ECMO: A retrospective cohort study

PurposeManagement of dual antiplatelet therapy (DAPT) in patients on venoarterial-extracorporeal membrane (VA-ECMO) after acute myocardial infarction (AMI) is challenging. Our objective was to describe the frequency, management and outcomes of severe bleeding complications and determine their occurrence risk factors. Material and methodsWe conducted a retrospective observational cohort study including post-AMI cardiogenic shock patients requiring VA-ECMO. Severe bleeding was defined based on the Bleeding Academic Research Consortium classification. We calculated multivariable Fine–Gray models to assess factors associated with risk of severe bleeding. ResultsFrom January 2015 to July 2019, 176 patients received VA-ECMO after AMI and 132 patients were included. Sixty-five (49%) patients died. Severe bleeding occurred in 39% of cases. Severe thrombocytopenia (< 50 G/L) and hypofibrinogenemia (<1,5 g/L) occurred in respectively 31% and 19% of patients. DAPT was stopped in 32% of patients with a 6% rate of stent thrombosis. Anticoagulation was stopped in 39% of patients. Using a multivariate competing risk model, female sex, time on ECMO, troponin at admission and Impella® implantation were independently associated with severe bleeding. ConclusionsBleeding complications and coagulation disorders were frequent and severe in patients on VA-ECMO after AMI, leading of antiplatelet therapy withdrawal in one third of patients.

Real-world experience of direct oral anticoagulant use in a single pediatric center.

Pediatric venous thromboembolism has increased by 130%-200%, specifically in hospitalized children, and direct oral anticoagulants (DOACs) offer several therapeutic advantages. This study aims to evaluate the real-world epidemiological and outcome data from a retrospective review of pediatric patients treated with DOACs from January 1, 2013 to December 31, 2022. In this single-center, IRB-approved study, 65 patients were identified and analyzed using SPSS statistical software, and a descriptive statistical analysis was conducted. Of the 65 patients, 37% were on apixaban, 61.5% were on rivaroxaban, and 1.5% were on dabigatran. Per the 2023 ISTH outcome definitions, one (2%) patient had a major bleeding episode, six (9%) had clinically relevant non-major bleeding, three (5%) patients had patient-important heavy menstrual bleeding (HMB), and one (1.5%) patient had minor bleeding. Seven (19%) of 37 postmenarchal patients had evidence of HMB. Six (9.2%) patients had recurrent venous thromboembolism while on a DOAC (one was on apixaban, and five were on rivaroxaban) and were transitioned to other forms of anticoagulation. Thus, bleeding rates after DOAC therapy are comparable to previous DOAC trials, as well as other anticoagulants in pediatrics. HMB is an important outcome measure and should continue to be investigated. This study reports a higher rate of recurrent thrombosis (9.2%) compared to other trials. However, this observation may be attributed to patients who had ongoing risk factors, as well as a longer duration of study follow-up. Additional multicentered outcome studies evaluating DOAC use in children are needed to determine long-term recurrence and HMB risks.

Prevalence and patterns of cerebral venous sinus thrombosis following vestibular schwannoma surgery: a systematic review and meta-analysis.

Cerebral venous sinus thrombosis (CVST) is a potentially serious complication following surgical treatment of vestibular schwannoma, a benign tumor originating from Schwann cells of the vestibulocochlear nerve. This study aimed to determine the prevalence of CVST following surgical treatment of vestibular schwannoma and the factors contributing to its occurrence. Two independent researchers searched the global databases of PubMed, Web of Science, Scopus, and the Cochrane Library up to September 01, 2023. We employed a random-effects model for data analysis. Heterogeneity was evaluated using the I2 test. To assess the quality of the studies meeting our inclusion criteria, we employed the Joanna Briggs Institute Critical Appraisal Checklist. We included 23 articles in this meta-analysis. The pooled prevalence of CVST after vestibular schwannoma surgery was 6.4% (95%CI 3.4-11.5%). The pooled prevalence of CVST following the retrosigmoid (RS), translabyrinthine (TL), and middle cranial fossa (MCF) approaches was 4.8% (95%CI 2.0-11.0%), 9.6% (95%CI 4.3-20.3%) and 9.9% (95%CI 1.6-42.2%), respectively, revealing a significant difference between the TL and the RS approaches (Odds ratio=2.10, 95%CI 1.45-3.04, P< 0.001).The sigmoid sinus exhibited the highest post-operative thrombosis rate (7.9%), surpassing the transverse sinus (3.7%) and involvement of both sigmoid and transverse sinuses (1.6%), respectively. No significant associations were found with demographic or surgical factors. In the current meta-analysis, we identified a 6.4% CVST prevalence following vestibular schwannoma surgery, with varying rates depending on the surgical approach. No significant associations with patient or surgical factors were found, emphasizing the need for heightened clinical vigilance and further research in this context. PROSPERO ID: CRD42023453513.

SYNERGY—Everolimus-Eluting Stent With a Bioabsorbable Polymer in ST-Elevation Myocardial Infarction: CLEAR SYNERGY OASIS-9 Registry

Our objective was to evaluate the clinical effectiveness of the SYNERGY stent in patients with ST elevation myocardial infarction (STEMI). The only drug eluting stent approved for treatment of STEMI by the FDA is the Taxus stent which is no longer commercially available, so further data are needed. The CLEAR SYNERGY stent registry was embedded into a larger randomized trial of patients with STEMI (N=7000), comparing colchicine vs. placebo and spironolactone vs. placebo. The primary outcome for the SYNERGY stent registry is major adverse cardiac events (MACE) as defined by cardiovascular death, recurrent MI, or unplanned ischemia driven target vessel revascularization (TVR) within 12 months. We estimated a MACE rate of 6.3% at 12 months after primary percutaneous coronary intervention (PPCI) for STEMI based on the TOTAL trial. Success was defined as upper bound of confidence interval (CI) to be less than the performance goal of 9.45%.Overall, 733 patients were enrolled from 8 countries with a mean age 60.2 years, 19% diabetes, 41.3% anterior MI and median door to balloon time of 72 minutes. The MACE rate was 4.8% (95% CI 3.2-6.3%) at 12 months which met the success criteria against performance goal of 9.45%. The rates of cardiovascular death, recurrent MI or TVR were 2.7%, 1.9%, 1.0% respectively. The rates of acute definite stent thrombosis were 0.3%, subacute 0.4%, late 0.4% and cumulative stent thrombosis of 1.1% at 12 months. In conclusion, the SYNERGY stent in STEMI performed well and was successful compared to the performance goal based on prior trials.Trial Registration: ClinicalTrials.gov Identifier: NCT03048825

Incidence rate of venous thrombosis in women switching combined oral contraceptives: a cohort study

BackgroundThe incidence rate of venous thrombosis (VT) in women switching combined oral contraceptives (COCs) is unknown. ObjectivesWe hypothesize that women switching COCs may have a similar increased incidence rate of VT as women who start COCs. Switching means starting with a new COC, which may biologically approximate starting. MethodsWe conducted a cohort study with data from the Netherlands and Denmark. First, we identified starters who were defined as women who did not use COCs in the 2 years prior to the start of their first COC prescription within the study period. Switchers were a subset of COC starters who redeemed a COC formulation different from their initial COC during follow-up but not longer than 12 months after starting. We estimated incidence rate ratios (adjusted incidence rate ratio [aIRR]) of VT with 95% CIs among COC switchers as compared with COC starters using Poisson regression adjusted for age, COC progestogen generation, and preexisting obesity. ResultsIn both countries, we found an increased risk of VT among switchers as compared with starters during the first 3 months of the follow-up (aIRR = 1.77; 95% CI, 1.22-2.56 in the Netherlands and aIRR = 1.50; 95% CI, 1.04-2.16 in Denmark). ConclusionSwitchers, particularly in the first 3 months after switching, may experience a renewed starter effect thereby increasing the risk of VT.

Clinical Use of Tranexamic Acid in High Tibial Osteotomy: A Systematic Review and Meta-analysis.

High tibial osteotomy (HTO) can cause postoperative hemorrhage. The use of tranexamic acid to reduce the hemorrhage is still controversial. To investigate the efficacy and safety of tranexamic acid in HTO. Systematic review; Level of evidence, 4. Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, the authors conducted a comprehensive search of the Embase, Cochrane Library, PubMed, Web of Science, MEDLINE, and Foreign Medical Literature Retrieval Service databases between their inception and January 1, 2023. All clinical studies comparing the use of tranexamic acid versus no tranexamic acid during HTO were collected. The primary outcome measures were hemoglobin decrease, drainage volume, and blood loss, and the secondary outcome measures were wound complications, blood transfusion, and postoperative thrombosis. All indicators were analyzed using meta-analysis software. Results were reported as mean differences or risk ratios with 95% confidence intervals. Of 152 initial results, 9 studies involving 908 patients were included. The tranexamic acid group had lower indicators for total blood loss, hemoglobin decrease, and total drainage volume (P < .00001 for all). There were no differences between patients with versus without tranexamic acid in wound complications, including hematoma (P = .21) or infection (P = .18), nor were there any group differences in the prevalence of blood transfusion (P = .21) or postoperative thrombosis (P = .36). Tranexamic acid was able to effectively reduce postoperative hemorrhage in patients undergoing HTO without affecting the rates of wound complications, blood transfusion, or postoperative thrombosis.

Primary thrombophilia in Mexico XVIII: Increased rate of thrombosis in persons with the sticky platelet syndrome in the COVID-19 era.

Primary thrombophilia in Mexico XVIII: Increased rate of thrombosis in persons with the sticky platelet syndrome in the COVID-19 era.

Inappropriate Use of Peripherally Inserted Central Catheters in Pediatrics: A Multisite Study.

This study aimed to describe how the current practice of peripherally inserted central catheter (PICC) use in hospitalized children aligns with the Michigan Appropriateness Guide for Intravenous Catheters (miniMAGIC) in Children recommendations, explore variation across sites, and describe the population of children who do not receive appropriate PICCs. A retrospective study was conducted at 4 children's hospitals in the United States. Children with PICCs placed January 2019 to December 2021 were included. Patients in the NICU were excluded. PICCs were categorized using the miniMAGIC in Children classification as inappropriate, uncertain appropriateness and appropriate. Of the 6051 PICCs identified, 9% (n = 550) were categorized as inappropriate, 9% (n = 550) as uncertain appropriateness, and 82% (n = 4951) as appropriate. The number of PICCs trended down over time, but up to 20% of PICCs each year were not appropriate, with significant variation between sites. Within inappropriate or uncertain appropriateness PICCs (n = 1100 PICC in 1079 children), median (interquartile range) patient age was 4 (0-11) years, 54% were male, and the main reason for PICC placement was prolonged antibiotic course (56%, n = 611). The most common admitting services requesting the inappropriate/uncertain appropriateness PICCs were critical care 24%, general pediatrics 22%, and pulmonary 20%. Complications resulting in PICC removal were identified in 6% (n = 70) of inappropriate/uncertain PICCs. The most common complications were dislodgement (3%) and occlusion (2%), with infection and thrombosis rates of 1% (n = 10 and n = 13, respectively). Although the majority of PICCs met appropriateness criteria, a substantial proportion of PICCs were deemed inappropriate or of uncertain appropriateness, illustrating an opportunity for quality improvement.

Angiographic characteristics of patients with STEMI and COVID-19: Insights from NACMI registry

BackgroundTo date, there has been no independent core lab angiographic analysis of patients with COVID-19 and STEMI. The study characterized the angiographic parameters of patients with COVID-19 and STEMI. MethodsAngiograms of patients with COVID-19 and STEMI from the North American COVID-19 Myocardial Infarction (NACMI) Registry were sent to a Core Laboratory in Vancouver, Canada. Culprit lesion(s), Thrombolysis In Myocardial Infarction (TIMI) flow, Thrombus Grade Burden (TGB), and percutaneous coronary intervention (PCI) outcome were assessed. ResultsFrom 234 patients, 74% had one culprit lesion, 14% had multiple culprits and 12% had no culprit identified. Multivessel thrombotic disease and multivessel CAD were found in 27% and 53% of patients, respectively. Stent thrombosis accounted for 12% of the presentations and occurred in 55% of patients with previous coronary stents. Of the 182 who underwent PCI, 60 (33%) had unsuccessful PCI due to post-PCI TIMI flow <3 (43/60), residual high thrombus burden (41/60) and/or thrombus related complications (27/60). In-hospital mortality for successful, partially successful, and unsuccessful PCI was 14%, 13%, and 27%, respectively. Unsuccessful PCI was associated with increased risk of in-hospital mortality (risk ratio [RR] 1.96; 95% CI: 1.05-3.66, P = .03); in the adjusted model this estimate was attenuated (RR: 1.24; 95% CI: 0.65-2.34, P = .51). ConclusionIn patients with COVID-19 and STEMI, thrombus burden was pervasive with notable rates of multivessel thrombotic disease and stent thrombosis. Post-PCI, persistent thrombus and sub-optimal TIMI 3 flow rates led to one-third of the PCI's being unsuccessful, which decreased over time but remained an important predictor of in-hospital mortality.

Delayed Closure of Guillotine Lower Extremity Amputation in Obese Patients is Associated with Increased Mortality

OBJECTIVEStaged surgery with open guillotine amputation (OGA) prior to a definitive major lower extremity amputation (LEA) has been shown to be effective for sepsis control and improving wound healing. Studies have evaluated postoperative complications including infection, return to the operating room for re-amputation, and amputation failure following OGA. However, the role of timing to close OGA for predictive outcomes remains poorly understood. We aim to assess outcomes of major LEA related to the time of OGA closure. METHODSData from patients who underwent major LEA from 2015 to 2021 was collected retrospectively. The study included all patients undergoing below-, through-, or above-knee amputations. Next, patients who had OGA prior to a definitive amputation were selected. Patients who died before amputation closure were excluded. Post-amputation outcomes such as surgical site infection (SSI), postoperative sepsis, postoperative ambulation, hospital length of stay (LOS), and 30-day, 1-year, and 5-year mortality were reviewed. The study cohort was stratified by demographics and comorbidities. Receiver operating characteristic (ROC) curve analysis was performed to determine the time of closure (TOC) cut-off value. Univariate and multivariate analysis was performed to assess outcomes. Statistical significance was set at p < 0.05. RESULTOf 688 patients who underwent major LEA, 322 underwent staged amputation with OGA before the formalization procedure and were included. The TOC ranged from 1-47 days with a median of 4 days (interquartile range (IQR) from 3 to 7). The optimal TOC point of 8 days (ranging from 2 - 42 days) in obese patients (199/322) for predicting mortality showed the largest area under the curve (AUC) (0.709) with 64.71% sensitivity and 78.3% specificity. Patients who are obese and grouped in TOC less than 8 days had no 30-day mortality, significantly lower 1-year mortality, better survival, and a lower rate of deep venous thrombosis (DVT) complication. There was no significant difference in LOS, postoperative SSI, sepsis, and ambulation between the two subgroups of obese patients. Multivariable analysis showed that gender, CKD, and postoperative ambulation independently predict overall mortality in obese patients. CONCLUSIONTOC cutoff in obese patients showed statistically significant results in predicting mortality. Our findings indicated better survival in obese patients with a lower TOC (less than 8 days). This emphasizes the importance of earlier closure of OGA in obese patients.

Thrombotic Complications, Disease Progression, and Survivals in BCR::ABL1-Negative Myeloproliferative Neoplasms: A 12-Year Retrospective Study at a Single Center in Thailand

Objective: To assess the incidence of thrombotic events among patients with BCR::ABL1-negative myeloproliferative neoplasm (MPN) within a single center in Thailand. Materials and Methods: Conducted as a retrospective cohort study between 2008 and 2019, the present research focused on patients diagnosed with BCR::ABL1-negative MPN. Diagnoses were reviewed and reclassified based on the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues (2017). Data collected encompassed demographic details, comorbidities, investigation results, treatments, and outcomes. The primary focus was on thrombosis rates in arterial and venous sites. Secondary outcomes included the incidence of major bleeding, thrombosisfree survival (TFS), and overall survival (OS). Results: One hundred seventy-five patients participated in the present study and comprised of 46 patients (26.3%) with polycythemia vera (PV), 123 (70.3%) patients with essential thrombocythemia (ET), and six patients (3.4%) with primary myelofibrosis (PMF). Most patients were over 60 years old. The rate of overall thrombosis rate was 28.0%, with 43.5% in PV and 23.6% in ET. Common sites of thrombotic events included the cerebral artery at 16.6%, coronary artery at 6.3%, peripheral artery at 4.0% and venous thromboembolism at 3.4%. The overall bleeding event rate was 13.7%, with 70.8% classified as major bleeding. The all-cause mortality rate within the present cohort was 30.9%. TFS and OS stood 72.0% and 69.1%, respectively. Conclusion: Thrombosis emerged as a significant complication in patients with BCR::ABL1-negative MPN, affecting 28.0% of individuals in the present cohort. Arterial thromboses, particularly ischemic stroke and cardiovascular events, were the predominant occurrences. Keywords: Myeloproliferative neoplasm; Polycythemia vera; Essential thrombocythemia; Thrombosis; Bleeding

Vaccine-Induced Immune Thrombotic Thrombocytopenia: Clinicopathologic Features and New Perspectives on Anti-PF4 Antibody-Mediated Disorders.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare yet severe adverse complication first identified during the global vaccination effort against SARS-CoV-2 infection, predominantly observed following administration of the ChAdOx1-S (Oxford-AstraZeneca) and Ad26.CoV2.S (Johnson & Johnson/Janssen) adenoviral vector-based vaccines. Unlike other anti-platelet factor 4 (PF4) antibody-mediated disorders, such as heparin-induced thrombocytopenia (HIT), VITT arises with the development of platelet-activating anti-PF4 antibodies 4-42 days post-vaccination, typically featuring thrombocytopenia and thrombosis at unusual sites. To explore the unique properties, pathogenic mechanisms, and long-term persistence of VITT antibodies in patients, in comparison with other anti-PF4 antibody-mediated disorders. This review highlights the complexity of VITT as it differs in antibody behavior and clinical presentation from other anti-PF4-mediated disorders, including the high incidence rate of cerebral venous sinus thrombosis (CVST) and the persistence of anti-PF4 antibodies, necessitating a re-evaluation of long-term patient care strategies. The nature of VITT antibodies and the underlying mechanisms triggering their production remain largely unknown. The rise in awareness and subsequent prompt recognition of VITT is paramount in reducing mortality. As vaccination campaigns continue, understanding the role of adenoviral vector-based vaccines in VITT antibody production is crucial, not only for its immediate clinical implications, but also for developing safer vaccines in the future.

(095) Comparative Analysis of Absolute Risk in Testosterone versus Clomiphene Therapy: A Bayesian Analysis of Adverse Effects

Abstract Introduction Clomiphene is a selective estrogen receptor modulator used to induce ovulation by increasing luteinizing (LH) and follicle-stimulating hormone (FSH) levels. Since the 1970’s, it has been used in males with hypogonadism as an alternative to testosterone therapy as it does not suppress the hypothalamic-pituitary-gonadal axis. Objective While there have been systematic reviews looking at the effectiveness of clomiphene, we sought to better characterize the average testosterone levels, as well as the rate of deep venous thrombosis (DVT), myocardial infarction (MI), stroke, and polycythemia in clomiphene vs. testosterone users. Methods We performed a retrospective chart review for 537 men with a hypogonadism diagnosis that were seen by two urology providers at our center. Of these 537 patients, 84 presented with prior use or were prescribed clomiphene. We measured the incidence of DVT, MI, stroke, polycythemia and average testosterone levels with clomiphene. Statistical analysis was conducted using both a beta binomial and linear model. Results Patients receiving testosterone (n=217) versus clomiphene (n=84) demonstrated a 99% chance of higher mean levels of testosterone (Difference=216.55, 95% CrI = 20.67-408.16). Among those taking testosterone or clomiphene at the final visit (N=237; testosterone n=185; clomiphene=52) adverse events included, polycythemia (n=28), one DVT, VTE’s (n=4), MI’s (n=4), and strokes (n=4). The absolute risk (AR) of experiencing at least one of these events (i.e. polycythemia, DVT, VTE, MI or stroke) was 13.8% (95% CrI = 10.1-17.9%) and 3.1% (95% CrI = 0.44-9.4%) for testosterone and clomiphene respectively (Absolute Risk Difference (ARD) = 10.5% (95% CrI = 3.4-15.7%); Posterior Probability (ARD&amp;gt;0) &amp;gt; 0.99. The AR of polycythemia was 12.6% (95% CrI = 8.9-16.7%) and 1.5% (95% CrI = 0.1-7.4%) for testosterone and clomiphene respectively (ARD = 10.7% (95% CrI = 4.3-15.6%); Posterior Probability (ARD &amp;gt; 0) &amp;gt; 0.99. The AR of stroke was 0.94% (95% CrI = 0.14-2.98%) and 1.56% (95% CrI = 0.1-7.4%) for testosterone and clomiphene respectively (ARD = -0.6% (95% CrI = -6.5-2.1%); Posterior Probability (ARD &amp;lt; 0) = 0.64. The AR of MI was 1.4% (95% CrI=0.33-3.8%) and 1.5% (95% CrI=0.1-7.4%) for testosterone and clomiphene respectively (ARD = 1.3% (95% CrI = -0.36-3.73%); Posterior Probability (ARD &amp;gt; 0) = 0.96. The AR of DVT was 0.37% (95% CrI = 0.01-1.99%) and &amp;lt;0.00001% (95% CrI = &amp;lt;0.00001-1.6%) for testosterone and clomid respectively (ARD = 0.30% (95% CrI = -1.24-1.92%); Posterior Probability (ARD &amp;gt; 0) = 0.88. Conclusions The absolute risk of experiencing at least one of the events was found to be significantly higher in patients receiving testosterone compared to those receiving clomiphene. The results should be interpreted with caution, given the broad credible intervals due to its small size. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Consultant for AbbVie, Marius, Tolmar, Endo, Petros, Boston Scientific, Coloplast Investor: Sprout.

The quality of pharmacist-led community warfarin management across 2 provinces in Canada: A cross-sectional observational study.

Guidelines for anticoagulation management services recommend personnel be specially trained in warfarin management and suggest using tools such as decision-support software. To date, there have been no Canadian studies documenting the quality of warfarin management using a similar guideline recommended approach. A cross-sectional, retrospective observational study was conducted to measure the quality of pharmacist-led warfarin management using point-of-care international normalized ratio (INR) testing and decision-support software in various ambulatory settings in Canada. Settings included 4 family health teams in Ontario and 40 community pharmacies across Nova Scotia. Quality was measured using time in therapeutic range (TTR) and was reported in 3 manners: mean TTR, median TTR and time-weighted mean TTR. The primary outcome included 963 patients. The combined mean and median TTR for the 2019 Ontario family health teams and Nova Scotia pharmacies was 74.2% and 77.3% (interquartile range 64%-87.9%), respectively. The time-weighted mean TTR was 76.3%. To the best of our knowledge, the TTR achieved by this model of care is the highest reported in Canadian general practice. Since Thrombosis Canada defines good-quality warfarin management as a TTR of 60% or greater, and many studies have reported an association between higher TTR values and lower rates of thrombosis and hemorrhage, this model of care may have significant benefits for patients. This study demonstrates the high quality of anticoagulation management provided by specially trained pharmacists using point-of-care INR testing and decision-support software. These results support expanded access to this service for all Canadians. Can Pharm J (Ott) 2024;157:xx-xx.