Thrombotic Adverse Events Research Articles

Impact in Clinical Practice of the European Medicines Agency Health Alert About the Restriction of the Use of JAK Inhibitors.

Background/Objectives: Janus kinase inhibitors (JAKi) have revolutionized the treatment of various inflammatory and immune disorders. Concerns about the potential increased risk of major adverse cardiovascular events (MACEs) associated with JAKi use led to a European Medicines Agency (EMA) health alert recommending restricting the use of JAKi in high-risk populations. Methods: This study aims to determine the proportion of patients who developed any cardiovascular, ischemic, neoplastic, or thrombotic adverse event in a cohort of patients receiving, or who have received, JAKi treatment between January 2017 and September 2023. In addition, we studied the impact of the alert in the clinical practice of our Rheumatology department. Results: In this retrospective, observational study, 101 patients were analysed, predominantly women (72.3%), with a mean age of 57.6 years. The most common diagnoses were rheumatoid arthritis (60.4%) and psoriatic arthritis (18.8%). The most frequent adverse events were infections (5.9%) and neoplasms (2.9%). Deep vein thrombosis and haemorrhagic stroke each occurred in 1% of patients, with no cases of ischemic stroke or ischemic heart disease. When the health alert was published, 75 patients were on treatment with JAKi, and 33 met the alert criteria. Of these, 12.1% changed treatment due to the alert, 9% had no other therapeutic options, 57.5% were in clinical remission or had low disease activity, and 9% maintained treatment at their own request. Conclusions: These findings suggest that, in this patient cohort, JAKi use did not result in new MACE cases. The alert concerning the use of JAKi has had a limited impact in our clinical practice.

Arterial Stiffness as a New Predictor of Clinical Outcome in Patients with Polycythemia Vera.

Background: Thrombotic adverse events and disease progression are crucial in Polycythemia Vera (PV), as it stands as the leading cause of mortality. The pulse wave velocity (PWV) is a valuable indicator of arterial aging and often plays a significant independent role in contributing to cardiovascular adverse events (CV-AEs). The aim of this study was to examine the relationship between PWV and critical vascular function parameters, with the goal of identifying new predictive factors of vascular damage and exploring a potential connection with disease progression. Methods: Non-invasive aortic stiffness was assessed through carotid-femoral PWV measurement. PWV was measured using the SphygmoCor device. History of arterial or venous thrombosis (TAEs) or other CV-AEs was collected at baseline. PWV measurements were repeated at baseline, at 6 and at 12 months. Results: The study involved 28 PV patients aged 27 to 77 years, with 57.1% being male. Fourteen patients (50%) reported a high-risk thrombotic score at diagnosis, and 60.7% had at least one comorbidity. Multivariable regression models showed that hemoglobin levels were independently associated with PWV (β: 0.68, SE 0.24, p < 0.01). During the follow-up period (median duration 21.3 months, range 6-33), a total of 13 events were documented. Specifically, two patients exhibited a loss of response to treatment, four patients presented an increase in spleen diameters, three patients displayed an escalation of systemic symptoms, and three patients had a clear progression to secondary myelofibrosis. PWV (per 1 m/s: OR 1.70, 95% CI 1.00-2.91, p = 0.047) and leukocyte count (per 1 × 103/μL: OR 1.47, 95% CI: 1.04-2.09, p = 0.043) were significant predictors of events, independently of waist circumference, blood pressure, treatment, and hematocrit. Conclusions: PWV has demonstrated its potential as an effective tool for monitoring PV patients. It stands as a clinical parameter that can predict the risk of progression in PV patients. Further investigation is essential to fully explore this potential. If successful, it could offer clinicians a valuable resource for effectively managing PV patients.

A rare HSC-derived megakaryocyte progenitor accumulates via enhanced survival and contributes to exacerbated thrombopoiesis upon aging.

Distinct routes of cellular production from hematopoietic stem cells (HSCs) have defined our current view of hematopoiesis. Recently, we challenged classical views of platelet generation, demonstrating that megakaryocyte progenitors (MkPs), and ultimately platelets, can be specified via an alternate and additive route of HSC-direct specification specifically during aging. This "shortcut" pathway generates hyperactive platelets likely to contribute to age-related platelet-mediated morbidities. Here, we used single-cell RNA/CITEseq to demonstrate that these age-unique, non-canonical (nc)MkPs can be prospectively defined and experimentally isolated from wild type mice. Surprisingly, this revealed that a rare population of ncMkPs also exist in young mice. Young and aged ncMkPs are functionally distinct from their canonical (c)MkP counterparts, with aged ncMkPs paradoxically and uniquely exhibiting enhanced survival and platelet generation capacity. We further demonstrate that aged HSCs generate significantly more ncMkPs than their younger counterparts, yet this is accomplished without strict clonal restriction. Together, these findings reveal significant phenotypic, functional, and aging-dependent heterogeneity among the MkP pool and uncover unique features of megakaryopoiesis throughout life, potentially offering cellular and molecular targets for mitigation of age-related adverse thrombotic events.

Use of preoperative erythropoietin-stimulating agents is associated with decreased thrombotic adverse events compared to red blood cell transfusion in surgical patients with anaemia.

Preoperative red blood cell (RBC) transfusions increase post-operative venous thromboembolic (VTE) events. Erythropoietin-stimulating agents (ESAs) increase VTE risk in cancer patients; we aimed to assess ESA versus RBC-associated VTE risks in a broad population of surgical patients. We queried TriNetX Diamond Network from 2006 to 2023, comparing patients with anaemia within 3 months preoperatively who received preoperative ESAs with or without intravenous (IV) iron to patients who received preoperative RBCs. Sub-analyses included (1) all surgeries and (2) cardiovascular surgeries. We propensity score matched for demographics, comorbidities, medical services, post-treatment haemoglobin (g/dL) and, for all-surgery comparisons, surgery type. Outcomes included 30-day post-operative mortality, VTE, pulmonary embolism (PE), disseminated intravascular coagulation (DIC) and haemoglobin. In our 19,548-patient cohorts, compared with preoperative RBC transfusion, ESAs without IV iron were associated with lower mortality (relative risk [RR] = 0.51 [95% confidence interval (CI), 0.45-0.59]), VTE (RR = 0.57 [0.50-0.65]) and PE (RR = 0.67 [0.54-0.84]). Post-operative haemoglobin was higher in the ESA without IV iron cohort compared with the transfusion cohort (10.0 ± 1.4 vs. 9.4 ± 1.8 g/dL, p = 0.002). Cardiac surgical patients receiving ESAs with or without IV iron had lower risk for post-operative mortality, VTE and PE (p < 0.001) than those receiving RBCs. Post-operative haemoglobin differed between patients receiving ESAs with IV iron versus RBCs (10.1 ± 1.5 vs. 9.4 ± 1.9 g/dL, p = 0.0009). Compared with surgical patients who were transfused RBCs, ESA recipients had reduced 30-day post-operative risk of mortality, VTE, PE and DIC and increased haemoglobin levels. IV iron given with ESAs improved mortality.

Outcomes Following Total Hip Arthroplasty in Patients Who Have Von Willebrand Disease Depend on Postoperative Anticoagulation

BackgroundVon Willebrand disease (VWD) is the most common congenital bleeding disorder. This autosomal dominant condition arises from quantitative or qualitative defects of Von Willebrand factor. To our knowledge, this study leveraged a national database to characterize the largest VWD cohort of total hip arthroplasty (THA) patients to date, assessing 90-day postoperative adverse events and 5-year revision-free survival. MethodsAdult patients who underwent primary THA for osteoarthritis were identified from January 2010 to October 2021 in a nationwide database. Patients who had and did not have VWD were matched (4:1) on age, sex, and Elixhauser Comorbidity Index and compared with multivariable logistic regression. Patients were then categorized based upon venous thromboembolism (VTE) chemoprophylaxis prescription patterns to compare bleeding and thrombotic adverse events. ResultsOf 544,851 THA patients, VWD was identified in 309 patients (0.06%). The matched cohorts contained 1,221 patients who did not have VWD and 306 patients who have VWD. On multivariable analysis, VWD patients had increased odds of 90-day VTE (odds ratio [OR] = 1.86) and hematoma (OR = 3.40) (P < .05 for all). No difference in 5-year revision-free survival was found. The VWD patients receiving aspirin or no prescriptions had greater odds of VTE (OR = 2.39, P = .048). Those on other chemoprophylaxis agents had greater odds of hematoma (OR = 4.84, P = .006). ConclusionsPatients with VWD undergoing THA had increased odds of 90-day VTE if using aspirin or no prescriptions, or hematoma if using other chemoprophylaxis. There is a delicate balancing act of clotting versus bleeding that must be considered in managing such patients, but it was reassuring that no difference in overall 5-year revision-free survival was found.

Comparison of thrombotic adverse events in patients treated with factor VIII products and emicizumab using the 2018-2022 US Food and Drug Administration Adverse Event Reporting System data

BackgroundRelatively little is known about thrombotic adverse events (AEs) of emicizumab in postmarketing real-world settings, particularly in comparison with factor VIII (FVIII) products. A recent European study reported a potentially greater thrombotic risk of emicizumab compared with FVIII products. ObjectivesThis drug safety study aims to investigate whether thrombotic AEs are more frequently reported for emicizumab than for FVIII products and if so, whether it is independent of bypassing agents as coreporting drugs using the United States Food and Drug Administration Adverse Event Reporting System data. MethodsDisproportionality analyses for thrombotic AEs of emicizumab vs FVIII products were conducted. Three signal detection indicators were used: proportional reporting ratio (PRR), reporting odds ratio (ROR), and informational component (IC). ResultsDuring 2018-2022, the proportions of thrombotic AEs among all AEs were 4.07% (97 out of 2383) and 1.44% (134 out of 9324) for emicizumab and FVIII products, respectively: PRR = 2.83 (2.19-3.66), ROR = 2.91 (2.23-3.79), and IC = 1.04 (0.70-1.28). Bypassing agents as coreporting drugs were identified in 36% and 15% of the total thrombotic AE reports associated with emicizumab and FVIII products, respectively. Even after thrombotic AE reports with bypassing agents were excluded, the reporting proportion of thrombotic AEs was still greater for emicizumab than for FVIII products: PRR = 2.19 (1.60-2.99). ConclusionThrombotic AEs in the United States Food and Drug Administration Adverse Event Reporting System data were about 3 times more frequently reported for emicizumab than for FVIII products. More research and efforts in the future are warranted for monitoring, elucidating, and preventing the potential risk of thrombotic AEs in hemophilia therapy, including emicizumab.

Clot or Not? Reviewing the Reciprocal Regulation Between Lipids and Blood Clotting.

Both hyperlipidemia and thrombosis contribute to the risks of atherosclerotic cardiovascular diseases, which are the leading cause of death and reduced quality of life in survivors worldwide. The accumulation of lipid-rich plaques on arterial walls eventually leads to the rupture or erosion of vulnerable lesions, triggering excessive blood clotting and leading to adverse thrombotic events. Lipoproteins are highly dynamic particles that circulate in blood, carry insoluble lipids, and are associated with proteins, many of which are involved in blood clotting. A growing body of evidence suggests a reciprocal regulatory relationship between blood clotting and lipid metabolism. In this review article, we summarize the observations that lipoproteins and lipids impact the hemostatic system, and the clotting-related proteins influence lipid metabolism. We also highlight the gaps that need to be filled in this area of research.

Association between COVID-19 Infection or Vaccination Outcomes and Methylenetetrahydrofolate Reductase Gene Polymorphism: A Systematic Review of the Literature.

Thrombosis is a detrimental sequala of COVID-19 infection; thus, prophylactic anti-coagulant therapy has been deemed mandatory in treatment unless serious contraindications are present. Susceptibility to thromboembolic events in COVID-19, or following COVID-19 vaccination, is likely attributable to an interplay of factors, including a patient's baseline clinical status and comorbidities, alongside genetic risk factors. In Europe, 8-20% of the population are homozygous for the MTHFR (methylene tetrahydrofolate reductase) variant, which compromises folate metabolism and elevates homocysteine levels. While heightened homocysteine levels are considered a risk factor for thromboembolic events, the precise clinical significance remains a contentious issue. However, recent research suggests elevated homocysteine levels may predict the course and severity of COVID-19 infection. Given the lack of reliable biomarkers predictive of COVID-19 thrombotic risk existing in practice, and the accessibility of MTHFR screening, we established two main outcomes for this study: (1) to determine the association between hereditary MTHFR mutations and COVID-19 severity and thromboembolic events and (2) to determine the link between MTHFR variants and adverse thrombotic events following COVID-19 vaccination. The review was conducted in accordance with PRISMA guidelines. Medline, Scopus, and Web of Science databases were searched from pandemic inception (11 March 2020) to 30 October 2023. Eligibility criteria were applied, and data extraction performed. From 63 citations identified, a total of 14 articles met the full inclusion criteria (8 of which were cross-sectional or observational studies, and 6 were case studies or reports). Among the eight observational and cross-sectional studies evaluating the relationship between MTHFR variants (C667T; A1298C) and thromboembolic events in COVID-19 infection, four studies established a connection (n = 2200), while the remaining four studies failed to demonstrate any significant association (n = 38). This systematic review demonstrated a possible association between the MTHFR gene variants and COVID-19 severity, thromboembolic events, and adverse events following vaccination. However, the paucity of robust data precluded any firm conclusions being drawn. Further prospective trials are required to determine the connection between the MTHFR gene variant and COVID-19 infection and vaccination outcomes.

Increase of Arterial Stiffness in Patients with Polycythemia Vera

Introduction: Preventing thrombotic adverse events (TAEs) is crucial in Polycythemia Vera (PV), as it is the leading cause of death. A targeted approach is required to achieve this, aiming to lower hematocrit (HCT) blood levels and manage thrombocytosis through cytoreductive therapy and anti-platelet treatments. The reasons behind the higher incidence of TAEs in PV are partially known. A novel perspective considers that increased blood vessel content may result in a stiffer aorta, which is clinically measurable with the Pulse Wave Velocity (PWV). The stiffer aorta, a proxy of arterial aging, has been recognized as a significant independent contributor to TAEs. Objectives: This study aimed to investigate the impact of hematological parameters on arterial stiffness in PV patients Methods: Clinical and laboratory information was collected for each patient. Aorta PWV (PWV) was estimated using the SphygmoCor System (AtCor Medical Pty Ltd., Head Office, West Ryde, Australia). The patients were observed and measured twice with a minimum interval of six months between sessions. Results: We evaluated patients with a diagnosis of PV according to WHO 2016 classification, attending from November 2021 to March 2023, the Hematology Unit of the Businco Hospital in Cagliari, Italy. The study involved 26 patients aged 27 to 77 years old. Among them, 58% were female. The median follow-up between diagnosis and PWV evaluation was 7±3 years. The median Hemoglobin (Hb) level was 13.9±1.7 g/dl, with an HCT level of 44.1±4.6 %. Leucocytes and platelets at evaluation time were 9.1±4.2×10 3/μL and 395±227 ×10 3/μL, respectively. Fourteen (53.8%) patients reported a high-risk thrombotic score at diagnosis, and 65.3% had at least one comorbidity. Two (7.7%) patients had diabetes. Moreover, 15.4% showed dyslipidemia, while 38.5% had arterial hypertension. The median body mass index (BMI) was 24.8 ± 3.6 Kg/m2, and the median waist circumference was 94.4 ±13.4 cm. Characteristics of patients were resumed in Table 1. A significant correlation with a high level of PWV was found with age (r:0.54, p=0.004), systolic and diastolic blood pressure (r:0.55, p=0.004 and r:0.44, p=0.025 respectively), heart rate (r:0.47, p=0.02), Hb (r:0.50, p=0.009), and use of hydroxycarbamide (r:0.42, p=0.03). Even after adjusting for age, waist circumference, BMI, and hypertension, the hemoglobin level still significantly correlated with PWV (β0.64 ± 0.27, p&amp;lt;0.05). No associations were found with hematocrit levels (β0.09 ± 0.12, p=0.42). When comparing patients treated only with phlebotomy versus those treated with hydroxycarbamide, PWV was significantly higher (stiffer artery) in the second group (8.9 ± 1.8 vs 11.2 ± 3.2, p&amp;lt; 0.05, respectively). Still, the difference lost significance when accounting for age and blood pressure levels. Conclusion: In PV, Hb levels showed a significant positive correlation with arterial stiffness, indexed as PWV, regardless of PV-specific treatment. The stiffer artery may contribute to the higher TAEs in PV patients. Reducing Hb levels in PV patients also seems beneficial for arterial aging. Further studies are necessary to determine the possible role of PWV in defining and preventing thrombotic events.

A Real-World Safety Analysis of Upadacitinib Based on FDA Adverse Event Reporting System (FAERS)

Objectives. To investigate adverse events (AEs) associated with upadacitinib in the real world using data mining from the FDA Adverse Event Reporting System (FAERS). Methods. Disproportionality analysis, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multiitem gamma Poisson shrinker (MGPS) algorithms, was used to quantify the signals of upadacitinib-associated AEs. Results. The study found 23683 reports of AEs associated with upadacitinib. A total of 149 substantial disproportionality preferred terms (PTs) that complied with all algorithms were identified. The infections discovered matched those mentioned in the specification and clinical trials, including pneumonia, upper respiratory tract infection, herpes zoster, and acne. Malignant and thrombotic AEs were also noted. Diverticulitis, myocardial infarction, transient ischaemic attack, and dysstasia were among the new AEs found. Upadacitinib-related AEs had a median onset time of 237 days and an interquartile range (IQR) of 78–509 days. Conclusions. The findings of our study were in line with clinical observations, and we also identified potential novel and unexpected AEs signals for upadacitinib, indicating the necessity for prospective clinical trials to corroborate these findings and demonstrate their link. Our results offered significant support for additional upadacitinib safety research.

Renin-angiotensin inhibitors reduce thrombotic complications in Essential Thrombocythemia and Polycythemia Vera patients with arterial hypertension

Essential Thrombocythemia (ET) and Polycythemia Vera (PV) are chronic myeloproliferative neoplasms (MPNs) characterized by thrombotic and hemorrhagic complications, leading to a high risk of disability and mortality. Although arterial hypertension was found to be the most significant modifiable cardiovascular (CV) risk factor in the general population, little is known about its role in MPNs as well as a possible role of renin-angiotensin system inhibitors (RASi) in comparison with other anti-hypertensive treatments. We investigated a large cohort of 404 MPN adult patients, 133 diagnosed with PV and 271 with ET. Over half of the patients (53.7%) reported hypertension at MPN diagnosis. The 15-year cumulative incidence of thrombotic-adverse events (TAEs) was significantly higher in patients with hypertension (66.8 ± 10.3% vs 38.5 ± 8.4%; HR = 1.83; 95%CI 1.08–3.1). Multivariate analysis showed that PV diagnosis and hypertension were independently associated with a higher risk of developing TAEs (HR = 3.5; 95%CI 1.928–6.451, p < 0.001 and HR = 1.8; 95%CI 0.983–3.550, p = 0.05, respectively). In multivariate analysis, the diagnosis of PV confirmed a significant predictive role in developing TAEs (HR = 4.4; 95%CI 1.92–10.09, p < 0.01), also considering only MPN patients with hypertension. In addition, we found that the use of RASi showed a protective effect from TAEs both in the whole cohort of MPN with hypertension (HR = 0.46; 95%CI 0.21–0.98, p = 0.04) and in the subgroup of thrombotic high-risk score patients (HR = 0.49; 95%CI 0.24–1.01, p = 0.04). In particular, patients with ET and a high risk of thrombosis seem to benefit most from RASi treatment (HR = 0.27; 95%CI 0.07–1.01, p = 0.03). Hypertension in MPN patients represents a significant risk factor for TAEs and should be adequately treated.

Sodium bicarbonate as a local adjunctive agent for limiting platelet activation, aggregation, and adhesion within cardiovascular therapeutic devices

Cardiovascular therapeutic devices (CTDs) remain limited by thrombotic adverse events. Current antithrombotic agents limit thrombosis partially, often adding to bleeding. The Impella® blood pump utilizes heparin in 5% dextrose (D5W) as an internal purge to limit thrombosis. While effective, exogenous heparin often complicates overall anticoagulation management, increasing bleeding tendency. Recent clinical studies suggest sodium bicarbonate (bicarb) may be an effective alternative to heparin for local anti-thrombosis. We examined the effect of sodium bicarbonate on human platelet morphology and function to better understand its translational utility. Human platelets were incubated (60:40) with D5W + 25 mEq/L, 50 mEq/L, or 100 mEq/L sodium bicarbonate versus D5W or D5W + Heparin 50 U/mL as controls. pH of platelet-bicarbonate solutions mixtures was measured. Platelet morphology was examined via transmission electron microscopy; activation assessed via P-selectin expression, phosphatidylserine exposure and thrombin generation; and aggregation with TRAP-6, calcium ionophore, ADP and collagen quantified; adhesion to glass measured via fluorescence microscopy. Sodium bicarbonate did not alter platelet morphology but did significantly inhibit activation, aggregation, and adhesion. Phosphatidylserine exposure and thrombin generation were both reduced in a concentration-dependent manner—between 26.6 ± 8.2% (p = 0.01) and 70.7 ± 5.6% (p < 0.0001); and 14.0 ± 6.2% (p = 0.15) and 41.7 ± 6.8% (p = 0.03), respectively, compared to D5W control. Platelet aggregation via all agonists was also reduced, particularly at higher concentrations of bicarb. Platelet adhesion to glass was similarly reduced, between 0.04 ± 0.03% (p = 0.61) and 0.11 ± 0.04% (p = 0.05). Sodium bicarbonate has direct, local, dose-dependent effects limiting platelet activation and adhesion. Our results highlight the potential utility of sodium bicarbonate as a locally acting agent to limit device thrombosis.

Thrombogenic potential of picomolar coagulation factor XIa is mediated by thrombin wave propagation.

Inhibitors of coagulation factor XIa (FXIa) are currently being investigated as potential anticoagulant therapies. We hypothesize that circulating FXIa could be a potential target for these therapies. Using previous analyses of FXIa impurities in immune globulin products involved in thrombotic adverse events, we estimated that picomolar levels of FXIa can be thrombogenic. In an invitro clot-growth assay, 0.1-3 pM of FXIa did not, by itself, activate clotting but increased the size of growing clots. Spatio-temporal reconstruction of thrombin activity inside the clot revealed that FXIa's effect was limited to the clot-plasma interface, in which FXIa produced a taller than standard wave of thrombin. Factor-depleted plasma and a panel of selective anti-FXIa antibodies showed that exogenous FXIa effects are (1) blocked by anti-FXIa antibodies, (2) independent of FXI activation inside the clot, and (3) larger than the contribution of in situ FXIa. In a thrombin generation (TG) assay, picomolar FXIa did not initiate TG but rather promoted TG triggered by tissue factor or thrombin, suggesting that the effect of FXIa on the thrombin wave is mediated by the elevation of thrombin-triggered TG. In circulating bovine blood, low doses of human FXIa did not initiate clotting but increased the size of stenosis-triggered thrombi. FXIa injection in mice enhanced TG in plasma for at least 6 hours exvivo, confirming the persistence of circulating FXIa. Our findings suggest that picomolar levels of circulating FXIa may not be able to initiate thrombosis but can facilitate thrombus growth through the facilitation of TG inside the clot.

Comparison of outcomes following polidocanol microfoam and radiofrequency ablation of incompetent thigh great and accessory saphenous veins

BackgroundMicrofoam ablation (MFA) and radiofrequency ablation (RFA) are both approved by the Food and Drug Administration for treatment of proximal saphenous truncal veins. The objective of our study was to compare early postoperative outcomes between MFA and RFA following treatment of incompetent thigh saphenous veins. MethodsA retrospective review of a prospectively maintained database was conducted of patients who underwent treatment of incompetent great saphenous veins (GSVs) or anterior accessory saphenous veins (AASVs) in the thigh. All the patients underwent duplex ultrasound of the treated leg at 48 to 72 hours postoperatively. Patients were excluded from analysis if concomitant stab phlebectomy was performed. Demographic data, CEAP (clinical, etiologic, anatomic, pathophysiologic) class, venous clinical severity score (VCSS), and adverse events were recorded. ResultsBetween June 2018 and September 2022, 784 consecutive limbs (RFA, n = 560; MFA, n = 224) underwent venous closure for symptomatic reflux. A total of 200 consecutive thigh GSVs and ASVs treated within the study period using either MFA (n = 100) or RFA (n = 100) were identified. The patients were predominantly women (69%) with a mean age of 64 years. The preoperative CEAP classification was similar between the MFA and RFA groups. The mean preoperative VCSS was 9.4 ± 2.6 for the RFA patients and 9.9 ± 3.3 for the MFA patients. Among the RFA patients, the GSV was treated in 98% and the AASV in 2% compared with the GSV in 83% and the AASV in 17% in the MFA group (P < .001). The mean operative time was 42.4 ± 15.4 minutes in the RFA group and 33.8 ±16.9 minutes in the MFA group (P < .001). The median follow-up was 64 days for the study cohort. The mean postoperative VCSS declined to 7.3 ± 2.1 in the RFA group and 7.8 ± 2.9 in the MFA group. Complete closure occurred in 100% of the limbs after RFA and 90% after MFA (P = .005). Eight veins were partially closed and two remained patent following MFA. The incidence of superficial phlebitis was 6% and 15% (P = .06) after RFA and MFA, respectively. Overall, symptomatic relief was 90% following RFA and 89.5% following MFA. The complete ulcer healing rate for the entire cohort was 77.8%. Deep venous proximal thrombus extension (RFA, 1%; vs MFA, 4%; P = .37) and remote deep vein thrombosis (RFA, 0%; vs MFA, 2%; P = .5) showed a trend toward being higher following MFA but the difference did not reach statistical significance. All were asymptomatic and resolved with short-term anticoagulation therapy. ConclusionsMFA and RFA are both safe and effective for treating incompetent thigh saphenous veins, with excellent symptomatic relief and a low incidence of postprocedure adverse thrombotic events. RFA resulted in improved complete closure rates following initial treatment compared with MFA. The operative times were shorter with MFA. Both modalities can be used for patients with active venous ulcers with good healing rates. Longer term studies are required to characterize the durability of MFA closure for above knee truncal veins.

Early results following comparison of radiofrequency and microfoam ablation of large diameter truncal veins demonstrate high closure rates and symptomatic relief

ObjectiveEndovenous closure of truncal veins with a large diameter (LD) (≥8 mm) has been associated with higher risk of post ablation thrombus propagation into the deep venous system. Similar findings after Varithena microfoam ablation (MFA) have not been characterized. The study objective was to analyze outcomes after both radiofrequency ablation (RFA) and MFA and of LD truncal veins. MethodsA retrospective review of a prospectively maintained database was performed. All patients who underwent MFA and RFA for LD symptomatic truncal vein reflux (≥8 mm) were identified. All patients had postoperative duplex (48-72 hours) scanning. Patients underwent subsequent clinical follow-up at 3 to 6 weeks. Demographic data, CEAP Classification, Venous Clinical Severity Score, procedure details, adverse thrombotic events, and follow-up data were abstracted. ResultsBetween June 2018 and September 2022, 784 consecutive limbs (RFA, n = 560; MFA, n = 224) underwent truncal vein (great, accessory, and small saphenous) closure for symptomatic reflux. Sixty-six limbs in the MFA group met inclusion criteria. Sixty-six consecutive limbs treated with RFA during the same time period were included as a comparison group. The mean truncal vein diameter treated was 10.5 mm (RFA, 10.0 mm; MFA, 10.9 mm). Twenty-nine limbs (44%) in the RFA group underwent concomitant phlebectomy. Tributary veins were concomitantly sclerosed in 34 MFA limbs (52%). Total procedural times were shorter in the MFA group (MFA, 31.6 minutes vs RFA, 55.7 minutes) (P < .001). Immediate closure rates were 100% and 95% in the RFA and MFA groups, respectively. Venous Clinical Severity Scores improved after treatment in both groups (RFA, from 9.5 to 7.8; P ≤ .001) (MFA, from 11.3 to 9.0; P ≤ .001). In the RFA and MFA groups, 83% and 79% of venous ulcers healed during the study period, respectively. Symptomatic superficial phlebitis occurred after RFA in 11% and 17% MFA. The incidence of postablation proximal deep venous thrombus extension was 3.0% in the RFA group and 6.1% in the MFA group, which was not statistically significant. All resolved with short-term oral anticoagulant therapy. No remote deep venous thromboses or pulmonary emboli occurred in either group. ConclusionsHigh early closure rates, symptom relief and ulcer healing rates can be achieved after RFA and MFA of LD saphenous veins. Both techniques can be used safely across a wide array of CEAP classes. Longer term studies are required to characterize the durability of MFA closure and sustained symptom relief in LD truncal veins.

Minor Oral Surgery with Out Stopping the Daily Low Dose of Aspirin Therapy

OBJECTIVES Patients with the low-dose long-term aspirin regime have a severe risk of excessive bleeding during surgery, placing them at risk of "adverse thrombotic events". This study aims to evaluate the bleeding in patients undergoing minor oral surgery procedures without stopping daily low-dose aspirin therapy. METHODOLOGY A descriptive cross-sectional hospital-based investigation involved the patient with minor oral surgery at "Altamash Institute of Dental Medicine, Karachi, Pakistan" from mid-April 2021 to mid-June 2021, who were between the age group 30 to 75 with a low-dose aspirin regime. The data was collected via a questionnaire to record the variables, i.e. duration of aspirin, postoperative medications, platelets count, clotting time, normal bleeding time, and intraoperative bleeding time. RESULTS 51 patients, of which 32 were males while 19, were females. The normal bleeding time was comparatively analyzed with the intraoperative bleeding time using SPSS statistical software version 22. The results revealed that the mean bleeding time for the patients with a low-dose aspirin regime during minor oral surgery was 5.49 ± 1.07, while for the patients with a stopped aspirin dose was 4.57 ± 1.07. The comparative analysis using a t-test doesn't reveal significant statistical differences of p&lt;0.05 between both groups. CONCLUSION We concluded that minor oral surgical procedures could safely be done without altering or stopping the low-dose, long-term aspirin regime.

A Case of COVID mRNA Vaccine Linked Antiphospholipid Syndrome

Introduction: There have been several reports of thrombotic adverse events after administration of the mRNA Covid vaccine [1, 2]. The onset of autoimmune disease has also been reported following viral illness as well as following vaccination [3]. Antiphospholipid syndrome (APS) is an autoimmune hypercoagulable state that can result in thrombotic events such as deep venous thrombosis, pulmonary embolus, and stroke [4]. Antiphospholipid antibodies (aPLs) are associated with APS syndrome. However, not all individuals with aPLs will develop antiphospholipid syndrome as antiphospholipid antibodies are also present in up to 5% of the healthy population. Antiphospholipid antibodies have been reported after infections and vaccines. Antiphospholipid syndrome has also been reported following natural Covid infection [5]. Herein we present a case of antiphospholipid syndrome following Covid mRNA vaccination associated with life-threatening thrombosis, dyspnea, and hypoxia coupled with multiple adverse reactions affecting skin, respiratory, nervous, and vascular systems.

Vascular thrombosis after single dose Ad26.COV2.S vaccine in healthcare workers in South Africa: open label, single arm, phase 3B study (Sisonke study)

ObjectiveTo assess the rates of vascular thrombotic adverse events in the first 35 days after one dose of the Ad26.COV2.S vaccine (Janssen/Johnson & Johnson) in healthcare workers in South Africa...

Bleeding and thrombotic events in bevacizumab-treated patients with colorectal cancer on novel oral anticoagulants and antiplatelet medications

BackgroundBevacizumab is a humanized monoclonal anti-VEGF antibody often given in combination with fluorouracil-based chemotherapy as therapy for metastatic colorectal cancer (mCRC). The bleeding and thrombotic event rates in the setting of concurrent novel oral anticoagulants with and without aspirin and bevacizumab treatment in patients with mCRC remain unclear. Methods462 patients with mCRC at Barnes-Jewish Hospital were identified between December 1, 2016 and December 1, 2021 and screened for concurrent treatment with bevacizumab and anticoagulant or antiplatelet therapy. Demographic and clinical information was extracted by electronic chart review. Results21 patients were identified who received bevacizumab and either apixaban or rivaroxaban for mCRC treatment. Aspirin was prescribed in some of these patients within three years of starting apixaban or rivaroxaban. Of the 13 patients without aspirin prescription, nine were given apixaban, and four were given rivaroxaban while on bevacizumab. Four out of nine of the patients who received apixaban had epistaxis, and only one case resulted in any treatment discontinuation. Three out of four of the patients who received rivaroxaban experienced bleeding, and one of these three patients discontinued bevacizumab. We also looked at eight patients who had received aspirin. Two out of seven patients who received apixaban/bevacizumab/aspirin experienced bleeding and discontinued a medication. The patient who received rivaroxaban/bevacizumab/aspirin experienced bleeding and discontinued bevacizumab. No patient experienced adverse thrombotic events. ConclusionsPatients with mCRC treated with bevacizumab and apixaban with no history of aspirin use within three years have a relatively low risk of bleeding that warrants treatment discontinuation.

Bleeding and thrombotic events in patients with colorectal cancer treated with bevacizumab and receiving novel oral anticoagulants and antiplatelet medications.

104 Background: Bevacizumab is a humanized monoclonal VEGF antibody given in combination with fluorouracil-based chemotherapy for metastatic colorectal cancer (mCRC). Many patients with mCRC also have cardiovascular comorbidities requiring anticoagulation or antiplatelet therapy. The bleeding and thrombotic event rates in the setting of concurrent novel oral anticoagulants (NOACs) and bevacizumab treatment in patients with mCRC remain unclear. Methods: 462 patients with mCRC at Barnes-Jewish Hospital were identified between December 1, 2016 and December 1, 2021 and screened for concurrent treatment with bevacizumab and anticoagulant or antiplatelet therapy. Demographic and clinical information was extracted by electronic chart review. Results: 21 patients were identified who received bevacizumab and either apixaban or rivaroxaban for mCRC treatment. Aspirin was prescribed in some of these patients within 3 years of starting apixaban or rivaroxaban. Of the 13 patients who had no history of aspirin prescription, 9 were given apixaban, and 4 were given rivaroxaban while on bevacizumab. 44.4% of the patients who received apixaban experienced bleeding. All these events were epistaxis, and only 25% of the cases resulted in any treatment discontinuation. 75% of the patients who received rivaroxaban experienced bleeding events, which 33.3% of the time resulted in discontinuation of either rivaroxaban or bevacizumab. We also looked at 8 patients who had received aspirin in the last three years: 7 patients were on apixaban, and one was on rivaroxaban while on concomitant aspirin and bevacizumab. 28.6% of the patients who received apixaban with bevacizumab and aspirin experienced an adverse bleeding event that resulted in some form of treatment discontinuation. Meanwhile, the patient who received rivaroxaban with bevacizumab and aspirin experienced a bleeding event that resulted in discontinuation of a medication. No patient experienced any adverse thrombotic events. Conclusions: Patients with mCRC treated with bevacizumab and apixaban with no history of prior aspirin use within three years have a relatively low risk of developing bleeding events that warrant treatment discontinuation. The addition of NOAC to bevacizumab therapy does not appear to increase the risk of adverse thrombotic events.