Long-term Anticoagulant Therapy Research Articles

Extensive Left Sided Venous Thrombi and Bilateral Pulmonary Emboli in the Context of May-Thurner Syndrome for a Patient Presenting with Acute Flank Pain: A Case Report

May-Thurner syndrome is an underappreciated differential in the context of deep venous thrombosis. It is a symptomatic congenital abnormality resulting from compression of the left common iliac vein, sometimes also referred to as iliac vein compression syndrome in the literature. This case reports the presentation of a female with acute flank pain to the emergency department following a recent laparotomy for a complicated tubo-ovarian abscess. She was subsequently diagnosed with a sub-acute thrombus extending from the left common femoral vein into the left inferior vena cava, as well as new bilateral pulmonary emboli. As the patient had relative contraindications to thrombolysis, a shared decision was made with the vascular team to opt for conservative management only. In this instance, this included long-term oral anticoagulant therapy and compression stockings. This case asserts that clinicians should maintain a high index of suspicion for May-Thurner syndrome in the context of extensive left-sided thrombus formation.

Warfarin-related nephropathy: unveiling the hidden dangers of anticoagulation

Warfarin-related nephropathy (WRN) is defined as acute kidney injury subsequent to excessive anticoagulation with warfarin. Patients with mechanical prosthetic valves require long-term anticoagulant therapy. Nonetheless, warfarin remains the sole available option for anticoagulant therapy. Consequently, patients with mechanical prosthetic valves constitute a special group among the entire anticoagulant population. The present study recorded two cases of patients who had undergone mechanical prosthetic valve surgery and were receiving warfarin therapy. They presented to the hospital with gross hematuria and progressive creatinine levels. Notably, their international normalized ratio (INR) did not exceed three. Subsequent renal biopsies confirmed WRN with IgA nephropathy. The two patients continued to receive warfarin as anticoagulation therapy and were prescribed oral corticosteroids and cyclophosphamide, which resulted in improved renal function during the follow-up. Based on a review of all relevant literature and the present study, we proposed a new challenge: must elevated INR levels be one of the criteria for clinical diagnosis of WRN? Perhaps some inspiration can be drawn from the present article.

Anesthetic Choice for Percutaneous Transcatheter Closure of the Left Atrial Appendage: A National Anesthesia Clinical Outcomes Registry Analysis.

Left atrial appendage closure (LAAC) was developed as a novel stroke prevention alternative for patients with atrial fibrillation, particularly for those not suitable for long-term oral anticoagulant therapy. Traditionally, general anesthesia (GA) has been more commonly used primarily due to the necessity of transesophageal echocardiography. Compare trends of monitored anesthesia care (MAC) versus GA for percutaneous transcatheter LAAC with endocardial implant and assess for independent variables associated with primary anesthetic choice. Multi-institutional data collected from across the United States using the National Anesthesia Clinical Outcomes Registry. Retrospective data analysis from 2017-2021. Independent-sample t tests or Mann-Whitney U tests were used for continuous variables and Chi-square tests or Fisher's exact test for categorical variables. Multivariate logistic regression was used to assess patient and hospital characteristics. A total of 19,395 patients underwent the procedure, and 352 patients (1.8%) received MAC. MAC usage trended upward from 2017-2021 (P < 0.0001). MAC patients were more likely to have an American Society of Anesthesiologists (ASA) physical status of≥ 4 (33.6% vs 22.89%) and to have been treated at centers in the South (67.7% vs 44.2%), in rural locations (71% vs 39.5%), and with lower median annual percutaneous transcatheter LAAC volume (102 vs 153 procedures) (all P < 0.0001). In multivariate analysis, patients treated in the West had 85% lower odds of receiving MAC compared to those in the Northeast (AOR: 0.15; 95% CI 0.03-0.80, P = 0.0261). While GA is the most common anesthetic technique for percutaneous transcatheter closure of the left atrial appendage, a small, statistically significant increase in MAC occurred from 2017-2021. Anesthetic management for LAAC varies with geographic location.

Transition from WATCHMAN generation-2.5 device to WATCHMAN FLX device for percutaneous left atrial appendage closure: Incidence and predictors of device-related thrombosis and short- to mid-term outcomes.

Patients with nonvalvular atrial fibrillation (AF) not suitable for long-term anticoagulant therapy undergo percutaneous left atrial appendage closure (LAAC) using the WATCHMAN device. The safety and efficacy of WATCHMAN-FLX (WM-FLX) compared with WATCHMAN-2.5 (WM-2.5), particularly in Asian populations, is unknown. We evaluated the background, procedure, and clinical outcomes of 199 patients who underwent LAAC between September 2019 and December 2022 and compared WM-2.5 (72 patients) with WM-FLX (127 patients). The mean age was 76 years, with 128 men, and 100 had nonparoxysmal AF (non-PAF). The mean CHA2DS2-VASc, and HAS-BLED were 5.1, and 3.2 points, respectively. WM-FLX group demonstrated a shorter procedure time than WM-2.5 group (50 vs. 42 min, p = 0.001). The WM-FLX group demonstrated no procedural-related acute cardiac tamponade, which was significantly low (5.6% vs. 0%, p = 0.02), and a significantly higher rate of complete seal at 45-day (63% vs. 80%, p = 0.04). WM-FLX group had a significantly higher cumulative 1-year incidence of device-related thrombosis (DRT) than WM-2.5 group (3.4% vs. 7.0%, Log-rank p = 0.01). Univariate analysis identified two DRT risk factors in the WM-FLX group: non-PAF (odds ratio [OR] 7.72; 95% confidence interval [CI] 1.20-48.7; p = 0.04), and 35-mm device (OR 5.13; 95% CI 1.31-19.8; p = 0.02). WM-FLX significantly improved the procedural quality and safety of LAAC. However, DRT remains an important issue even in the novel LAAC device, being a hazard for patients with high DRT risk, such as having non-PAF and using 35-mm devices.

Incidence and outcome of periinterventional atrial fibrillation in patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention

Abstract Background Peri-interventional atrial fibrillation (AF) may be detected in patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Data on the thromboembolic risk and long-term clinical outcome in patients with AF limited to the peri-interventional period is scarce. Purpose To assess the incidence and impact on long-term clinical outcome of peri-interventional de-novo AF in STEMI patients. Methods and Results This retrospective single-center cohort study included all patients who underwent PCI between January 2016 and November 2020 (n=491) due to STEMI. Patients were stratified to three cohorts of AF status: Pre-existing AF: n=42 [8.6%], newly diagnosed peri-interventional AF: n=56 [11.4%] and no AF: n=393 [80.0%]. Patients with newly diagnosed peri-interventional AF as well as patients with pre-existing AF had in median a mild-moderately reduced left ventricular ejection fraction (LVEF), patients in sinus rhythm in median a normal LVEF. During the average follow-up time of 4.7 years (min. 2 years, max. 7 years) the rate for readmission for AF or occurrence of AF without hospital admission was increased in patients with peri-interventional de-novo AF or pre-existing AF (n=6 [10.7%], n=10 [23.8%]) compared to those in sinus rhythm n=22 [5.6%] (p&amp;lt;0,001) The occurrence of ischemic stroke was higher in patients with peri-interventional de-novo AF (n=2 [3.6%] or with pre-existing AF (n=2 [4.8%]) compared to those in sinus rhythm (n=6 [1.5%]. (p=0.256) The risk of cardiovascular death was significantly higher in patients with newly diagnosed peri- interventional AF compared to patients with pre-existing or no AF (n=13 [23.2%], n=5 [11.9%], n= 37 [9.4%]) (p=0.009). In the patient group with peri-interventional de-novo AF, only 25.0% (n=13) received long-term oral anticoagulation therapy (OAK). The rate of stroke in patients who received OAK after peri- interventional de-novo AF was 7.7% (n=1) compared to those without OAK 2.6% (n=1). Conclusion Peri-interventional AF is a frequent finding in STEMI patients undergoing primary PCI. Patients with peri-interventional AF had a significantly increased risk for an adverse cardiovascular outcome. Optimal secondary prophylactic measures appear mandatory in this patient population. The significance of long-term OAK therapy is to be determined.

Treatment of thrombotic cardiovascular diseases in people with haemophilia: A Japanese consensus study.

Cardiovascular diseases (CVD) that require long-term anticoagulant and antiplatelet therapy presents a problem in people with haemophilia (PWH) who receive factor replacement therapy to reduce bleeding risk. Currently, there are no Japanese guidelines for the management of PWH with CVD. To develop expert guidance on managing CVD in PWH in Japan. A steering committee of four experts (two haemophilia specialists, one thrombosis specialist, one cardiologist) identified 44 statements related to five key themes. An online questionnaire was produced comprising a mix of 4-point Likert scale and multiple-choice questions that was sent to specialists in the management of PWH with CVD in Japan. Consensus was defined as high or very high if a respective ≥75% or ≥90% of respondents agreed with a statement. Of 16 potential respondents, responses were received from 15 specialists. Of the Likert scale questions, 71% (29/41) achieved ≥90% agreement (very strong agreement), 17% (7/41) achieved 75%-89% agreement (strong agreement) and 15% (6/41) did not achieve consensus agreement. The three multiple-choice questions failed to identify a strong preference. Agreement on specific target trough clotting factor levels for managing certain clinical situations, such as when in the presence of non-valvular atrial fibrillation or myocardial infarction, was also achieved. The results of this consensus study provide a framework for cardiologists and haematologists to manage PWH who are at risk of, or who have, CVD. Implementation of the recommendations provided herein may improve outcomes for PWH with CVD.

#326 Features of intrarenal hemodynamics in patients with chronic glomerulonephritis on the background of taking anticoagulants

Abstract Background and Aims Chronic glomerulonephritis (CGN)-glomerular, autoimmune kidney disease, where baseline therapy is clinically proven to be successful. The study evaluates hemodynamic disorders of renal blood flow in patients with CGN on the background of baseline treatment with the inclusion of rivaroxaban. Method We researched108 patients CGN against the background of 3-month basic therapy with the inclusion of rivaroxaban (group AC+, 55 patients) and without anticoagulant (group AC-, 53 patients). Initial and after 3 months evaluation in the mode of color Doppler mapping and pulse-wave doppler. Results In the course of 3-month therapy, the performance of dopplerography of renal arteries in patients with CGN did not change reliably. But there was a credible and clinically significant increase in the systolic blood flow rate at the level of the Interregional Artery (IA), both compared to the baseline data and towards the end of hospitalization (by 9.27 2.58% p &amp;lt; 0.001 the validity of the difference with the raw data, by 8.60 2.53%, p &amp;lt; 0.01 with the 10th day of therapy), remaining reliably lower than in control group (p &amp;lt; 0.001). The speed at the arc artery (АА) also increased slightly (by 2.46 1.03%, p &amp;lt; 0.05 reliability of the difference with the original data and the end of hospitalization), but although statistical reliability was achieved, the dynamics was clinically insignificant and was less than 2.5%. The resistivity index (RI) at both IA and AA levels did not change reliably. Conclusion In CGN patients, intrarenal hemodynamics change with decreased blood flow rates in IA and AA. In the future, against the background of 3-month basic HGH therapy, there was some improvement in blood flow at the IA level but not AA, but no qualitative changes in intrarenal hemodynamics were achieved. The supplementation of long-term anticoagulation therapy with rivaroxaban has increased the effect of therapy on hemodynamic rates, resulting in some improvement in blood flow at both IA and AA levels, but no qualitative improvement has been achieved, possible due to pronounced structural remodeling of kidney vessels in patients with CGN.

#1312 Warfarin-related nephropathy in two patients with mechanical valves

Abstract Background and Aims Warfarin-related nephropathy (WRN) is defined as acute kidney injury subsequent to excessive anticoagulation with warfarin. Patients with mechanical valves required long-term anticoagulant therapy, and warfarin remains the sole available option for anticoagulant therapy. Consequently, patients with mechanical valves constitute a special group among the entire anticoagulant population. Method The present study recorded two patients receiving warfarin therapy for mechanical valve presented to the hospital with gross hematuria and progressive creatinine levels. Results The first patient was a 56-year-old female, who had previously undergone mechanical aortic valve replacement surgery nine months ago and was prescribed warfarin, was admitted to the hospital due to the occurrence of gross hematuria six days before hospitalization. Additionally, her creatinine levels exhibited a rapid increase from 120.5umol/L to 207.5 μmol/L within three days. Laboratory analysis revealed a creatinine level of 167.8 μmol/L, albumin level of 39.6 g/L, and an INR value of 2.08. The urinary test results indicated the presence of urinary protein (+) and urinary occult blood (3+). The quantification of urinary protein over a 24-hour period was measured at 0.69 g. The immunoglobulin, complements, ANA, ANCA, anti-GBM antibody, serum protein electrophoresis, serum light chains and PLAR2 were within normal range. The second patient was a 63-year-old male, who has been diagnosed with hypertension for the twenty years, underwent Bentall+Sun's surgery for type A aortic dissection five years ago. Following the surgery, the patient was prescribed warfarin. The patient was admitted to the hospital due to persistent gross hematuria for a duration of twenty days and an increase in creatinine levels. Upon admission, laboratory analysis revealed a creatinine level of 169.9μmol/L (which was within the normal range one year ago), and an INR of 2.69. The urinary test indicated the presence of urinary protein (2+) and urinary occult blood (3+). Urinary protein quantification was 3.06 g/24 hours. The serum IgA level was measured at 4.55 g/L (normal range: 1.0-4.2 g/L). The complements, ANA, ANCA, anti-GBM antibody, serum protein electrophoresis, serum light chains and PLAR2 were within normal range. Pathology of two patients all showed red blood casts and tubular injury consistent with ARN and underlying IgA nephropathy (Fig. 1). The two patients was administered a daily dosage of 20 mg of prednisolone and an oral dosage of 50 mg of cyclophosphamide every other day. During a subsequent follow-up after a two-month period, the first patient's creatinine had decreased to 109.2μmol/L, and the urine protein quantification was recorded as 119.7 mg/24 hours. The second patient's creatinine had decreased to 159.2 μmol/L, and the quantification of urine protein was recorded at 310 mg/24 hours. Conclusion Clinicians should maintain a state of increased alertness with regards to the potential occurrence of WRN who exhibit hematuria and elevated creatinine levels while on warfarin therapy, even if their INR remains within the normal range. Considering most patents of WRN have an underlying glomerular disease (mostly IgA nephropathy), the use of steroids and immunosuppressive drugs may appear to be an attractive option, particularly in patients who are unable to replace warfarin with direct oral anticoagulants (NOACs).

Comparing clinical outcomes of vitamin K antagonists vs non-vitamin K antagonists in anticoagulant therapy for mesenteric venous thrombosis

ObjectiveNon-vitamin K antagonist oral anticoagulants have shown similar efficacy and lower bleeding rates than vitamin K antagonists for venous thromboembolism. However, this has not been proven in mesenteric vein thrombosis. This study aimed to compare the clinical outcomes of vitamin K antagonists and non-vitamin K antagonist oral anticoagulants. MethodsBetween January 2014 and July 2022, mesenteric vein thrombosis was diagnosed on computed tomography in 225 patients in a tertiary hospital. Among them, a total of 44 patients who underwent long-term anticoagulation therapy over 3 months were enrolled in this study. Patients were divided into two groups based on the anticoagulant used: vitamin K antagonists (Group 1, n = 21) and non-vitamin K antagonist oral anticoagulants (Group 2, n = 23). The efficacy outcomes were symptom recurrence and thrombus resolution on follow-up computed tomography, and the safety outcome was bleeding complications. ResultsThe median age of the patients was 56 years (range, 46-68 years), and 52% were men. The most common risk factors were unprovoked intra-abdominal infections (30%). The median duration of anticoagulation therapy was 13 months (20 months in Group 1 vs 6 months in Group 2; P = .076). Of the 44 patients, 17 (39%) received the standard treatment. The median follow-up period was longer in Group 1 than in Group 2 (57 vs 28 months; P = .048). No recurrence of mesenteric vein thrombosis-related symptoms were observed in either group. The median duration of follow-up computed tomography was 31 months (42 months in Group 1 vs 18 months in Group 2; P = .064). Computed tomography revealed complete thrombus resolution, partial resolution, and no changes in 71%, 19%, and 10%, respectively (P = .075). Regarding bleeding complications, varix bleeding and melena developed in two patients in Group 2, and anticoagulation treatment thereafter ceased. ConclusionsDespite the short follow-up duration in the non-vitamin K antagonist oral anticoagulants group, there was no clinically significant difference in the thrombus resolution rate or bleeding complications when compared with the vitamin K antagonists group. Although research on the long-term effects of non-vitamin K antagonist oral anticoagulants in patients is limited, non-vitamin K antagonist oral anticoagulants can be considered an alternative to conventional treatments.

Recurrent splanchnic and extrasplanchnic thrombotic events in patients with non-cirrhotic portal vein thrombosis associated with local factors

One third of recent non-cirrhotic portal vein thrombosis are associated with local factors. The risk of rethrombosis after anticoagulation withdrawal is unknown. We aimed to determine factors associated with splanchnic or extrasplanchnic new thrombotic events in that setting. MethodsRetrospective study including recent non-cirrhotic portal vein thrombosis associated with local factors. High and low prothrombotic risk factors, prespecified according to Riport study criteria, were assessed. Quantitative and qualitative variables are presented as median (inter-quartile range), and absolute and relative frequencies respectively. Univariate and multivariate Cox models assessed the influence of different variables on the occurrence of a new thrombotic event. ResultsAt baseline, 83/154 (53.9%) had at least one prothrombotic factor including 50 (32.5%) high-risk and 33 (21.4%) low-risk prothrombotic factors. Oestrogen containing contraception was discontinued in all patients. During follow up, 63/140 (45%) patients had at least one prothrombotic factor, including 47 (33.6%) with a high risk, and 16 (11.4%) a low risk prothrombotic factor. Seventeen new thrombotic events occurred after a median follow-up of 52 (IQR 14-62) (min–max 3.0-69.0) months. New thrombosis were associated with high risk factors (HR 3.817, 95% CI [1.303-11.180], p= 0.015), but inversely related to recanalization (HR 0.222, 95% CI [0.078-0.635], p=0.005) and anticoagulation (HR 0.976, 95% CI [0.956-0.995], p=0.016). When a high-risk factor was present a new thrombotic event occurred in 7.4%, 14.6%, 14.6% and 28.8% of patients at 1, 3, 5 and 7 years under anticoagulants compared to 21.2%, 21.2%, 58% and 58% without anticoagulants. ConclusionsIn recent non-cirrhotic portal vein thrombosis associated with local factors, high risk factors for thrombosis are associated with new thrombotic events. Permanent anticoagulation appears beneficial in this high-risk situation. Impact and implicationsIn noncirrhotic portal vein thrombosis (NCPVT) associated with local factors, systematic screening for prothrombotic factors is recommended, but prevalence of the latter is not clearly established, and the risk of recurrent intra or extra splanchnic thromboembolism is poorly described. Thus, interest in permanent anticoagulation therapy is still pending.NCPVT associated with local factors, is a matter of concern for hepatologists, gastroenterologists and digestive surgeons. Due to a lack of knowledge, practices are heterogeneous.Our findings highlight that systematic screening for prothrombotic factors in NCPVT is strongly needed even when associated with local factors, as it may justify long-term anticoagulation therapy for the prevention of new intra or extra-splanchnic thrombotic events in at least one-third of cases.The interest in long-term anticoagulation should be investigated prospectively in the absence of prothrombotic factors with high risk of thrombosis. Clinical trial numberNCT0536064

Outcomes of Unicompartmental Knee Arthroplasty in Patients Receiving Long-Term Anticoagulation Therapy: A Propensity-Matched Cohort Study

BackgroundAlthough total knee arthroplasty has been considered the gold-standard treatment for severe osteoarthritis of the knee, unicompartmental knee arthroplasty (UKA) has become an increasingly favorable alternative for single-compartment osteoarthritis of the knee. Few studies have examined potential high-risk populations undergoing this procedure. The purpose of this study was to investigate the outcomes of UKA in patients receiving long-term anticoagulation therapy. MethodsIn this study, a large administrative database was queried to identify patients undergoing UKA between 2009 and 2019, who were then divided into a cohort receiving long-term anticoagulation and a control cohort. Propensity scores were utilized to match these patients. Multivariable logistic regression was utilized to compare 90-day and 2-year complication rates between cohorts. ResultsPatients who were on long-term anticoagulation had significantly increased odds of extended length of stay, surgical site infection, wound complication, transfusion, deep vein thrombosis, pulmonary embolism, and readmission at 90-day follow-up. The long-term anticoagulation cohort also experienced significantly higher odds of periprosthetic joint infection and mechanical complications at 2-year follow-up; however, odds of conversion to total knee arthroplasty were not increased. ConclusionsThis study demonstrated that long-term anticoagulation use was associated with poorer medical and surgical outcomes at both 90 days and 2 years postoperatively in patients undergoing UKA, even after rigorous adjustment for confounders.

Novel Oral Anticoagulants in Cardiovascular Practice

In the recent era of medicine, Novel Oral Anticoagulants (Apixaban, Dabigatran, Edoxaban, and Rivaroxaban) have become the preferred drugs for long-term anticoagulation therapy in the majority of cardiovascular conditions, along with non-cardiac co-morbid conditions with few necessary exceptions. This preference is based on their easy availability, therapeutic efficacy, all-cost effectiveness, safety profile, and more convenient usage for both patients and clinicians. Novel Oral Anticoagulants (NOACs) have different pharmacokinetics and pharmacodynamics than oral vitamin K antagonists. This article highlights the basic pharmacology, common complications, available antidotes, and the utility of NOACs in different common cardiovascular diseases requiring long-term oral anticoagulation, including stroke prevention in valvular and non-valvular atrial fibrillation, coronary artery disease, myocardial infarction, left ventricular thrombus and cerebrovascular attacks. NOACs are still underutilized in cardiovascular practice because the concomitant co-morbid conditions hinder a clinician from prescribing these drugs confidently. This manuscript will provide a brief critical overview to help clinicians prescribe NOACs more conveniently.

Genetic Landscape of Thrombotic Microangiopathies with Focus on Plasminogen Mutation Variants

Background: Complement-mediated thrombotic microangiopathy (CM-TMA) or atypical hemolytic uremic syndrome (aHUS) is a subtype of thrombotic microangiopathy (TMA) characterized by a triad of thrombocytopenia, hemolytic anemia, and kidney injury, presumably caused by dysregulation of the complement system. Around 50-60% of all the patients carry a genetic mutation that predisposes them to CM-TMA and influences primarily their risk of recurrence if therapy is stopped. While most of these mutations are in the complement pathway, other genes beyond the complement system have also been recognized. Plasminogen (PLG) gene encodes for plasminogen and plays a role in the coagulation pathway. Bu et al screened 36 patients with clinical diagnosis of aHUS and found 4 patients with variants in the PLG gene ( Bu et al. J Am Soc Nephrol 2014). However, phenotypic correlation with PLG gene mutations and comparisons to other CM-TMAs have not been reported. Aims: 1) To summarize the genetic variants identified in individuals with CM-TMA from a single center cohort and compare the clinical characteristics of individuals with complement mutation versus coagulation pathway mutation 2) Describe the unique phenotypic features of patients with PLG mutations. Methods: This was a single center retrospective study of patients referred or presenting to the Ohio State University for evaluation for an initial clinical diagnosis of CM-TMA that had TMA gene panel testing performed from 2011 until February 2023. Patients were excluded if the diagnosis of CM-TMA was inconclusive or information regarding their initial presentation or treatment were not available. For individuals who met the criteria, data were collected regarding demographics, clinical features at their first presentation, management, renal outcomes, genetic test findings and disease recurrence. Results: We initially identified 121 individuals who met the study criteria. Final analysis included 105 individuals. Median age at diagnosis was 42 years. Two-thirds of the cohort was female. About half of the patients had no identifiable mutation (n=59, 58.6%). Of those with an identifiable mutation (n=46), 66% (n=30) had a complement mutation and 21% (n=9) had a coagulation pathway mutation. When comparing the presentation at diagnosis, individuals with a coagulation pathway mutation had a comparable degree acute kidney injury (AKI) as reflected by elevated creatinine at presentation, but less thrombocytopenia and hemolysis compared to patients with complement pathway mutations (Table 1). Within the coagulation pathway gene variants cohort, there were initially 6 individuals with PLG mutation and 4 with THBD mutation. We excluded one individual with PLG mutation from this cohort since he also had MCP mutation, and his clinical course was well explained by the presence of MCP mutation. The 5 patients with PLG mutation were females (Table 2). Compared to THBD and complement gene variants, patients with PLG mutation had less AKI, thrombocytopenia, and hemolysis at presentation. These individuals demonstrated quicker recovery of renal function within a few weeks to a month, even in the absence of complement blockade therapy, and most were independent of hemodialysis by 3 months after diagnosis. 2 of the 5 (40%) had recurrent TMA and one of had recurrent TMA episodes despite being on long-term complement blockade therapy which was started after a future relapse. These recurrent events resolved completely with supportive therapy that included plasmapheresis. Three patients are on long-term anticoagulation therapy. None have had any aHUS recurrences while on anticoagulation. None of the patients with PLG mutations developed postpartum presentations despite multiple pregnancies in this limited cohort. Conclusions: Our cohort of CM-TMA subjects shows that patients with PLG mutation associated TMAs have a distinct clinical presentation and possible a lack of response to complement blockade therapy compared with complement gene variants in this cohort. Larger multicenter studies are needed to further validate our findings. Given the role of plasminogen in the coagulation pathway, studies are indicated to explore the role of anticoagulation to prevent recurrence in this subset of patients. Additionally, functional studies of these disease specific PLG variants are vital to identify the pathogenic mechanisms for what might be a distinct form of TMA from CM-TMA.

Retrospective Analysis of Clinical Outcomes of Utilizing R-CHOP Plus Zanubrutinib for High-Risk Diffuse Large B Cell Lymphoma Patients with Extranodal Involvement or MYC/BCL2 Double Expression

Background: Diffuse large B-cell lymphoma (DLBCL) patients with extranodal involvement and double expression of MYC and BCL2 often have a poorer prognosis when treated with the standard first-line R-CHOP regimen. The 5-year progression-free survival (PFS) and overall survival (OS) rates are both below 40% for these high-risk DLBCL cases. In this study, we perform a retrospective analysis of the clinical outcomes and adverse events of the high-risk DLBCL patients with extranodal involvement and double expression, who were admitted to our center and used Bruton's tyrosine kinase inhibitor (BTKi) zanubrutinib on the basis of R-CHOP regimen. Methods: We conducted a retrospective analysis of 26 DLBCL patients with extranodal involvement or MYC/BCL2 double expression who were admitted to our center and used R-CHOP regimen in combination with zanubrutinib between 1 st January 2021 and 30 th April 2023 (Figure A). Of these patients, 19 had extranodal involvement, and 7 were identified as double expression cases. The patients had a median age of 70 years, ranging from 34 to 87. Among them, 20 cases (77%) were aged over 60, and 8 cases (30%) were aged over 75. Moreover, 20 cases (76.9%) exhibited an Eastern Cooperative Oncology Group (ECOG) performance status score higher than 2 points. All the patients received an induction regimen consisting of zanubrutinib in combination with R-CHOP for a total of 4 cycles. After the fourth cycle, treatment efficacy was assessed using 18FDG-PET/CT scans. Patients achieving partial response (PR) or better continued with rituximab in combination with zanubrutinib for consolidation maintenance therapy, lasting for 1 year. For patients at risk of central nervous system involvement, oral administration of zanubrutinib continued for 2 years. During the treatment period, imaging evaluations were performed every 3 months to assess treatment response (Figure B). Results: After the induction therapy, a mid-term PET/CT evaluation showed that all patients achieved PR or above, resulting in an overall response rate (ORR) of 100%. Among them, 19 patients (73.1%) achieved complete response (CR), while 7 patients (26.9%) achieved PR. During the consolidation and maintenance therapy, 7 patients who were initially in PR converted to CR. As of the latest follow-up, with a median follow-up duration of 11 months (ranging from 4.1 to 30.0 months), 2 patients (7.7%) were lost to follow-up, and 2 patients (7.7%) experienced disease progression. The median PFS and OS were not reached. The 2-year PFS was 69.7±13.4% (Figure C), and the 2-year OS was 77.4±12.2% (Figure D). Non-hematological adverse events included fatigue (38.5%), hypertension (15.38%), neurological symptoms (7.7%), and infections (100%). Among the infections, 3 cases (11.5%) were of &amp;gt;3-grade and led to treatment discontinuation. Additionally, one patient experienced immune encephalitis and went into a coma. Hematological adverse events included granulocytopenia (55%), anemia (26%), thrombocytopenia (42.3%), and bleeding (38.5%). Among them, &amp;gt;3-grade granulocytopenia occurred in 4.5% of the patients. Five patients who were on long-term anticoagulant therapy due to concurrent cardiovascular diseases experienced a reduction in zanubrutinib dosage during the follow-up period, resulting in an improvement in bleeding symptoms. Conclusions: The combination of 4 cycles of R-CHOP regimen with zanubrutinib in the induction treatment of DLBCL patients with high-risk factors, such as extranodal involvement or MYC/BCL2 double expression, has shown promising clinical outcomes especially in older or unfit/frail patients. This approach allows for a reduction in the number of cytotoxic drug cycles, thereby improving the patients' tolerance to the treatment. Moreover, the efficacy of this regimen is superior to the traditional 6-8 cycles of R-CHOP induction therapy. Furthermore, the consolidation and maintenance therapy with rituximab in combination with zanubrutinib has demonstrated good safety and manageable adverse effects. This approach exhibits hope for further enhancing the prognosis of high-risk DLBCL patients.

Efficacy and Safety of Different Doses of Rivaroxaban and Risk Factors for Bleeding in Elderly Patients with Venous Thromboembolism: A Real-World, Multicenter, Observational, Cohort Study.

Venous thromboembolism (VTE) consists of deep vein thrombosis (DVT) and pulmonary embolism (PE). Rivaroxaban is a direct oral anticoagulant (DOAC) inhibiting activated coagulation factorX (FXa), and exerts several advantages in the treatment of VTE compared to conventional therapy. However, the efficacy and safety of rivaroxaban in elderly patients with VTE was still poorly understood. The study was carried out using an observational and non-interventional approach. A total of 576 patients aged ≥ 60years with newly diagnosed VTE were included in the study. All patients received rivaroxaban with recommended treatment duration of ≥ 3months for secondary prevention. In addition, 535 elderly patients with various diseases except VTE were included in the study in a retrospective and randomized way. The total bleeding rate was 12.2% (70/576). Major bleeding and non-major clinically relevant (NMCR) bleeding occurred in 4 (0.69%) patients and 5 (0.87%) patients, respectively. The rate of recurrent VTE was 5.4%. The mean level of D-dimers was increased by 467.2% in the elderly patients with VTE compared with the elderly patients without VTE. The elderly patients with VTE receiving rivaroxaban at a dose of 10mg once daily (n = 134) had lower risk for bleeding (3.7% vs 14.7%; P = 0.001) and a similar rate of recurrent VTE (4.5% vs 5.7%; P = 0.596) as compared to the elderly patients with VTE receiving rivaroxaban at higher doses including 15mg once daily and 20mg once daily (n = 442). In addition, age, concomitant aspirin, hemoglobin, activated partial thromboplastin time (APTT), and rivaroxaban doses were independent predictive factors for bleeding events. The study suggested that a dose of 10mg once daily should be the priority in elderly patients with VTE receiving long-term rivaroxaban anticoagulation therapy in view of reduced bleeding risk.

Effect of pre-procedural anticoagulation in patients undergoing ablation: a meta-analysis of randomized controlled trials

Abstract Background Atrial fibrillation (AF) is the most common type of arrhythmia seen in a clinical setting. Patients have a high risk of stroke, especially in the first two years of diagnosis. Anticoagulation therapy is prescribed to patients with a high CHAD2S2-VASc score. Based on recent evidence, catheter ablation (CA) is emerging as the preferred first-line treatment of modality. The benefit of interruption of anticoagulation before CA is unclear. Interruption of anticoagulation and insertion of a foreign body during CA can lead to an increased risk of thromboembolism (TE). Anticoagulation is interrupted before the procedure to balance the risk of TE and bleeding. Objective To assess the risk of bleeding and TE in patients undergoing CA with uninterrupted versus interrupted anticoagulation. Methods We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) strategy to search PubMed/MEDLINE, EMBASE, and Cochrane databases from inception till January 2023. We included randomized controlled trials and excluded observational studies. The data was extracted from full texts. Data Random effects model and Mantel-Haenszel method were used to calculate pooled risk ratio and 95% confidence interval. Results A total of 10 studies were included, with 4,584 participants. The risk of TE [1.76; 95% confidence interval (CI): 0.33, 9.46] and bleeding [1.10; 95% CI: 0.59, 2.05] did not change significantly with the interruption of all anticoagulation agents. Similarly, interruption of individual anticoagulants such as heparin [0.81, 95% CI: 0.19, 3.39], vitamin K antagonists (VKA) [9.21, 95% CI: 0.02, 5627.42], and direct oral anticoagulants (DOAC) [1.36, 95% CI: 0.26, 7.23] did not show any change in the risk of TE. There was no significant change in the risk of bleeding with heparin discontinuation (Figure 1). Conclusion Our study supports recent trials such as Randomized Evaluation of Long-term Anticoagulant Therapy (RE-LY) and emerging data that support uninterrupted anticoagulation prior to ablation as there is no increased risk of bleeding or TE.

Intracardiac thrombi in pediatrics: anticoagulation approach and treatment outcomes

BackgroundIntracardiac thrombi (ICT) are associated with significant morbidity and mortality. Anticoagulation is the first line of treatment and may be complemented by thrombectomy or thrombolysis. However, optimal anticoagulant duration remains ill-defined. High-risk features of ICT that may warrant long-term anticoagulation therapy have not been established. ObjectivesTo describe anticoagulation duration and patterns of ICT resolution. To identify potential risk factors for persistent ICT despite anticoagulation. MethodsA single-institution retrospective chart review identified patients diagnosed with ICT by echocardiogram between January 2014 and March 2022. Descriptive statistics and logistic regression were used. ResultsFifty-one patients with ICT were identified. Median age at diagnosis was 9.2 years (IQR, 0.4-15.2). The most common underlying diagnoses were congenital heart disease (41%), infection (25%), and malignancy (24%). The majority of ICT were in the right atrium (n = 30). The median longest ICT dimension was 1.5 cm (range, 0.4-4.0). The median duration of anticoagulation was 4.3 months (IQR, 2.2-9.1). Among 48 patients who received anticoagulation as first-line treatment, 32 had partial or complete response with 3 to 6 months of anticoagulation, while remaining 16 patients had no response to anticoagulation. Patients with a central venous line had a delayed resolution of ICT [hazards ratio = 0.45 (95% CI, 0.22-0.93)]. ConclusionOur study demonstrates the wide variability in duration of anticoagulation for children with ICT. Majority of the individuals benefit from 3-to-6 month treatment; however, individuals with a central venous line may benefit from a longer course of anticoagulation. Further large-scale studies are recommended to validate our findings.

Efficacy and Safety of Long-Term Anticoagulation Therapy with Direct Oral Anticoagulants versus Vitamin K Antagonist in Patients with Cerebral Venous Thrombosis

Efficacy and Safety of Long-Term Anticoagulation Therapy with Direct Oral Anticoagulants versus Vitamin K Antagonist in Patients with Cerebral Venous Thrombosis

Role of Anticoagulation in Nonagenarian Patients with Acute Limb Ischemia

Preoperative anticoagulant therapy is known to have a positive impact on the prognosis of patients with acute limb ischemia (ALI). However, little is known about its efficacy in elderly patients. We aimed to investigate the potential effect of anticoagulation in nonagenarian patients managed for ALI. Between January 2015 and December 2021, we identified all nonagenarian patients managed for ALI at a single center. Long-term anticoagulation and hemostasis parameters (prothrombin rate, activated partial thromboplastin time [APTT], platelet count) measured on admission were reviewed. The primary end point was mortality at 30-day mortality (D30) in patients with or without long-term anticoagulation therapy. We also studied the effect of these factors on the occurrence of revascularization failure in operated patients (initial failure, ischemic recurrence during hospitalization, necrosis requiring major amputation). A total of 68 nonagenarian patients were managed for ALI, with a mean age of 93.8years (from 90-107years), 76.5% of whom were women. Of these patients, 47 (69%) were managed surgically. Long-term anticoagulation therapy was associated with better survival at D30, both in nonoperated (P<0.01) and operated (P<0.05) patients. In operated patients, the absence of long-term anticoagulation therapy was associated with the occurrence of revascularization failure (P<0.05). In operated patients, survival to D30 and successful revascularization were associated with a longer APTT (P<0,05). We were able to observe the survival of 4 patients contraindicated for surgery and treated with a single medical therapy (intravenous unfractionated heparin). Anticoagulation appears to have an impact on the survival and postoperative prognosis of nonagenarian patients with ALI. In addition, curative anticoagulation therapy may be an alternative treatment when surgery is contraindicated in this frail population.

Multisystem inflammatory syndrome complicated by pulmonary embolism in a child

Purpose - to present a clinical case of a particular complication of post-COVID multisystem inflammatory syndrome (MIS) - pulmonary embolism (PE) which developed due to primary hereditary thrombophilia in a child for better understanding of the MIS evolution and prognosis in children (MIS-C). Case report. In an 11-year-old boy who previously had no hemorrhagic manifestations, the first symptoms of the disease occurred in the form of fever and a hemorrhagic rash on the lower extremities. Later, he developed signs of respiratory failure, his condition worsened, and bilateral community-acquired viral pneumonia caused by COVID-19 was diagnosed. The child presented with post-COVID MIS manifested as PE, which caused further genetic examinations for hereditary thrombophilia. Primary thrombophilia was detected (F2 gene - prothrombin (20210 G&gt;A) D68.5). Concomitant hereditary pathology was probably the reason for a severe course of the infection and the development of a complication in the form of PE requiring intensive and long-term anticoagulant therapy. Conclusions. In case of PE detection, especially in young patients, examinations to confirm or rule out hereditary or acquired thrombophilia are required, that defines recurrent venous thromboembolism prevention programs. This clinical case report is a contribution to the study on the issues of MIS-C, defining links between pulmonary complications (transient or persistent) and serious sequelae in the future. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.