Episodes Of Thrombosis Research Articles

Real-world data on direct oral anticoagulants in BCR::ABL1-negative myeloproliferative neoplasms (MPNs): a multicenter retrospective study on behalf of scientific subcommittee on MPNs for Turkish society of hematology.

BCR::ABL1-negative myeloproliferative neoplasms (MPNs) pose a substantial risk of thrombosis, leading to significant morbidity and mortality. Anticoagulant therapy, historically based on vitamin K antagonists (VKAs), has limitations in preventing recurrent thrombotic events and managing bleeding complications. Direct oral anticoagulants (DOACs) offer a potential alternative with improved pharmacokinetics and compliance. However, evidence on DOAC efficacy and safety in MPNs remains limited, necessitating further investigation. In this multicenter retrospective study in Türkiye, we assessed real-world usage patterns and outcomes of DOACs in MPN patients. Data from 220 patients with PV, ET, or PMF receiving DOACs or VKAs for thrombosis or nonvalvular atrial fibrillation (NVAF) were collected from medical records. Thrombotic events and bleeding episodes were documented based on ISTH criteria. DOACs were used in 126 patients as first-line anticoagulant therapy or following VKAs. Ninety-four patients were on VKAs, of which 83 as a first-line treatment. There were eight thromboses (6.3%) seen in 126 DOAC patients, and similarly, seven episodes (9.4%) of thrombosis were observed in 94 patients using VKA. Major bleeding occurred in seven patients (5.6%) on DOAC and 3 (3.2%) in VKA. Thrombotic and bleeding risks were comparable between DOACs and VKAs (p = 0.708 and p = 0.158, respectively). The incidence rate of thrombosis in the VKA group is 1.1% and in the DOAC group is 1.9%. The incidence of major bleeding in the VKA group is 0.6% and 1.6% in the DOAC group. To the best of our knowledge, our study included the largest number of MPN patients to date, comparing DOACs with VKA in terms of both efficacy and safety, which suggests DOACs as promising alternatives to VKAs for managing thrombotic risk in MPNs with manageable toxicity. Despite the limitations of retrospective studies, DOACs' benefits in terms of efficacy and compliance warrant further investigation through prospective trials. Individualized treatment decisions should consider patient-specific factors, emphasizing collaborative efforts between specialists to optimize DOAC therapy in patients with MPNs. Comparable efficacy and safety between DOACs and VKAs were observed in MPN patients.

Comparison of the Efficacy and Safety of Low Molecular Weight Heparins and Fondaparinux in Patients With COVID-19: A Systematic Review and Meta-Analysis.

Individuals diagnosed with COVID-19 are at a higher risk of arterial and venous thrombosis, mostly pulmonary microvascular thrombosis, which may significantly impair treatment and result in morbidity. This is a systematic review and meta-analysis of research papers that aimto evaluate the risk of bleeding and thrombosis among patientstreated with low molecular weight heparin or fondaparinux (LMWH/F). Additionally, we measured the overall death events. This study was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. A search was conducted in the Clinicaltrials.gov, PubMed, Scopus, and Web of Science databases to identify observational cohort studies and randomized-controlled clinical trials (RCTs) that compared LMWH/F in proven COVID-19 patients. A total of 220 people from two studies were included. Patients who were treated with fondaparinux had a lower risk of developing venous thromboembolism (VTE) (odds ratio (OR) 0.39; 95% confidence interval (CI) (0.14, 1.096); p = 0.168); pulmonary embolism (OR 0.169, 95% CI (0.021, 1.356), p = 0.094); and deep vein thrombosis compared to patients who received LMWH therapy. The data show a lower mortality rate in the LMWH groups (OR 1.135, 95% CI (0.463, 2.785), p = 0.781) and a lower frequency of bleeding (OR 1.657, 95% CI (0.456, 5.908), p = 0.436). Both drugs have shown anti-thrombotic properties in COVID-19 patients. Fondaparinux was somewhat more effective in reducing thrombosis episodes. This research demonstrates the safe use of LMWH for VTE prophylaxis in hospitalized COVID-19 patients based on bleeding and mortality outcomes.

Beyond traditional venous access: Midline catheter use in pediatric apheresis.

The objective of this study was to assess the use of midline catheters as venous access for apheresis procedures in pediatric patients. A retrospective analysis of medical records was conducted from September 2019 to June 2022 to evaluate the safety and efficacy of midline catheters for therapeutic pediatric apheresis. During the study period, a total of 121 procedures were inserted in 22 unique patients. The age of the subjects ranged from 2.7 to 21 years. The blood flow rates achieved with midline catheters met or exceeded the recommended rates for apheresis in children (40 mL/min), by the Wilcoxon signed-rank test (p < 0.0001). There was one episode of catheter-related thrombosis, but no cases of bloodstream infection or catheter dislodgement were reported. In conclusion, this study supports the use of midline catheters as a safe and effective alternative for venous access during therapeutic and donor apheresis procedures in pediatric patients.

#2559 “Remote software technology to assist clinical decision in vascular access surveillance: single UK centre experience”

Abstract Background and Aims Optimal arteriovenous access monitoring and surveillance aims for early detection of dysfunctional access, enabling pre-emptive referral for angioplasty or surgery to prevent access loss or thrombosis. Here we compared the addition of remote software surveillance to standard clinical care in our units. Method From January–December 2023 we conducted a 12-month prospective study of maintenance hemodialysis (HD) patients. We used Vasc-Alert software technology to assist clinical decision making for vascular access (VA) surveillance in 2 out of 5 HD units. In these units, vascular access risk score was calculated using Vasc-Alert software platform from routinely collected data from the dialysis procedure as previously described [1]. Patients with high Vasc-Alert access risk score (≥7) underwent clinical assessment and were referred for fistulogram if they met the relevant KDOQI criteria [2]. The following variables were collected from all 5 HD units: baseline permanent VA prevalence, subsequent VA events (stenosis or thrombosis), access abandonment (i.e. unsalvageable access loss), complication free days (CFD)-extended over one year (defined as days without serious vascular access events, radiological or surgical intervention, VA infection, hospitalisation or use of central venous catheter). Data was collected on patients who were pre-emptively referred for diagnostic fistulogram ± angioplasty but thrombosed while awaiting intervention. Median time interval from the date of fistulogram request till the date of confirmed thrombosed access was calculated. Comparison between HD units with Vasc-Alert use (Group 1) or without (Group 2) was performed using appropriate statistical tests depending on the type and distribution of the data. Survival analysis of post-intervention primary patency rate was conducted at 3 and 6 months defined as the time from the index procedure until the next access thrombosis or reintervention [3]. Results There were 81 (53.6%) patients with permanent VA in group 1and 201 (59.3%) patients in group 2at the start of the study. We recorded 23 (28.4%) episodes of stenosis and 6 (7.4%) episodes of thrombosis in Group 1 and 40 (19.9%) episodes of stenosis and 21 (10.4%) episodes of thrombosis in Group 2 (p value 0.121 and 0.432, respectively). In Group 2, 11 patients (5.5%) developed repeated stenosis and 2 patients (1%) repeated thrombosis. In Group 1, 5 /6 (83%) cases preemptively referred for diagnostic fistulogram ± angioplasty developed thrombosis whilst awaiting elective intervention, compared with 4/21 (19%) in group 2 (p value = 0.008) (Fig. 1). The median time interval from the date of fistulogram request till date of thrombosed VA was 26 days with Interquartile range (IQR 25-75%) of 21-34 days. Group 1 had better post-intervention primary patency rate of VA (Fig. 2) and longer CFD-extended compared to group 2 (p values &amp;lt; 0.001 and 0.002 respectively) (Table 1). Conclusion Our study shows that integrating Vasc-Alert technology into the VA surveillance program was associated with improved early detection of high-risk access, higher primary patency rates and CFD-extended. Additionally, our data emphasizes the need to enhance interventional radiology capacity for timely access intervention, to realise the true potential of Vasc-Alert technology in prevent access thrombosis.

#2430 Comparison of the efficacy of gentamicin-citrate and gentamicin-citrate/Taurolock-urokinase locks for non-tunneled catheters in hemodialysis patients

Abstract Background and Aims Catheter-related complications, such as dysfunction, thrombosis and infection, are associated with significant morbidity and mortality in patients on hemodialysis (HD) receiving dialysis through temporary non-tunneled double-lumen central venous catheters (CVC). Catheter lock solutions containing antibiotics and antitrombolytics are commonly used to prevent such complications. The aim of the present study was to compare impact of a different prophylactic catheter lock solutions on the incidence of catheter-related complications (catheter-related bloodstream infection (CRBSI) and catheter thrombosis) and mortality compared with heparin catheter locks. Method We performed a single-centre prospective, randomized, single-blinded controlled trial of 96 adult patients undergoing HD in our institution from Jun 2018 to Jun 2023. Patients were randomized 1:1:1 to receive either a lock solution combining gentamicin-citrate twice a week with taurolidine-citrate (Taurolock)/urokinase at the end of the third hemodialysis session before the end of the week (TAURO group) or gentamicin-citrate at the end of all hemodialysis sessions (GENTAM group) or unfractionated heparin 5000 U/mL thrice weekly as control (HEPARIN group). Catheter lock solutions were administered for 3 months after insertion of CVC and patients were followed for at least 6 months after insertion of CVC. Demographic, clinical and laboratory parameters, as well as used medications, were analyzed. Episodes of acute catheter thrombosis and incidence of CRBSI were recorded, along with dialysis adequacy (Kt/V) and adverse events. Results The study population (96 patients, 32 in each group) had a median age of 60 years (range 19–85 years), 56.3% man. In the majority of patients (88.5%) the indication for placement of the CVC was the initiation of dialysis, while in the remaining patients indication was thrombosis of the existing vascular access. The most important baseline clinical and laboratory values are presented in Table 1. The catheter median length of stay was of 125.94 ± 87.48 (from 50 to 535) days in TAURO group, 113.44 ± 35.68 (from 54 to 233) days in GENTAM group and 108.59 ± 37.84 (from 42 to 212) days in HEPARIN group (p = 0.831). There was no difference between groups with regard to catheter thrombosis (3.3 events/1000 catheter-days in all groups). The CRBSI rate of 3.2 episodes/1000 catheter-days in TAURO group was slightly lower than the rate of 5.3 episodes/1000 catheter-days in GENTAM group (p = 0.479) and 4.3 episodes/1000 catheter-days in control HEPARIN group (p = 0.705). The CRBSI-free survival time in TAURO group was 197 ± 220 (from 28 to 447) days, longer than in the GENTAM group (38 ± 33 days, from 8 to 86) and HEPARIN group (37 ± 35 days, from 4 to 86), p = 0.21. Impact of catheter lock solution on dialysis adequacy as measured by Kt/V in time is presented in Fig. 1. No significant differences were found between study groups in survival after 6 months (p = 0.810) and at the end study period (p = 0.096)-presented in Fig. 1. Conclusion We observed no difference in the incidence of catheter thrombosis and mortality rate in groups with prophylactic catheter lock solutions and control group. The use of Gentamicin-citrate/Taurolock-urokinase as a dialysis catheter lock solution, as compared with gentamicin-citrate or heparin administered three times a week, led to a nonsignificant reduction of CRBSI incidence and longer CRBSI-free survival time in patients on HD receiving dialysis through temporary non-tunneled double-lumen CVC.

Red blood cell distribution width is a useful biomarker to predict bleeding and thrombosis risks in patients with immune thrombocytopenic purpura.

Bleeding and thrombosis are common complications during immune thrombocytopenic purpura (ITP) treatment. There is a strong need to predict bleeding and thrombosis risks before ITP treatment to optimize therapy and appropriately manage these complications. We performed a retrospective cohort study of 120 patients with primary ITP to identify a biomarker to predict bleeding and thrombosis. We compared blood test results at diagnosis between patients with and without bleeding or thrombosis episodes. The standard deviation of red blood cell distribution width (RDW-SD) differed significantly between those with and without bleeding and between those with and without thrombosis, leading us to identify it as a variable representative of risk. RDW-SD was significantly associated with patient age and with histories of several vascular diseases. Multivariate regression analyses showed that RDW integrated several variables associated with vascular risks. RDW-SD was significantly associated with difficulty with corticosteroid discontinuation (hazard ratio [HR], 2.22, p=0.01), incidence of bleeding (HR, 2.75, p< 0.01), incidence of thrombosis (HR, 2.67, p< 0.01) and incidence of infection (HR, 1.78, p=0.04). The RDW-SD value at the time of ITP diagnosis is a useful biomarker to predict the risks of bleeding, thrombosis, and other complications.

The course of the pulmonary embolism in patients with oncological diseases

The aim – to identify factors associated with in-hospital mortality among patients with acute pulmonary embolism (PE) and oncological diseases. Materials and methods. A retrospective analysis of 647 medical records of patients with acute PE treated at one center from January 1, 2018, to January 1, 2020, was conducted. Among them, 115 patients had verified oncological diseases. PE diagnosis in all patients was confirmed by computed tomography and/or autopsy results. Alongside laboratory studies, patients underwent ultrasound examination. Results and discussion. A comparative assessment of clinical and anamnestic parameters in patients with PE, depending on the presence of oncological diseases, was conducted. The analysis revealed that patients with PE associated with oncological process were on average 5 years older, with higher proportion of elderly patients, and less frequently had anamnestic episodes of venous thrombosis (13.9 % vs. 24.6 %), but predictably more often had additional risk factors, such as blood transfusions, central venous catheters, and laparoscopic interventions. According to the results of the multifactorial regression analysis, factors independently influencing the risk of in-hospital death in patients with acute PE and oncological diseases included decrease of blood pressure, saturation, an increase of the pulmonary artery pressure, leukocytosis and presence of atrial fibrillation. The ROC analysis results allowed determining threshold values of parametric indicators associated with the risk of death during the hospital period in a patient with PE and oncological diseases, i.e. blood pressure ≤ 105 mm Hg, SpO2 ≤ 87 %, pulmonary artery pressure &gt; 48 mm Hg, and leukocyte count &gt; 9.8  109/l. Conclusion. The risk factors of in-hospital death in patients with PE associated with oncological disease are atrial fibrillation, increased pulmonary artery pressure, leukocyte count, low blood pressure and saturation.

Comparison of Dual vs. Triple Antithrombotic Therapy in Non-Valvular AF and Acute Coronary Syndrome: A Malaysian Cohort Study

Objectives: This study aimed to compare Dual Antithrombotic Therapy (DAT) and Triple Antithrombotic Therapy (TAT) concerning bleeding and thrombosis outcomes in Malaysian patients with non-valvular atrial fibrillation (NVAF) and acute coronary syndrome (ACS), considering demographic characteristics and comorbidities. Methodology: A retrospective observational cohort study was conducted at Hospital Serdang from January 1, 2020, to May 1, 2022. A total of 206 patients were selected via purposive sampling and divided into two groups. The TAT group received warfarin, clopidogrel, and aspirin, while the DAT group received warfarin and clopidogrel over a 1-year follow-up. Multivariate logistic regression analysis was employed. Results: A higher incidence of thromboembolic episodes was observed in the DAT group (24.3% vs. 8.7% in the TAT group; adjusted odds ratio (aOR) 4.53, 95% CI 1.806-11.379, P= 0.001), signifying a 4.5-fold increase in thromboembolic events in DAT compared to TAT. Conversely, more bleeding episodes were observed in the TAT group (25.2% vs. 15.5% in the DAT group; aOR 2.22, 95% CI 0.993-4.970, P= 0.52), although the difference was not statistically significant. Conclusion: The DAT protocol showed significantly more thrombosis episodes than the TAT protocol, while TAT exhibited a non-significant increase in bleeding events compared to DAT at one year follow-up in patients with NVAF and ACS.

Thrombosis Tendency After Splenectomy in a Danish Family With Hemoglobin Volga, and a Literature Review

Hemoglobin (Hb) Volga is a rare, unstable β-chain hemoglobin variant (β27 Ala→Asp), causing chronic hemolytic anemia. This study presents two members of a Danish family, splenectomized due to Hb Volga at and with multiple thrombotic events. The proband was diagnosed with Hb Volga 9 years old and splenectomy was performed as a part of treatment. Throughout his life, he experienced multiple superficial thrombophlebitis, two episodes of distal deep venous thrombosis (DVT) on lower extremities (age 32 and 33) and a transient ischemic attack (TIA) presented as amaurosis fugax (age 51). Thrombophilia investigation was normal. The proband’s son was diagnosed with Hb Volga and underwent splenectomy at the age of 6. Despite anticoagulation therapy, he suffered from multiple venous thromboembolic events in his youth and died of chronic pulmonary embolism (PE)/pulmonary hypertension combined with infection. Given the observed propensity for multiple thromboses in these two patients, a literature review was conducted investigating reported occurrence of thrombotic events in individuals with Hb Volga. Currently 25 cases of Hb Volga are reported worldwide. The clinical symptoms primarily described are related to hemolytic anemia. Splenectomy is reported in 15 patients. Thromboses have previously been reported in only three patients who were also splenectomized. These cases involved DVT and PE, myocardial infarction, and an unspecified thrombotic event. The proband represents the first reported Hb Volga case with both venous and arterial thrombotic disorders. The exact mechanism underlying thrombotic tendency in patients with Hb Volga remains unknown, but it is probably associated with splenectomy.

Abstract 136: The Incidence of Newly Diagnosed Cancer After a First-Ever Episode of Cerebral Venous Thrombosis: A Registry- and Population-Based Cohort Study

Introduction: Active cancer is a known risk factor for cerebral venous thrombosis (CVT), but it is unknown whether CVT is also associated with occult cancer. We evaluated the incidence of newly diagnosed cancer after CVT. Methods: We performed a registry- and population-based cohort study using the Dutch hospital discharge registry. Patients admitted to any Dutch hospital between 1997 and 2020 with a first episode of CVT were identified using ICD-9 and ICD-10 codes. Patients with a history of cancer and patients diagnosed with cancer during admission for the index CVT were excluded. We calculated the cumulative incidence of cancer after CVT with death as a competing risk. Standardized incidence ratios (SIRs) were calculated relative to a control group matched by age, sex, and calendar year with data from the Netherlands Cancer Registry. Results: We identified 2649 patients, 1856 (70%) were women and the median age was 44 (IQR 31-56) years. Cancer was diagnosed in 119 patients during follow-up (median duration 4.7 [IQR 1.9-8.9] years), of which hematologic (24%) and gastrointestinal tract (20%) cancers were the most common. The cumulative incidence of cancer in the overall cohort was 5.9% (95%CI 4.8-7.2) after 10 years. The highest cumulative incidence after 10 years was observed in patients ≥50 years (10.5% [95%CI 7.9-13.4]) and in men (9.9% [95%CI 7.1-13.1]). Patients with CVT had an increased rate of cancer compared to controls during the entire follow-up, but the difference narrowed over time (SIR 3.4 [95%CI 2.4-4.5] at 1 year and 1.4 [1.1-1.7] at 10 years). The rate was increased in both patients younger than 50 (SIR 6.7 [95%CI 4.0-10.6] at 1 year and 1.7 [1.2-2.3] at 10 years) and older than 50 years (SIR 2.4 [95%CI 1.5-3.6] at 1 year and 1.2 [0.96-1.6] at 10 years), as well as in men (SIR 3.6 [95%CI 2.2-5.6] at 1 year and 1.7 [1.2-2.2] at 10 years) and women (SIR 3.2 [95%CI 2.0-4.8] at 1 year and 1.2 [0.9-1.6] at 10 years). Conclusion: Patients with CVT have an increased risk of cancer compared to peers from the general population, regardless of age group or sex. The absolute risk of cancer was highest in older patients and men, while the relative risk was highest in younger patients. These results support the need for further research on screening for occult cancer in patients with CVT.

Endovenous laser ablation of great saphenous vein and pharmacotherapy of acute ascending thrombophlebitis: results of a three-month follow-up

Aim. In patients with acute ascending thrombophlebitis of the great saphenous vein and/or its large tributaries, assess the incidence of venous thrombosis progression over 3 months with 1,5-month fondaparinux sodium therapy and endovenous laser ablation of the saphenofemoral junction in combination with short-term (7-day) anticoagulant therapy or without anticoagulation.Material and methods. This single-center, prospective, randomized, open-label study included data from 91 patients with acute ascending thrombophlebitis of the great saphenous vein and/or its large tributaries, of which 30 were in the group of endovenous laser ablation without anticoagulation, 32 — in the group of endovenous laser ablation in combination with 7-day fondaparinux therapy, and 29 — in the 1,5-month fondaparinux therapy group. Venous thrombosis progression rate within 90±2 days was assessed. Compression ultrasonography of lower limb veins was performed on days 7±2, 45±2 and 90±2 after randomization, as well as in case of thrombosis progression suspicion.Results. The mean age of patients was 49,4±14,2 years. There were more women (73,6%). There was a low prevalence of risk factors for the development and progression of venous thrombosis: obesity — 6,6%, type 2 diabetes — in 2 patients, class 2 heart failure — in 1, autoimmune disease (scleroderma in remission) — in 1, prior cancer — in 1. Previous episodes of thrombophlebitis were noted in 3 cases (3,3%). Following external factors provoking venous thrombosis were identified in 19 patients (20,9%): lower leg injury in 14, high physical activity in 3, long flight in 1, recent coronavirus disease 2019 in 1. Median duration of thrombophlebitis manifestations was 6 days. Thrombosis was located in the trunk of the great saphenous vein in 96,7% of patients, while large tributaries were involved in 29,7%. The median distance from the thrombus proximal part to the saphenofemoral junction was 42,5 cm. Over 90±2 days, there were no cases of involvement of the suprafascial segment of the perforating vein in thrombosis to the fascia level, spread of thrombosis to the deep veins, or pulmonary embolism. Subsequently, a new episode of superficial vein thrombosis was noted only in 2 patients from the pharmacotherapy group with a history of thrombophlebitis.Conclusion. In patients with a low risk of venous thrombosis progression and predominantly distal location of acute ascending thrombophlebitis of the great saphenous vein and/or its large tributaries after endovenous laser ablation, progression of venous thrombosis is not expected over the next 3 months, despite an anticoagulation reduction to 7 days or its refusal.

Prevention of thrombotic complications in patients with AL amyloidosis

Background. The problem of hemostasis system pathology in patients with AL amyloidosis (AL-A) is of great practical importance. Currently, there are no recommendations concerning indications and methods of prevention of thrombotic complications.Aim. To study the main parameters of blood coagulation system in patients with AL amyloidosis, to determine the indications for anticoagulant therapy, to evaluate the efficacy and safety of apixaban prophylactic use during antitumor therapy.Materials and methods. A prospective single-center study included 65 patients with newly diagnosed systemic AL amyloidosis. The median age was 58 (34–74) years. Induction therapy according to the program BorCyDex (bortezomib, cyclophosphamide, dexamethasone) was given to 59 (90 %) patients, of which 5 patients received the combination of BorCyDex with a monoclonal antibody to CD38 – daratumumab. The remaining 6 (10 %) patients were treated with melphalan. Patients with laboratory signs of hypercoagulability or thrombotic complications were treated with apixaban in therapeutic or prophylactic dose. Indications for apixaban therapy in therapeutic dose (10 mg/day): atrial fibrillation, arterial thrombosis or pulmonary embolism less than 1 year ago. Indications for apixaban therapy in prophylactic dose (5 mg/day) were considered the presence of one or more factors: hypoalbuminemia less than 20 g/L; increase in D-dimer level more than 500 ng/mL without instrumentally verified arterial or venous thrombosis; increase in D-dimer level more than 500 ng/mL within 3 months after resolved episode of thrombosis; increase in fibrinogen level more than 4 g/L; increase in FVIII activity more than 150 %. When two or more factors were present, an antiplatelet agent (acetylsacylicylic acid) was added to apixaban therapy. The follow-up period was 4–9 months (median 6 months).Results. Before the start of antitumor therapy, thrombotic complications were diagnosed in 15 (23 %), bleeding – in 3 (5 %) patients. Hemostasis study revealed an increase in one or more laboratory parameters reflecting hypercoagulability in 92 % of patients. Increase in fibrinogen level was found in 70 %, D-dimer – in 72 %, FVIII activity – in 92 % of patients. 3 (5 %) patients received a therapeutic dose of apixaban, 58 (89 %) patients ‒ a prophylactic dose. Therapy with apixaban and antiplatelet agent was performed in 10 (15 %) patients. During the follow-up 3 patients developed complications related to hemostasis system disorders: 1 (2 %) patient had thrombosis (ischemic stroke), 2 (3 %) – gastrointestinal bleeding of mild severity. All these patients received a prophylactic dose of apixaban due to the presence of 1 thrombosis risk factor: an increase in FVIII activity of more than 150 %.Conclusion. Clinical signs of hemostasis system pathology were observed in 28 % of AL amyloidosis patients, and laboratory signs of hypercoagulability were detected in 92 %. Our developed indications for thrombosis prophylaxis in AL amyloidosis were effective. The issue of FVIII activity increase as the only indication for anticoagulant therapy in AL amyloidosis patients requires further research.

A Comparison of Bleeding Events Among Patients on Apixaban, Rivaroxaban, and Warfarin for Atrial Fibrillation and/or Venous Thromboembolism

Introduction Apixaban and rivaroxaban are the most commonly used direct oral anticoagulants (DOACs) for atrial fibrillation (AF) and venous thromboembolism (VTE). Both have been compared to warfarin in landmark clinical trials. However, there are limited comparative efficacy data between these drugs in a real-world setting. We sought to assess patient characteristics and outcomes of apixaban, rivaroxaban, and warfarin in a non-trial based study cohort. Methods Retrospective registry-based cohort of adults starting apixaban, rivaroxaban, or warfarin therapy or switching between these anticoagulants for the indications of VTE and/or non-valvular AF. Through the Michigan Anticoagulation Quality Improvement Initiative (MAQI 2) collaborative of six anticoagulation clinics, warfarin treated patients were followed from January 2009 to June 2023. Four of these clinics contributed DOAC patient data from June 2011 to June 2023. Patients treated with other anticoagulants, with valvular AF, or with less than 3 months of follow-up were excluded. Propensity matched cohorts (apixaban versus warfarin [1:1], rivaroxaban versus warfarin [1:3], and apixaban versus rivaroxaban [1:1]) of patients were analyzed based on DOAC use at study enrollment, using 1:1-3:1 matching ratios. Patients were matched based on demographics, social history, comorbidities, medications, bleeding/thrombotic history, indication for anticoagulation, and follow-up. The primary outcome was any new bleeding event. Secondary outcomes included new episodes of thrombosis, bleeding event type (major, fatal, life threatening, central nervous system, and non-major bleeding), emergency room (ER) visits, hospitalizations, and death. Random chart audits were done to confirm the accuracy of the abstracted data. Event rates were compared using Poisson regression. Results Of 13,435 patients on OAC who met the study inclusion criteria (3,536 on apixaban, 1,395 on rivaroxaban, and 8,504 on warfarin), the average age was 66.7 years (standard deviation [SD] 14.9 years), 51.1% identified as male, most (58.0%) were on anticoagulation for AF, and the average follow-up was 28.2 months (SD 30.7 months). After propensity matching, 3,527 patients on apixaban were compared to 3,527 patients on warfarin. Any bleeding was similar between groups, but major bleeding was higher with warfarin (3.4 versus 4.7 events/100 patient years, p&amp;lt;0.001). Thrombotic event rates were higher with apixaban (2.6 versus 2.1 events/100 patient years, p=0.026), including the thrombotic subtype of other thrombosis (1.0 versus 0.5 events/100 patient years, p&amp;lt;0.001). Rates of ER visits and hospitalizations for bleeding were higher with warfarin. Mortality was higher with warfarin (3.7 versus 4.4 deaths/100 patient years, p=0.027). After propensity matching, 1,395 patients on rivaroxaban were compared to 4,185 patients on warfarin. Any bleeding and major bleeding were higher with rivaroxaban (37.9 versus 24.9 events/100 patient years, p&amp;lt;0.001; 4.7 versus 3.6 events/100 patient years, p=0.041 respectively). Thrombotic event rates were similar, aside from a higher rate of the thrombotic subtype of other thrombosis with rivaroxaban (1.0 versus 0.3 events/100 patient years, p=0.002). ER visits, hospitalizations, and mortality were similar between rivaroxaban and warfarin. After propensity matching, 1,395 patients on apixaban were compared to 1,395 patients on rivaroxaban. Any bleeding and major bleeding were higher with rivaroxaban (37.9 versus 25.7 events/100 patient years, p&amp;lt;0.001; 4.7 versus 2.6 events/100 patient years, p&amp;lt;0.001). Thrombotic event rates were similar. ER visits occurred more frequently on rivaroxaban (12.8 versus 10.1 events/100 patient years, p=0.003) as did patient mortality (3.5 versus 2.6 deaths/100 patient years, p=0.047). Conclusions For patients on oral anticoagulation for AF and/or VTE we observed that bleeding was highest with rivaroxaban, followed by warfarin, and then apixaban. Rates of thrombosis were higher with apixaban compared to warfarin, seemingly largely driven by “other” thrombotic events. Thrombotic event rates were otherwise similar between apixaban, rivaroxaban, and warfarin. We observed apixaban to be associated with lower mortality than rivaroxaban and warfarin. While these findings should be confirmed with randomized studies, they may have implications for anticoagulant selection.

Derangements of TLR2 Likely Play a Significant Role in the Thrombosis of Ph(-) Myeloproliferative Neoplasm

Introduction . We had previously reported that TLR 2 levels were significantly elevated in patients with polycythemia vera and MPN ( PV , ET, MF grouped together ) and TLR2 levels were related to JAK2 mutation and leukocytosis ( Blood (2022) 140 (Supplement 1): 12185-12186.). Since MPN has increased incidence of thrombosis in patients with JAK2V617F mutation and leukocytosis , therefore , current studies were done to test whether TLR-2 is related to thrombosis in MPN . In vitro platelet activation ( an pre-thrombotic marker) and clinical episodes of thrombosis were then investigated. . Material and Methods. 119 patients ( 51ET, 37 PV, 31MF, 21 CTR) were studied . 1) platelet activation. : The diluted blood was incubated with platelet agonists Pam3CSK4 (TLR2 agonist) or lipopolysaccharide (LPS) (TLR4 agonist) for 15 minutes at room temperature , then platelet activation was measured by Flow cytometry assaying CD40L, P-selectin, PAC-1 and LPI ( leukocyte-platelet-interaction). We obtained more consistent results from the LPI methods . Therefore, LPI methods were used to measure the platelet activation. LPI method was measured by CD45 and CD41 antibodies (Miltenyi Biotec, Auburn, CA), and platelet activation were measured as the percentage of CD45 cells with aggregated CD41. To test whether TLR2 or TLR4 were responsible for the LPI response ,TLR2 inhibitor C29 (InvivoGen, San Diego, CA) or the TLR4 inhibitor C34 ((Sigma-Aldrich, St. Louis, MO) were added to the LPI assay. Effects of inhibitions were measured by fold-changes which were calculated by dividing the LPI values after activation by either Pam3CSK4 (TLR2 agonist) or LPS (TLR4 agonist), with or without added inhibitors, by the LPI values before activation or inhibition. Results . 1) As shown in Fig A, a) un-activated MPN (U-MPN) patients had more LPI than un-activated controls (u-CTR), with mean ± SE of 13.01 ± 1.12 and 5.01 ± 0.97 in U-MPN and U-CTR, respectively (P&amp;lt;0.01). This is consistent with previous reports that un-activated MPN patients have more intrinsically activated platelets than un-activated controls .b) Greater LPI response by activation by Pam3CSK4, (TLR2 agonist ) than by LPS ( lipopolysaccharide)) (TLR4 agonist) . MPN and controls ( mean ± SE ) were of 22.25 ± 0.99 and 10.46 ± 0.44 ( by Pam3CSK4) and 12.12 ± 2.16 and 4.34 ± 0.32 ( by LPS) (P&amp;lt;0.0005) respectively . 2). Fig B showed the TLR2 inhibitor C29 significantly suppressed LPI ( measured by fold-changes ) , in un-activated MPN (0.38 ± 0.05), activated controls (0.42 ± 0.11), and activated MPN (0.42 ± 0.05). Conversely, the TLR4 inhibitor C34 had no inhibitory effect on un-activated MPN (0.98 ± 0.03), activated MPN (1.02 ± 0.02), or activated controls (0.84 ± 0.06) . 3) As shown in Table 2 , TLR 2 levels elevated Patients ( TLR2-E) ( defined as more than mean plus 2 standard deviation of controls (&amp;gt; 310 MFI) , have more thrombosis episode (29%) than TLR2 -normal patients (11%) . Conclusion . TLR2 likely plays a significant role in thrombosis in MPN patients on the basis : 1) JAK2 mutated patients have more TLR2 levels 2) TLR2-E patients have more leukocytosis than TLR-N patients 3) LPI was significantly elevated with TLR2 agonist ( Pam3SK4) but not by TLR4 agonist ( LPS) , and LPI was significantly decreased by TLR2 inhibitor and not by TLR4 inhibitor. 4) clinical evidence of more thrombosis in TLR -E patients than TLR-N patients.

Outcomes of Oral Anticoagulation with Concomitant NSAID Use: A Registry Based Cohort Study

Introduction Nonsteroidal anti-inflammatory drugs (NSAIDs), available without a prescription, are some of the most commonly used drugs in the United States. For patients on oral anticoagulation (OAC), concomitant NSAID use can increase the risk of bleeding. Patients are often advised to avoid this drug combination, or else consider adding a proton pump inhibitor (PPI) or H2 receptor antagonists (H2RA) for gastroprotection when both NSAIDs and OAC are used. However, there are limited data on how NSAID use impacts thrombotic and hemorrhagic outcomes. Available data may be biased due to selection bias, confounding, misclassification, and variable NSAID exposure. We sought to determine the frequency of NSAID use among patients on OAC, the impact on clinical outcomes, and if gastroprotection may mitigate bleeding risk. We hypothesized that NSAIDs would increase bleeding risk without impacting thrombotic risk. We did not anticipate gastroprotection would mitigate this risk. Methods We conducted a retrospective registry-based cohort study of adults starting a direct oral anticoagulant (DOAC) or warfarin therapy for the indications of venous thromboembolism and/or non-valvular atrial fibrillation between June 2011 and June 2023. As part of the Michigan Anticoagulation Quality Improvement Initiative (MAQI 2), warfarin-treated patients were followed by six anticoagulation clinics, and four of the six clinics contributed data for patients on DOACs. Patients were excluded if they had a history of valvular AF, less than 3 months of follow-up, or on more than one antiplatelet drug. Two propensity matched cohorts (OAC alone vs. OAC+NSAID) of patients were analyzed based on NSAID use at the time of study enrollment, using a 4:1 matching ratio. Both prescribed and over the counter NSAIDs were included, potentially with the former being more frequently captured in the study registry. The primary outcome was any new bleeding event. Secondary outcomes included new episodes of arterial or venous thrombosis, bleeding event type (major, fatal, life threatening, central nervous system, and non-major bleeding), emergency room visits, hospitalizations, transfusions, and death. Random chart audits were done to confirm the accuracy of the abstracted data. Event rates were compared using Poisson regression. Results Of 12,083 patients on OAC, 449 (3.7%) were on concomitant NSAIDs. After propensity matching, we compared 1,796 patients on OAC to 449 patients on OAC+NSAIDs. Patient demographics, co-morbidities, indication for anticoagulation, history of bleeding or clotting, medications, and duration of follow-up were well-balanced after matching. Patients were followed for an average of 30 months (standard deviation 34.2 months). For patients on OAC alone vs. OAC+NSAIDs, bleeding event rates were similar: 25.1 (95% confidence interval [CI] 23.7-26.6) versus 24.3 (95% CI 21.4-27.3) bleeds per 100 patient years ( P=0.56). Rates of non-major, major, life-threatening, central nervous system, and fatal bleeding were also similar. Furthermore, rates of thrombosis, emergency room visits, hospitalizations, transfusion, and death were similar. A pre-defined subgroup analysis comparing patients on OAC+NSAIDs with gastrointestinal prophylaxis (PPIs or H2RAs, N=179) to patients on OAC+NSAIDs without gastrointestinal prophylaxis (N=270) also showed similar rates of bleeding and healthcare utilization. Conclusions Nearly 4% of patients were taking NSAIDs with OAC and outcomes were similar to patients on OAC alone. Study limitations include NSAIDs and gastroprotection were only reliably known at time of enrollment. In addition, the potential for unmeasured or unadjusted confounding inherent to observational studies. Further research is needed to determine if there is a “safe” level of NSAID use for patients on OAC and to better define the role of gastrointestinal prophylaxis.

Zanubrutinib-lenalidomide-rituximab (ZR2) in unfit diffuse large B-cell lymphoma: efficient and tolerant.

The objective of this study is to examine the effectiveness and safety of zanubrutinib, rituximab, and lenalidomide (ZR2) in unfit patients with diffuse large B-cell lymphoma (DLBCL). Thrombosis or bleeding risk of ZR2 regimen, especially when antiplatelet agents were co-prescribed, was also evaluated. We retrospectively reviewed unfit newly diagnosed (ND) and refractory or relapsed (R/R) patients with DLBCL who were administered with ZR2 regimen in two medical centers between December 2019 and February 2022. Response rates, progression-free survival (PFS), overall survival (OS), bleeding adverse events (AEs), and thrombosis episodes were analyzed. Furthermore, we investigated the effects of zanubrutinib alone or in combination with lenalidomide on platelet functions in vitro and in vivo. A total of 30 unfit patients (13 ND DLBCL and 17 R/R DLBCL patients) who received ZR2 regimen were enrolled in the study (median age: 69.5years). The ultimate ORRs for the ND DLBCL and R/R DLBCL were 77.0% and 50.1%, respectively. The median follow-up was 16.6months. The median PFS and OS were not achieved during the follow-up time. Subcutaneous hemorrhage AEs occurred in four cases, three cases suffered severe bleeding events, and thrombosis events were observed in two patients. ZR2 regimen inhibited platelet functions (aggregation, clot retraction, spreading and activation) in vitro and in vivo function testing especially in response to collagen. ZR2 is an efficient treatment option for unfit patients with DLBCL and could be well tolerated. Notably, this regimen inhibited platelet functions. Antiplatelet agents should be used with caution in patients treated with this regimen.

The many faces of thrombosis in post-cardiac surgery newborn

We present a clinical case showing the development of two episodes of postoperative thrombosis of varying mechanisms in one patient. The first episode of thrombosis in the systemic-pulmonary anastomosis was due to shear stress-induced secretion and transformation of the von Willebrand factor (vWF) in the performed anastomosis. The altered vWF/ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) ratio in favor of the former was accompanied by platelet adhesion and activation in the anastomotic area that resulted in its thrombosis. The second episode of thrombosis within the superior and inferior vena cava was developed in parallel with escalated infectious process and characterized not only by thrombocytopenia, but also by decreased fibrinogen concentration. In this clinical situation, resolution of the infectious process as well as the use of proper antithrombotic therapy led to patient recovery.

Efficacy and Safety of Rivaroxaban As Thromboprophylaxis in Newly Diagnosed Multiple Myeloma Patients Receiving Immunomodulatory and Dexamethasone Based Treatment: Comorbidities Risk Adapted Score

The risk for venous thromboembolism (VTE) is high patients with multiple myeloma (MM) receiving thalidomide or lenalidomide with dexamethasone based induction treatment (IMiDs-Dex), especially in the first 6 months. There are multiple scores for risk stratification (IMPEDE and SAVED for example), that give different points for the same variable and can be classified in low or high risk depending which is used, the same patient can receive Aspirin in one score or LMWH in the other. In our country, Mexico, the prevalence of overweight and obesity is 75.2%, hypertension 49.4% and diabetes 16.8% (Salud Publica Mex 2021;63:692-704); factors that contribute to develop VTE. In 2018 we reported the use of Aspirin or Rivaroxaban in low risk patient with DM or obesity: could be intermediate risk (Blood 2018;132:5068); since then we adapted a risk score based in the high prevalence comorbidities of our population. From January 2018 to December 2022, 117 patients were diagnosed with active MM and 109 patients that received IMiDs-Dex based triplet induction and maintenance with IMiDs were eligibles for study. Patients were assigned into three groups for prophylaxis: a) low risk (treatment only) Aspirin 100 mg daily, b) intermediate risk (treatment and one from overweight or obesity, hypertension and diabetes) randomized 1:1 to Aspirin 100 mg or Rivaroxaban 10 mg daily, c) high risk (treatment and 2 or 3 from overweight or obesity, hypertension and diabetes; or treatment and another known high risk) Rivaroxaban 10 mg daily. Lower limbs doppler ultrasound was performed every two months or as medical indication, pulmonary CT scan if pulmonary embolism was suspected. Twenty-three patients (21.1%) had low risk and received Aspirin, one patient developed DVT from right lower limb, she received anticoagulation with Rivaroxaban for 6 months and then placed in prophylactic dose, no further DVT developed. Thirty-eight patients (34.9%) had intermediate risk; 19 received Aspirin, one patient developed DVT with pulmonary embolism and received anticoagulation with Rivaroxaban for 6 months and then placed in prophylactic dose, no further thrombosis developed; 19 received Rivaroxaban, no patient developed thrombosis. Forty-eight patients (44.0%) had high risk and received Rivaroxaban; two patients developed DVT, none with pulmonary embolism, both with more than four risk factors, they received anticoagulation with Rivaroxaban for 6 months and then placed in prophylactic dose, no further thrombosis developed. In all groups less than 5 percent of patients had easy bruising and mild epistaxis or gingivorrhagia that no required hold of dose; no major bleeding was detected. In low risk patients that received Aspirin, 4.34% developed DVT; the change to Rivaroxaban was beneficial as no further thrombosis developed. In intermediate risk, 2.6% developed DVT-PE in the Aspirin arm and none in the Rivaroxaban, demonstrating the efficacy of Rivaroxaban. In the high risk patients all received Rivaroxaban, 4.16% developed DVT, similar result as Aspirin in the low risk patients, but the patients had more than four risk factors, that could be a very high group and a more intense prophylactic or complete anticoagulation is advised; in high risk patients with less than three factors Rivaroxaban is effective in preventing thrombosis episodes. The safety of Rivaroxaban is demonstrating again, as the bleeding in both groups were similar. An external cohort is needed to validate our results and this comorbidity risk adapted score can be national and international-wide used, as the prevalence of overweight or obesity, hypertension and diabetes are high among occidental countries, especially Mexico, as they impact in the morbidity and mortality not only in neoplastic diseases (Arch Med Res 2022;53:100-108) . A very high risk patients group will be considered for Rivaroxaban in dose of 15 or 20 mg in following studies. As a final statement, these results complement our first report and give more solid evidence in the efficacy and safety of Rivaroxaban as thromboprophylaxis in Multiple Myeloma patients with IMiDs-Dex based triplet induction and maintenance with IMiDs.

Protein C Deficiency with Recurrent Deep Vein Thrombosis Complicated with Post Thrombotic Syndrome- A Case Report and Mini Review

Protein C is a vitamin K dependent glycoprotein produced by the liver. Protein C acts as a naturally occurring anticoagulant and its deficiency, predisposes the individual to a state of thrombosis, particularly venous thromboembolism. Post-thrombotic syndrome (PTS) is a chronic venous insufficiency manifestation following an episode of deep-vein thrombosis (DVT). We presented a case of 56 year old Malay man who was diagnosed with Protein C deficiency and presented with recurrent DVT complicated with PTS.

Very long-term efficacy and safety of paclitaxel-eluting balloon after a bare-metal stent for the treatment of ST-elevation myocardial infarction: 8-year results of a randomized clinical trial (PEBSI study).

Drug-eluting stents (DES) are considered the therapy of choice in ST-segment elevation myocardial infarction (STEMI); however, a low persistent rate of revascularizations and stent thrombosis exist over the time. We have previously shown that a paclitaxel (PTX)-drug-coated balloon (DCB) after a bare-metal stent (BMS) implantation (DCB-combined strategy) yields superior angiographic and clinical results compared to BMS in the short term. However, the long-term safety and efficacy of this approach remain uncertain. An 8-year clinical follow-up was conducted on patients enrolled in the randomized PEBSI-1 trial (NCT01839890). The original trial included patients who suffered a STEMI, patients were randomly assigned to receive a DCB-combined strategy or BMS only and the primary endpoint was in-stent late luminal loss (LLL) at 9-month follow-up. After the completion of this study, death, myocardial re-infarction, ischemia-driven repeated revascularizations included target lesion revascularization (TLR) and target vessel revascularization (TVR), and stent thrombosis, were assessed by yearly contact by a clinical visit, telephone or by electronic records. These outcomes were adhered to ARC-2 criteria. The rate of incomplete follow-up was very low, with only 3 out of 111 patients (2.7%) in the DCB-combined strategy group and 1 out of 112 patients (0.9%) in the BMS group. At 8 years there were a lower rate of TVR [3.7% vs. 14.3%; hazard ratio (HR): 0.243; 95% confidence interval (CI): 0.081-0.727; P=0.006], and a trend towards lower TLR (2.8% vs. 8.9%; HR: 0.300; 95% CI: 0.083-1.090; P=0.052) in the DCB-combined strategy group. No statistical difference between the DCB-combined strategy and BMS groups were found for all causes of death, deaths from cardiovascular disease, reinfarctions or stent thrombosis. Notably in the DCB-combined strategy group, no episode of stent thrombosis occurred after the first year. Similarly, there were no cardiovascular deaths, TVR and TLR in the DCB-combined strategy group after 5 years. In contrast, during the period from year 5 to 8, the BMS group experienced an additional cardiovascular death, as well as one case of TVR, one case of TLR, and one case of stent thrombosis. In STEMI patients, the DCB-combined strategy maintains its safety and clinical efficacy over time. Our rates of TVR, TLR, and very late stent thrombosis (VLST) at very long-term are the lowest ever found in a STEMI trial. Further studies are warranted to assess the potential superiority of this novel strategy as compared with new-generation DES to prevent very late events in these patients. ClinicalTrials.gov; identifier: NCT01839890.