Chronic Anticoagulation Therapy Research Articles

Persistent Gastrointestinal Bleeding after Aortic Valve Replacement in Heyde's Syndrome.

Heyde's syndrome (HS) represents an association between aortic stenosis and intestinal angiodysplasias, and it has been demonstrated that acquired von Willebrand disease plays a pivotal role in the pathophysiology of this syndrome. In patients with HS, von Willebrand factor deficiency represents an additional risk factor, further contributing to the risk of bleeding and anemia. We present the case of an 86-year-old patient diagnosed with HS and von Willebrand deficiency in 2018. Four years prior, the patient underwent surgical aortic valve replacement. Since then, she has been receiving chronic oral anticoagulation therapy with a vitamin K antagonist. The patient was admitted to the Internal Medicine Clinic due to semi-solid dark stools, diffuse abdominal pain, and asthenia. Upon examination, the patient presented with an altered general status and clinical signs suggestive of anemia. Laboratory findings revealed anemia with elevated INR and aPTT values. Colonic angiodysplasias were identified during a colonoscopy, although no sources of active bleeding were detected. On the 9th day of hospitalization, the patient experienced an episode of lower gastrointestinal bleeding. The pharmacological management was adjusted, and argon plasma coagulation was recommended. Following treatment of the angiodysplastic lesions, the patient's clinical evolution was favorable, with the correction of the anemia.

Morbidity and Mortality of Trauma Patients 55 and Older: A Study of Nontrauma Risk Factors.

Introduction: The American College of Surgeons (ACS) recommends that special considerations be made during triage of trauma patients aged ≥55 due to an observed increase in morbidity and mortality in this population. The geriatric population aged ≥65 represents 30% of all trauma patients. Our objective was to assess which pre-existing conditions (PECs) are associated with worse outcomes in trauma patients aged ≥55. Methods: Study population was selected from the local trauma registry (2020-22). Bi-variate analysis compared PEC status with outcomes controlling for each Injury Severity Score (ISS) category. Injury Severity Score was defined as mild (1-8), moderate (9-15), severe (16-24), and critical (≥25). Results: A total of 5,168 patients were identified (54.9% female, 56.7% age ≥75, 49.1% mild injury). Patients who had chronic renal failure (CRF) were at increased odds of mortality after adjusting for mild (adjusted odds ratio [aOR]: 2.63), moderate (aOR: 2.97), severe (aOR: 2.84), and critical (aOR: 2.62) injuries. Patients who had cirrhosis or congestive heart failure (CHF) were at increased odds of mortality after adjusting for mild (aOR: 3.03, 1.61), moderate (aOR: 3.63, 2.14), and severe (aOR: 3.46, 1.93) injuries, respectively. In addition, there was a relationship between having chronic obstructive pulmonary disease (COPD), dementia, anticoagulant therapy, or diabetes with unplanned intensive care unit (ICU) admission and development of acute kidney injury (AKI). Discussion: There is an association between certain pre-exiting conditions and worse outcomes. Early identification of these factors could provide a foundation for better interdisciplinary management, prevention of complications and associated mortality.

PERCUTANEOUS CORONARY INTERVENTIONS IN PATIENTS TREATED WITH ORAL ANTICOAGULANT THERAPY: BASELINE CLINICAL CHARACTERISTICS OF THE PERSEO REGISTRY

Abstract Background International guidelines recommend a dual antithrombotic therapy (DAT) with direct oral anticoagulant (DOAC) for patients on chronic oral anticoagulant therapy (OAT) undergoing percutaneous coronary intervention with stent implantation (PCI–S). However, the implementation of practice Guidelines in the “real world” is often a complex exercise. Aim of the multicenter prospective observational PERSEO (PERcutaneouS coronary intErventions in patients treated with Oral anticoagulant therapy) registry was to evaluate the management of the different antithrombotic regimens strategies in patients with an indication for OAT undergoing PCI–S in a “real world” setting and its association with clinical outcomes. Methods The PERSEO registry has been designed to enrol patients requiring OAT and treated by PCI–S in 25 Italian Cardiology Centres. No exclusion criteria have been defined. The primary end–point was a combined measure of efficacy and safety outcome (NACE), including major bleeding events + major adverse cardiac and cerebral events at one year follow up in patients treated with DOAC compared to vitamin K antagonists. Results From February 2018 to February 2022, a total of 1233 patients were enrolled: mean age 74±9 years, 900 males and 333 females. The primary indication for OAT was atrial fibrillation (1066 patients, 87%) while an acute coronary syndrome was the leading reason for PCI–S (789 patients, 64%). Of those, 271 patients had an ST elevation myocardial infarction at admission. Mean CHA2DVAS2C score and HASBLED score were respectively 4±2 and 4±1. Six patients died during hospitalization and 1227 were discharged alive: 1027 on triple antithrombotic therapy (oral anticoagulant and dual antiplatelet therapy), 196 patients on DAT (oral anticoagulant and single antiplatelet therapy) and 4 patients on oral anticoagulant alone. The majority of patients enrolled were discharged on DOAC (1006 patients, 82%), whereas only a minority received vitamin K antagonists (221 patients, 18%). Conclusions The Italian PERSEO Registry is the largest prospective observational study comparing different antithrombotic strategies in patients with an indication for OAT undergoing PCI–S in a “real world” setting. Baseline characteristics, depicted a population at high thrombotic and haemorrhagic risk. In agreement with current guidelines the majority of patients were discharged on DOAC, yet the use of a DAT was still limited to a minority of the patients included.

Chronic anticoagulation therapy and acute hip trauma

Regardless of the association between hip fracture surgery and mortality, morbidity and bleeding risks, there are still significant contradictions in various published articles concerning hip fracture surgery outcomes when patients are prescribed anticoagulant medication. The primary objective of this study was to investigate if patients prescribed anticoagulants experienced delayed surgery when compared to non-users. The secondary goal was to investigate if patients prescribed anticoagulants underwent an extended hospital stay and complications such as increased bleeding, mortality and a higher rate of comorbidities when compared to non-users. Data from proximal hip fracture patients were prospectively collected at a level I university trauma center. From 1 January, 2020, through 1 January, 2021, 519 eligible patients were identified. Anticoagulant medication upon admission, time prior to surgery, hospitalized days, 30-day mortality rates, 1-year mortality, blood transfusion requirement and various comorbidities were noted. 222 of the 519 hip fracture patients were prescribed anticoagulants. Of the 222 patients, 75% were females and 25% were males. In total, 46% required a blood transfusion, with no significant differences between the anticoagulated and non-anticoagulated patients. 50% of the anticoagulated group and 42% of the control group required perioperative blood transfusion. Neither the 30-day nor the 1-year mortality rate showed statistically significant differences between the groups. However, the time to surgery and the length of hospital stay was significantly longer in the anticoagulated group. Comorbidities were found in 87% of the patients: in 95% of the anticoagulated group and in 81% of the non-anticoagulated group. Patients prescribed anticoagulants at the time of hip fracture experienced delayed surgery, longer hospital stays and more comorbidities when compared to patients not on anticoagulants. Neither a blood transfusion requirement, 30-day mortality rate nor a 1-year mortality rate showed no significant difference between the two cohorts.

Association of sex and aspirin use with postoperative bleeding in patients with lower extremity long bone fractures

ObjectiveThe perioperative management of patients on antiplatelet drugs is a rising challenge in orthopedic trauma because antiplatelet drugs are frequently encountered and carry an increased risk of hemorrhagic consequences. The...

Is It Safe to Resume Direct Oral Anticoagulants upon Discharge after Hip Fracture Surgery? A Retrospective Study.

This study aimed to examine the incidence rate of early reoperations following hip fracture surgery and determine the safety of resuming direct oral anticoagulants. Many orthopedic surgeons are reluctant to resume chronic anticoagulation therapy for patients after surgical intervention for hip fractures. One of the main reasons is the potential for reoperation in the case of surgical complications. We conducted a retrospective cohort study at an Academic Level I trauma center, reviewing the records of 425 geriatric patients (age > 60) who underwent hip fracture surgery between 2018 and 2020, including a subgroup treated with direct oral anticoagulants prior to hospitalization. The study assessed the incidence rate of complications requiring early reoperation. Out of the 425 patients, only nine (2%) required reoperation within a month after discharge, with two (0.5%) on chronic anticoagulation therapy. None of the reoperations were urgent, and all were performed at least 24 h after re-admission. The findings revealed a very low incidence rate of reoperations in patients who underwent hip fracture surgery, with no reoperations performed within 24 h of re-admission. Consequently, we believe that resuming chronic direct oral anticoagulants is a safe and effective approach when discharging patients after hip fracture surgery.

Differential Host Response Contributing to Incidence of Arterial and Venous Thromboembolism at Index Hospitalization for Sars-Cov-2 Infection across Wuhan, Delta, Omicron and Omicron BA.x Variants

Introduction SARS-CoV-2 induced coagulopathy has been associated with increased risk of arterial and venous thromboembolism. Literature demonstrates that incidence of thromboembolism has varied widely throughout the COVID-19 pandemic, with many reports preceding emergence of Delta and Omicron variants. This study aimed to characterize the incidence of arterial and venous thromboembolic events among patients hospitalized with acute SARS-CoV-2 infection during Wuhan, Delta, Omicron, or Omicron BA.x waves. To our knowledge, this study debuts variant specific analyses to shed some light on reported substantive differences pooled across SARS-CoV-2 variants regarding host response, clinical course, and outcomes. Intensity of pathophysiologic anomalies may have been associated with macro- and micro-circulatory clotting. Therefore, we hypothesized variant idiosyncratic host responses would be evoked and aimed to link our patient's demographics and comorbidity patterns with risk of thromboembolism. Methods This is a retrospective study including patients with laboratory confirmed SARS-CoV-2 infection who underwent index hospitalization during Wuhan (March 14, 2020- June 18, 2021), Delta (June 19, 2021- December 18, 2021), Omicron (December 19-March 30, 2022) or Omicron BA.x (March 31, 2022 - April 14, 2023) variant waves at an 820-bed academic public health trust hospital in Florida. Demographics, laboratory at presentation, ICD-10-CM-based comorbidity, SARS-CoV-2 directed treatment and administrative data were extracted under IRB exemption from electronic medical records. Generalized regression with adaptive LASSO identified variables associated with embolism in at least one variant wave controlling for extant dysrhythmia, chronic anticoagulation therapy, and COVID-19 directed treatment. Prespecified 2-way ANOVA examined interactions between intra- vs. inter-variant waves but was ruled out due to strong imbalances in variation. Thus, only within-variant contrasts were performed. Continuous data summarized with mean [±SD] were compared using an ANOVA test adjusting p-value for parametric vs. non-parametric distribution. Discrete data summarized as proportions were compared with chi-squared test. A p<.05 was considered significant. Results We studied 6490 patients consecutively discharged across Wuhan (n=2249), Delta (n=1196), Omicron (n=953) and Omicron BA.x (n=2092) variants with respective embolic event(s) of 3%, 2%, 2%, and 4%. Table 1 summarizes demographics, anthropometric, comorbidities and laboratory biomarkers obtained within 24h of hospitalization across variants. Table 2 presents clinical course and outcomes. Discussion Incidence of embolic events was isomorphically distributed among waves tending to affect older males harboring hypertension, neurologic disease, and/or heart failure. D-dimer levels at presentation significantly distinguished risk of thromboembolism with Wuhan, Delta, or Omicron, but not Omicron BA.x variant infection. Indeed, Omicron BA.x infection was associated with numerically lower ICU visits, mechanical ventilation requirement, hospital LOS and mortality. Elevated D-dimer consistently has been associated with excess risk of progression to severe illness and mortality (Milenkovic M et al., 2022), mostly via pooled results across SARS-CoV variant waves. Some have suggested that D-dimer guided anticoagulation management improves outcomes in patients with COVID-19 (Ronderos Botero DM et al., 2023). Deeper phenotyping of patients infected with Omicron BA.x variants may reveal unique prothrombotic features driving what appears to be a less severe hypercoagulable state.

Hemorrhagic risk in patients who undergo deep brain stimulation on chronic antiplatelet or anticoagulation therapy

Hemorrhagic risk in patients who undergo deep brain stimulation on chronic antiplatelet or anticoagulation therapy

Prospective observational registry of perioperative and periprocedural management of antithrombotic therapy in “real world”: the REQXAA study

Introduction and objectivesThere is scarce real-world evidence on the management of perioperative antithrombotic treatment according to current recommendations. The aim of this study was to analyze the management of antithrombotic treatment in patients undergoing surgery or another invasive intervention and to assess the consequences of this management on the occurrence thrombotic or bleeding events. MethodsThis prospective, observational, multicenter and multispecialty study analyzed patients receiving antithrombotic therapy who underwent surgery or another invasive intervention. The primary endpoint was defined as the incidence of adverse (thrombotic and/or hemorrhagic) events after 30 days of follow-up with respect to management of perioperative antithrombotic drugs. ResultsWe included 1266 patients (male: 63.5%; mean age 72.6 years). Nearly half of the patients (48.6%) were under chronic anticoagulation therapy (mainly for atrial fibrillation; CHA2DS2-VASC: 3.7), while 53.3% of the patients were under chronic antiplatelet therapy (mainly for coronary artery disease). Low ischemic and hemorrhagic risk was found in 66.7% and 51.9%, respectively. Antithrombotic therapy management was in line with current recommendations in only 57.3% of the patients. Inappropriate management of antithrombotic therapy was an independent risk factor for both thrombotic and hemorrhagic events. ConclusionsThe implementation of recommendations on the perioperative/periprocedural management of antithrombotic therapy in real-world patients is poor. Inappropriate management of antithrombotic treatment is associated with an increase in both thrombotic and hemorrhagic events.

A Review of FXIa Inhibition as a Novel Target for Anticoagulation.

Limitations of vitamin K antagonists as chronic oral anticoagulant therapy have largely been supplanted by direct factor IIa and factor Xa inhibitor oral anticoagulants with similar efficacy but an overall better safety profile, lack of routine monitoring, and very limited drug-drug interactions compared with agents such as warfarin. However, an increased risk of bleeding remains even with these new-generation oral anticoagulants in fragile patient populations, in patients requiring dual or triple antithrombotic therapy, or high bleed risk surgeries. Epidemiologic data in patients with hereditary factor XI deficiency and preclinical studies support the notion that factor XIa inhibitors have the ability to be an effective but potentially safer alternative to existing anticoagulants, based on their ability to prevent thrombosis directly within the intrinsic pathway without affecting hemostatic mechanisms. As such, various types of factor XIa inhibitors have been studied in early phase clinical studies, including inhibitors of the biosynthesis of factor XIa with antisense oligonucleotides or direct inhibitors of factor XIa using small peptidomimetic molecules, monoclonal antibodies, aptamers, or natural inhibitors. In this review, we discuss how different types of factor XIa inhibitors work and present findings from recently published Phase II clinical trials across multiple indications, including stroke prevention in atrial fibrillation, dual pathway inhibition with concurrent antiplatelets post-myocardial infarction, and thromboprophylaxis of orthopaedic surgery patients. Finally, we refer to ongoing Phase III clinical trials of factor XIa inhibitors and their potential to provide definitive answers regarding their safety and efficacy in preventing thromboembolic events in specific patient groups.

Chronic anti-coagulation therapy reduced mortality in patients with high cardiovascular risk early in COVID-19 pandemic

BackgroundCoronavirus disease 2019 (COVID-19) is associated with provoked thrombo-inflammatory responses. Early in the COVID-19 pandemic this was thought to contribute to hypercoagulability and multi-organ system complications in infected patients. Limited studies have evaluated the impact of therapeutic anti-coagulation therapy (AC) in alleviating these risks in COVID-19 positive patients. Our study aimed to investigate whether long-term therapeutic AC can decrease the risk of multi-organ system complications (MOSC) including stroke, limb ischemia, gastrointestinal (GI) bleeding, in-hospital and intensive care unit death in COVID-19 positive patients hospitalized during the early phase of the pandemic in the United States.MethodsA retrospective analysis was conducted of all COVID-19 positive United States Veterans between March 2020 and October 2020. Patients receiving continuous outpatient therapeutic AC for a least 90 days prior to their initial COVID-19 positive test were assigned to the AC group. Patients who did not receive AC were included in a control group. We analyzed the primary study outcome of MOSC between the AC and control groups using binary logistic regression analysis (Odd-Ratio; OR).ResultsWe identified 48,066 COVID-19 patients, of them 879 (1.8%) were receiving continuous therapeutic AC. The AC cohort had significantly worse comorbidities than the control group. On the adjusted binary logistic regression model, therapeutic AC significantly decreased in-hospital mortality rate (OR; 0.67, p = 0.04), despite a higher incidence of GI bleeding (OR; 4.00, p = 0.02). However, therapeutic AC did not significantly reduce other adverse events.ConclusionAC therapy reduced in-hospital death early in the COVID-19 pandemic among patients who were hospitalized with the infection. However, it did not decrease the risk of MOSC. Additional trials are needed to determine the effectiveness of AC in preventing complications associated with ongoing emerging strains of the COVID-19 virus.

Registro observacional prospectivo sobre la utilización del tratamiento antitrombótico durante el periodo perioperatorio y periprocedimiento en el «mundo real»: estudio REQXAA

Introduction and objectivesThere is scarce real-world evidence on the management of perioperative antithrombotic treatment according to current recommendations. The aim of this study was to analyze the management of antithrombotic treatment in patients undergoing surgery or another invasive intervention and to assess the consequences of this management on the occurrence thrombotic or bleeding events. MethodsThis prospective, observational, multicenter and multispecialty study analyzed patients receiving antithrombotic therapy who underwent surgery or another invasive intervention. The primary endpoint was defined as the incidence of adverse (thrombotic and/or hemorrhagic) events after 30 days of follow-up with respect to management of perioperative antithrombotic drugs. ResultsWe included 1266 patients (male: 63.5%; mean age 72.6 years). Nearly half of the patients (48.6%) were under chronic anticoagulation therapy (mainly for atrial fibrillation; CHA2DS2-VASC: 3.7), while 53.3% of the patients were under chronic antiplatelet therapy (mainly for coronary artery disease). Low ischemic and hemorrhagic risk was found in 66.7% and 51.9%, respectively. Antithrombotic therapy management was in line with current recommendations in only 57.3% of the patients. Inappropriate management of antithrombotic therapy was an independent risk factor for both thrombotic and hemorrhagic events. ConclusionsThe implementation of recommendations on the perioperative/periprocedural management of antithrombotic therapy in real-world patients is poor. Inappropriate management of antithrombotic treatment is associated with an increase in both thrombotic and hemorrhagic events.

30-Day Post-Discharge Prophylaxis with Rivaroxaban Prevents Porto-mesenteric Venous Thrombosis Following Laparoscopic Sleeve Gastrectomy.

Porto-mesenteric venous thrombosis (PMVT) is a significant complication that occurs more frequently after laparoscopic sleeve gastrectomy (SG) than other bariatric procedures and presents later than other venous thromboembolic (VTE) events often 2weeks after the operation. The common current practice in bariatric surgery of perioperative chemoprophylaxis until discharge may not adequately prevent PMVT. Therefore, a 30-day post-discharge chemoprophylaxis (PDC) might reduce the incidence of PMVT. The objective of this study is to determine whether 30-day PDC with rivaroxaban 10mg daily following SG can reduce the incidence of PMVT. In a retrospective cohort study, 292 consecutive patients undergoing SG by a single surgeon were either prescribed rivaroxaban 10mg daily for 30days upon discharge (group A) or did not receive any PDC (group B). Primary outcome was PMVT and secondary outcome was bleeding. Patients on chronic anticoagulation therapy were excluded from the study. PMVT events differences were significant between the groups while bleeding events were not. Group A had zero PMVT events, while group B had four (p = .045). There were 4 bleeding events in group A and 7 bleeding events on group B (p = .341). A 30-day PDC regimen of rivaroxaban 10mg daily is both safe and effective. This study demonstrated zero PMVT events without an increased risk of bleeding using this regimen.

Perioperative management in chronically anticoagulated children undergoing tonsillectomy.

Tonsillectomy is a common procedure in children. Patients at high risk for thrombosis who require chronic anticoagulation therapy pose a special challenge when undergoing tonsillectomy, as bleeding may occur up to two weeks after surgery. Due to a lack of evidence-based data, there is no consensus on the best management for such patients. The objective of our manuscript is to review perioperative anticoagulation bridging strategies in children undergoing tonsillectomy. Retrospective case series of chronically anticoagulated patients at high risk for a thromboembolic event, who underwent tonsillectomy from 2010 to 2021. Patients whose anticoagulation treatment was discontinued due to a low risk of thromboembolic events were excluded. Four patients met inclusion criteria (age range 1.5-16.1 years). All patients were admitted prior to surgery for bridging therapy with intravenous unfractionated heparin (UFH) drip titrated to a therapeutic dose until 4-6 hours prior to surgery. The estimated blood loss during surgery was minimal in all surgeries. UFH was readministered per hospital protocol on the night of surgery and titrated to a therapeutic dose. Postoperative warfarin was restarted within 2 days for all patients. High-risk patients were kept in the hospital until postoperative day 6-8 due to concern for delayed bleeding. One patient was noticed to have blood-tinged sputum requiring no intervention, and none of the patients developed early or delayed hematemesis. Our data show that bridging therapy with UFH has been successful. Chronically anticoagulated patients undergoing tonsillectomy require multidisciplinary care for the management of their pre- and postoperative course.

747 HIGH PLATELET REACTIVITY AFTER DAPT IN PATIENTS WITH ACUTE CORONARY SYNDROME AND ATRIAL FIBRILLATION

Abstract Background The incidence of atrial fibrillation (AF) in patients who undergo percutaneous coronary intervention (PCI) is not negligible, especially in the elderly. Both oral anticoagulation (OAC) and dual anti-platelet therapy (DAPT) are recommended by main guidelines, therefore is essential to balance the prevention of ischemic events with the risk of bleeding. Evidences from literature suggest that incidence of anti-platelet therapy resistance is higher in elderly patients. There is a paucity of data about the response to antiplatelet therapy in patients with AF. The purpose of this study is to analyze platelet reactivity during DAPT (aspirin + clopidogrel) in elderly patients hospitalized for acute coronary syndrome (ACS), stratifying them by the presence or absence of AF. Methods We analyzed data of patients admitted to our center for ACS. All patients were ≥ 75 years old and treated with DAPT (Aspirin 100 mg daily and Clopidogrel 75 mg daily). At discharge they were tested with a point-of-care antiplatelet-function test (VerifyNow assay) to assess the platelet response to aspirin in aspirin-reaction units (ARU) and to clopidogrel in P2Y12-reaction units (PRU). Low response to aspirin was defined as ARU ≥550; low response to clopidogrel was defined as PRU ≥208; high response was defined as PRU values ≤ 85. Results Among the 216 patients included in the registry we selected 154 of these [median age 81 (IQR 77-87) years; 45% female] who were submitted to the platelet function tested before discharge. Patients were divided into two groups: AF (43 pts); non-AF (111 pts). The table shows the platelet reactivity values by two groups. Conclusions In this series of elderly patients with ACS, AF was associated with higher residual platelet reactivity with both clopidogrel and aspirin. AF patients were significantly less responsive to clopidogrel than non-AF, while among non-AF patients there were significantly more high responders. No difference was found for aspirin low responders between AF and non-AF group. This evidence could assume clinical significance in the choice of antiplatelet drugs to be combined with chronic anticoagulant therapy for AF.

Perioperative Management of Vitamin K Antagonists and Direct Oral Anticoagulants: A Systematic Review and Meta-analysis

The management of patients who are receiving chronic oral anticoagulation therapy and require an elective surgery or an invasive procedure is a common clinical scenario. What is the best available evidence to support the development of American College of Chest Physicians guidelines on the perioperative management of patients who are receiving long-term vitamin K agonist (VKA) or direct oral anticoagulant (DOAC) and require elective surgery or procedures? A literature search including multiple databases from database inception through July 16, 2020, was performed. Meta-analyses were conducted when appropriate. In patients receiving VKA (warfarin) undergoing elective noncardiac surgery, shorter (< 5days) VKA interruption is associated with an increased risk of major bleeding. In patients who required VKA interruption, heparin bridging (mostly with low-molecular-weight heparin [LMWH]) was associated with a statistically significant increased risk of major bleed (relative risk [RR], 9.1; 95%CI, 1.62-51.3), representing a very low certainty of evidence (COE). Compared with DOAC interruption 1 to 4days before surgery, continuing DOACs was not associated with a statistically significant difference in the risk of bleeding, representing a very low COE. Continuing dabigatran was associated with a statistically significant increased risk of thromboembolism (RR, 2.2; 95%CI, 1.3-3.8), representing a low COE. In patients who needed DOAC interruption, bridging with LMWH was associated a with statistically significant increased risk of minor bleeding compared with no bridging (RR, 1.7; 95%CI, 1.13-2.7), representing a low COE. The certainty in the evidence supporting the perioperative management of anticoagulants remains limited. No high-quality evidence exists to support the practice of heparin bridging during the interruption of VKA or DOAC therapy for an elective surgery or procedure or for the practice of interrupting VKA therapy for minor procedures, including cardiac device implantation, or continuation of a DOAC vsshort-term interruption of a DOAC (1-4days) in the perioperative period.

Predictors and Clinical Complications Associated with Antiphospholipid Antibodies in Sickle Cell Disease

Introduction. The antiphospholipid syndrome is characterized by the presence of anti-phospholipid autoantibodies (aPL) leading to a hypercoagulable state as well as an arterial, venous, and microcirculatory vasculopathy. Under several physiological and pathological situations, including the sickling of red blood cells (RBC), negatively charged phospholipids translocate from the inner to the outer surface of cell membranes leading to the potential generation of the antigenic target of aPL. We tested the following two-part hypothesis: 1) repeated exposure of the immune system of patients with sickle cell disease (SCD) to the antigenic target of aPL leads to an increased formation of aPL; and 2) the presence of aPL is associated with pregnancy and SCD-related complications. Methods. We conducted a cross-sectional study in 63 adults with SCD who had aPL testing performed during a hospital admission between August 1999 & June 2017. We compared individual aPL levels with categorical and linear variables using the Kruskal-Wallis test and linear regression analysis, respectively. The anticardiolipin (aCL) IgG and lupus anticoagulant (LA) levels were log-transformed for these analyses. An abnormal aPL was defined as any of the following: IgM or IgG anti-b2GPI >20 IU/mL, IgM or IgG aCL > 20 IU/mL, LA > 10 seconds. Clinical complications were compared by abnormal aPL status using the chi-square test. Results. The median age of the SCD cohort was 32 years (IQR, 21 - 39 years), 49 (78%) were female, 62 (98%) were African American, 5 (8%) had a diagnosis of systemic lupus erythematosus (SLE), 43 (68%) were Hgb SS genotype, 17 (27%) were on hydroxyurea, and 16 (25%) were on chronic anticoagulation therapy. SCD patients with SLE had higher median aCL IgM (6 vs. 1 IU/mL, respectively; P=0.02) and anti-b2GPI IgG (3.5 vs. 0 IU/mL, respectively; P=0.008) levels compared to those without SLE, while lower hemoglobin concentrations were associated with higher aCL IgG levels (β -0.12; P=0.07) and longer LA times (β -0.18; P=0.02). Fifteen of 63 (24%) patients with SCD had an abnormal aPL. Patients with an abnormal aPL had a lower hemoglobin concentration (Figure 1A), a higher white blood cell (WBC; 13.5 vs. 11.8 x109/L, respectively; P=0.06) count, and a lower platelet (268 vs. 340 x109/L, respectively; P=0.05) count at the time of hospitalization compared to those with a normal aPL. A lower hemoglobin concentration (odds ratio [OR], 1.9; P=0.008), a higher WBC count (OR 1.2; P=0.03), and a lower platelet count (10 platelets/µL increment: OR 1.05, P=0.06) were independently associated with the presence of an abnormal aPL by logistic regression analysis, adjusting for age, sex, and prior SLE diagnosis. Consistent with the second part of our hypothesis, several adverse outcomes trended higher in SCD patients with an abnormal aPL. An abnormal aPL was more prevalent among women with ≥ 3 miscarriages, preterm deliveries, or pre-eclampsia as well as during a hospitalization complicated by acute chest syndrome or multiorgan failure (Figure 1B). Conclusions. These data support the hypothesis that patients with SCD have a high predilection to form aPL, and that the presence of an abnormal aPL is associated with pregnancy complications and the severity of acute SCD-related complications during hospitalization. Our study is limited by its small number of patients. Further larger studies are needed to assess the mechanisms of aPL generation as well as to determine the prevalence and associated risk of abnormal aPL status in patients with SCD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A Phase 3 Study to Evaluate the Efficacy and Safety of Caplacizumab without First-Line Therapeutic Plasma Exchange in Adults with Immune-Mediated Thrombotic Thrombocytopenic Purpura

Background: Caplacizumab (CPLZ) is a von Willebrand factor-directed antibody fragment that is indicated, in combination with therapeutic plasma exchange (TPE) and immunosuppressive therapy (IST), for the treatment of immune-mediated TTP (iTTP), also known as acquired thrombotic thrombocytopenic purpura (aTTP). While TPE is considered a mainstay of iTTP treatment, it is burdensome and associated with complications. Although reports from real-world clinical practice suggest the efficacy of TPE-free CPLZ regimens in iTTP, the use of CPLZ without first-line TPE has not been evaluated in the clinical trial setting. Aim: To evaluate the efficacy and safety of CPLZ in combination with IST without first-line TPE in adults with iTTP. Methods: MAYARI (NCT05468320) is a Phase 3, single-arm, open-label, multicenter study (13 countries and 49 sites) in adults experiencing an acute episode of iTTP. Study Population: Adults with a clinical diagnosis of initial or recurrent iTTP, defined as thrombocytopenia (platelet count <100×109/L), microangiopathic hemolytic anemia, and a French thrombotic microangiopathy score of 1 or 2, are eligible for the study pending confirmation of diagnosis with an ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity level within 48 hours of enrollment. Exclusion criteria include other known etiologies of thrombocytopenia, serum creatinine >2.26 mg/dL if platelet count is >30×109/L, severe neurological or cardiac disease, clinically significant active bleeding or high bleeding risk, or concomitant use of chronic anticoagulant or antiplatelet therapy. Interventions: All enrolled participants will begin CPLZ and corticosteroid therapy immediately based on the clinical diagnosis of iTTP and a French score of 1 or 2. Anti-CD20 antibody therapy can be initiated after confirmation of iTTP diagnosis (ADAMTS13 <10%). If, after initiation of CPLZ therapy, baseline ADAMTS13 activity level is found to be 10%-20%, the investigator may use their judgment to decide whether to continue CPLZ. If ADAMTS13 level is found to be >20% CPLZ should be discontinued. Otherwise, CPLZ treatment will be continued until sustained ADAMTS13 activity level of ≥50% at 2 consecutive visits after platelet count normalization. The maximum duration allowed for treatment of the presenting episode is 12 weeks (on-treatment period). The post-treatment follow-up period will be 12 weeks. Participants will not receive TPE as first-line therapy, but TPE may be started after 24 hours for a lack of adequate response per prespecified criteria or clinical deterioration at any time point. Study Outcomes: The primary endpoint is the proportion of participants achieving remission without requiring TPE during the overall study period (Table). Secondary endpoints include proportion of participants achieving remission, proportion of participants requiring TPE, proportion of participants achieving a clinical response, time to initial platelet count response (≥150×109/L sustained for ≥2 days), proportion of participants with iTTP-related exacerbation or death, refractoriness, and overall mortality. Patient-reported clinical outcome assessments will also be utilized in this study to assess impact on quality of life measures. Safety and tolerability will also be assessed. Revised outcomes definitions from the International Working Group for iTTP will be utilized (Cuker et al. Blood. 2021;137[14]:1855-1861). Statistical Approach: An adequate number of participants will be enrolled to ensure at least 55 participants with ADAMTS13 activity levels <10% at baseline are available for analysis of the primary endpoint. It is anticipated that approximately 61 participants will be enrolled in the study. With the sample size of 55, assuming the true responder rate of participants who achieve remission without requiring TPE during the overall study period is 70%, the lower bound of 95% confidence interval would be 58%. Summary: The current standard of care in patients with iTTP includes a combination of TPE, IST, and CPLZ. This novel study will define the efficacy and safety of CPLZ and IST without first-line TPE in adults with iTTP. This regimen would avert the risks for substantial complications associated with TPE and represents a paradigm shift in the frontline management of iTTP. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Design of the PERSEO Registry on the management of patients treated with oral anticoagulants and coronary stent.

Percutaneous coronary intervention with stent implantation (PCI-S) in patients requiring chronic oral anticoagulant therapy (OAC) is associated with an increased risk of bleeding and ischemic complications. Different randomized studies showed a significant advantage of a double antithrombotic therapy and superiority of direct oral anticoagulant (DOAC) compared with warfarin, but real-world data are limited. Aim is to evaluate the antithrombotic management and clinical outcome of patients with an indication for OAC who undergo PCI-S in a 'real-world' setting. The multicentre prospective observational PERSEO (PERcutaneouS coronary intErventions in patients treated with Oral anticoagulant therapy) Registry (ClinicalTrials.gov Identifier: NCT03392948) has been designed to enrol patients requiring OAC treated by PCI-S in 25 Italian centres. A target of at least 1080 patients will be followed for 1 year and data on thromboembolic and bleeding events and changes in antithrombotic therapy will be registered. The primary end point is a combined measure of efficacy and safety outcome (NACE), including major bleeding events and major adverse cardiac and cerebral events at 1-year follow-up in patients treated with DOAC (and dual or triple antiplatelet therapy) compared with the corresponding strategies with vitamin K antagonists. A secondary prespecified analysis has been defined to evaluate NACE in dual versus triple antithrombotic therapy after hospital discharge at 1-year follow-up. The PERSEO Registry will investigate in a 'real world' setting the safety and efficacy of DOAC versus warfarin and dual versus triple antithrombotic therapy in patients with indication for oral anticoagulant therapy who undergo PCI-S.

Anesthetic Management in Parturients With Fontan Physiology

Anesthetic Management in Parturients With Fontan Physiology