Showing papers by "Alfonso Tafur published in 2020"

Pharmacological Agents Targeting Thromboinflammation in COVID-19: Review and Implications for Future Research.

Abstract: Coronavirus disease 2019 (COVID-19), currently a worldwide pandemic, is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The suspected contribution of thrombotic events to morbidity and mortality in COVID-19 patients has prompted a search for novel potential options for preventing COVID-19-associated thrombotic disease. In this article by the Global COVID-19 Thrombosis Collaborative Group, we describe novel dosing approaches for commonly used antithrombotic agents (especially heparin-based regimens) and the potential use of less widely used antithrombotic drugs in the absence of confirmed thrombosis. Although these therapies may have direct antithrombotic effects, other mechanisms of action, including anti-inflammatory or antiviral effects, have been postulated. Based on survey results from this group of authors, we suggest research priorities for specific agents and subgroups of patients with COVID-19. Further, we review other agents, including immunomodulators, that may have antithrombotic properties. It is our hope that the present document will encourage and stimulate future prospective studies and randomized trials to study the safety, efficacy, and optimal use of these agents for prevention or management of thrombosis in COVID-19.

Guidance for the management of patients with vascular disease or cardiovascular risk factors and COVID-19 position paper from vas-european independent foundation in angiology/vascular medicine

Abstract: COVID-19 is also manifested with hypercoagulability, pulmonary intravascular coagulation, microangiopathy, and venous thromboembolism (VTE) or arterial thrombosis. Predisposing risk factors to severe COVID-19 are male sex, underlying cardiovascular disease, or cardiovascular risk factors including noncontrolled diabetes mellitus or arterial hypertension, obesity, and advanced age. The VAS-European Independent Foundation in Angiology/Vascular Medicine draws attention to patients with vascular disease (VD) and presents an integral strategy for the management of patients with VD or cardiovascular risk factors (VD-CVR) and COVID-19. VAS recommends (1) a COVID-19-oriented primary health care network for patients with VD-CVR for identification of patients with VD-CVR in the community and patients' education for disease symptoms, use of eHealth technology, adherence to the antithrombotic and vascular regulating treatments, and (2) close medical follow-up for efficacious control of VD progression and prompt application of physical and social distancing measures in case of new epidemic waves. For patients with VD-CVR who receive home treatment for COVID-19, VAS recommends assessment for (1) disease worsening risk and prioritized hospitalization of those at high risk and (2) VTE risk assessment and thromboprophylaxis with rivaroxaban, betrixaban, or low-molecular-weight heparin (LMWH) for those at high risk. For hospitalized patients with VD-CVR and COVID-19, VAS recommends (1) routine thromboprophylaxis with weight-adjusted intermediate doses of LMWH (unless contraindication); (2) LMWH as the drug of choice over unfractionated heparin or direct oral anticoagulants for the treatment of VTE or hypercoagulability; (3) careful evaluation of the risk for disease worsening and prompt application of targeted antiviral or convalescence treatments; (4) monitoring of D-dimer for optimization of the antithrombotic treatment; and (5) evaluation of the risk of VTE before hospital discharge using the IMPROVE-D-dimer score and prolonged post-discharge thromboprophylaxis with rivaroxaban, betrixaban, or LMWH.

Emergence of Institutional Antithrombotic Protocols for Coronavirus 2019

Abstract: The coronavirus infection (COVID-19), first identified in December 2019 in Wuhan, China, is a major public health crisis with new infections increasing exponentially worldwide. COVID-19 is an acute infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) and has contributed to significant morbidity and mortality, including the development of coagulopathy. Similar thrombotic and thromboembolic events have occurred during other viral outbreaks, including severe acute respiratory syndrome (SARS), Middle Eastern respiratory syndrome (MERS-CoV), and influenza A H1N1.

Evidence-Based Practical Guidance for the Antithrombotic Management in Patients With Coronavirus Disease (COVID-19) in 2020.

Abstract: This practical guidance, endorsed by the Brazilian Society of Thrombosis and Hemostasis and The Brazilian Society of Angiology and Vascular Surgery, the International Union of Angiology and the European Venous Forum, aims to provide physicians with clear guidance, based on current best evidence-based data, on clinical strategies to manage antithrombotic strategies in patients with coronavirus disease 2019.

Assay-Based Differentiation in the Neutralization Profile of Unfractionated Heparin, Enoxaparin, and Fondaparinux by Andexanet Alfa.

Abstract: Andexanet alfa is a recombinant factor Xa decoy protein, designed to reverse bleeding associated with oral anti-Xa agents. Andexanet alfa is also reported to neutralize the effects of heparin-related drugs. This study focused on the neutralization profiles of unfractionated heparin (UFH), enoxaparin, and, a chemically synthetic pentasaccharide, fondaparinux by andexanet alfa. Whole blood clotting studies were carried out using thromboelastography (TEG) and activated clotting time (ACT). The anticoagulant profile of UFH, enoxaparin, and fondaparinux was studied using the activated partial thromboplastin time (aPTT), thrombin time (TT), and amidolytic anti-Xa, and anti-IIa methods. Thrombin generation inhibition was studied using the calibrated automated thrombogram system. Reversal of each of these agents was studied by supplementing andexanet alfa at 100 µg/mL. In the TEG, andexanet alfa produced almost a complete reversal of the anticoagulant effects of UFH and enoxaparin; however, it augmented the effects of fondaparinux. In the ACT, aPTT, and TT, UFH produced strong anticoagulant effects that were almost completely neutralized by andexanet alfa. Enoxaparin produced milder anticoagulant responses that were partially neutralized, whereas fondaparinux did not produce any sizeable effects. In the anti-Xa and anti-IIa assays, UFH exhibited partial neutralization whereas enoxaparin and fondaparinux did not show any neutralization. All agents produced varying degrees of the inhibition of thrombin generation, which were differentially neutralized by andexanet alfa. These results indicate that andexanet alfa is capable of differentially neutralizing anticoagulant and antiprotease effects of UFH and enoxaparin in an assay-dependent manner. However, andexanet alfa is incapable of neutralizing the anti-Xa effects of fondaparinux.

Predictors of Bleeding in the Perioperative Anticoagulant Use for Surgery Evaluation Study.

Abstract: Background In the PAUSE (Perioperative Anticoagulant Use for Surgery Evaluation) Study, a simple, standardized, perioperative interruption strategy was provided for patients with nonvalvular atrial fibrillation taking direct oral anticoagulants (DOACs). Our objective was to define the factors associated with perioperative bleeding. Methods and Results We analyzed bleeding as the composite of major and clinically relevant nonmajor bleeding. Putative predictors of bleeding, and preoperative DOAC level were prospectively collected during recruitment. We used stratified logistic regression models for analysis. All statistical analyses were performed in R version 3.6.0. There were 3007 patients requiring perioperative DOAC interruption. More than one third of the included patients underwent a high bleeding risk procedure. The 30-day rates of major and clinically relevant nonmajor bleeding were 3.02% in apixaban (n=1257), 2.84% in dabigatran (n=668), and 4.16% for rivaroxaban (n=1082). Multivariate analysis stratified by region found more bleeding for hypertension (odds ratio [OR], 1.79; 95% CI 1.07-2.99; P=0.027), and prior bleeding (OR, 1.71; 95% CI, 1.08-2.71; P=0.021). Surgical bleed risk classification (high- versus low-risk) as a predictor of bleeding was only significant in the univariate analysis. The prediction model for major and clinically relevant nonmajor bleeding had an area under the curve of 0.71, and the preoperative DOAC level did not improve the area under the curve of the model. Conclusions In patients treated with DOACs who required an elective surgery/procedure and were managed with standardized DOAC interruption and resumption, there we did not find reversible risk factors for bleeding, suggesting that adjustment of the PAUSE management protocol to mitigate against bleeding is not needed.

The Novel Coronavirus Disease (COVID-19) and Its Impact on Cardiovascular Disease.

Abstract: The coronavirus disease 2019 (COVID-19) pandemic has placed a significant strain on healthcare providers. As the number of patients continue to surge, healthcare workers are now forced to find different approaches to practicing medicine that may affect patient care. In addition, COVID-19 has many cardiovascular complications that affect the clinical course of patients. In this article, we summarize the cardiovascular impact of COVID-19 and some of the challenges that patients and the healthcare system will face during this pandemic.

Incidence of major adverse cardiovascular events among patients with provoked and unprovoked venous thromboembolism: Findings from the Registro Informatizado de Enfermedad Tromboembólica Registry

Abstract: Objective Overlap exists between the risk factors for coronary artery disease and venous thromboembolism (VTE). However, a paucity of data is available on the incidence of major acute cardiovascular events (MACE) and major adverse limb events (MALE) among patients presenting with VTE. Moreover, it is unknown whether the rate of cardiovascular outcomes differs among patients with unprovoked vs provoked VTE. Methods We analyzed the data from 2009 to 2017 in the Registro Informatizado de Enfermedad Tromboembolica registry, an ongoing, multicenter, international registry of consecutive patients with a diagnosis of objectively confirmed VTE. The query was restricted it to patients with data entry for the arterial outcomes. The baseline prevalence of coronary artery disease risk factors was compared between patients with provoked (ie, immobility, cancer, surgery, travel >6 hours, hormonal causes) and unprovoked VTE. After the initial VTE event, we followed up patients for the composite primary outcome of incident MACE (ie, stroke, myocardial infarction, unstable angina) and/or MALE (ie, major limb events). We used the χ2 test for baseline associations and a Cox proportional hazard for multivariate analysis. We used IBM SPSS, version 24 (IBM Corp, Armonk, NY) for statistical analysis. A P value of Results We analyzed the data from 41,259 patients with VTE, of whom 22,633 (55.6%) had experienced a provoked VTE. During follow-up, the patients with provoked VTE were more likely to develop MACE or MALE than were patients with unprovoked VTE (hazard ratio [HR], 1.3; 95% confidence interval [CI], 1.1-1.5). The association of arterial events with recent immobility (HR, 1.4; 95% CI, 1.5-12.1) and cancer (HR, 1.7; 95% CI, 1.4-1.9) was strong. After adjusting for multiple conventional cardiovascular risk factors, provoked VTE, compared with unprovoked VTE, was significantly associated with an increased hazard for MACE (HR, 1.4; 95% CI, 1.1-1.7). Cancer remained a significant adjusted predictor for both MACE (HR, 1.7; 95% CI, 1.4-2.1) and MALE (HR, 2.1; 95% CI 1.01-4.6) in those with provoked VTE. Conclusions Among patients with VTE, provoked cases, specifically those with cancer-associated VTE, have an increased risk of major arterial events.

Outcomes after venous thromboembolism in patients with gastric cancer: Analysis of the RIETE Registry.

Abstract: Gastric cancer is the fifth most common malignancy worldwide. Venous thromboembolism is an independent predictor of death among patients with gastric cancer. We aimed to describe the factors associated with mortality, thrombosis recurrence, and bleeding complications in patients with gastric cancer who develop venous thromboembolism. We included 612 patients with gastric cancer and venous thromboembolism in the Registro Informatizado de la Enfermedad TromboEmbolica (RIETE) registry from 2001 to 2018. We used Cox proportional hazard ratios and a Fine-Gray model to define factors associated with outcomes. The overall mortality at 6 months was 44.4%. Factors associated with increased 6-month mortality included immobility (HR 1.8, 95% CI 1.3-2.4; p < 0.001), anemia (HR 1.4, 95% CI 1.1-1.8; p < 0.02), and leukocytosis (HR 1.8, 95% CI 1.4-2.3; p < 0.001). Recurrent thrombosis occurred in 6.5% of patients and major bleeding complications in 8.5% of the cohort. Male sex was the main factor associated with thrombosis recurrence (HR 2.1, 95% CI 1.1-4.0; p < 0.02) and hemoglobin below 10 g/dL (HR 1.6, 95% CI 1.05-2.50; p = 0.03) the main factor associated with bleeding. In conclusion, patients with gastric cancer who develop venous thrombosis have a very high likelihood of death. Low hemoglobin in this population is associated with poor outcomes.

Splenic Infarct Secondary to High Altitude Exposure in Sickle Cell Trait Patients: A Case Series.

Abstract: The sickle cell trait is considered a benign entity that generally does not show clinical manifestations. However, some complications have been described under certain conditions, such as a decrease in oxygen level, dehydration, and strenuous physical efforts. Among them, splenic infarct is a rare complication that presents as left upper abdominal pain in a situation of stress such as high altitude exposure. We present two cases of splenic infarcts in patients with undiagnosed sickle cell trait who showed to our institution with severe abdominal pain after coming from high altitude cities.

Drive-Through Model for Anticoagulation Clinics During the COVID-19 Pandemic.

Abstract: The coronavirus disease of 2019 (COVID-19) has posed a major challenge for providers and patients. A large number of patients with atrial fibrillation, venous thromboembolism, or valvular heart disease are chronically anticoagulated with vitamin K antagonists and rely on frequent follow ups at anticoagulation clinics for management of their anticoagulation therapy. The need for isolation during COVID-19 pandemic can potentially limit access to health care including anticoagulation clinics and directly affect the care of patients on chronic anticoagulation. Therefore, we created a drive-through clinic to bridge the gap of continuation of care and preservation of social distancing precautions. In this manuscript, we report the steps in implementing such initiative which can be applied to other clinics during a pandemic.

National Physician Survey for Nonvalvular Atrial Fibrillation (NVAF) Anticoagulation Comparing Knowledge, Attitudes and Practice of Cardiologist to PCPs.

Abstract: Introduction:NVAF is estimated to affect between 6.4 and 7.4 million Americans in 2018, and increases the risk of stroke 5-fold. To mitigate this risk, guidelines recommend anticoagulating AF patie...

Real-Time Dissemination of Aggregate Data on Presentation and Outcomes of Patients With Venous Thromboembolism: The RIETE Infographics Project:

Abstract: In the current era of patient empowerment and precision medicine, access to timely information is critical to decision-making. Unfortunately, we currently lack patient-specific, real-time data abou...

Effect of Direct Oral Anticoagulant, Patient, and Surgery Characteristics on Clinical Outcomes in the Perioperative Anticoagulation Use for Surgery Evaluation Study.

Abstract: Introduction The Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) Study assessed a standardized perioperative management strategy in patients with atrial fibrillation who were taking a direct oral anticoagulant (DOAC) and required an elective surgery or procedure. The aim of this substudy is to analyze the safety of this management strategy across different patient subgroups, according to four presurgical variables: (1) DOAC type and dose, (2) surgery/procedure bleed risk, (3) patient renal function, and (4) age. Methods Clinical outcomes analyzed included major bleeding (MB), arterial thromboembolism, any bleeding, and any thromboembolism. We used descriptive statistics to summarize clinical outcomes, where the frequency, proportion, and 95% confidence interval were reported. Fisher's exact tests were used for testing the null hypothesis of independence between the clinical outcome and patient characteristic, where the test p-values were reported. Results There were 3,007 patients with atrial fibrillation requiring perioperative DOAC management. There was no significant difference in bleeding or thromboembolic outcomes according to DOAC type/dose regimen, renal function, or patient age. The rate of MB was significantly higher with high bleed risk procedures than low bleed risk procedures in apixaban-treated patients (2.9 vs. 0.59%; p Conclusion Our results suggest that in DOAC-treated patients who received standardized perioperative management, surgical bleed risk is an important determinant of bleeding but not thromboembolic outcomes, although this finding was not consistent across all DOACs. There were no differences in bleeding and thromboembolism according to DOAC type and dose, renal function, or age.

Frequently Asked Questions about Thrombosis during COVID-19 Pandemic

Abstract: The coronavirus disease 2019 (COVID-19) pandemic and the “shelter-in-place” orders have placed a significant strain on patients and providers. We believe that patient education is crucial during these times, so together with their health care providers, the patients can make the best decisions in regard to their health. Anchored on a patient-perspective, we summarize frequently asked questions illustrating a growing thrombosis concern.

First three months of anticoagulation for venous thromboembolism in non-cancer patients: LMWH VS. VKAs. Findings from the RIETE registry

Abstract: Background The use of low-molecular-weight heparin (LMWH) for long-term therapy of venous thromboembolism (VTE) in patients without cancer has not been consistently evaluated. Methods We used the data in the RIETE registry to compare the 3-month outcomes (VTE recurrences, major bleeding or death) in non-cancer patients with VTE, according to long-term therapy with LMWH or vitamin K antagonists (VKAs). Results As of March 2018, 14,582 non-cancer patients with VTE had received initial therapy with LMWH and then switched to VKAs, while 9151 were prescribed LMWH for initial and long-term therapy. Overall, 11,494 had initially presented with pulmonary embolism (PE) and 12,239 with isolated deep vein thrombosis (DVT). Among 11,494 patients initially presenting with PE, 84 had VTE recurrences, 204 major bleeding and 406 died. Among 12,239 patients with isolated DVT, 133 developed VTE recurrences, 137 bled and 289 died. On propensity score analysis, PE patients on long-term LMWH therapy were at increased risk for PE recurrences (OR: 3.30; 95%CI: 1.67–6.48), major bleeding (OR: 1.68; 95%CI: 1.21–2.32) or death (OR: 3.16; 95%CI: 2.43–4.09) compared with those receiving VKAs. In patients with DVT, those on long-term LMWH also were at increased risk for PE recurrences (OR: 2.31; 95%CI: 1.13–4.73), major bleeding (OR 2.28; 95%CI: 1.51–3.44) or death (OR: 2.32; 95%CI: 1.54–3.51). Conclusions In the RIETE non-cancer patients with VTE, long-term therapy with VKAs was associated with a lower risk for recurrences, major bleeding or death.

Thrombin Generation Profile in Various Lymphoma Sub-Groups and Its Augmentation by Andexanet Alfa.

Abstract: The prevalence of thrombosis in lymphoma patients is reportedly high and ranges from 3-10%. Vascular malfunction and inflammatory processes further contribute to the thrombotic activation process in these patients. Andexanet alfa (AA) is an antidote for factor Xa inhibitors and its usage has been reported with thrombotic complications. This study was designed to compare the effect of AA on the thrombin generation (TG) potential. Blood samples from 78 patients with confirmed diagnosis of non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL) and Chronic lymphocytic leukemia (CLL) were collected from the University of Belgrade Clinic, Serbia. Normal human plasma (NHP) was used for referencing purposes. Individual samples were supplemented with AA at 100 ug/ml. TG studies were carried out using a commercially available fluorogenic substrate method. TG parameters such as peak thrombin (PT), lag time (LT) and area under the curve (AUC) were compiled. Cumulatively, lymphoma patients showed an increase in LT compared to NHP which decreases with AA. The PT and AUC levels were decreased compared to NHP and increases with AA. Upon sub-grouping of lymphoma patients, PT levels for all sub-groups were increased with AA. The AUC values increased for HL and NHL and decreased for CLL with AA. Variations in lag time were noted in all 3 sub-groups. Lymphoma represents a heterogenous group of patients where both the hypercoagulable state and inflammatory responses simultaneously occur. Increased thrombin generation in post AA supplemented samples suggest that the use of this agent may potentially be associated with thrombotic complications.