Post-COVID-19 superior mesenteric artery and jejunal branches thromboembolism.

The World Health Organization has declared the novel coronavirus disease 2019 (COVID-19) a global public health emergency. Despite the predominating respiratory symptoms occurring in COVID-19, thrombosis can occur in some patients, with morbidity and mortality increase due to the respiratory worsening. This article reports the case of a 62-year-old man with a flu-like illness that was diagnosed as COVID-19 by RT-PCR of SARS-CoV-2. After three weeks, he subsequently developed abdominal pain in addition to bloating, nausea, and vomiting. He underwent exploratory laparotomy after imaging tests suggested mesenteric ischemia. Intestinal ischemia was evident, due to the absence of flow in the superior mesenteric artery and jejunal branches. Embolectomy and enterectomy were performed and they resulted in a favorable outcome, with clinical improvement. This case adds data to the limited literature on extrapulmonary complications of COVID-19, notably those related to thromboembolic events.

La Organización Mundial de la Salud ha declarado la enfermedad del nuevo coronavirus 2019 (COVID-19) una emergencia de salud pública mundial. A pesar de los síntomas respiratorios predominantes en COVID-19, la trombosis puede ocurrir en algunos pacientes, con un aumento de la morbimortalidad debido al empeoramiento respiratorio. Presentamos el caso de un hombre de 62 años con enfermedad similar a la gripe que fue diagnosticada como COVID-19 por RT-PCR de SARS-CoV-2. Después de tres semanas, desarrolló dolor abdominal además de hinchazón, náuseas y vómitos. Fue sometido a laparotomía exploradora luego de que las pruebas de imagen sugirieran isquemia mesentérica. Se evidenció isquemia intestinal por ausencia de flujo en la arteria mesentérica superior y ramas yeyunales. Se realizó embolectomía y enterectomía con evolución favorable, con mejoría clínica. Este caso añade datos a la limitada literatura sobre las complicaciones extrapulmonares del COVID-19, en particular las relacionadas con eventos tromboembólicos.

SARS-COV-ATE risk assessment model for arterial thromboembolism in COVID-19.

Patients with SARS-CoV-2 infection are at an increased risk of cardiovascular and thrombotic complications conferring an extremely poor prognosis. COVID-19 infection is known to be an independent risk factor for acute ischemic stroke and myocardial infarction (MI). We developed a risk assessment model (RAM) to stratify hospitalized COVID-19 patients for arterial thromboembolism (ATE). This multicenter, retrospective study included adult COVID-19 patients admitted between 3/1/2020 and 9/5/2021. Among 3531 patients from the training cohort, 15.5% developed acute in-hospital ATE, including stroke, MI, and other ATE, compared to 13.4% in the validation cohort. The 16-item final score was named SARS-COV-ATE (Sex: male = 1, Age [40-59 = 2, > 60 = 4], Race: non-African American = 1, Smoking = 1 and Systolic blood pressure elevation = 1, Creatinine elevation = 1; Over the range: leukocytes/lactate dehydrogenase/interleukin-6, B-type natriuretic peptide = 1, Vascular disease (cardiovascular/cerebrovascular = 1), Aspartate aminotransferase = 1, Troponin-I [> 0.04 ng/mL = 1, troponin-I > 0.09 ng/mL = 3], Electrolytes derangement [magnesium/potassium = 1]). RAM had a good discrimination (training AUC 0.777, 0.756-0.797; validation AUC 0.766, 0.741-0.790). The validation cohort was stratified as low-risk (score 0-8), intermediate-risk (score 9-13), and high-risk groups (score ≥ 14), with the incidence of ATE 2.4%, 12.8%, and 33.8%, respectively. Our novel prediction model based on 16 standardized, commonly available parameters showed good performance in identifying COVID-19 patients at risk for ATE on admission.

Thrombosis and thromboembolism: Brighton collaboration case definition and guidelines for data collection, analysis, and presentation of immunization safety data.

This is a Brighton Collaboration case definition of thrombosis and thromboembolism to be used in the evaluation of adverse events following immunization, and for epidemiologic studies for the assessment of background incidence or hypothesis testing. The case definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of SARS-CoV-2 vaccines. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network and by selected expert reviewers prior to submission.

A Rare Case of Multiple Thrombosis Associated with COVID-19 Pneumonia.

Coronavirus disease 2019 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 virus. Hypoxic respiratory failure, multiorgan dysfunction, septic shock, thrombosis, and thromboembolic complications have been associated with the severe acute respiratory syndrome coronavirus 2 infection. We report the presentation of the severe acute respiratory syndrome coronavirus 2 infection with acute upper extremity ischemia and mesenteric ischemia clinic. We also report that this patient had an aortic arch mural thrombus as a possible source of thromboembolism, and we emphasize that the aorta should also be carefully evaluated in thromboembolic patients with coronavirus disease 2019.

Anticoagulation in COVID-19 patients - An updated systematic review and meta-analysis.

BACKGROUND: Thromboembolic events are common complications of COVID-19. Clinical study results on safety and efficacy of anticoagulation in COVID-19 are controversial. MATERIAL AND METHODS: This report updates our systematic review and random-effects meta-analysis on randomized controlled trials (RCTs) comparing standard prophylactic anticoagulation and intermediate or therapeutic anticoagulation in COVID-19 patients. We searched eligible studies for the update up to 4 February 2022 by weekly monitoring of RCTs in the Cochrane COVID-19 Study Register. Certainty of evidence was assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: For this update we included five new trials; a total of 13 RCTs with 7364 patients. Certainty of evidence was very low to low. We are uncertain whether low-dose prophylactic anticoagulation is favoured over placebo or no anticoagulation in the outpatient- or post-discharge-setting. In hospitalized patients with moderate and severe COVID-19, intermediate-dose anticoagulation may have little or no effect on thrombotic events or death (RR 1.03, 95 % CI 0.86-1.24), but may increase severe bleeding non-significantly (RR 1.48, 95 % CI 0.53-4.15). Therapeutic-dose anticoagulation may decrease thrombotic events or deaths in hospitalized patients with moderate COVID-19 (RR 0.64, 95 % CI 0.38-1.07; fixed-effect model RR 0.72, 95 % CI 0.57-0.91), but may have little or no effect in patients with severe disease (RR 0.98, 95 % CI 0.86-1.12). With therapeutic-dose anticoagulation, the risk of major bleeding may increase regardless of COVID-19 severity (RR 1.78, 95 % CI 1.15-2.74). CONCLUSIONS: Hospitalized, moderately ill COVID-19 patients may benefit from therapeutic-dose anticoagulation, while critically ill patients may not. Risk of major bleeding must be considered.

Real-World Analysis of Thromboembolic Events and Mortality of COVID-19 Outpatients in the United States.

Limited data are available on thromboembolic events (TEEs) and mortality in outpatients with coronavirus disease 2019 (COVID-19). This retrospective, observational cohort study identified non-hospitalized COVID-19 outpatients (01/21/2020-01/07/2021) using de-identified Optum® COVID-19 Electronic Health Records data. Patient characteristics, occurrence of TEEs, all-cause mortality, and anticoagulant or thrombolytic medication use were evaluated. Of 1,246,067 patients with COVID-19 diagnosis, 141 471 met entry criteria. Mean (standard deviation [SD]) age was 46.1 (17.2) years, 56.8% were female, 72.9% Caucasian, 11.2% African American, and 11.1% Hispanic. Comorbidity burden was low (mean [SD] Quan-Charlson comorbidity index score of 0.43 [1.10]); however, of those with body mass index data, half were obese. During the follow-up period, a TEE occurred in 1.4%, with the proportion of patients with ischemic stroke, myocardial infarction, deep vein thrombosis, and pulmonary embolism being similar (approximately 0.4% each). All-cause mortality was 0.7%. Medications included corticosteroids (13.7%), anticoagulants (4.9%), and antiplatelets (2.9%). Overall, in this large cohort analysis, certain demographic and clinical characteristics of patients who experienced TEEs were identified and may help guide management decisions and future clinical trials for COVID-19 outpatients.

Thromboembolic events after Ad.26.COV2.S COVID-19 vaccine: Reports to the Vaccine Adverse Event Reporting System.

PURPOSE: The Food and Drug Administration (FDA) has identified a potential safety concern for thromboembolic events (TEEs) after Ad.26.COV2.S COVID-19 Vaccine. We sought to characterize the frequency, severity, type, and anatomic location of TEEs reported to the Vaccine Adverse Event Reporting System (VAERS) following Ad.26.COV2.S. METHODS: Reports of TEEs after Ad.26.COV2.S were identified in VAERS, and demographics, clinical characteristics, and relevant medical history were summarized. For a subset of reports, physicians reviewed available medical records and evaluated clinical presentation, diagnostic evaluation, risk factors, and treatment. The crude reporting rate of TEEs was estimated based on case counts in VAERS and vaccine administration data. RESULTS: Through February 28, 2022, FDA identified 3790 reports of TEEs after Ad.26.COV2.S. Median age was 56 years, and 1938 individuals (51.1%) were female. Most reports, 2892 (76.3%), were serious, including 421 deaths. Median time to onset was 12 days post-vaccination. Obesity and ischemia were among the most commonly documented risk factors. Thrombocytopenia (platelet count less than 150 000/µl) was documented in 63 records (11.5%) and anti-platelet 4 antibodies in 25 (4.6%). Medical review identified cases of severe clot burden (e.g., bilateral, saddle, or other massive pulmonary embolism with or without cor pulmonale; lower extremity thrombus involving the external iliac, common femoral, popliteal, posterior tibial, peroneal, and gastrocnemius veins). The crude reporting rate was ~20.7 cases of TEE per 100 000 doses of Ad.26.COV2.S administered. CONCLUSIONS: Life-threatening or fatal TEEs have been reported after Ad.26.COV2.S, including bilateral massive pulmonary embolism or other severe clot burden.

A novel evidence-based algorithm to predict thromboembolism in patients with COVID-19: preliminary data from a single-center cohort.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-related disease (COVID-19) is an infectious disease characterized by systemic inflammation, which might enhance baseline thrombotic risk, especially in hospitalized patients. Little is, however, known about predictors of thrombotic complications in patients with COVID-19. METHODS: We prospectively followed up 180 hospitalized COVID-19 patients. Demographics, clinical and laboratory features at presentation and past medical history were tested as predictors of the first thrombotic complication through multivariate Cox regression analysis and a categorical score generated based on the results. RESULTS: Sixty-four thromboses were recorded in 54 patients, of whom seven with thrombosis on admission and 47 with thrombosis during hospitalization. Patients with thrombosis were mainly Caucasian and diabetic, had marked baseline signs of inflammation and organ damage, lower PaO2/FiO2 ratio, higher D-dimer levels and history of major hemorrhages. The latter three variables were independently associated to thrombotic complications and concurred to a 0-5 score, which accounted for 80% of the total sample variability. Patients with three or more points of the newly generated score were at higher risk for thrombotic complications (HR=4.9, P<0.001). Patients with thrombotic complications were more likely to be admitted to intensive care and/or to die (HR=1.9, P=0.036). Five of 180 patients were diagnosed with disseminated intravascular coagulation and three of them died. Eleven minor and no major bleeding events were observed. CONCLUSIONS: Patients with COVID-19 are at increased risk for thrombosis and might be stratified on admission based on lower Pao2/FiO2 ratio, higher D-dimer levels and history of major hemorrhages.

Safety of heterologous primary and booster schedules with ChAdOx1-S and BNT162b2 or mRNA-1273 vaccines: nationwide cohort study.

OBJECTIVE: To assess the risk of adverse events associated with heterologous primary (two dose) and booster (three dose) vaccine schedules for covid-19 with Oxford-AstraZeneca's ChAdOx1-S priming followed by mRNA vaccines (Pfizer-BioNTech's BNT162b2 or Moderna's mRNA-1273) as compared with homologous mRNA vaccine schedules for covid-19. DESIGN: Nationwide cohort study. SETTING: Denmark, 1 January 2021 to 26 March 2022. PARTICIPANTS: Adults aged 18-65 years who received a heterologous vaccine schedule of priming with ChAdOx1-S and one or two mRNA booster doses (with either the BNT162b2 or mRNA-1273 vaccine) were compared with adults who received a homologous BNT162b2 or mRNA-1273 vaccine schedule (ie, two dose v two dose, and three dose v three dose schedule). MAIN OUTCOME MEASURES: The incidence of hospital contacts for a range of adverse cardiovascular and haemostatic events within 28 days after the second or third vaccine dose, comparing heterologous versus homologous vaccine schedules. Secondary outcomes included additional prioritised adverse events of special interest. Poisson regression was used to estimate incidence rate ratios with adjustment for selected covariates. RESULTS: Individuals who had had a heterologous primary vaccine (n=137 495) or a homologous vaccine (n=2 688 142) were identified, in addition to those who had had a heterologous booster (n=129 770) or a homologous booster (n=2 197 213). Adjusted incidence rate ratios of adverse cardiovascular and haemostatic events within 28 days for the heterologous primary and booster vaccine schedules in comparison with the homologous mRNA vaccine schedules were 1.22 (95% confidence interval 0.79 to 1.91) and 1.00 (0.58 to 1.72) for ischaemic cardiac events, 0.74 (0.40 to 1.34) and 0.72 (0.37 to 1.42) for cerebrovascular events, 1.12 (0.13 to 9.58) and 4.74 (0.94 to 24.01) for arterial thromboembolisms, 0.79 (0.45 to 1.38) and 1.09 (0.60 to 1.98) for venous thromboembolisms, 0.84 (0.18 to 3.96) and 1.04 (0.60 to 4.55) for myocarditis or pericarditis, 0.97 (0.45 to 2.10) and 0.89 (0.21 to 3.77) for thrombocytopenia and coagulative disorders, and 1.39 (1.01 to 1.91) and 1.02 (0.70 to 1.47) for other bleeding events, respectively. No associations with any of the outcomes were found when restricting to serious adverse events defined as stay in hospital for more than 24 h. CONCLUSION: Heterologous primary and booster covid-19 vaccine schedules of ChAdOx1-S priming and mRNA booster doses as both second and third doses were not associated with increased risk of serious adverse events compared with homologous mRNA vaccine schedules. These results are reassuring but given the rarity of some of the adverse events, associations cannot be excluded.

Impairment of Anti-Aggregatory Responses to Nitric Oxide and Prostacyclin: Mechanisms and Clinical Implications in Cardiovascular Disease.

The propensity towards platelet-rich thrombus formation increases substantially during normal ageing, and this trend is mediated by decreases in platelet responsiveness to the anti-aggregatory nitric oxide (NO) and prostacyclin (PGI2) pathways. The impairment of soluble guanylate cyclase and adenylate cyclase-based signalling that is associated with oxidative stress represents the major mechanism of this loss of anti-aggregatory reactivity. Platelet desensitization to these autacoids represents an adverse prognostic marker in patients with ischemic heart disease and may contribute to increased thrombo-embolic risk in patients with heart failure. Patients with platelet resistance to PGI2 also are unresponsive to ADP receptor antagonist therapy. Apart from ischemia, diabetes and aortic valve disease are also associated with impaired anti-aggregatory homeostasis. This review examines the association of impaired platelet cyclic nucleotide (i.e., cGMP and cAMP) signalling with the emerging evidence of thromboembolic risk in cardiovascular diseases, and discusses the potential therapeutic strategies targeting this abnormality.

Post-COVID-19 hematologic complications: a systematic review.

INTRODUCTION: COVID-19 crisis continues around the world. Some patients developed complications after the disease, which have been reported in limited studies. The aim of this study is to comprehensively assess the post-COVID hematologic complications in patients. AREAS COVERED: We searched PubMed, Scopus, and Google Scholar between January 2020 and August 2021 using related keywords. Evaluation of the article was performed by two independent researchers. The extracted data included the number of patients, age, type of hematological complication, duration of follow-up, response to treatment and prognosis. EXPERT OPINION: Sixty-five articles reported post-COVID hematologic complications. The most frequent hematologic complication in COVID-19 patients is thromboembolic events, which often occur in two forms: deep vein thrombosis (DVT) and pulmonary embolism (PE). In a group of patients after the diagnosis of COVID-19, a significant decrease in platelets was observed, which was attributed to the ITP induced by COVID-19. Hemolytic anemia and aplastic anemia have also been reported rarely in patients. Finally, post-COVID hematologic complications appear to go beyond thromboembolic events. Although these complications have rarely been reported, searching for methods to identify susceptible patients and prevent these complications could be the subject of future research.

To Study the Clinical Profile of Thromboembolic Events in Covid 19 Patients.

The sars -cov 2 causing covid 19 disease. B/l pneumonia, systemic inflammation, coagulation activation, ards , multiorgan failure are key features of covid 19. Patients need icu admission. Proinflammatory cytokines, tnf, il 6, 8, 1 beta, causes cytokine storm in covid 19 disease. MATERIAL: In this single-center, retrospective, cross sectional study, the clinical and laboratory characteristics of 154 patients with severe covid-19 were collected. 38 Patients with severe covid -19 had incidence of thromboembolism with its symptoms, and 116 patients (ie, the controls) did not have incidence of thromboembolism. A severe case was defined as including at least one of the following criteria: (1) respiratory rate >30/ min. (2) Oxygen saturation ≤90%. (3) Pao2 /fio2 ≤300mm hg. (4) Patients, either with shock or respiratory failure, requiring mechanical ventilation, or combined with other organ failure, requiring admission to intensive care unit (icu). Also pe cases were those patients with high clinical suspicion [tachycardia >100 bpm, systolic arterial tension <100 mmhg or signs of right ventricular pressure overload]. Pe severity was assessed using the simplified pulmonary embolism severity index (s -pesi). OBSERVATION: Of 154 patients with severe covid-19, 38 (24.67%) Had incidence of thromboembolism. Compared with patients with severe covid-19 without incidence of thromboembolism, patients with incidence of thromboembolism were older, susceptible to receiving mechanical ventilation and admission to icu, and had higher mortality. In addition, patients with severe covid-19 with thromboembolism had higher levels of leukocyte count, neutrophil count, high-sensitivity c reaction protein, procalcitonin, ferritin, interleukin (il) 2 receptor, il-6, il-8, tumor necrosis factor α, D-dimer, fibrinogen, lactic dehydrogenase and n-terminal probrain natriuretic peptide. Among patients with severe covid-19 with incidence of thromboembolism, more non-survivors were men (30 (75%) vs women (25%)). Non-survivors had severe inflammatory response, and cardiac, hepatic, renal and coagulation impairment. Finally, the kaplan-meier survival curve showed a trend towards poorer survival in patients with severe covid-19 with incidence of thromboembolism than patients without incidence of thromboembolism. The hr was 2.24 [95% Ci 1.17-4.29], P = 0.015). After adjustment for age, sex, hypertension, cardiovascular disease and cerebrovascular disease by cox regression. The median survival durations from hospital admission in patients with severe covid-19 with and without incidence of thromboembolism were 8 days and 15 days, respectively. CONCLUSION: The mortality rate in patients with severe covid-19 with incidence of thromboembolism is high. Incidence of thromboembolism may lead to an increase in the risk of death.

COVID-19 and thrombosis: The role of hemodynamics.

Severe coronavirus disease 2019 (COVID-19) is characterized by an increased risk of thromboembolic events, a leading cause for adverse outcomes in patients afflicted by the more serious manifestation of the disease. These thromboembolic complications expressed as sepsis-induced coagulopathy, disseminated intravascular coagulation, venous and arterial thromboembolism, pulmonary embolism, microthrombosis, and thrombotic microangiopathy have been observed to affect different organs such as the lungs, heart, kidneys, and brain. Endothelial injury and dysfunction have been identified as the critical pathway towards thrombogenesis, and contributions of other mechanisms such as hypercoagulability, cytokine storm, neutrophils have been studied. However, the contribution of hemodynamic pathways towards thrombosis in severe COVID-19 cases has not been investigated. From the classical theory of Virchow's triad to the contemporary studies on the effect of shear enhanced platelet activation, it is well established that hemodynamics plays a role in the initiation and growth of thrombosis. This article reviews recent studies on COVID-19 related thrombotic events and offers hypotheses on how hemodynamics may be responsible for some of the adverse outcomes observed in severe COVID-19 cases. While thrombogenesis through endothelial injury and the effects of hypercoagulability on thrombosis are briefly addressed, the crux of the discussion is focused on hemodynamic factors such as stasis, turbulent flow, and non-physiological shear stress and their effects on thrombosis. In addition, hemodynamics-dependent venous, arterial, and microvascular thrombosis in COVID-19 cases is discussed. We also propose further investigation of diagnostic and therapeutic options that address the hemodynamics aspects of COVID-19 thrombus formation to assess their potential in patient care.