Riesgo de recurrencia de la trombosis en pacientes con tromboembolia venosa asociada a COVID-19 y a cirugía / Risk of thrombosis recurrence among patients with COVID-19- and surgery-associated venous thromboembolism

Introducción La cirugía reciente es un factor de riesgo transitorio mayor y conocido de tromboembolia venosa (TEV) debido al bajo riesgo de recurrencia de la TEV una vez suspendida la anticoagulación. Por otro lado, se desconoce el riesgo de recurrencia de la TEV en los pacientes con TEV asociada a COVID-19. El objetivo de este estudio consistió en comparar el riesgo de recurrencia de la TEV entre pacientes con TEV asociada a COVID-19 y a cirugía. Método Se realizó un estudio prospectivo, observacional y unicéntrico en el que participaron pacientes consecutivos diagnosticados de TEV en un hospital terciario entre enero de 2020 y mayo de 2022 y que fueron objeto de seguimiento durante un mínimo de 90 días. Se evaluaron las características iniciales, el cuadro clínico y los resultados clínicos. Se compararon las incidencias de recurrencia de la TEV, hemorragias y muertes entre ambos grupos. Resultado En el estudio se incluyó a un total de 344 pacientes: 111 con TEV asociada a cirugía y 233 con TEV asociada a COVID-19. Entre los pacientes con TEV asociada a COVID-19 hubo una mayor frecuencia de varones (65,7 vs. 48,6%, p = 0,003). La recurrencia de la TEV fue de 3% en los pacientes con COVID-19 y de 5,4% en los pacientes quirúrgicos, sin diferencias significativas (p = 0,364). La tasa de incidencia de TEV recurrente fue de 1,25 y 2,29 por 1.000 personas-meses en los pacientes con COVID-19 y quirúrgicos, respectivamente, sin diferencias significativas (p = 0,29). En el análisis multifactorial, la COVID-19 se asoció a una mayor mortalidad (HR = 2,34; IC 95%, 1,19-4,58), pero no a un mayor riesgo de recurrencia (HR = 0,52; IC 95%, 0,17-1,61). En el análisis multifactorial de riesgos competitivos no se observaron diferencias en cuanto a recurrencias (SHR = 0,82; IC 95%, 0,40-2,05). Conclusiones El riesgo de recurrencia fue bajo en los pacientes con TEV asociada a COVID-19 y a cirugía, sin diferencias entre ambos grupos (AU)

Introduction Recent surgery is a well-known major transient risk factor for venous thromboembolism (VTE) due to the low risk of VTE recurrence after anticoagulation is discontinued. On the other hand, the risk of VTE recurrence among patients with COVID-19-associated VTE is unknown. This study aimed to compare the risk of VTE recurrence between patients with COVID-19- and surgery-associated VTE. Methods A prospective observational single-center study was performed including consecutive patients diagnosed with VTE in a tertiary hospital from January 2020 to May 2022 and followed up for at least 90 days. Baseline characteristics, clinical presentation, and outcomes were assessed. The incidence of VTE recurrence, bleeding, and death was compared between both groups. Result A total of 344 patients were included in the study: 111 patients with surgery-associated VTE and 233 patients with COVID-19-associated VTE. Patients with COVID-19-associated VTE were more frequently men (65.7% vs 48.6%, p = 0.003). VTE recurrence was 3% among COVID-19 patients and 5.4% among surgical patients, with no significant differences (p = 0.364). The incidence rate of recurrent VTE was 1.25 per 1000 person-months in COVID-19 patients and 2.29 person-months in surgical patients, without significant differences (p = 0.29). In the multivariate analysis, COVID-19 was associated with higher mortality (HR 2.34; 95% CI 1.19-4.58), but not with a higher risk of recurrence (HR 0.52; 95% CI 0.17-1.61). No differences were found in recurrence in the multivariate competing risk analysis (SHR 0.82; 95% CI 0.40 – 2.05). Conclusions In patients with COVID-19 and surgery-associated VTE, the risk of recurrence was low, with no differences between both groups (AU)

NEUT-SFL in Patients with COVID-ARDS: A Novel Biomarker for Thrombotic Events?

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped RNA virus first identified in December 2019 in Wuhan, China, and responsible for coronavirus disease 2019 (COVID-19). The ongoing COVID-19 pandemic is impacting healthcare worldwide. Patients who develop coagulopathy have worse outcomes. The pathophysiology of COVID-19 suggests a strong interplay between hemostasis and immune cells, especially neutrophils. Our purpose was to assess neutrophil fluorescence as a potential biomarker of deep vein thrombosis (DVT) in patients with COVID-acute respiratory distress syndrome (COVID-ARDS). Sixty-one patients with COVID-ARDS admitted to the four intensive care units (ICUs) of a French general hospital were included in this prospective study. Neutrophil activation was assessed by measuring neutrophil fluorescence (NEUT-Side Fluorescence Light, NEUT-SFL) with a specific fluorescent dye staining analyzed by a routine automated flow cytometer Sysmex XN-3000™ (Sysmex, Kobe, Japan). DVT was diagnosed by complete duplex ultrasound (CDU). We found that NEUT-SFL was elevated on admission in patients with COVID-ARDS (49.76 AU, reference value 46.40 AU, p < 0.001), but did not differ between patients with DVT (49.99 AU) and those without (49.52 AU, p = 0.555). NEUT-SFL is elevated in patients with COVID-ARDS, reflecting neutrophil activation, but cannot be used as a marker of thrombosis. Because neutrophils are at interface between immune response and hemostasis through release of neutrophil extracellular traps, monitoring their activation could be an interesting approach to improve our management of coagulopathy during COVID-ARDS. Further research is needed to better understand the pathophysiology of COVID-19 and identify high-performance biomarkers.

Thrombotic risk in patients with COVID-19.

Emerging evidences prove that the ongoing pandemic of coronavirus disease 2019 (COVID-19) is strictly linked to coagulopathy even if pneumonia appears as the major clinical manifestation. The exact incidence of thromboembolic events is largely unknown, so that a relative significant number of studies have been performed in order to explore thrombotic risk in COVID-19 patients. Cytokine storm, mediated by pro-inflammatory interleukins, tumor necrosis factor α and elevated acute phase reactants, is primarily responsible for COVID-19-associated hypercoagulopathy. Also comorbidities, promoting endothelial dysfunction, contribute to a higher thromboembolic risk. In this review we aim to investigate epidemiology and clarify the pathophysiological pathways underlying hypercoagulability in COVID-19 patients, providing indications on the prevention of thromboembolic events in COVID-19. Furthermore we aim to reassume the pathophysiological paths involved in COVID-19 infection.

Pulmonary Vein Thrombosis in COVID-19.

Research on COVID-19, the cause of a rapidly worsening pandemic, has led to the observation of laboratory derangements such as a propensity towards a hypercoagulable state. However, there are currently no reports on the incidence of pulmonary venous thrombosis in the setting of COVID-19. We report a case in which follow-up chest CT scans revealed an expansile filling defect in a branch of the right inferior pulmonary vein, which is consistent with pulmonary venous thrombosis. Our objective was to provide insight into an uncommon sequela of COVID-19 and consequently garner increased clinical suspicion for pulmonary VTE during hospitalization.

Cerebral Venous Thrombosis Associated with COVID-19 Infection: An Observational, Multicenter Study.

BACKGROUND AND PURPOSE: Coronavirus disease 2019 (CO-VID-19) has an increased propensity for systemic hypercoagulability and thromboembolism. An association with cerebrovascular diseases, especially cerebral venous thrombosis (CVT), has been reported among these patients. The objective of the present study was to identify risk factors for CVT as well as its presentation and outcome in COVID-19 patients. METHODS: This is a multicenter and multinational observational study. Ten centers in 4 countries (Pakistan, Egypt, Singapore, and the United Arab Emirates) participated in this study. The study included patients (aged >18 years) with symptomatic CVT and recent COVID-19 infection. RESULTS: Twenty patients (70% men) were included. Their mean age was 42.4 years, with a male-to-female ratio of 2.3:1. Headache (85%) and seizures (65%) were the common presenting symptoms, with a mean admission Glasgow Coma Scale (GCS) score of 13. CVT was the presenting feature in 13 cases (65%), while 7 patients (35%) developed CVT while being treated for COVID-19 infection. Respiratory symptoms were absent in 45% of the patients. The most common imaging finding was infarction (65%), followed by hemorrhage (20%). The superior sagittal sinus (65%) was the most common site of thrombosis. Acute inflammatory markers were raised, including elevated serum D-dimer (87.5%), erythrocyte sedimentation rate (69%), and C-reactive protein (47%) levels. Homocysteine was elevated in half of the tested cases. The mortality rate was 20% (4 patients). A good functional outcome was seen in the surviving patients, with a mean modified Rankin Scale score at discharge of 1.3. Nine patients (45%) had a modified Rankin Scale score of 0-1 at discharge. CONCLUSION: COVID-19-related CVT is more common among males at older ages when compared to previously reported non-COVID-19-related CVT cases. CVT should be suspected in COVID-19 patients presenting with headache or seizures. Mortality is high, but functional neurological outcome is good among survivors.

Acute superior mesenteric vein thrombosis in the setting of cytomegalovirus mononucleosis: a case report and review of the literature.

Cytomegalovirus is a viral genus of the overarching family Herpesviridae, and is of particular importance because of its relevance to human disease. This association is predominantly due to human cytomegalovirus, a well-studied pathogen. In addition to the mononucleosis syndrome that can occur during acute cytomegalovirus viraemia, this virion has been recurrently implicated as a provoking factor for thromboembolic disease in the published scientific literature. As physicians increasingly forgo extensive laboratory investigation in the setting of clinical hypercoagulability, it has also become evident that in some circumstances whether or not a particular investigation alters clinical management is not necessarily the only important question. Viraemia as a provoking factor for thrombosis stands as such an example. The aim of this Grand Round is to further explore the role of cytomegalovirus as it pertains to thromboembolic disease, especially in the present era of viral-associated thromboembolism.

Multiple cardiovascular complications of COVID-19 infection in a young patient: a case report.

COVID-19 infection is responsible for many complications, which can lead to a high risk of mortality in some patients. Among them are cardiovascular complications which are classified as the most severe. We report a case of a young woman, with no relevant pathological history, admitted for COVID-19 infection, complicated by myocarditis with severe ventricular dysfunction, cardiogenic shock and a large thrombosis into the left ventricle (LV) that was responsible for a left lower limb ischemia associated with a deep venous thrombosis of right lower limb.

Deep vein thrombosis and pulmonary embolism among hospitalized coronavirus disease 2019-positive patients predicted for higher mortality and prolonged intensive care unit and hospital stays in a multisite healthcare system.

OBJECTIVE: We assessed the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) in hospitalized patients with coronavirus disease 2019 (COVID-19) compared with that in a matched cohort with similar cardiovascular risk factors and the effects of DVT and PE on the hospital course. METHODS: We performed a retrospective review of prospectively collected data from COVID-19 patients who had been hospitalized from March 11, 2020 to September 4, 2020. The patients were randomly matched in a 1:1 ratio by age, sex, hospital of admission, smoking history, diabetes mellitus, and coronary artery disease with a cohort of patients without COVID-19. The primary end point was the incidence of DVT/PE and the odds of developing DVT/PE using a conditional logistic regression model. The secondary end point was the hospitalization outcomes for COVID-19 patients with and without DVT/PE, including mortality, intensive care unit (ICU) admission, ICU stay, and length of hospitalization (LOH). Multivariable regression analysis was performed to identify the variables associated with mortality, ICU admission, discharge disposition, ICU duration, and LOH. RESULTS: A total of 13,310 patients had tested positive for COVID-19, 915 of whom (6.9%) had been hospitalized across our multisite health care system. The mean age of the hospitalized patients was 60.8 ± 17.0 years, and 396 (43.3%) were women. Of the 915 patients, 82 (9.0%) had had a diagnosis of DVT/PE confirmed by ultrasound examination of the extremities and/or computed tomography angiography of the chest. The odds of presenting with DVT/PE in the setting of COVID-19 infection was greater than that without COVID-19 infection (0.6% [5 of 915] vs 9.0% [82 of 915]; odds ratio [OR], 18; 95% confidence interval [CI], 8.0-51.2; P < .001). The vascular risk factors were not different between the COVID-19 patients with and without DVT/PE. Mortality (P = .02), the need for ICU stay (P < .001), duration of ICU stay (P < .001), and LOH (P < .001) were greater in the DVT/PE cohort than in the cohort without DVT/PE. On multivariable logistic regression analysis, the hemoglobin (OR, 0.71; 95% CI, 0.46-0.95; P = .04) and D-dimer (OR, 1.0; 95% CI, 0.33-1.56; P = .03) levels were associated with higher mortality. Higher activated partial thromboplastin times (OR, 1.1; 95% CI, 1.00-1.12; P = .03) and higher interleukin-6 (IL-6) levels (OR, 1.0; 95% CI, 1.01-1.07; P = .05) were associated with a greater risk of ICU admission. IL-6 (OR, 1.0; 95% CI, 1.00-1.02; P = .05) was associated with a greater risk of rehabilitation placement after discharge. On multivariable gamma regression analysis, hemoglobin (coefficient, -3.0; 95% CI, 0.03-0.08; P = .005) was associated with a prolonged ICU stay, and the activated partial thromboplastin time (coefficient, 2.0; 95% CI, 0.003-0.006; P = .05), international normalized ratio (coefficient, -3.2; 95% CI, 0.06-0.19; P = .002) and IL-6 (coefficient, 2.4; 95% CI, 0.0011-0.0027; P = .02) were associated with a prolonged LOH. CONCLUSIONS: A significantly greater incidence of DVT/PE occurred in hospitalized COVID-19-positive patients compared with a non-COVID-19 cohort matched for cardiovascular risk factors. Patients affected by DVT/PE were more likely to experience greater mortality, to require ICU admission, and experience prolonged ICU stays and LOH compared with COVID-19-positive patients without DVT/PE. Advancements in DVT/PE prevention are needed for patients hospitalized for COVID-19 infection.

Haemostatic and thrombo-embolic complications in pregnant women with COVID-19: a systematic review and critical analysis.

BACKGROUND: As pregnancy is a physiological prothrombotic state, pregnant women may be at increased risk of developing coagulopathic and/or thromboembolic complications associated with COVID-19. METHODS: Two biomedical databases were searched between September 2019 and June 2020 for case reports and series of pregnant women with a diagnosis of COVID-19 based either on a positive swab or high clinical suspicion where no swab had been performed. Additional registry cases known to the authors were included. Steps were taken to minimise duplicate patients. Information on coagulopathy based on abnormal coagulation test results or clinical evidence of disseminated intravascular coagulation (DIC), and on arterial or venous thrombosis, were extracted using a standard form. If available, detailed laboratory results and information on maternal outcomes were analysed. RESULTS: One thousand sixty-three women met the inclusion criteria, of which three (0.28, 95% CI 0.0 to 0.6) had arterial and/or venous thrombosis, seven (0.66, 95% CI 0.17 to 1.1) had DIC, and a further three (0.28, 95% CI 0.0 to 0.6) had coagulopathy without meeting the definition of DIC. Five hundred and thirty-seven women (56%) had been reported as having given birth and 426 (40%) as having an ongoing pregnancy. There were 17 (1.6, 95% CI 0.85 to 2.3) maternal deaths in which DIC was reported as a factor in two. CONCLUSIONS: Our data suggests that coagulopathy and thromboembolism are both increased in pregnancies affected by COVID-19. Detection of the former may be useful in the identification of women at risk of deterioration.

Flegmasia cerúlea dolorosa y gangrena venosa asociada a infección por SARS-CoV-2: reporte de caso y revisión de la literatura / Flegmasia cerúlea dolens and venous gangrena associated with infection by SARS-CoV-2: case report and literature review

La flegmasia cerúlea dolorosa (FCD) y la gangrena venosa son las manifestaciones más graves de la trombosis venosa profunda aguda (TVP). Se presenta el caso de una mujer de 64 años que ingresó en el servicio de emergencias por dolor de la extremidad inferior izquierda y edema localizado en el pie, con diagnóstico de gangrena venosa tras los análisis correspondientes de clínica, laboratorio e imagen. Ante la evolución tórpida se realizaron fasciotomías, con mejoría evidente el cuadro. Al fi liar la causa de este evento, se adjudica a la infección por SARS-CoV-2 como desencadenante de esta gangrena venosa

Cerulean phlegmasy dolens (CDF) and venous gangrene are the most serious manifestations of acute deep vein thrombosis (DVT ). We present the case of a 64-year-old woman who was admitted to the emergency service for pain in the left lower limb and localized edema in the foot with a diagnosis of venous gangrene after the corresponding clinical, laboratory and imaging analysis. Given the torpid evolution, fasciotomies were performed with evident improvement in the picture. When fi ling the cause of this event, it is attributed to the infection by SARS-CoV-2 as the trigger for this venous gangrene

Superficial Cerebral Venous Thrombosis and Intracerebral Hematoma in a 48-Year-Old Man with SARS-CoV-2 Infection: A Case Report.

BACKGROUND Pandemic coronavirus disease 2019 (COVID-19) originated in Wuhan, China, and is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Severe respiratory symptoms are a hallmark of the disease, which may also include complications related to a hypercoagulable state and central nervous system involvement. These complications can occur during either the acute or the recovery phase. The cerebral involvement typically manifests as intracranial hypertension, intracerebral hemorrhage, diffuse encephalopathy, or cerebral venous thrombosis. The hemorrhagic form of cerebral venous thrombosis can be a diagnostic challenge and is treated by anticoagulation therapy, despite the existence of an intracerebral hemorrhage. This report describes a case of superficial cerebral venous thrombosis and intracerebral hematoma in a 48-year-old man weeks after recovering from the acute phase of SARSCoV-2 infection. CASE REPORT A 48-year-old man with a past medical history of SARS-CoV-2 infection confirmed by SARS-CoV-2 reverse-transcription polymerase chain reaction presented with left upper-limb numbness, weakness, and impaired positional sensorium. After initial stabilization, noncontrast computerized tomography and magnetic resonance imaging confirmed an intracerebral hemorrhage with underlying cerebral venous thrombosis. The patient was successfully treated with enoxaparin anticoagulation therapy, and symptoms improved over the following 12 days. CONCLUSIONS Central nervous system venous thrombosis is an atypical presentation of the hypercoagulable state primarily seen in younger patients, and it can occur in a delayed fashion after recovery from mild forms of COVID-19.

Utility of d-dimer for diagnosis of deep vein thrombosis in coronavirus disease-19 infection.

OBJECTIVE: The objective of this study was to investigate the clinical usefulness of d-dimer in excluding a diagnosis of deep vein thrombosis (DVT) in patients with coronavirus disease (COVID-19) infection, potentially limiting the need for venous duplex ultrasound examination. METHODS: We retrospectively reviewed consecutive patients admitted to our institution with confirmed COVID-19 status by polymerase chain reaction between March 1, 2020, and May 13, 2020, and selected those who underwent both d-dimer and venous duplex ultrasound examination. This cohort was divided into two groups, those with and without DVT based on duplex ultrasound examination. These groups were then compared to determine the value of d-dimer in establishing this diagnosis. RESULTS: A total of 1170 patients were admitted with COVID-19, of which 158 were selected for this study. Of the 158, there were 52 patients with DVT and 106 without DVT. There were no differences in sex, age, race, or ethnicity between groups. Diabetes and routine hemodialysis were less commonly seen in the group with DVT. More than 90% of patients in both groups received prophylactic anticoagulation, but the use of low-molecular-weight heparin or subcutaneous heparin prophylaxis was not predictive of DVT. All patients had elevated acute-phase d-dimer levels using conventional criteria, and 154 of the 158 (97.5%) had elevated levels with age-adjusted criteria (mean d-dimer 16,163 ± 5395 ng/mL). Those with DVT had higher acute-phase d-dimer levels than those without DVT (median, 13,602 [interquartile range, 6616-36,543 ng/mL] vs 2880 [interquartile range, 1030-9126 ng/mL], P < .001). An optimal d-dimer cutoff of 6494 ng/mL was determined to differentiate those with and without DVT (sensitivity 80.8%, specificity 68.9%, negative predictive value 88.0%). Wells DVT criteria was not found to be a significant predictor of DVT. Elevated d-dimer as defined by our optimal metric was a statistically significant predictor of DVT in both univariate and multivariable analyses when adjusting for other factors (odds ratio, 6.12; 95% confidence interval, 2.79-13.39; P < .001). CONCLUSIONS: d-dimer levels are uniformly elevated in patients with COVID-19. Although standard predictive criteria failed to predict DVT, our analysis showed a d-dimer of less than 6494 ng/mL may exclude DVT, potentially limiting the need for venous duplex ultrasound examination.

Pulmonary Embolism in Hospitalized Patient with Coronavirus Disease 2019 (COVID-19).

Coronavirus disease 2019 (COVID-19) has been a global pandemic for over a year. Meanwhile, thrombosis occurs in up to one-third of hospitalized patients with the disease, while pulmonary embolism has been reported to be the most dangerous thrombosis which greatly increases mortality in COVID-19.Hospitalized patients with COVID-19 are at high risk of thromboembolic complications such as deep vein thrombosis and pulmonary embolism. The hypercoagulable state caused by COVID-19 leads to activation of coagulation cascade, meanwhile, CT pulmonary angiography is used to diagnose or exclude pulmonary embolism. Furthermore, ground-glass opacities are also evaluated using this modality. Low molecular weight heparin is the anticoagulant of choice due to simplicity in administration and low risk of drug-drug interactions.Pulmonary embolism occurs in COVID-19 patients without DVT. Based on the results, parenteral anticoagulant followed by DOAC is the mainstay of treatment in COVID-19 coagulopathy.

Neurovascular complications that can be seen in COVID-19 patients.

Coronavirus disease 2019 (COVID-19), a clinical manifestation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was declared a global pandemic by the World Health Organization on March 11, 2020. Hypercoagulable state has been described as one of the hallmarks of SARS-CoV-2 infection and has been reported to manifest as pulmonary embolisms, deep vein thrombosis, and arterial thrombosis of the abdominal small vessels. Here we present cases of arterial and venous thrombosis pertaining to the head and neck in COVID-19 patients.