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Background & Aims: The underlying mechanisms and clinical impact of portal microthrombosis in severe COVID-19 are unknown. Intrapulmonary vascular dilation (IPVD)-related hypoxia has been described in severe liver diseases. We hypothesised that portal microthrombosis is associated with IPVD and fatal respiratory failure in COVID-19., Methods: Ninety-three patients who died from COVID-19 were analysed for portal microvascular damage (histology), IPVD (histology and chest-computed tomography, CT), and hypoxemia (arterial blood gas). Seventeen patients who died from COVID-19-unrelated pneumonia served as controls. Vascular lesions and microthrombi were phenotyped for endothelial (vWF) and pericyte (αSMA/PDGFR-β) markers, tissue factor (TF), viral spike protein and nucleoprotein (SP, NP), fibrinogen, and platelets (CD41a). Viral particles in vascular cells were assessed by transmission electron microscopy. Cultured pericytes were infected with SARS-CoV-2 to measure TF expression and tubulisation of human pulmonary microvascular endothelial cells was assessed upon vWF treatment., Results: IPVD was present in 16/66 patients with COVID-19, with available liver and lung histology, and was associated with younger age (62 vs. 78 years-old), longer illness (25 vs. 14 days), worsening hypoxemia (PaO 2 /FiO 2 from 209 to 89), and an increased requirement for ventilatory support (63% vs. 22%) compared to COVID-19/Non-IPVD. IPVD, absent in controls, was confirmed by chest CT. COVID-19/IPVD liver histology showed portal microthrombosis in >82.5% of portal areas, with a thicker wall of αSMA/PDGFR-β + /SP + /NP + pericytes compared with COVID-19/Non-IPVD. Thrombosed portal venules correlated with αSMA + area, whereas infected SP + /NP + pericytes expressed TF. SARS-CoV-2 viral particles were observed in portal pericytes. In vitro SARS-CoV-2 infection of pericytes upregulated TF and induced endothelial cells to overexpress vWF, which expanded human pulmonary microvascular endothelial cell tubules., Conclusions: SARS-CoV-2 infection of liver pericytes elicits a local procoagulant response associated with extensive portal microthrombosis, IPVD and worsening respiratory failure in fatal COVID-19., Impact and Implications: Vascular involvement of the liver represents a serious complication of COVID-19 infection that must be considered in the work-up of patients with long-lasting and progressively worsening respiratory failure, as it may associate with the development of intrapulmonary vascular dilations. This clinical picture is associated with a procoagulant phenotype of portal venule pericytes, which is induced by SARS-CoV-2 infection of pericytes. Both observations provide a model that may apply, at least in part, to other vascular disorders of the liver, featuring obliterative portal venopathy, similarly characterised at the clinical level by development of hypoxemia and at the histological level by phlebosclerosis and reduced calibre of the portal vein branches in the absence of cirrhosis. Moreover, our findings shed light on an overlooked player in the pathophysiology of thrombosis, i.e. pericytes, which may present a novel therapeutic target., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Laure Stiel et al.)

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., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

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.

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., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s). Published by IMR Press.)

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., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

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.

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., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

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.

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., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Little is known about coronavirus disease 2019 (COVID-19)-associated hypercoagulability. We sought to characterize patients with deep venous thrombosis (DVT) identified after admission for COVID-19., Methods: All adult patients admitted to Montefiore Medical Center from March 1, 2020, to April 10, 2020, and undergoing lower extremity venous duplex for DVT evaluation were included. Patients admitted with suspicion of COVID-19 were divided into severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive and SARS-CoV-2 negative groups based on in-hospital test results. Patients without clinical suspicion for COVID-19 were not tested. A retrospective case-control study design was used to identify potential risk factors for DVT in patients with COVID-19. Demographic, radiographic, and laboratory values were abstracted and analyzed., Results: During the study period, 3404 patients with confirmed COVID-19 were admitted to the hospital. Of the 135 SARS-CoV-2 patients who underwent duplex scanning, there were 18 (13.3%) noted to have DVT compared with 72 of the 711 patients (10.1%) who were either SARS-CoV-2 negative or untested. The odds ratio for DVT in COVID-19 was 1.35 (95% confidence interval, 0.78-2.34; P = .289). Baseline characteristics for COVID-19 patients with and without DVT were overall similar. COVID-19 patients with DVT had an elevated median first d-dimer (18.88 μg/mL [interquartile range (IQR), 7.79-20.00] vs 2.55 μg/mL [IQR, 1.45-6.28]; P = .002; reference value, <0.5 μg/mL), average in-hospital d-dimer (median, 11.93 μg/mL [IQR, 8.25-16.97] vs 3.54 μg/mL [IQR, 2.05-8.53]; P < .001) and median fibrinogen level (501.0 [IQR, 440.0-629.0] vs 654.5 [IQR, 535.8-780.0]; P = .002; reference range, 187-502 mg/dL). There was a trend to significance for COVID-19 patients with DVT compared with without DVT in median d-dimer levels at the time of the duplex (13.61 μg/mL [IQR, 4.04-19.97] vs 3.58 μg/mL [IQR, 2.51-9.62]; P = .055) and median ferritin levels (1679.0 ng/mL [IQR, 1168.0-2577.0] vs 1103.0 ng/mL [IQR, 703.5-2076.5]; P = .055; reference range, 25-270 ng/mL). Twelve of the 18 patients with COVID who developed DVT did so despite chemical thromboprophylaxis, and 2 developed DVT despite therapeutic anticoagulation CONCLUSIONS: We found only a modestly increased risk of DVT in patients with COVID-19, likely underestimated owing to limitations in duplex testing early in the epidemic. Elevated d-dimer and a less elevated fibrinogen are associated with DVT in patients with COVID-19 who seem to form thrombus despite conventional chemical thromboprophylaxis. Additionally, an increasing d-dimer over time may be a reflection of the development of DVT in patients with COVID-19., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

We present a previously healthy man in his 30s who presented with typical viral prodrome symptoms and worsening abdominal pain. He was found to have portal vein thrombosis, with extensive hypercoagulability workup performed. It was determined that the aetiology of thrombus was secondary to acute cytomegalovirus infection. The patient was started on anticoagulation therapy, with later clot resolution demonstrated on abdominal Doppler ultrasound and abdominal CT scan. Given the atypical presentation of this common virus, we performed a literature review of cytomegalovirus-associated portal vein thrombosis in healthy individuals; we found that most patients present with non-specific symptoms of fever and abdominal pain in the setting of a viral prodrome. This case and literature review suggest physicians must consider cytomegalovirus-associated portal vein thrombosis as a potential diagnosis when patients present with abdominal pain and viral symptoms. The literature highlights the need for a consensus on anticoagulation and antiviral therapy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is emerging evidence of an increased risk of venous thromboembolism as well as several reports of cerebral venous thrombosis in COVID-19., Case Presentation: A previously healthy man in his fifties was admitted due to sudden confusion and reduced consciousness. One month earlier the patient had symptoms with headache, fever, dry cough, vomiting and diarrhoea and reduced sense of taste and smell. He was diagnosed with COVID-19 and the symptoms were mainly resolved within three weeks. On admission the patient was disorientated with aphasia. Brain imaging revealed a haemorrhagic infarction in the left temporal lobe due to thrombosis of the left transverse sinus and low-molecular weight heparin was instituted. On follow-up four months later, there was clinical improvement with only slight problems with short term memory and concentration., Interpretation: This case illustrates the risk of serious neurological complications due to cerebral venous thrombosis in COVID-19.

There is growing evidence that coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state. To date, all patients reported with venous thromboembolic disease and COVID-19 have shown evidence of viral pneumonia. Here, we report the case of a 31-year-old patient with unexplained extensive DVT and bilateral pulmonary embolism in the absence of COVID-19 pneumonia, leading to the diagnosis of otherwise asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the context of the COVID-19 pandemic, given the high rates of otherwise asymptomatic patients, testing for SARS-CoV-2 should be performed in all patients with unexplained VTE occurring in COVID-19-endemic areas, even in the absence of other disease manifestations suggestive of SARS-CoV-2 infection., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors declare that they have no conflict of interest.

Background: Abnormal coagulation parameters have been reported in COVID-19-infected patients. Although the underlying mechanism of COVID-19 coagulopathy remains unknown, it has been suggested to be a form of disseminated intravascular coagulation (DIC)., Objectives: The aim of our study was to analyze the coagulation parameters of patients with COVID-19, determine whether coagulation factors consumption occurs and identify potential prognostic biomarkers of the disease., Patients/methods: Blood samples from hospitalized patients with COVID-19 pneumonia were collected. We performed basic coagulation tests and quantification of coagulation factors and physiological inhibitor proteins. Laboratory data were compared with clinical data and outcomes., Results: The study involved 206 patients (63.6% male). D-dimer was particularly elevated (median 450 ng/mL; IQR 222.5-957.3). Free protein S levels were below the normal range (median 56.6%; IQR: 43.6-68.9), and factor VIII showed an increasing trend (median 173.4%; IQR: 144.1-214.9). However, all coagulation factors were within normal limits. We found no correlation between abnormal coagulation parameters and thrombosis, except for higher D-dimer (HR 1.99; 95% CI 1.3-3.1; P = .002)., Conclusions: COVID-19 is associated with coagulopathy that correlates with poor prognosis. However, we did not demonstrate a consumption of coagulation factors, as seen in DIC., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: COVID-19 pneumonia exhibits several extra-pulmonary complications., Case Presentation: A 23-year old, asthmatic male with coronavirus pneumonia developed with generalized, acute abdominal pain. Further evaluations revealed a mild ascites and portal vein thrombosis although the patient received proper anticoagulation therapy. Routine lab data regarding the secondary causes of portal vein thrombosis were normal., Conclusion: We speculated that the underlying cause of portal vein thrombosis in our case was coronaviruses. Therefore, clinicians should always consider thrombosis and other hypercoagulable diseases in patients with COVID-19.

Background: Coronavirus disease 2019 (COVID-19) can result in profound changes in blood coagulation. The aim of the study was to determine the incidence and predictors of venous thromboembolic events (VTE) among patients with COVID-19 requiring hospital admission. Subjects and Methods . We performed a retrospective study at the Lausanne University Hospital with patients admitted because of COVID-19 from February 28 to April 30, 2020., Results: Among 443 patients with COVID-19, VTE was diagnosed in 41 patients (9.3%; 27 pulmonary embolisms, 12 deep vein thrombosis, one pulmonary embolism and deep vein thrombosis, one portal vein thrombosis). VTE was diagnosed already upon admission in 14 (34.1%) patients and 27 (65.9%) during hospital stay (18 in ICU and nine in wards outside the ICU). Multivariate analysis revealed D-dimer value > 3,120 ng/ml ( P < 0.001; OR 15.8, 95% CI 4.7-52.9) and duration of 8 days or more from COVID-19 symptoms onset to presentation ( P 0.020; OR 4.8, 95% CI 1.3-18.3) to be independently associated with VTE upon admission. D-dimer value ≥ 3,000 ng/l combined with a Wells score for PE ≥ 2 was highly specific (sensitivity 57.1%, specificity 91.6%) in detecting VTE upon admission. Development of VTE during hospitalization was independently associated with D-dimer value > 5,611 ng/ml ( P < 0.001; OR 6.3, 95% CI 2.4-16.2) and mechanical ventilation ( P < 0.001; OR 5.9, 95% CI 2.3-15.1)., Conclusions: VTE seems to be a common COVID-19 complication upon admission and during hospitalization, especially in ICU. The combination of Wells ≥ 2 score and D - dimer ≥ 3,000 ng/l is a good predictor of VTE at admission., Competing Interests: All authors state that they have no conflict of interest to report., (Copyright © 2020 Eleftheria Kampouri et al.)

Purpose: The aim of this study was to evaluate the applicability of bedside ultrasonography for the diagnosis of deep venous thrombosis (DVT) in patients infected with corona virus disease 2019 (COVID-19) with and without treatment with low molecular weight heparin (LMWH)., Methods: We retrospectively analyzed the records of deceased and surviving patients in whom ultrasonography detected or not a DVT, and in whom LMWH was or not prescribed., Results: The incidence of DVT is higher in the deceased (33/35) than in the surviving (22/46) patients. LMWH was administered in a larger proportion of surviving (18/22) than of deceased (18/33) patients. D-dimer concentrations decreased in patients who received LMWH in both groups., Conclusions: There was a high incidence of DVT in patients who succumbed to COVID-19. Bedside ultrasonography can detect the presence of DVT as early as possible and help assessing the risk of venous thromboembolism, allowing early and reasonable use of LMWH., (© 2020 Wiley Periodicals LLC.)

Background: Venous thromboembolism (VTE) is increasingly reported in seriously ill patients with COVID-19 infection. Incidence of VTE has been reported before and results varied widely in study cohorts., Area of Uncertainty: Incidence of major VTE (segmental pulmonary embolism and above and proximal deep vein thrombosis) which is a contributor to mortality and morbidity is not known. Also, data is unclear on the optimal anticoagulation regimen to prevent VTE., Data Sources: Multiple databases including PubMed were searched until May 12, 2020, to include studies reporting VTE in hospitalized COVID-19 adult patients. MOOSE guidelines were followed in selection, and 11 studies were included. We conducted a systematic review and meta-analysis to quantitatively assess the VTE burden in hospitalized COVID-19 patients and potential benefits of therapeutic dosing of anticoagulation compared with prophylaxis dosing for VTE prevention., Therapeutic Advances: Many societies and experts recommend routine prophylactic anticoagulation with heparin for VTE prevention in hospitalized COVID-19 patients. In this meta-analysis, the pooled rate of major VTE was 12.5% in hospitalized patients and 17.2% in intensive care unit patients. When therapeutic anticoagulation dosing was compared with prophylactic anticoagulation, the pooled odds ratio of VTE was 0.33 (95% confidence interval 0.14-0.75; P = 0.008, I = 0%) suggesting statistical significance with therapeutic dosing of anticoagulation for primary prevention of VTE in all hospitalized patients. However, this should be interpreted with caution as the bleeding events and safety profile could not be ascertained because of lack of adequate information. We recommend applying this finding to hospitalized COVID 19 patients only after carefully weighing individual bleeding risks and benefits., Conclusion: Major VTE events, especially pulmonary embolism, seem to be high in COVID-19 patients admitted to the intensive care unit. Therapeutic anticoagulation dosing seems to significantly benefit the odds of preventing any VTE when compared with prophylactic dosing in all hospitalized patients.

Patients with coronavirus disease 2019 (COVID-19) frequently experience a coagulopathy associated with a high incidence of thrombotic events leading to poor outcomes. Here, biomarkers of coagulation (such as D-dimer, fibrinogen, platelet count), inflammation (such as interleukin-6), and immunity (such as lymphocyte count) as well as clinical scoring systems (such as sequential organ failure assessment [SOFA], International Society on Thrombosis and Hemostasis disseminated intravascular coagulation [ISTH DIC], and sepsis-induced coagulopathy [SIC] score) can be helpful in predicting clinical course, need for hospital resources (such as intensive care unit [ICU] beds, intubation and ventilator therapy, and extracorporeal membrane oxygenation [ECMO]) and patient's outcome in patients with COVID-19. However, therapeutic options are actually limited to unspecific supportive therapy. Whether viscoelastic testing can provide additional value in predicting clinical course, need for hospital resources and patient's outcome or in guiding anticoagulation in COVID-19-associated coagulopathy is still incompletely understood and currently under investigation (eg, in the rotational thromboelastometry analysis and standard coagulation tests in hospitalized patients with COVID-19 [ROHOCO] study). This article summarizes what we know already about COVID-19-associated coagulopathy and-perhaps even more importantly-characterizes important knowledge gaps.

COVID-19 is associated with a variety of clinical complications including coagulopathy, which frequently results in venous thromboembolism (VTE). Retrospective analyses reported a markedly increased rate of VTEs in COVID-19. However, most recent studies on coagulopathy in COVID-19 were only focused on critically ill patients, and without suitable control groups. We aimed to evaluate the rate of VTEs in an all-comers cohort with suspected COVID-19 during a 30-days follow-up period. We also studied the level of D-dimers and their association with the course of disease. In our prospective single-center study (DRKS00021206, 03/30/2020), we analyzed 190 patients with suspected COVID-19 admitted to the emergency department between March and April 2020. Forty-nine patients were SARS-CoV-2 positive (25.8%). The 141 SARS-CoV-2-negative patients served as control group. After completion of a 30-days follow-up, VTE was diagnosed in 3 patients of the SARS-CoV-2-positive group (6.1%, amongst these 2 ICU cases) versus 5 patients in the SARS-CoV-2-negative group (3.5%), however the difference was not statistically significant (p = 0.427). 30-days mortality was similar in both groups (6.1% vs. 5%, p = 0.720). Disease severity correlated with the maximum level of D-dimers during follow-up in COVID-19. The rate of VTE was numerically higher in SARS-CoV-2 positive all-comers presenting with suspected COVID-19 as compared to well-matched controls suffering from similar symptoms. VTEs in the COVID-19 group predominantly occurred in ICU courses. The maximum level of D-dimers during follow-up was associated with disease severity in COVID-19, whereas the level of D-dimers at admission was not.

COVID-19 disease is a viral illness that predominantly causes pneumonia and severe acute respiratory distress syndrome. The endothelial injury and hypercoagulability secondary to the inflammatory response predisposes severely ill patients to venous thromboembolism. The exact mechanism of hypercoagulability is still under investigation, but it is known to be associated with poor prognosis. The most common thrombotic complication reported among these patients is pulmonary embolism. To our knowledge, gonadal vein thrombosis is an uncommon phenomenon that has not been reported in the setting of COVID-19-associated coagulopathy. We report an unusual case of ovarian vein thrombosis and pulmonary embolism associated with COVID-19 presenting with abdominal pain. To our knowledge, this is the first reported case of COVID-19 with absent respiratory symptoms and presentation with venous thrombosis in an unusual location., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: None.

Aim: An increased risk of venous thromboembolism (VTE) in patients with COVID-19 pneumonia admitted to intensive care unit (ICU) has been reported. Whether COVID-19 increases the risk of VTE in non-ICU wards remains unknown. We aimed to evaluate the burden of asymptomatic deep vein thrombosis (DVT) in COVID-19 patients with elevated D-dimer levels., Method: In this prospective study consecutive patients hospitalized in non-intensive care units with diagnosis of COVID-19 pneumonia and D-dimer > 1000 ng/ml were screened for asymptomatic DVT with complete compression doppler ultrasound (CCUS). The study was approved by the Institutional Ethics Committee., Results: The study comprised 156 patients (65.4% male). All but three patients received standard doses of thromboprophylaxis. Median days of hospitalization until CCUS was 9 (IQR 5-17). CCUS was positive for DVT in 23 patients (14.7%), of whom only one was proximal DVT. Seven patients (4.5%) had bilateral distal DVT. Patients with DVT had higher median D-dimer levels: 4527 (IQR 1925-9144) ng/ml vs 2050 (IQR 1428-3235) ng/ml; p < 0.001. D-dimer levels > 1570 ng/ml were associated with asymptomatic DVT (OR 9.1; CI 95% 1.1-70.1). D-dimer showed an acceptable discriminative capacity (area under the ROC curve 0.72, 95% CI 0.61-0.84)., Conclusion: In patients admitted with COVID-19 pneumonia and elevated D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series. Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The aim of this study was to evaluate the occurrence of pulmonary embolism in returning travelers with hypoxemic pneumonia due to COVID-19. All returning travelers to Reunion Island with hypoxemic pneumonia due to COVID-19 underwent computed tomography pulmonary angiography (CTPA) and were included in the cohort. Thirty-five patients were returning travelers with hypoxemic pneumonia due to COVID-19 and had recently returned from one of the countries most affected by the COVID-19 outbreak (mainly from France and Comoros archipelago). Five patients (14.3%) were found to have pulmonary embolism and two (5.9%) were incidentally found to have deep vein thrombosis on CTPA. Patients with pulmonary embolism or deep vein thrombosis had higher D-dimer levels than those without pulmonary embolism or deep vein thrombosis ( P = 0.04). Returning travelers with hypoxemic pneumonia due to COVID-19 should be systematically screened for pulmonary embolism.

Background: Infection by the 2019 novel coronavirus (COVID-19) has been reportedly associated with a high risk of thrombotic complications. So far information is scarce and rapidly emerging., Methods: We conducted a scoping review using a single engine search for studies assessing thrombosis and coagulopathy in COVID-19 patients. Additional studies were identified by secondary review and alert services., Results: Studies reported the occurrence of venous thromboembolism and stroke in approximately 20% and 3% of patients, respectively. A higher frequency seems to be present in severely ill patients, in particular those admitted to intensive care units. The thrombotic risk is elevated despite the use of anticoagulant prophylaxis but optimal doses of anticoagulation are not yet defined. Although an increase of biomarkers such as D-dimer has been consistently reported in severely ill COVID-19, the optimal cut-off level and prognostic value are not known., Discussion: A number of pressing issues were identified by this review, including defining the true incidence of VTE in COVID patients, developing algorithms to identify those susceptible to develop thrombotic complications and severe disease, determining the role of biomarkers and/or scoring systems to stratify patients' risk, designing adequate and feasible diagnostic protocols for PE, establishing the optimal thromboprophylaxis strategy, and developing uniform diagnostic and reporting criteria., Competing Interests: Declaration of competing interest Authors declare no conflicts., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The outbreak of 2019 novel coronavirus disease (COVID-19) began since early December 2019, and has been declared as a public health emergency by the World Health Organization. Due to the hypercoagulable state, blood stasis and endothelial injury, severe patients with COVID-19 are at high risk for thrombosis. We report a case of very severe COVID-19 complicated with venous thrombosis and arteriosclerosis obliterans of lower extremities. Risk stratification for deep vein thrombosis and peripheral arterial disease are of vital importance for the prognosis of COVID-19.

Background: Coagulopathy is a common abnormality in patients with COVID-19. However, the exact incidence of venous thromboembolic event is unknown in anticoagulated, severe COVID-19 patients., Objectives: Systematic assessment of venous thromboembolism (VTE) using complete duplex ultrasound (CDU) in anticoagulated COVID-19 patients., Patients and Methods: We performed a retrospective study in 2 French intensive care units (ICU) where CDU is performed as a standard of care. A CDU from thigh to ankle at selected sites with Doppler waveforms and images was performed early during ICU stay in patients admitted with COVID-19. Anticoagulation dose was left to the discretion of the treating physician based on the individual risk of thrombosis. Patients were classified as treated with prophylactic anticoagulation or therapeutic anticoagulation. Pulmonary embolism was systematically searched in patients with persistent hypoxemia or secondary deterioration., Results: From March 19 to April 11, 2020, 26 consecutive patients with severe COVID-19 were screened for VTE. Eight patients (31%) were treated with prophylactic anticoagulation, whereas 18 patients (69%) were treated with therapeutic anticoagulation. The overall rate of VTE in patients was 69%. The proportion of VTE was significantly higher in patients treated with prophylactic anticoagulation when compared with the other group (100% vs 56%, respectively, P = .03). Surprisingly, we found a high rate of thromboembolic events in COVID-19 patients treated with therapeutic anticoagulation, with 56% of VTE and 6 pulmonary embolisms., Conclusion: Our results suggest considering both systematic screening of VTE and early therapeutic anticoagulation in severe ICU COVID-19 patients., (© 2020 International Society on Thrombosis and Haemostasis.)