Cavernous sinus thrombosis linked to COVID-19 infection: a case report. (preprint)

Introduction: The severity of SARS-CoV-2 virus infection is mainly related to its respiratory complications. However, it can also lead to numerous and varied thromboembolic events. Symptoms may include headache, fever, and neurological disorders. Since 2020, the clinical presentation of COVID-19 infection have become increasingly varied, leading in some cases to complex symptom associations, including numerous neurological symptoms. SARS-CoV-2 may lead to neurotropism which could reach the central nervous system and all cranial nerves. Cavernous sinus thrombosis is a rare condition, occurring as a complication of an ear, nose, and throat (ENT) or facial infection.Case presentation: A 73-year-old man without personal or family history of thrombosis, was referred to the emergency room for a sudden appearance of diplopia and ptosis, 3 days after testing positive for COVID-19 infection. An initial head CT-scan found no signs of stroke. He underwent a cerebral MRI 7 days later, which revealed a thrombosis of his right cavernous sinus. A brain CT scan follow-up 7 days later showed regression of the thrombosis with complete recanalization of the cavernous sinus. This was accompanied by a complete regression of diplopia and fever. He was discharged from the hospital 10 days after hospital admission.Conclusions In this case report, we describe a rare event of cavernous thrombophlebitis following a COVID-19 infection.

Lemierre's syndrome: case report of "the forgotten disease" in current COVID-19 pandemic.

Lemierre's syndrome refers to infectious thrombophlebitis of the internal jugular vein developed as complication of an oropharyngeal infection. It is a rare syndrome, affecting otherwise healthy young adults, which may lead to sepsis complicated by septic embolization. Although there is a characteristic clinical picture, many modern physicians are unaware of this syndrome, leading it to be termed 'the forgotten disease'. The authors report a case of late diagnosis due to initial suspicion of COVID-19 and highlight the pitfalls on its diagnosis.

Mechanical thrombectomy of COVID-19 DVT with congenital heart disease leading to phlegmasia cerulea dolens: a case report.

BACKGROUND: COVID-19 and Fontan physiology have each been associated with an elevated risk of venous thromboembolism (VTE), however little is known about the risks and potential consequences of having both. CASE PRESENTATION: A 51 year old male with tricuspid atresia status post Fontan and extracardiac Glenn shunt, atrial flutter, and sinus sick syndrome presented with phlegmasia cerulea dolens (PCD) of the left lower extremity in spite of supratherapeutic INR in the context of symptomatic COVID-10 pneumonia. He was treated with single session, catheter directed mechanical thrombectomy that was well-tolerated. CONCLUSIONS: This report of acute PCD despite therapeutic anticoagulation with a Vitamin K antagonist, managed with emergent mechanical thrombectomy, calls to attention the importance of altered flow dynamics in COVID positive patients with Fontan circulation that may compound these independent risk factors for developing deep venous thrombosis with the potential for even higher morbidity.

A Case of Phlegmasia Cerulea Dolens in a Patient With COVID-19, Effectively Ttreated With Fasciotomy and Mechanical Thrombectomy.

Coronavirus disease 2019 (COVID-19) has been widely reported to be associated with increased risk of Venous Thromboembolism, both deep vein thrombosis (DVT) and pulmonary embolism. A rare and extreme manifestation of DVT is Phlegmasia cerulea dolens, characterized by poor tissue perfusion due to marked limb swelling which can progress to limb and life-threatening venous gangrene. We report the case of a 53-year-old man with severe SARS-CoV2 pneumonia who developed acute iliofemoral DVT leading to acute limb ischemia due to Phlegmasia cerulea dolens. The patient underwent successful emergent fasciotomy and mechanical thrombectomy with removal of extensive thrombus burden and restoration of normal venous circulation. Our case highlights the importance of clinical vigilance and early implementation of therapeutic interventions to avoid adverse outcomes in patients who develop SARS-CoV2 induced Venous Thromboembolism complications.

Phlegmasia cerulea dolens superimposed on disseminated intravascular coagulation in COVID-19.

COVID-19 infection has several cardiovascular implications, and coagulopathy is a common abnormality in these patients, often coupled with elevated plasma fibrinogen and D-dimer levels, contributing to adverse outcomes. Phlegmasia cerulea dolens (PCD) is a rare manifestation of deep vein thrombosis. It is life-threatening and can rapidly lead to venous gangrene of the extremity. Only a few cases of COVID-19 associated with PCD are reported in the literature, despite thromboembolism being the common paradigm between the two diseases. We present the case of a 64-year-old adult with acute severe COVID-19 pneumonia who developed PCD despite constantly elevated activated partial thromboplastin time and international normalized ratio.

COVID-19 susceptibility variants associate with blood clots, thrombophlebitis and circulatory diseases.

Epidemiological studies suggest that individuals with comorbid conditions including diabetes, chronic lung, inflammatory and vascular disease, are at higher risk of adverse COVID-19 outcomes. Genome-wide association studies have identified several loci associated with increased susceptibility and severity for COVID-19. However, it is not clear whether these associations are genetically determined or not. We used a Phenome-Wide Association (PheWAS) approach to investigate the role of genetically determined COVID-19 susceptibility on disease related outcomes. PheWAS analyses were performed in order to identify traits and diseases related to COVID-19 susceptibility and severity, evaluated through a predictive COVID-19 risk score. We utilised phenotypic data in up to 400,000 individuals from the UK Biobank, including Hospital Episode Statistics and General Practice data. We identified a spectrum of associations between both genetically determined COVID-19 susceptibility and severity with a number of traits. COVID-19 risk was associated with increased risk for phlebitis and thrombophlebitis (OR = 1.11, p = 5.36e-08). We also identified significant signals between COVID-19 susceptibility with blood clots in the leg (OR = 1.1, p = 1.66e-16) and with increased risk for blood clots in the lung (OR = 1.12, p = 1.45 e-10). Our study identifies significant association of genetically determined COVID-19 with increased blood clot events in leg and lungs. The reported associations between both COVID-19 susceptibility and severity and other diseases adds to the identification and stratification of individuals at increased risk, adverse outcomes and long-term effects.

A case of COVID-19 with superficial thrombophlebitis caused by an indwelling peripheral venous catheter (preprint)

Background: COVID-19 is caused by SARS-CoV-2 infection, and cytokine storm and microthrombus formation affect the severity of the disease, which is often complicated by venous thrombosis due to a systemic hypercoagulable state. On the other hand, indwelling peripheral venous catheters can cause catheter-related bloodstream infections and venous thrombus formation, albeit less frequently. Case presentation: A 53-year-old man was admitted to the hospital with severe COVID-19. He had bilateral pneumonia and required ventilator management but recovered after steroid and anticoagulation. On the 26th day after onset, redness, swelling, and pain developed around the insertion site of the catheter placed in the cephalic vein of the left forearm. Vascular ultrasonography revealed a thrombus in this vein accompanied by inflammation in the surrounding tissues. Catheter-related bloodstream infection was suspected and vancomycin was administered; however, blood cultures were negative, leading to the diagnosis of non-infectious superficial thrombophlebitis. The skin findings improved after removal of the peripheral venous catheter. Conclusions: This case suggested that catheter placement in peripheral veins during COVID-19 treatment increases the risk of thrombus formation. Although anticoagulant therapy is able to control the systemic hypercoagulable state caused by COVID-19, indwelling catheters can induce a local hypercoagulable state, leading to superficial thrombophlebitis.

Upper-Extremity Phlegmasia Cerulea Dolens With Compartment Syndrome in Coronavirus Disease 2019 Sepsis.

A 54-year-old woman with leukemia presented with coronavirus disease 2019 and a right upper-extremity indwelling peripherally inserted central catheter line for chemotherapy administration. On hospital admission day 9, she developed acute right upper-extremity edema and pain. Ultrasound demonstrated complete superficial and deep venous thrombosis up to the proximal subclavian vein. Her examination result was consistent with acute phlegmasia cerulea dolens and compartment syndrome, but respiratory instability prevented transfer and vascular surgery intervention. Instead, we performed bedside fasciotomies and administered therapeutic heparin, and the limb was salvaged. This case underscores the potential for successful limb salvage in patients with phlegmasia in the setting of coronavirus disease 2019 via compartment release and therapeutic anticoagulation.

COVID-19 susceptibility variants associate with blood clots, thrombophlebitis and circulatory diseases (preprint)

Objective Epidemiological studies suggest that individuals with comorbid conditions including diabetes, chronic lung diseases and others, are at higher risk of adverse COVID-19 outcomes. Genome-wide association studies have identified several loci associated with increased susceptibility and severity for COVID-19. However, it is not clear whether these associations are genetically determined or not. We used a Phenome-Wide Association (PheWAS) approach to investigate the role of genetically determined COVID-19 susceptibility on disease related outcomes. Approach and Results PheWAS analyses were performed in order to identify traits and diseases related to COVID-19 susceptibility and severity, evaluated through a predictive COVID-19 risk score. We utilised phenotypic data in up to 400,000 individuals from the UK Biobank, including Hospital Episode Statistics and General Practice data. We identified a spectrum of associations between both genetically determined COVID-19 susceptibility and severity with a number of traits. COVID-19 risk was associated with increased risk for phlebitis and thrombophlebitis (OR = 1.11, p = 5.36e-08). We also identified significant signals between COVID-19 susceptibility with blood clots in the leg (OR= 1.1, p = 1.66e-16) and with increased risk for blood clots in the lung (OR = 1.12, p = 1.45 e-10). Conclusions Our study identifies significant association of genetically determined COVID-19 with increased blood clot events in leg and lungs. The reported associations between both COVID-19 susceptibility and severity and other diseases adds to the identification and stratification of individuals at increased risk, adverse outcomes and long-term effects.

The Anticoagulant Therapy for Otogenic Sigmoid Sinus Thrombophlebitis: A Case Report and Literature Review.

Sigmoid sinus thrombophlebitis is a severe and potentially fatal intracranial complication of acute otitis media and middle ear cholesteatoma. Early administration of broad-spectrum antibiotics and immediate radical mastoidectomy are the recommended standard treatments; however anticoagulant therapy is always an option worthy of clinical consideration. Here, we report a case of middle ear cholesteatoma complicated with sigmoid sinus thrombophlebitis in a patient who received anticoagulant therapy for 1 year before the operation because of the coronavirus disease 2019 pandemic.

Lower limb deep vein thrombosis in COVID-19 patients admitted to intermediate care respiratory units.

COVID-19 has been associated with an increased risk of thrombotic events; however, the reported incidence of deep vein thrombosis varies depending, at least in part, on the severity of the disease. Aim of this prospective, multicenter, observational study was to investigate the incidence of lower limb deep vein thrombosis as assessed by compression ultrasound in consecutive patients admitted to three pulmonary medicine wards designated to care for patients with COVID-19 related pneumonia, with or without respiratory failure but not requiring admission to an intensive care unit. Consecutive patients admitted between March 27 and May 6, 2020 were enrolled. Patients were excluded if they were less than 18-year-old or if compression ultrasound could not be performed for any reason. Patients were assessed at admission (t0) and after 7 days (t1). Major and non-major clinically relevant bleedings were recorded. Sixty-eight patients were enrolled. Two were excluded due to anatomical abnormalities that prevented compression ultrasound; sixty patients were retested at (t1). All patients were started on antithrombotic prophylaxis, unless therapeutic anticoagulation was required. Deep vein thrombosis as assessed by compression ultrasound was observed in 2 patients (3%); one of them was later deemed to represent a previous episode. No new episodes were detected at t1. One major and 2 non-major clinically relevant bleedings were observed. In the setting of patients with COVID-related pneumonia not requiring admission to an intensive care unit, the incidence of deep vein thrombosis is low and our data support not screening asymptomatic patients.

Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Thrombosis: Phlegmasia Cerulea Dolens Presenting with Venous Gangrene in a Child.

A 12-year-old girl with severe acute respiratory syndrome coronavirus 2 infection presented as phlegmasia cerulea dolens with venous gangrene. Emergent mechanical thrombectomy was complicated by a massive pulmonary embolism and cardiac arrest, for which extracorporeal cardiopulmonary resuscitation and therapeutic hypothermia were used. Staged ultrasound-assisted catheter-directed thrombolysis was used for treatment of bilateral pulmonary emboli and the extensive lower extremity deep vein thrombosis while the patient received extracorporeal membrane oxygenation support. We highlight the need for heightened suspicion for occult severe acute respiratory syndrome coronavirus 2 infection among children presenting with unusual thrombotic complications.

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

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