Immunohistologic Features of Cerebral Venous Thrombosis Due to Vaccine-Induced Immune Thrombotic Thrombocytopenia.

OBJECTIVES: Vaccine-induced immune thrombotic thrombocytopenia (VITT), a recently described entity characterized by thrombosis at unusual locations such as cerebral venous sinus and splanchnic vein, has been rarely described after adenoviral-encoded COVID-19 vaccines. In this study, we report the immunohistological correlates in 3 fatal cases of cerebral venous thrombosis related to VITT analyzed at an academic medical center. METHODS: Detailed neuropathologic studies were performed in 3 cases of cerebral venous thrombosis related to VITT after adenoviral COVID-19 vaccination. RESULTS: Autopsy revealed extensive cerebral vein thrombosis in all 3 cases. Polarized thrombi were observed with a high density of neutrophils in the core and a low density in the tail. Endothelial cells adjacent to the thrombus were largely destroyed. Markers of neutrophil extracellular trap and complement activation were present at the border and within the cerebral vein thrombi. SARS-CoV-2 spike protein was detected within the thrombus and in the adjacent vessel wall. DISCUSSION: Data indicate that neutrophils and complement activation associated with antispike immunity triggered by the vaccine is probably involved in the disease process.

Superior ophthalmic vein and cavernous sinus thrombosis associated with COVID-19: a case report / Trombose de veia oftálmica superior e seio cavernoso associada à COVID-19: relato de caso

ABSTRACT Cavernous sinus and superior ophthalmic vein thrombosis is a rare clinical condition, and little described in the literature. The clinical presentation is nonspecific and highly variable, and symptoms may include red eye, ophthalmoplegia, coma, and death. The main etiology results from infection of the paranasal sinuses. The final diagnosis must be made through imaging tests such as magnetic resonance imaging. We describe a case of cavernous sinus and superior ophthalmic vein thrombosis after COVID-19 infection in a 64-year-old patient with persistent ocular hyperemia and pain on eye movement. Ophthalmological examination showed preserved visual acuity, conjunctival hyperemia, dilation of episcleral vessels and retinal vascular tortuosity in the right eye. Magnetic resonance imaging confirmed the diagnosis. The association with the COVID-19 was raised, excluding other infectious causes. Enoxaparin and Warfarin were started with significant improvement in the ocular clinical presentation and maintenance of initial visual acuity after 12 months of follow-up.

RESUMO A trombose de seio cavernoso e veia oftálmica superior é uma condição clínica rara e pouco descrita na literatura. A apresentação clínica é inespecífica e altamente variável. Os sintomas podem incluir olho vermelho, oftalmoplegia, coma e morte. A etiologia principal resulta da infecção dos seios paranasais. O diagnóstico final deve ser efetuado por meio de exames de imagem, como ressonância magnética. Descrevemos um caso de trombose de seio cavernoso e veia oftálmica superior após COVID-19 em paciente de 64 anos e com quadro de hiperemia ocular persistente e dor à movimentação ocular. Ao exame oftalmológico, observou-se acuidade visual preservada, hiperemia conjuntival, dilatação de vasos episclerais e tortuosidade vascular retiniana em olho direito. A ressonância confirmou o diagnóstico. A associação com a COVID-19 foi levantada, excluindo-se demais causas infecciosas. Prescrevemos enoxaparina e varfarina, com melhora do quadro clínico ocular e manutenção da acuidade visual inicial após 12 meses de acompanhamento.

Plantar Vein Thrombosis in a Patient with COVID-19: Case Report.

Plantar thrombophlebitis is a rare abnormality with few cases reported in the literature. Coexistence with severe acute respiratory syndrome coronavirus 2 infection increases its relevance. The disease is generally classified as idiopathic, and it is suggested that it is attributed to conditions that lead to hypercoagulability. We present the case of a 68-year-old female patient with thrombosis of the lateral plantar veins and a diagnosis of coronavirus disease of 2019. The plantar vein thrombosis diagnosis was made by means of Doppler ultrasonography and magnetic resonance imaging. Severe acute respiratory syndrome coronavirus 2 infection was suspected per clinical information and confirmed with reverse-transcriptase polymerase chain reaction technique. Treatment was successful using rivaroxaban and nonsteroidal antiinflammatory drugs.

Prophylactic Inferior Vena Cava Filters for Venous Thromboembolism in Adults With Trauma: An Updated Systematic Review and Meta-Analysis.

Background: Trauma is an independent risk factor for venous thromboembolism (VTE). Due to contraindications or delay in starting pharmacological prophylaxis among trauma patients with a high risk of bleeding, the inferior vena cava (IVC) filter has been utilized as alternative prevention for pulmonary embolism (PE). Albeit, its clinical efficacy has remained uncertain. Therefore, we performed an updated systematic review and meta-analysis on the effectiveness and safety of prophylactic IVC filters in severely injured patients. Methods: Three databases (MEDLINE, EMBASE, and Cochrane) were searched from August 1, 2012, to October 27, 2021. Independent reviewers performed data extraction and quality assessment. Relative risk (RR) at 95% confidence interval (CI) pooled in a randomized meta-analysis. A parallel clinical practice guideline committee assessed the certainty of evidence using the GRADE approach. The outcomes of interest included VTE, PE, deep venous thrombosis, mortality, and IVC filter complications. Results: We included 10 controlled studies (47 140 patients), of which 3 studies (310 patients) were randomized controlled trials (RCTs) and 7 were observational studies (46 830 patients). IVC filters demonstrated no significant reduction in PE and fatal PE (RR, 0.27; 95% CI, 0.06-1.28 and RR, 0.32; 95% CI, 0.01-7.84, respectively) by pooling RCTs with low certainty. However, it demonstrated a significant reduction in the risk of PE and fatal PE (RR, 0.25; 95% CI, 0.12-0.55 and RR, 0.09; 95% CI, 0.011-0.81, respectively) by pooling observational studies with very low certainty. IVC filter did not improve mortality in both RCTs and observational studies (RR, 1.44; 95% CI, 0.86-2.43 and RR, 0.63; 95% CI, 0.3-1.31, respectively). Conclusion: In trauma patients, moderate risk reduction of PE and fatal PE was demonstrated among observational data but not RCTs. The desirable effect is not robust to outweigh the undesirable effects associated with IVC filter complications. Current evidence suggests against routinely using prophylactic IVC filters.

Prenatal and Neonatal Pulmonary Thrombosis as a Potential Complication of SARS-CoV-2 Infection in Late Pregnancy.

Neonatal venous thrombosis is a rare condition that can be iatrogenic or occur due to viral infections or genetic mutations. Thromboembolic complications are also commonly observed as a result of SARS-CoV-2 infections. They can affect pediatric patients, especially the ones suffering from multisystem inflammatory syndrome in children (MIS-C) or multisystem inflammatory syndrome in neonates (MIS-N). The question remains whether the maternal SARS-CoV-2 infection during pregnancy can lead to thromboembolic complications in fetuses and neonates. We report on a patient born with an embolism in the arterial duct, left pulmonary artery, and pulmonary trunk, who presented several characteristic features of MIS-N, suspecting that the cause might have been the maternal SARS-CoV2 infection in late pregnancy. Multiple genetic and laboratory tests were performed. The neonate presented only with a positive result of IgG antibodies against SARS-CoV-2. He was treated with low molecular weight heparin. Subsequent echocardiographic tests showed that the embolism dissolved. More research is necessary to evaluate the possible neonatal complications of maternal SARS-CoV-2 infection.

Acute Myocardial Infarction, Subclavian Vein Thrombosis, and Pulmonary Embolism Secondary to COVID-19-A Case Report.

Introduction: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The majority of infected patients develop the clinical picture of a respiratory disease, although some may develop various complications, such as arterial or venous thrombosis. The clinical case presented herein is a rare example of sequential development and combination of acute myocardial infarction, subclavian vein thrombosis (Paget Schroetter syndrome), and pulmonary embolism in the same patient after COVID-19. Case presentation: A 57-year-old man with a 10-day history of a SARS-CoV-2 infection was hospitalized with a clinical, electrocardiographic, and laboratory constellation of an acute inferior-lateral myocardial infarction. He was treated invasively and had one stent implanted. Three days after implantation, the patient developed shortness of breath and palpitation on the background of a swollen and painful right hand. The signs of acute right-sided heart strain observed on the electrocardiogram and the elevated D-dimer levels strongly suggested pulmonary embolism. A Doppler ultrasound and invasive evaluation demonstrated thrombosis of the right subclavian vein. The patient was administered pharmacomechanical and systemic thrombolysis and heparin infusion. Revascularization was achieved 24 h later via successful balloon dilatation of the occluded vessel. Conclusion: Thrombotic complications of COVID-19 can develop in a significant proportion of patients. Concomitant manifestation of these complications in the same patient is extremely rare, presenting at the same time, quite a therapeutic challenge to clinicians due to the need for invasive techniques and simultaneous administration of dual antiaggregant therapy combined with an anticoagulant treatment. Such a combined treatment increases the hemorrhagic risk and requires a serious accumulation of data for the purpose of a long-term antithrombotic prophylaxis in patients with such pathology.

Management, control, and decision making in unexpected recurrent venous thromboembolism in COVID-19: a case report.

BACKGROUND: Coronavirus disease 2019 was spread worldwide, as a pandemic, from December 2019. Venous thromboembolism events can inflict patients with coronavirus disease 2019 during the hospitalization or convalescent period. Therefore, monitoring of these patients, in terms of venous thromboembolism events signs and symptoms, and timely management of antithrombotic agents are of great importance. CASE REPORT: A 45-year-old Iranian man, who is the first author of this case report, was infected by severe acute respiratory syndrome coronavirus 2 and displayed the typical signs and symptoms of coronavirus disease 2019. Although reverse transcription polymerase chain reaction for coronavirus disease 2019, and specific immunoglobulin M and immunoglobulin G against severe acute respiratory syndrome coronavirus 2, were negative at first, chest computed tomography scan showed the characteristic pattern of lung involvement of a coronavirus disease 2019 infection including bilateral and multilobar ground-glass opacities. At that time, there were no signs or symptoms of deep-vein thrombosis or pulmonary thromboembolism, so these were not investigated. About 30 hours after hospital discharge, the patient presented back to the hospital with acute-onset chest pain. We instantly tested his blood for D-dimer, and sent him to take a Doppler sonography of his lower legs and a chest computed tomography angiography in search of pulmonary thromboembolism and deep-vein thrombosis. Although we could confirm pulmonary thromboembolism with computed tomography angiography in our patient, there were no signs or symptoms of venous thromboembolism in his lower legs, and color Doppler sonography of lower limbs was normal. So, the patient was treated with rivaroxaban as an antithrombotic agent. After some days, he was discharged in good condition. About 1 month later, he was referred to our hospital because of left lower limb edema. Although he was under antithrombotic therapy, color Doppler sonography of lower limbs revealed acute deep-vein thrombosis of the left leg. Hence, we decided to shift antithrombotic therapy from rivaroxaban to warfarin, as it is more potent than rivaroxaban in recurrent venous thromboembolism and when taking new oral anticoagulants. Unlike rivaroxaban, which needs no blood test to monitor its efficacy but has a warning for signs and symptoms of bleeding, warfarin therapy must be monitored carefully by regular blood tests for prothrombin time and international normalized ratio to maintain them in the therapeutic range. The patient was informed about the bleeding cautions, and required regular check of prothrombin time and international normalized ratio to maintain them in the proper and advised range of treatment (international normalized ratio therapeutic range 2-3). CONCLUSION: In the case of unexpected recurrent venous thromboembolism in coronavirus disease 2019, especially when patients are taking rivaroxaban or other new oral anticoagulants, such drugs should be substituted by warfarin, with routine follow-up, to maintain the value of prothrombin time and international normalized ratio within the therapeutic range.

EFFECTS OF SARS COVID-19 POSITIVITY STATUS ON VENOUS THROMBOSIS AND PULMONARY EMBOLISM RATES IN TRAUMA PATIENTS.

ABSTRACT: Introduction : COVID-19-induced coagulopathy (CIC) can increase the risk of thromboembolism without underlying clotting disorders, even when compared with other respiratory viruses. Trauma has a known association with hypercoagulability. Trauma patients with concurrent COVID-19 infection potentially have an even greater risk of thrombotic events. The purpose of this study was to evaluate venous thromboembolism (VTE) rates in trauma patients with COVID-19. Methods : This study reviewed all adult patients (≥18 years of age) admitted to the Trauma Service from April through November 2020 for a minimum of 48 hours. Patients were grouped based off COVID-19 status and compared for inpatient VTE chemoprophylaxis regimen, thrombotic complications defined as deep vein thrombosis, pulmonary embolism, myocardial infarction, and cerebrovascular accident, intensive care unit (ICU) length of stay, hospital length of stay, and mortality. Results : A total of 2,907 patients were reviewed and grouped into COVID-19-positive (n = 110) and COVID-19-negative (n = 2,797) groups. There was no difference in terms of receiving deep vein thrombosis chemoprophylaxis or type, but a longer time to initiation in the positive group ( P = 0.0012). VTE occurred in 5 (4.55%) positive and 60 (2.15%) negative patients without a significant difference between the groups, as well as no difference in type of VTE observed. Mortality was higher ( P = 0.009) in the positive group (10.91%). Positive patients had longer median ICU LOS ( P = 0.0012) and total LOS ( P < 0.001). Conclusion : There were no increased rates of VTE complications between COVID-19-positive and -negative trauma patients, despite a longer time to initiation of chemoprophylaxis in the COVID-19-positive group. COVID-19-positive patients had increased ICU LOS, total LOS, and mortality, which are likely due to multifactorial causes but primarily related to their underlying COVID-19 infection.

In Situ Pulmonary Arterial Thrombosis: Literature Review and Clinical Significance of a Distinct Entity.

Filling defects identified in the pulmonary arterial tree are commonly presumed to represent an embolic phenomenon originating from thrombi formed in remote veins, particularly lower-extremity deep venous thrombosis (DVT). However, accumulating evidence supports an underappreciated cause for pulmonary arterial thrombosis (PAT), namely, de novo thrombogenesis-whereby thrombosis arises within the pulmonary arteries in the absence of DVT. Although historically underrecognized, in situ PAT has become of heightened importance with the emergence of SARS-CoV-2 infection. In situ PAT is attributed to endothelial dysfunction, systemic inflammation, and acute lung injury and has been described in a range of conditions including COVID-19, trauma, acute chest syndrome in sickle cell disease, pulmonary infections, and severe pulmonary arterial hypertension. The distinction between pulmonary embolism and in situ PAT may have important implications regarding management decisions and clinical outcomes. In this review, we summarize the pathophysiology, imaging appearances, and management of in situ PAT in various clinical situations. This understanding will promote optimal tailored treatment strategies for this increasingly recognized entity.

Inferior vena cava and renal vein thrombosis: a rare cause of acute kidney injury in tuberculosis.

Recent studies show active tuberculosis induces a prothrombotic state and increases the risk of venous thromboembolism. We report a recently diagnosed case of tuberculosis who presented to our hospital with painful bilateral lower limb swelling and several episodes of vomiting with abdominal pain for 2 weeks. Investigations by a hospital elsewhere 2 weeks ago showed abnormal renal function, misdiagnosed as antitubercular therapy-induced acute kidney injury. D-dimer levels were increased on admission with us, with still deranged renal function. Imaging revealed thrombus at the origin of left renal vein, inferior vena cava and bilateral lower limbs. We started treatment with anticoagulants, which gradually improved kidney function. This case highlights that early diagnosis of renal vein thrombosis and prompt treatment are associated with good clinical outcomes. It also highlights the importance of further studies for risk assessment, prevention strategies and reduction of the burden of venous thromboembolism in patients with tuberculosis.

The poorly understood yet potent risk of pulmonary artery thrombosis in-situ in Post-Acute COVID-19 syndrome.

Pulmonary artery thrombosis in-situ is a term used to describe a pulmonary embolism occurs in the absence of deep vein thrombosis in the lower extremities. Most cases occur in a patient who had a recent traumatic injury to the chest. Other risk factors include the presence of hypercoagulable conditions, including inflammatory state, hypoxia and vascular endothelial injury. Although it has been discussed extensively in the acute COVID-19 disease, pulmonary artery thrombosis in-situ that occur in the setting of Post-Acute COVID-19 syndrome is not commonly reported and poorly understood.

Risk Factors for Severe COVID-19 Among Health Care Workers.

OBJECTIVE: Evaluate potential risk factors for severe coronavirus disease 2019 (COVID-19) among health care workers (HCWs) at the University of Virginia Medical Center in Charlottesville, Virginia. METHODS: We conducted a retrospective manual chart review of data from HCWs who were diagnosed with COVID-19 from March 2020 to March 2021. Using data from patient medical histories, we ascertained risk factors for COVID-19-related emergency department encounter, hospitalization, or death. RESULTS: We had 634 patients in total, and 9.8% had a severe COVID-19-related outcome. A history of deep vein thrombosis/pulmonary embolism/stroke (odds ratio, 19.6; 95% confidence interval, 5.11 to 94.7), as well as asthma, chronic lung disease, diabetes, or current immunocompromised status, was associated with increased adjusted odds of COVID-19-related emergency department encounter/hospitalization/death. CONCLUSIONS: A preexisting history of deep vein thrombosis/pulmonary embolism/stroke is a novel risk factor for poor COVID-19 outcomes among a cohort of HCWs.

SARS-CoV-2 Possible Etiology of Cerebral Venous Thrombosis in a Teenager: Case Report and Review of Literature.

Cerebral venous thrombosis in pediatric patient has a varied etiology. The authors present the case of a teenager who, since the debut of SARS-CoV-2 infection, has accused intermittent right side hemicrania, which has become persistent in association with nausea and vomiting since the 5th day of quarantine. She was hospitalized in the 9th day since the debut. Neuroimaging revealed extended venous cerebral thrombosis affecting the right sigmoid sinus, the transverse sinus bilaterally, the confluence of the transverse sinuses and the right internal jugular vein. The evolution was favorable under anticoagulant and symptomatic treatment. Laboratory tests excluded other etiological causes for the cerebral venous thrombosis, thus the authors consider that cerebral thrombosis is a possible complication of SARS-CoV-2 infection in teenagers.

Incidence of lower limb deep vein thrombosis in patients with COVID-19 pneumonia through different waves of SARS-CoV-2 pandemic: A multicenter prospective study.

OBJECTIVE: The aim of this study was to evaluate the incidence of deep vein thrombosis (DVT) of the lower limbs in patients hospitalized with COVID-19 pneumonia in a non-ICU setting according to the different waves of the SARS-CoV-2 pandemic. METHODS: Multicenter, prospective study of patients with COVID-19 pneumonia admitted to Internal Medicine units in Italy during the first (March-May 2020) and subsequent waves (November 2020 -April 2021) of the pandemic using a serial compression ultrasound (CUS) surveillance to detect DVT of the lower limbs. RESULTS: Three-hundred-sixty-three consecutive patients were enrolled. The pooled incidence of DVT was 8%: 13.5% in the first wave, and 4.2% in the subsequent waves (p = 0.002). The proportion of patients with early (< 4 days) detection of DVT was higher in patients during the first wave with respect to those of subsequent waves (8.1% vs 1.9%; p = 0.004). Patients enrolled in different waves had similar clinical characteristics, and thrombotic risk profile. Less patients during the first wave received intermediate/high dose anticoagulation with respect to those of the subsequent waves (40.5% vs 54.5%; p = 0.005); there was a significant difference in anticoagulant regimen and initiation of thromboprophylaxis at home (8.1% vs 25.1%; p<0.001). CONCLUSIONS: In acutely ill patients with COVID-19 pneumonia, the incidence of DVT of the lower limbs showed a 3-fold decrease during the first with respect to the subsequent waves of the pandemic. A significant increase in thromboprophylaxis initiation prior to hospitalization, and the increase of the intensity of anticoagulation during hospitalization, likely, played a relevant role to explain this observation.

Thromboembolic events in hospitalised patients with COVID-19: ecological assessment with a scoping review.

OBJECTIVES: Thrombosis is a common complication of the novel COVID-19. Pre-COVID-19 studies reported racial differences in the risk of developing thrombosis. This study aimed to describe the geographical variations in the reported incidences and outcomes of thromboembolic events and thromboprophylaxis in hospitalised patients with COVID-19. The final search for randomised clinical trials was carried out in January 2022. Screening eligible articles and data extraction were independently performed in duplicate by multiple reviewers. DESIGN: Scoping review. MEDLINE, Embase, Cochrane Libraries were searched using terms related to COVID-19 and thromboembolism. SETTING: Hospitals all over the world. PARTICIPANTS: In-hospital patients with COVID-19. OUTCOME MEASURES: The incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE), and the prophylactic anticoagulation therapy. RESULTS: In total, 283 studies were eligible, representing (239 observational studies, 39 case series and 7 interventional studies). The incidence of DVT was the highest in Asia (40.8%) and hospital mortality was high (22.7%). However, the incidence of PE was not very high in Asia (3.2%). On the contrary, the incidence of PE was the highest in the Middle East (16.2%) and Europe (14. 6%). Prophylactic anticoagulation therapy with low-molecular-weight heparin was the main treatment provided in all areas. Four of the seven randomised clinical trials were conducted internationally. CONCLUSIONS: The incidence of DVT was the highest in Asia. The incidence of PE was higher in the Middle East and Europe; however, detection bias during the pandemic cannot be ruled out. There were no major differences in the type or dose of prophylactic anticoagulants used for thromboprophylaxis among the regions.

Deep Venous Thrombosis after Conservative Treatment of Clavicular Fracture in COVID-19 Negative Children: Two Case Reports.

A 13-year-old girl suffered fracture of her left clavicle. A figure-of-8 bandage was placed during initial treatment. Six days after trauma her distal arm, elbow and proximal forearm were swollen, pain and tenderness of distal part of brachial vein was recognized during clinical examination. Duplex ultrasonography revealed partial thrombosis of the brachial vein. Bandage was immediately removed and administration of LMWH (enoxaparin) was started. Complete recanalization was achieved after a few days. The fracture was healed without further complication, patient was without sonographic and clinical signs of post-thrombotic syndrome. The second case report describes a 14-year-old boy. Initially, the fixation was a figure-of-8 bandage. 5 days after the injury he had swollen arm and elbow on the injured side, according to duplex ultrasonography deep venous thrombosis of the axillary and the brachial vein was recognized. There was only partial recanalization at the first sonographic follow up, the patient was converted to Warfarin for 3 months after injury after initial LMWH therapy. At the last follow-up, fracture of the left clavicle was healed and there were no DUSG or clinical signs of post-thrombotic syndrome. Key words: clavicle, deep venous thrombosis of the upper extremity, anticoagulant therapy.