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.

OpenSAFELY: impact of national guidance on switching anticoagulant therapy during COVID-19 pandemic.

BACKGROUND: Early in the COVID-19 pandemic, the National Health Service (NHS) recommended that appropriate patients anticoagulated with warfarin should be switched to direct-acting oral anticoagulants (DOACs), requiring less frequent blood testing. Subsequently, a national safety alert was issued regarding patients being inappropriately coprescribed two anticoagulants following a medication change and associated monitoring. OBJECTIVE: To describe which people were switched from warfarin to DOACs; identify potentially unsafe coprescribing of anticoagulants; and assess whether abnormal clotting results have become more frequent during the pandemic. METHODS: With the approval of NHS England, we conducted a cohort study using routine clinical data from 24 million NHS patients in England. RESULTS: 20 000 of 164 000 warfarin patients (12.2%) switched to DOACs between March and May 2020, most commonly to edoxaban and apixaban. Factors associated with switching included: older age, recent renal function test, higher number of recent INR tests recorded, atrial fibrillation diagnosis and care home residency. There was a sharp rise in coprescribing of warfarin and DOACs from typically 50-100 per month to 246 in April 2020, 0.06% of all people receiving a DOAC or warfarin. International normalised ratio (INR) testing fell by 14% to 506.8 patients tested per 1000 warfarin patients each month. We observed a very small increase in elevated INRs (n=470) during April compared with January (n=420). CONCLUSIONS: Increased switching of anticoagulants from warfarin to DOACs was observed at the outset of the COVID-19 pandemic in England following national guidance. There was a small but substantial number of people coprescribed warfarin and DOACs during this period. Despite a national safety alert on the issue, a widespread rise in elevated INR test results was not found. Primary care has responded rapidly to changes in patient care during the COVID-19 pandemic.

Evaluation of Bleeding Rate and Time in Therapeutic Range in Patients Using Warfarin Before and During the COVID-19 Pandemic-Warfarin Treatment in COVID-19.

The treatment process of patients using warfarin is expected to be hindered during the COVID-19 pandemic. Therefore we investigated whether the time in therapeutic range (TTR) and bleeding complications were affected during the COVID-19 pandemic. 355 patients using warfarin were included between March 2019 to March 2021. Demographic parameters, INR (international normalized ratio), and bleeding rates were recorded retrospectively. The TTR value was calculated using Rosendaal's method. The mean age of the patients was 61 ± 12 years and 55% of them were female. The mean TTR value during the COVID-19 pandemic was lower than the pre-COVID-19 period (56 ± 21 vs 68 ± 21, P < 0.001). Among the patients, 41% had a lack of outpatient INR control. During the COVID-19 pandemic, 71 (20%) patients using VKA suffered bleeding. Among patients with bleeding, approximately 60% did not seek medical help and 6% of patients performed self-reduction of the VKA dose. During the COVID-19 pandemic, TTR values have decreased with the lack of monitoring. Furthermore, the majority of patients did not seek medical help even in case of bleeding.

Gene variants of coagulation related proteins that interact with SARS-CoV-2.

Thrombosis is a recognized complication of Coronavirus disease of 2019 (COVID-19) and is often associated with poor prognosis. There is a well-recognized link between coagulation and inflammation, however, the extent of thrombotic events associated with COVID-19 warrants further investigation. Poly(A) Binding Protein Cytoplasmic 4 (PABPC4), Serine/Cysteine Proteinase Inhibitor Clade G Member 1 (SERPING1) and Vitamin K epOxide Reductase Complex subunit 1 (VKORC1), which are all proteins linked to coagulation, have been shown to interact with SARS proteins. We computationally examined the interaction of these with SARS-CoV-2 proteins and, in the case of VKORC1, we describe its binding to ORF7a in detail. We examined the occurrence of variants of each of these proteins across populations and interrogated their potential contribution to COVID-19 severity. Potential mechanisms, by which some of these variants may contribute to disease, are proposed. Some of these variants are prevalent in minority groups that are disproportionally affected by severe COVID-19. Therefore, we are proposing that further investigation around these variants may lead to better understanding of disease pathogenesis in minority groups and more informed therapeutic approaches.

An unexpected case of recurrence of pulmonary embolism in a patient recovered from COVID19 in full regimen dose of direct oral anticoagulant drug.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is a pandemic affecting all countries in the world. Italy has been particularly afflicted by the health emergency, and since the peak phase has passed, major concern regarding medium to long term complications due to COVID-19 is arising. Little is known in literature regarding thromboembolic complications once healed after COVID-19. CASE PRESENTATION: A 51-year-old patient recovered from COVID-19 pneumonia complicated by pulmonary embolism (PE) came to the hospital for palpitations and chest pain. Although he was on treatment dose of direct oral anticoagulation (DOAC), massive recurrent PE was diagnosed. CONCLUSION: In the early post COVID-19 era, the question remains regarding the efficacy of DOACs in COVID-19 patients.

Comparison of Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation and Bioprosthetic Heart Valves.

There are limited data regarding direct oral anticoagulants (DOACs) for stroke prevention in patients with bioprosthetic heart valves (BHVs) and atrial fibrillation (AF). The objectives of this study were to evaluate the ambulatory utilization of DOACs and to compare the effectiveness and safety of DOACs versus warfarin in patients with AF and BHVs. We conducted a retrospective cohort study at a large integrated health care delivery system in California. Patients with BHVs and AF treated with warfarin, dabigatran, rivaroxaban, or apixaban between September 12, 2011 and June 18, 2020 were identified. Inverse probability of treatment-weighted comparative effectiveness and safety of DOACs compared with warfarin were determined. Use of DOACs gradually increased since 2011, with a significant upward in trend after a stay-at-home order related to COVID-19. Among 2,672 adults with BHVs and AF who met the inclusion criteria, 439 were exposed to a DOAC and 2233 were exposed to warfarin. For the primary effectiveness outcome of ischemic stroke, systemic embolism and transient ischemic attack, no significant association was observed between use of DOACs compared with warfarin (HR 1.19, 95% CI 0.96 to 1.48, p = 0.11). Use of DOACs was associated with lower risk of the primary safety outcome of intracranial hemorrhage, gastrointestinal bleeding, and other bleed (HR 0.69, 95% CI 0.56 to 0.85, p < 0.001). Results were consistent across multiple subgroups in the sensitivity analyses. These findings support the use of DOACs for AF in patients with BHVs.

Venous thromboembolism and COVID-19: a case report and review of the literature.

BACKGROUND: Currently, there is minimal data available highlighting the prevalence of venous thromboembolism in patients infected with coronavirus disease 2019 (COVID-19). This case report with a literature review emphasizes a unique presentation of COVID-19 that is highly important for health care providers to consider when treating their patients. CASE REPORT: A 65-year-old Caucasian male patient presented to the emergency department with a 2-day history of dyspnea on exertion after his wife's recent diagnosis of COVID-19. He additionally had experienced a couple of episodes of self-resolving diarrhea a few days before presentation. Based on the patient's clinical presentation and the laboratory workup identifying an elevated D-dimer, a computed tomography angiogram of the chest was obtained, which was significant for moderately large, bilateral pulmonary emboli with a saddle embolus, and an associated small, left lower lobe, pulmonary infarct. Ultrasound of the lower extremity showed non-occlusive deep vein thrombosis at the distal left femoral vein to the left popliteal vein. The patient was additionally diagnosed with COVID-19 when the results of the COVID-19 polymerase chain reaction test returned as positive. The patient was admitted to the COVID unit, and he was started on an intravenously administered, unfractionated heparin drip for management of his bilateral pulmonary emboli and deep vein thrombosis. The patient's clinical condition improved significantly with anticoagulation, and he was observed in the hospital for 3 days, after which he was discharged home on the enoxaparin bridge with warfarin. Post-discharge telephone calls at day 10 and week 4 revealed that the patient was appropriately responding to anticoagulation treatment and had no recurrence of his symptoms related to venous thromboembolism and COVID-19. CONCLUSION: As COVID-19 continues to lead to significant mortality, more data is emerging that is exposing its perplexing pathogenicity. Meanwhile, the presentation of venous thromboembolism in patients with COVID-19 remains an unusual finding. It is imperative for health care providers to be mindful of this unique association to make necessary diagnostic evaluations and provide appropriate treatment for the patients.

COVID-19 associated with extensive pulmonary arterial, intracardiac and peripheral arterial thrombosis.

We describe a patient with COVID-19 who developed simultaneous pulmonary, intracardiac and peripheral arterial thrombosis. A 58-year-old man, without major comorbidity, was admitted with a 14-day history of breathlessness. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection was confirmed by laboratory testing. Initial imaging revealed COVID-19 pneumonia but no pulmonary thromboembolism (PTE) on CT pulmonary angiography (CTPA). The patient subsequently developed respiratory failure and left foot ischaemia associated with a rising D-dimer. Repeat CTPA and lower limb CT angiography revealed simultaneous bilateral PTE, biventricular cardiac thrombi and bilateral lower limb arterial occlusions. This case highlights a broad range of vascular sequalae associated with COVID-19 and the fact that these can occur despite a combination of prophylactic and treatment dose anticoagulation.

Anticoagulation clinic drive-up service during COVID-19 pandemic in Qatar.

Coronavirus Disease 2019 (COVID-19) is a pandemic affecting many countries worldwide. Given the increasing incidence especially in elderly and individuals with comorbid conditions, it is advised by health authorities to stay home if possible, maintain social distancing and stay away from those who are sick or could be infected. Patients with comorbidities especially cardiovascular disease are at higher risk of getting infected with COVID-19 and have worse prognosis. Among efforts to safely manage warfarin patients during this pandemic, we introduced a hospital drive-up anticoagulation testing service. This service can reduce the risk of exposure of anticoagulation patients to COVID-19 by reducing the contact time with the different personnel at the hospital and by maintaining those patients at a safe distance from others.