key: cord-0923322-dckuhrlf authors: Khan, Inayat Hussain; Savarimuthu, Sugeevan; Tsun Leung, Marco Shiu; Harky, Amer title: The need to manage the risk of thromboembolism in COVID-19 patients date: 2020-05-14 journal: J Vasc Surg DOI: 10.1016/j.jvs.2020.05.015 sha: 2d487321089dbed74c832b98f9204462d038d93d doc_id: 923322 cord_uid: dckuhrlf COVID-19 first presented in Wuhan, Hubei Province, China, in December 2019. Thought to be of zoonotic origin, it has been named SARS-CoV-2 (COVID-19) and has spread rapidly. As of April 20(th), 2020, there have been more than 2.4 million cases recorded worldwide. The inflammatory process, cytokine storm, and lung injury that are associated with COVID-19 can put patients at an increased risk of thrombosis. It is uncertain what the total incidences of thrombotic events in COVID-19 patients is currently at. Those with more severe disease and with other risk factors, including increasing age, male sex, obesity, cancer, comorbidities, and intensive care unit admission, are at higher risk of these events. However, there is little international guidance on managing these risks in COVID-19 patients. In this paper, we explore the current evidence and theories surrounding thrombosis in these unique patients and reflect on experience from our center. COVID-19 appears to be associated with both venous and arterial thrombosis. This was 20 observed by Klok et al., who found that despite thromboprophylaxis, patients developed 21 venous thrombosis with pulmonary embolism (PE) being the most common. Incidences of 22 arterial thrombosis including ischaemic strokes were also noted. 1 23 24 A recent study identified that those who were critically ill with SARS-CoV-2 had elevated D-25 dimer levels, fibrinogen, and fibrinogen degradation products compared to healthy controls. 2 26 This may be due to endothelial injury resulting in thrombin generation and fibrinolysis shut 27 down, contributing to a hypercoagulable state. A similar relationship between acute 28 respiratory distress syndrome (which can occur in patients with COVID-19) and deep vein 29 thrombosis (DVT) has been shown with Influenza A (H1N1). 3 The inflammatory disease 30 process, prolonged hospital stay, and pre-existing co-morbidities can contribute to venous 31 thromboembolism (VTE). 4 A summary of these factors can be seen in Figure 1 . 32 33 SARS-CoV-2 has been shown to gain entry to cells by binding to Angiotensin-converting 34 enzyme 2 (ACE2) receptors, and the spike (S) protein plays a vital role in this. 5 This protein 35 is cleaved by plasmin, which is found to be higher in individuals with cardiovascular disease, 36 thus potentially making them more susceptible to poorer outcomes. 6,7 The interaction of 37 SARS-CoV-2 with ACE2 receptor may cause endothelial damage as a five-fold rise of von 38 Willebrand factor (VWF) levels has been reported in COVID-19 patients. 8 profiles. These patients showed elevated D-dimer levels, prolonged prothrombin (PT), and 76 activated partial thromboplastin times (aPTT) and thrombocytopenia. Another study using 77 thromboelastography to evaluate whole blood from 24 ICU patients showed similar elevated 78 D-dimer. However, they showed normal or increased fibrinogen, platelet count, PT, and 79 aPTT, which is consistent with hypercoagulability than DIC. 18 Although both groups of 80 patients were admitted to ICU, these differences may be explained by the stage of the disease. Myocardial injury can also occur through various mechanisms in COVID-19 patients, 95 especially in those with pre-existing cardiovascular disease. Systemic inflammation, as well 96 as shear stress due to increased coronary blood flow, can result in plaque rupture, thus 97 causing myocardial infarction. 22 A study showed that acute cardiac injury is more common 98 with raised troponin-I as well as significant ST elevation, which could mimic acute coronary 99 occlusion. In patients with COVID-19, there is a higher prevalence of myocardial injury, 100 particularly in patients admitted to ICU and is a poor prognostic factor in the critically ill. (LMWH (40-60 mg enoxaparin/day) or UFH (10,000-15,000 U/day)) than those without 111 heparin. 25 Interestingly, there was no difference in mortality in the COVID-19 negative 112 patients with the use of heparin. Heparin has previously been shown to play an anti-113 inflammatory role and to offer endothelial protection. 26 Its antiviral effect is also being 114 studied in experimental models and is an avenue that requires further study. 115 Generous use of thromboprophylaxis may help to improve outcomes, especially in those at 117 high risk of VTE. 4 In a study including 407 patients who were considered at high risk of VTE, it was found that 137 44 (11%) patients were at a high risk of bleeding. 28 Incidence of 195 thrombotic complications in critically ill ICU patients with COVID-19 Prominent changes in blood coagulation 198 of patients with SARS-CoV-2 infection Empirical systemic 201 anticoagulation is associated with decreased venous thromboembolism in critically ill 202 influenza A H1N1 acute respiratory distress syndrome patients Anticoagulant treatment is associated with 205 decreased mortality in severe coronavirus disease 2019 patients with coagulopathy Receptor Recognition by the Novel 208 Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of 209 Severe COVID-19 infection associated with endothelial 217 activation New findings on venous thrombogenesis Upsurge of deep venous thrombosis in patients affected by COVID-221 19: preliminary data and possible explanations Lymphatic Disorders Venous thrombosis and arteriosclerosis obliterans of 224 lower extremities in a very severe patient with 2019 novel coronavirus disease: a case 225 report A risk 227 assessment model for the identification of hospitalized medical patients at risk for venous 228 thromboembolism: the Padua Prediction Score Risk assessment of venous 231 thromboembolism and bleeding in COVID-19 patients. PREPRINT (Version 1) available 232 at Research Square The versatile heparin in COVID-19 Attention should be paid to 272 venous thromboembolism prophylaxis in the management of COVID-19 Hematology Issues during COVID-19 Massachusetts General Hospital Thrombocytopenia is associated with severe coronavirus 279 disease 2019 (COVID-19) infections: A meta-analysis Laboratory abnormalities in patients with COVID-2019 infection Point-of-care lung ultrasound in patients with 284 COVID-19 -a narrative review Subtype Drug Atazanavir Single (↓/↑) arrow denotes potential interaction, likely to be of weak intensity -dose adjustment is unlikely. Double (↑↑/↓↓) arrows indicate possible interaction that may require dose adjustment or close monitoring. Triple arrow (↑↑↑/↓↓↓) indicates that these two drugs should not be co-administered. Horizontal arrow (↔) indicates no significant interaction reported.