key: cord-0892293-mbomfmwe authors: Ong, Jeremy; Walker, Patricia; Singh, Kasha P; Bishop, Emma; Htun, Kay title: Low rates of venous thromboembolism in hospitalised COVID‐19 patients: an Australian experience date: 2021-09-15 journal: Intern Med J DOI: 10.1111/imj.15536 sha: 79cbc98090b94e0845f6b65443f766a703427359 doc_id: 892293 cord_uid: mbomfmwe BACKGROUND: Venous thromboembolic (VTE) complications appear common in hospitalised COVID‐19 patients, particularly among critically ill patients in intensive care units. However, there is significant heterogeneity in the reported use of thromboprophylaxis. AIMS: The primary objective was to determine rates of symptomatic VTE in hospitalised COVID‐19 patients. Secondary objectives were to assess adherence to an institutional risk‐adapted thromboprophylaxis guideline, and rates of bleeding complications. METHODS: A retrospective, single‐centre, cohort study was performed in consecutive hospitalised COVID‐19 patients over a six‐month period (March – August 2020). Enoxaparin was used as thromboprophylaxis in all patients without a contraindication, with dose adjusted according to disease severity, weight and renal function. RESULTS: Among 86 hospitalised COVID‐19 patients, no VTEs were identified. Eighty‐one patients (94%) received anticoagulation, with 90% adherence to institutional thromboprophylaxis guidelines. Four bleeding events occurred, with one clinically relevant non‐major bleeding event and three minor bleeding events. CONCLUSION: Low rates of VTE were identified in hospitalised COVID‐19 patients using a risk‐ adapted thromboprophylaxis protocol. This article is protected by copyright. All rights reserved. A retrospective study was performed of consecutive hospitalised patients with COVID-19 admitted to Peninsula Health, located in Victoria, Australia from March 2020 to August 2020. COVID-19 was confirmed in all patients with a positive reverse-transcription polymerase chain reaction test for SARS-CoV-2 on a nasopharyngeal or sputum sample. Disease severity was categorised as mild, moderate or severe/critical based on national consensus recommendations, combining clinical symptoms and signs, radiological findings, degree of hypoxia and respiratory support, and other features of organ failure. 9 Thromboprophylaxis Institutional management guidelines for COVID-19 patients were developed, which incorporated the routine use of anticoagulation as thromboprophylaxis ( Figure 1 ). Therapeutic anticoagulation was continued in patients with a pre-existing indication. All other patients without a contraindication received enoxaparin, with dose adjusted according to disease severity, weight and renal function. Dosage was not adjusted to D-dimer level. The primary outcome was radiologically confirmed symptomatic DVT or PE during hospital admission. Routine lower limb screening ultrasounds were not performed. Secondary outcomes were adherence to local thromboprophylaxis guidelines and rates of bleeding complications. Accepted Article This article is protected by copyright. All rights reserved. No in-hospital VTEs were diagnosed. No lower limb ultrasounds were performed in any patient during their hospital admission. Six patients were investigated for PE with either computed tomography pulmonary angiogram or nuclear ventilation-perfusion scan. Eighty-one patients (94%) received anticoagulation, either continuation of pre-existing therapeutic anticoagulation or thromboprophylaxis. In the five patients who did not receive anticoagulation, three patients were admitted for end-of-life care, one patient had a brief admission less than 24 hours, and no reason was identified for the other patient. Seventythree patients (73/81, 90%) received anticoagulation as per institutional guidelines. Deviation from the guidelines were noted for eight patients (10%). Among them, underdosing was noted in six patients for their weight (four patients) and disease severity (two patients). A higher dose than recommended for the disease severity was noted in two patients. Twenty-six patients (30%) had no recorded weight, of which 21 patients (21/26, 81%) received anticoagulation; enoxaparin 40mg daily in 19 patients, and enoxaparin 20mg daily in two patients with renal impairment. Bleeding complications were uncommon, with four recorded events (5%). One clinically relevant non-major bleeding event occurred in a patient on therapeutic anticoagulation for pre-existing VTE. The three cases of minor bleeding included one patient on pre-existing therapeutic anticoagulation for stroke prevention in atrial fibrillation, one patient on an intensified dose of enoxaparin for their critical illness, and one patient on standard dose thromboprophylaxis. D-dimer was performed in 82 patients, with elevated levels in 61 patients (61/82, 74%). Ddimer was elevated in 57% of patients with mild disease (median level 0.78g/mL), elevated The correlation between disease severity and risk of VTE is well established. In their systematic review, Nopp et al report a 7.9% prevalence of VTE in non-ICU patients, compared with 22.7% in ICU patients. 1 Our cohort of inpatients appeared to have less severe disease compared to other published cohorts, resulting in low rates of VTE. We noted that 75% of our hospitalised patients had asymptomatic/mild disease (19 patients, 34%) and moderate disease (35 patients, 41%) respectively. Only four patients were admitted to ICU, three of whom required mechanical ventilation. Patients from residential aged care facilities accounted for 48% of the total hospital admissions, and 68% of mortality. Due to the advanced age of this cohort (median age 83 years, range 66 to 97 years), and the presence of multiple medical co-morbidities, these patients were commonly deemed unsuitable for treatment escalation, further investigations and ICU support. Therefore, it is possible that VTE was under-reported in this patient population. Previous studies have shown an association between elevated D-dimer level and VTE, severe disease and mortality in COVID-19 patients. 14, 15 Despite low rates of VTE, D-dimer was elevated in most of our patients, including patients with asymptomatic or mild disease. D-dimer level appeared to correlate with disease severity. We included consecutive patients and reported high adherence to local thromboprophylaxis protocols, however we acknowledge that our study has several limitations. It is a singlecentre retrospective study with a small sample size. Investigations to detect VTE were Accepted Article infrequently performed, which may underestimate the true prevalence of VTE. Main reasons for the low rate of VTE investigations include the need to avoid spreading the virus within the hospital setting, acute deterioration resulting in rapid death, and deteriorations managed palliatively in frail residential aged care residents. In addition, we reported only symptomatic VTE, which may cause reporting bias due to underreporting of symptoms as almost three quarters of patients from residential aged care facilities had significant cognitive impairment. We assessed patients only during their hospital admission, and therefore outpatient VTE rates following discharge were not reported. However, recent data suggests that post-discharge VTE risk can be as low as 0.6%. 16 Therefore, we felt that the lack of post-discharge data would not significantly alter the overall rate of VTE. In summary, our study provides retrospective and observational data on the use of riskadapted thromboprophylaxis according to disease severity, body weight and renal function in hospitalised COVID-19 patients. To our knowledge, this is the only report describing such experience in an Australian setting. Given the small number of patients with severe disease in our cohort, further prospective research is required to better define VTE risk and optimal thromboprophylaxis strategy in these patients. Accepted Article Risk of venous thromboembolism in patients with COVID-19: A systematic review and meta-analysis. Res Pract Thromb Haemost Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis Incidence of venous thromboembolism in hospitalized patients with COVID-19 Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia Frequency of venous thromboembolism in 6513 patients with COVID-19: a retrospective study Thrombotic complications and anticoagulation in COVID-19 pneumonia: a New York City hospital experience Clinical Characteristics of Covid-19 in New York City Scientific and Standardization Committee communication: Clinical guidance on the diagnosis, prevention, and treatment of venous thromboembolism in hospitalized patients with COVID-19 National COVID-19 Clinical Evidence Taskforce. Australian guidelines for the clinical care of people with COVID-19 Characteristics and outcomes of patients hospitalized for COVID-19 and cardiac disease in Northern Italy Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial Thrombosis in Hospitalized Patients With COVID-19 in a New York City Health System COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection Prevalence and Outcomes of D-Dimer Elevation in Hospitalized Patients With COVID-19 Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China Accepted Article