key: cord-1010572-0vajpo98
authors: Doyle, Andrew J.; Thomas, Will; Retter, Andrew; Besser, Martin; MacDonald, Stephen; Breen, Karen A.; Desborough, Michael J.R.; Hunt, Beverley J.
title: Updated hospital associated venous thromboembolism outcomes with 90-days follow-up after hospitalisation for severe COVID-19 in two UK critical care units
date: 2020-10-08
journal: Thromb Res
DOI: 10.1016/j.thromres.2020.10.007
sha: 632e4aa00795bd69d5b8d7f91299c121362670c5
doc_id: 1010572
cord_uid: 0vajpo98

nan

Hospitalisation with COVID-19 infection has been associated with an increased incidence of thrombosis, particularly in the critical care setting. Our two centres have previously described the early in-patient incidence of venous thromboembolism (VTE) at the peak of the COVID-19 outbreak in the United Kingdom1,2. The cohort from Cambridge showed 6 patients out of a total of 63 who developed VTE with a median follow-up of 8 days whereas London showed 10 patients of 66 had VTE with a median follow-up of 30 days. The risk of hospital-associated VTE (HAT) for patients has been shown to extend from admission to 90 days following discharge with an early peak within the first weeks of this period3. However, it has not yet been established whether the risk of VTE following COVID-19 pneumonia also persists to 90 days.

We conducted an observational study of our previous cohorts with a minimum of 90 days follow-up from their critical care admission at our centres. Our methods have previously been described and approval was obtained from the Research and Development departments at both Trusts1,2. The composite endpoint was image-proven pulmonary embolism (PE) and deep vein thrombosis (DVT) including catheter-associated thrombi. The index date was admission to critical and censorship data was 17th July 2020. We assessed the D-dimer levels at the time of imaging in those with and without thrombosis, which we and others have previous shown to be significantly higher in those developing VTE2.

Cumulative incidence was adjusted for the competing risk of death but not for hospital discharge although the majority of patients had been discharged in this study4.

In total, 129 patients with COVID-19 infection confirmed by polymerase chain reaction on nasopharyngeal swab or bronchoalveolar lavage were included. Both centres performed J o u r n a l P r e -p r o o f Journal Pre-proof VTE risk assessments using the Department of Health tool5. Our guidance for thromboprophylaxis was based originally on NICE guidance for medical patients using dalteparin that was prescribed according to weight and renal function unless contraindicated in all patients. Post-discharge (i.e. extended thromboprophylaxis) was not used. The demographics of these patients are described fully in the previous articles. To summarise, there was predominance of males in both cohorts (69% Cambridge and 73% London), high rates of mechanical ventilation use (83% and 79%) and the mean ages was 62 and 56 years, respectively.

The median number of days of follow-up was 113 (range 96 -138 days) for those who were alive at review. The median duration of critical care admission was 13.5 days (range 1 -130 days). At the censorship date, 40/129 patients had died (31%), 6/129 patients (5%) remained in critical care, 7/129 (5%) were in-patients but had been discharged from critical care, 3/129 (2%) were transferred to their local hospitals and 73/129 (57%) were alive and discharged from hospital. 48/73 (66%) of the patients discharged alive at follow-up had a hospital discharge duration of ≥90 days. 24/129 (19%) patients developed 26 VTE events. The estimated cumulative incidence of VTE over a minimum of 90 days following critical care admission was 18.6% shown in Figure 1 (a) (95% confidence interval 12.4-25.8). When segmental/sub-segmental pulmonary embolism was excluded, the cumulative incidence of VTE was 4.1% (95% CI 1.5-8.8%), which is displayed in Figure 1 Due to the concerns of an extended prothrombotic risk with COVID-19, particularly in those with severe disease, the use of extended thromboprophylaxis has been considered although there is no clinical trial data yet. In a meta-analysis in medically unwell patients who did not have COVID-19 infection, extended chemical thromboprophylaxis compared to standard duration thromboprophylaxis resulted in no overall change in mortality rates but a 32% relative risk reduction in VTE and a 104% relative risk increase in major haemorrhage10. At present, we feel that this data however cannot be extrapolated to the setting of patients with COVID-19. The International Society on Thrombosis and Haemostasis (ISTH) and

American College of Chest Physicians (ACCP) in their expert-led guidance advocated the use of low molecular weight heparin during hospitalisation with COVID-19 infection and ISTH advocated consideration of using extended thromboprophylaxis while ACCP did not11,12. 

Thrombotic complications of patients admitted to intensive care with COVID-19 at a teaching hospital in the United Kingdom

Image-proven thromboembolism in patients with severe COVID-19 in a tertiary critical care unit in the United Kingdom

Fatal venous thromboembolism associated with hospital admission: a cohort study to assess the impact of a national risk assessment target

Beware overestimation of thrombosis in ICU: Mortality is not the only competing risk!

Incidence of thrombotic complications in critically ill ICU patients with COVID-19

Incidence of venous thromboembolism in hospitalized patients with COVID-19

High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients

Post-discharge venous thromboembolism following hospital admission with COVID-19

Extended vs. standard-duration thromboprophylaxis in acutely ill medical patients: A systematic review and meta-analysis

Subcommittee on Perioperative, Critical Care Thrombosis, Haemostasis of the Scientific, Standardization Committee of the International Society on Thrombosis, Haemostasis. Scientific and Standardization Committee Communication: Clinical Guidance on the Diagnosis, Prevention and Treatment of Venous Thromboembolism in Hospitalized Patients with COVID-19

Prevention, Diagnosis, and Treatment of VTE in Patients With Coronavirus Disease 2019: CHEST Guideline and Expert Panel Report