Arterial or venous thromboembolism is a common complication in patients hospitalised in intensive care for a severe form of covid-19. The incidence of pulmonary embolism in this situation is about 20%, but varies widely between studies (1). The incidence of pulmonary embolism in hospitalised patients not requiring intensive care is about 4% on average (1,2).

The risk of thromboembolism in patients who are not hospitalised is probably even lower, in particular because they remain more mobile. However, some patients treated at home are bedridden for a long time due to extreme fatigue or another health problem (2,3). Is anticoagulation justified to prevent deep vein thrombosis in patients with covid-19 who remain at home?

Our literature search identified no data obtained in randomised comparative trials of prophylactic anticoagulation in either hospitalised or non-hospitalised covid-19 patients. Trials in hospitalised patients are in progress. As no data were available in non-hospitalised patients, we analysed results from studies in hospitalised patients providing lower-level evidence.

A group from New York has published two retrospective studies in a few thousand patients hospitalised for covid-19 (4,5). In the most detailed study, 24% of the patients died while hospitalised. After adjusting for thromboembolic risk factors and the clinical circumstances that warranted anticoagulation, the estimated risk of in-hospital death appeared about twice as great without anticoagulation (4,5). A comparison of curative versus preventive doses of anticoagulant found the dose made little difference to mortality rates (5). However, the risk of bleeding during anticoagulation is known to be dose-dependent, and about 3% of patients in these studies receiving curative doses had a major bleed (4,5). These results are not robust, because the groups compared differed considerably and the published data are incomplete.

Despite the tenuous nature of these data, the high risk of thromboembolic events led to the adoption of systematic anticoagulation strategies for covid-19 patients in intensive care and, more generally, in all hospitalised covid-19 patients. It was reported that implementation of this strategy in a Belgian intensive care unit appeared to have markedly reduced mortality (6).

Various clinical practice guidelines have recommended anticoagulation with low molecular weight heparin (LMWH) for all patients hospitalised for covid-19, including patients with no history indicating an increased risk of thromboembolism (7,8).

However, neither the Belgian, British, US nor French guidelines recommend prophylactic anticoagulation for non-hospitalised patients with no risk factors for thromboembolism besides covid-19 (2,7,8,9).

On 16 September 2020, the website of the French Society for Vascular Medicine featured a set of proposals for the prevention, diagnosis and treatment of venous thromboembolic disease in non-hospitalised patients with covid-19, adopting a similar position to that of other specialist societies (7,9). These specialists advise against using D-dimer levels or venous Doppler ultrasound to screen non-hospitalised patients with no signs suggestive of thrombosis. In the absence of robust data on the risk of thrombosis in non-hospitalised covid-19 patients, they propose deciding whether to give LMWH  prophylaxis on the basis of criteria similar to those used for other hospitalised patients with severe acute disease: greatly reduced mobility in a patient with another major risk factor for venous thrombosis, such as obesity, age over 70 years, cancer undergoing treatment, personal history of venous thromboembolism, or major surgery within the past 3 months. Commenting on these criteria, the Belgian Centre for Pharmacotherapeutic Information (CBIP) remarked that (our translations) "these risk factors are not specific to covid-19 patients (…) they are based on data on the risk of thrombosis in hospitalised patients with severe acute disease, because there are practically no data on the risk of thrombosis in ambulatory patients" (3).

The Dutch College of General Practitioners (NHG) recommends encouraging patients with covid-19 who are confined to bed at home to move regularly, for example by getting out of bed. It also proposes discussing LMWH prophylaxis with bedridden patients at high risk of thromboembolism, informing them of the advantages and disadvantages of such treatment. The NHG considers that, in other patients, the advantage of prophylactic anticoagulation has not been demonstrated, yet "the increased risk of bleeding during LMWH use is well known, in particular in frail elderly patients" (2).

As well as increasing the risk of bleeding, heparins can provoke potentially serious thrombocytopenia, which can increase the risk of thrombosis. They can also provoke thrombocytosis, rare cases of skin necrosis at the injection site, rare hypersensitivity reactions, and other disorders (10).

In practice, as of late September 2020, no robust evaluation data are available in patients with covid-19 who remain at home. In patients who are not bedridden for a long period, prophylactic anticoagulation appears unjustified. Extrapolating from low-quality data in hospitalised patients, it seems reasonable to offer LMWH prophylaxis to patients treated for covid-19 at home if they also have a risk factor for thromboembolism and markedly reduced mobility. LMWH seems the best choice of anticoagulant as it has been in use for a long time, unless the patient has severe renal impairment.

©Prescrire 24 September 2020

Sources:

1. Porfidia A et al. "Venous thromboembolism in patients with COVID-19: systematic review and meta-analysis" Thromb Res 2020; 196: 67 74. > HERE
2. Geersing GJ et al. "NHG-leidraad. Stollingsafwijkingen bij COVID-19 voor de huisarts" undated, accessed 21 September 2020: 3 pages. > HERE
3. CBIP "COVID-19 et coagulopathie: qu’en est-il des patients en ambulatoire?" 13 July 2020: 4 pages. > HERE
4. Paranjpe I et al. "Association of treatment dose anticoagulation with in-hospital survival among hospitalized patients with COVID-19" J Am Coll Cardiol 2020; 76 (1): 122 124. > HERE
5. Nadkarni GN et al. "Anticoagulation, mortality, bleeding and pathology among patients hospitalized with COVID-19: a single health system study" J Am Coll Cardiol 20 August 2020 (pre-print): 33 pages. > HERE
6. Stessel B et al. "Impact of implementation of an individualised thromboprophylaxis protocol in critically ill ICU patients with COVID-19: a longitudinal controlled before-after study" Thromb Res 2020; 194: 209-215. > HERE
7. Belgian Society on Thrombosis and Haemostasis "Anticoagulation management in COVID-19 positive patients BSTH consensus guideline" (undated), accessed 21 September 2020: 9 pages. > HERE
8. "Antithrombotic therapy in patients with COVID-19". In: National Institutes of Health "Coronavirus disease 2019. Treatment Guidelines" 12 May 2020: 160-165. > HERE
9. SFMV "Propositions de la Société Française de Médecine Vasculaire pour la prévention, le diagnostic et le traitement de la maladie thromboembolique veineuse des patients avec COVID 19 non hospitalisés" (undated) accessed 16 September 2020: 7 pages. > HERE
10. Prescrire Rédaction "Héparines" Interactions Médicamenteuses Prescrire 2020.
     

For more information:

• "Covid-19: Follow Prescrire's independent, evidence-based analysis of the pandemic" > HERE