At pro-COAG, an annual scientific and educational event on coagulation sponsored by Roche Diagnostics that was last held in Mar 2022, Prof Alex C Spyropoulos, a Professor of Medicine at the Zucker School of Medicine at Hofstra/Northwell and Director of Anticoagulation and Clinical Thrombosis Services for the multi-hospital Northwell Health System in New York, spoke on the management of thrombosis in hospitalised patients. His presentation focused on thromboprophylaxis in post-discharge acute medical patients and patients with severe SARS-CoV-2 (COVID-19).

An estimated 20 million patients are at risk of venous thromboembolism (VTE) across the US and EU, a situation worsened by the severe COVID-19-associated hypercoagulable state. Not accounting for COVID-19 cases, 50–70% of symptomatic VTEs and 70–80% of fatal pulmonary embolisms (PEs) occur in acute medically ill patients, a group characterised by age over 70 years, significant periods of immobilisation (defined as 3 days or more), and multiple co-morbidities associated with compromised cardiopulmonary reserve and/or elevated thrombotic risk [1].

In clinical settings, inpatient thromboprophylaxis reduces the incidence of thrombotic complication without unacceptably elevated bleeding risk; foreshortened length of stay has moved the burden of management to outpatient settings. Furthermore, whilst 80% of VTEs occur within 6 weeks of hospital discharge, less than 4% of hospitalised patients receive thromboprophylaxis on discharge.

Practitioners and guidelines need to recognise this period of elevated risk. Trials of outpatient direct oral anticoagulant (DOAC; rivaroxaban and betrixaban) prophylaxis has emphasised the importance of targeting high VTE risk, low hemorrhagic risk populations and  applying an individualised, risk adapted approach with clinical decision support and/or electronic health record interoperability [2,3]. The application of validated VTE risk models/tools, such as Padua and IMPROVE+D-Dimer at both admission and discharge would aid decision making, but guidelines remain mixed [4,5].

SARS-CoV-2 presents a related yet distinct challenge. The infection mediated combination of vascular dysfunction and elevated inflammatory cytokines/coagulation parameters induces an atypical hypercoagulable state. The markers of this state include a 3–5 times higher rate of VTEs, D-Dimer elevated 4–6 times or more above the upper-limit of normal (associated with a 2–5 fold increase in mortality), unusual coagulation typing, and thrombotic breakthrough [6].

Timing and dosage of DOAC and low molecular weight heparin (LMWH) thromboprophylaxis is therefore critical; while all COVID-19 inpatients without unacceptably high bleed risk should receive universal thromboprophylaxis with a prophylactic (low-dose) LMWH, very high risk groups such as those with elevated D-Dimer that are over twice the upper limit of normal levels or with oxygen requirements may benefit from therapeutic-dose LMWH as thromboprophylaxis.

Additionally, those patients with an IMPROVE VTE score of 4 or more or a score of 2-3 with elevated D-Dimer over twice the upper limit of local laboratory normal will benefit from extended post-discharge thromboprophylaxis with rivaroxaban 10mg for 35 days, provided that they are at a low bleeding risk. Revised COVID-19 guidelines will reflect these developments.

Prof Alex C Spyropoulos serves as Professor of Medicine, Zucker School of Medicine; Director of Anticoagulation and Clinical Thrombosis Services, Northwell Health System. NY.; Professor of the Center for Health Innovations and Outcomes, Feinstein Institute for Medical Research. Co-chair of the Council on Leadership of Thrombosis, Northwell Health System; Section Editor, Thrombosis and Haemostasis; Member of the editorial staff, Hospital Medicine.

References: 

[1] Decousus, H, et al. Chest, 2011. 139(1):69–79.
[2] Spyropoulos, AC, et al. TH Open, 2020. 04(01):e59–e65.
[3] Cohen, AT, et al., J Thromb Haemost, 2014. 12(4):479–487.
[4] Spyropoulos, AC, et al. Res Pract Thromb Haemost, 2021. 5(2):296–300.
[5] Rosenberg, DJ, et al. Thromb Haemost, 2016. 116(09):530–536.
[6] Goldin, M, et al. J Thromb Thrombolysis, 2021. 52(4):1032–1035.