Incidence of thrombotic complications in hospitalized COVID-19 patients remained high in second wave

Incidence of thrombotic complications and overall survival in hospitalized patients with COVID-19 in the second and first wave

Literature - Kaptein FHJ, Stals MAM, Grootenboers M et al., - Thrombosis Research 2020. S0049-3848(20)30675-7 doi: 10.1016/j.thromres.2020.12.019

Introduction and methods

Coagulopathy and high incidences of thrombotic complications have been linked with severe COVID-19 [1-3]. Treatment of hospitalized COVID-19 patients has evolved since the first wave. In response to the high rates of thrombotic complications, guidelines were adjusted to improve proper diagnosis of venous thromboembolism (VTE) and appropriate treatment with low-molecular-weight heparin (LMWH) thromboprophylaxis in COVID-19 patients [4-7]. Remdesivir was suggested to be beneficial in shortening time to recovery in hospitalized COVID-19 patients, compared to placebo [8]. It was also shown that dexamethasone reduces mortality in critically ill patients [9]. It is unknown whether these treatment developments have resulted in less thrombotic complications and mortality in COVID-19 patients in second wave, compared to the first wave. This observational study assessed the incidence of thrombotic complications and overall mortality in COVID-19 patients in the Netherlands in the second wave and compared results with data from patients hospitalized in the first wave.

A total of 947 adult COVID-19 patients admitted between September 1st and November 30th 2020 to eight hospitals in the Netherlands were included in this study. 860 Patients were admitted to general wards, 358 patients to the ICU and 271 patients were admitted to both general ward and ICU. Mean age was 66 (SD 13) years, 64% were male and 13% used therapeutic anticoagulation at admission. All patients received pharmacological thromboprophylaxis according to local protocols. Remdesivir and dexamethasone were given to ward patients with need for supplemental oxygen. Patients on ICU were not treated with remdesivir [10]. Incidence of thrombotic complications and mortality were compared with data from a previous study in 579 COVID-19 patients hospitalized in the Netherlands in the first wave (between February 24th and April 26th 2020) [11].

Main results

Cumulative incidences, adjusted for competing risk of death, of all thrombotic complications in patients hospitalized in the second wave (ward and ICU combined) were 12% (95%CI 9.8-15) after 10 days, 16% (95%CI 13-19) after 20 days and 21% (95%CI 17-25) after 30 days. 144 Patients (15%) died after a median of 14 days (IQR 7-22).
Adjusted cumulative incidences of all thrombotic complications in patients on general wards after 10, 20, and 30 days were 8.6% (95%CI 6.6-11), 11% (95%CI 8.6-15), and 13% (95%CI 9.1-18), respectively. Adjusted cumulative incidences of all thrombotic complications in patients on the ICU after 10, 20, and 30 days were 13% (95%CI 8.8-17), 21% (95%CI 15-28), and 26% (95%CI 19-36), respectively.
Baseline characteristics of patients in the first and second wave were comparable. Risk of overall mortality in COVID-19 patients (ward and ICU combined) was lower in the second wave compared to the first wave (adjusted HR: 0.53, 95%CI 0.41-0.70). Adjusted HRs in ward patients and ICU patients separately were 0.41 (95%CI 0.29-0.59) and 0.80 (95%CI 0.54-1.2), respectively.
Adjusted HRs for any thrombotic complications in the second wave compared to the first wave were 0.89 (95%CI 0.65-1.2) in all patients, 1.8 (95%CI 1.1-3.2) in ward patients and 0.46 (95%CI 0.30-0.70) in ICU patients.
VTEs were diagnosed after a median of 6 days after hospital admission in the first wave and after a median of 4 days in the second wave.

Conclusion

This observational study showed that risk of overall mortality in COVID-19 patients hospitalized in the Netherlands was lower in the second wave, compared with the first wave. Cumulative incidences of thrombotic complications remained high in the second wave. Cumulative incidences of thrombotic complications among all patients (ward and ICU combined) in the second wave were comparable with those in the first wave. However, an increased cumulative incidence was found in ward patients in the second wave compared to the first wave, while a decrease in cumulative incidence was observed in ICU patients. These data underline the need for provision of appropriate thromboprophylaxis in hospitalized COVID-19 patients and a low threshold for diagnostic imaging upon suspicion of thrombotic complications. Randomized trials are needed to examine whether treatment with anticoagulants results in lower incidences of thrombotic complications in COVID-19 patients.

References

Show references

1. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. Journal of Thrombosis and Haemostasis 2020;18:844-7.

2. Levi M, Thachil J, Iba T, Levy JH. Coagulation abnormalities and thrombosis in patients with COVID-19. The Lancet Haematology 2020;7:e438-e40.

3. Cannegieter SC, Klok FA. COVID-19 associated coagulopathy and thromboembolic disease: Commentary on an interim expert guidance. Research and practice in thrombosis and haemostasis 2020;4:439-45.

4. Spyropoulos AC, Levy JH, Ageno W, et al. Scientific and Standardization Committee communication: Clinical guidance on the diagnosis, prevention, and treatment of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost 2020;18:1859-65.

5. Moores LK, Tritschler T, Brosnahan S, et al. Prevention, Diagnosis, and Treatment of VTE in Patients With Coronavirus Disease 2019: CHEST Guideline and Expert Panel Report. Chest 2020;158:1143-63.

6. Donze J, Rodondi N, Waeber G, Monney P, Cornuz J, Aujesky D. Scores to predict major bleeding risk during oral anticoagulation therapy: a prospective validation study. The American journal of medicine 2012;125:1095-102.

7. Piovella C, Dalla Valle F, Trujillo-Santos J, et al. Comparison of four scores to predict major bleeding in patients receiving anticoagulation for venous thromboembolism: findings from the RIETE registry. Internal and emergency medicine 2014;9:847-52.

8. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of Covid-19 – Final Report. The New England journal of medicine 2020;383:1813-26.

9. Group WHOREAfC-TW, Sterne JAC, Murthy S, et al. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Metaanalysis. Jama 2020;324:1330-41.

10. Kearon C. The American College of Chest Physicians score to assess the risk of bleeding during anticoagulation in patients with venous thromboembolism: More. Journal of thrombosis and haemostasis : JTH 2019;17:1180-2.

11. Stals MAM, Grootenboers MJJH, van Guldener C, et al. Risk of thrombotic complications in hospitalized patients with influenza versus COVID-19. (In press in preprints medRxiv).

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