Thrombosis and Bleeding Risk Scores Are Strongly Associated with Mortality in Hospitalized Patients with COVID-19: A Multicenter Cohort Study

Abstract

Background: Internationally established guidelines mention pharmacological prophylaxis for all hospitalized COVID-19 patients. However, there are concerns regarding the efficacy and safety of anticoagulants. This study investigated the associations between thrombosis/bleeding risk scores and clinical outcomes. Methods: We conducted a retrospective review of adult patients admitted to two hospitals between 2021 and 2022. We analyzed clinical data, laboratory results, low molecular weight heparin (LMWH) use, thrombosis, bleeding, and 30-day survival. Results: Of the 160 patients, 69.4% were female, and the median age was 59 years. The rates of thrombotic complications and mortality were 12.5% and 36.3%, respectively. LMWH prophylaxis was administered to 73 of the patients (45.6%). The patients with high Padua prediction scores (PPS) and high IMPROVE_VTE scores had a significantly higher risk of venous thromboembolism (VTE) compared to those with low scores (30.8% vs. 9.0%, p = 0.006 and 25.6% vs. 7.7%, p = 0.006). Similarly, elevated IMPROVE_VTE and IMPROVE_BRS scores were associated with increased mortality (hazard ratios of 7.49 and 6.27, respectively; p < 0.001). Interestingly, LMWH use was not associated with a decreased incidence of VTE when stratified by risk groups. Conclusions: this study suggests that COVID-19 patients with high thrombosis and bleeding risk scores have a higher mortality rate.

Keywords: COVID-19; IMPROVE score; Padua prediction score; mortality; venous thromboembolism.

Figure 1

Receiver operating characteristic (ROC) curves of the venous thromboembolism (PPS_VTE, IMPROVE_VTE) and bleeding (IMPROVE_BRS) risk score models for mortality prediction. The areas under the curves (AUC) were 0.68 (PPS_VTE), 0.79 (IMPROVE_VTE), 0.67 (IMPROVE_BRS), and 0.82 (IMPROVEDD_VTE).

Figure 2

Kaplan–Meier curve for cumulative survival according to difference venous thromboembolism and bleeding risk scores among 160 patients. (A) Comparison of cumulative survival rates between a Padual prediction score of VTE of <4 and ≥4 subgroup; p-value < 0.001. (B) Comparison of cumulative survival rates between an IMPROVE prediction score of VTE of <2 and ≥2 subgroup; p-value < 0.001. (C) Comparison of cumulative survival rates between an IMPROVEDD prediction score of VTE of <2 and ≥2 subgroup; p-value < 0.001. (D) Comparison of cumulative survival rates between an IMPROVE prediction score of bleeding of <7 and ≥7 subgroup; p-value < 0.001. (E) Comparison of cumulative survival rates between a combination of PPS_VTE (≥4) + IMPROVE_BRS (≥7) (high risk) and a combination of PPS_VTE (<4) or IMPROVE_BRS (<7) (low risk) prediction score subgroups; p-value < 0.001. (F) Comparison of cumulative survival rates between a combination of IMPROVE_VTE (≥2) + IMPROVE_BRS (≥7) (high risk) and a combination of IMPROVE_VTE (<2) or IMPROVE_BRS (<7) (low risk) prediction score subgroups; p-value < 0.001. (G) Comparison of cumulative survival rates between a combination of IMPROVEDD_VTE (≥2) + IMPROVE_BRS (≥7) (high risk) and a combination of IMPROVEDD_VTE (<2) or IMPROVE_BRS (<7) (low risk) prediction score subgroups; p-value < 0.001.

Figure 2

Kaplan–Meier curve for cumulative survival according to difference venous thromboembolism and bleeding risk scores among 160 patients. (A) Comparison of cumulative survival rates between a Padual prediction score of VTE of <4 and ≥4 subgroup; p-value < 0.001. (B) Comparison of cumulative survival rates between an IMPROVE prediction score of VTE of <2 and ≥2 subgroup; p-value < 0.001. (C) Comparison of cumulative survival rates between an IMPROVEDD prediction score of VTE of <2 and ≥2 subgroup; p-value < 0.001. (D) Comparison of cumulative survival rates between an IMPROVE prediction score of bleeding of <7 and ≥7 subgroup; p-value < 0.001. (E) Comparison of cumulative survival rates between a combination of PPS_VTE (≥4) + IMPROVE_BRS (≥7) (high risk) and a combination of PPS_VTE (<4) or IMPROVE_BRS (<7) (low risk) prediction score subgroups; p-value < 0.001. (F) Comparison of cumulative survival rates between a combination of IMPROVE_VTE (≥2) + IMPROVE_BRS (≥7) (high risk) and a combination of IMPROVE_VTE (<2) or IMPROVE_BRS (<7) (low risk) prediction score subgroups; p-value < 0.001. (G) Comparison of cumulative survival rates between a combination of IMPROVEDD_VTE (≥2) + IMPROVE_BRS (≥7) (high risk) and a combination of IMPROVEDD_VTE (<2) or IMPROVE_BRS (<7) (low risk) prediction score subgroups; p-value < 0.001.

Figure 3

Kaplan–Meier curve for cumulative survival rates between patients with and without low molecular weight heparin, according to each low venous thromboembolism and bleeding risk score. (A) Comparison of cumulative survival rates among patients with Padual prediction scores of VTE ≥ 4 subgroup; p-value = 0.054. (B) Comparison of cumulative survival rates among patients with IMPROVE prediction scores of VTE ≥ 2; p-value = 0.035. (C) Comparison of cumulative survival rates among patients with IMPROVEDD prediction scores of VTE ≥ 2; p-value = 0.123. (D) Comparison of cumulative survival rates among patients with IMPROVE prediction scores of bleeding ≥ 7; p-value = 0.002. (E) Comparison of cumulative survival rates among patients with PPS_VTE (≥4) + IMPROVE_BRS (≥7) (high risk) prediction score subgroup; p-value = 0.022. (F) Comparison of cumulative survival rates among patients with IMPROVE_VTE (≥2) + IMPROVE_BRS (≥7) (high risk) prediction score subgroup; p-value < 0.003. (G) Comparison of cumulative survival rates among patients with IMPROVEDD_VTE (≥2) + IMPROVE_BRS (≥7) (high risk) prediction score subgroup; p-value < 0.003.

Figure 3

Kaplan–Meier curve for cumulative survival rates between patients with and without low molecular weight heparin, according to each low venous thromboembolism and bleeding risk score. (A) Comparison of cumulative survival rates among patients with Padual prediction scores of VTE ≥ 4 subgroup; p-value = 0.054. (B) Comparison of cumulative survival rates among patients with IMPROVE prediction scores of VTE ≥ 2; p-value = 0.035. (C) Comparison of cumulative survival rates among patients with IMPROVEDD prediction scores of VTE ≥ 2; p-value = 0.123. (D) Comparison of cumulative survival rates among patients with IMPROVE prediction scores of bleeding ≥ 7; p-value = 0.002. (E) Comparison of cumulative survival rates among patients with PPS_VTE (≥4) + IMPROVE_BRS (≥7) (high risk) prediction score subgroup; p-value = 0.022. (F) Comparison of cumulative survival rates among patients with IMPROVE_VTE (≥2) + IMPROVE_BRS (≥7) (high risk) prediction score subgroup; p-value < 0.003. (G) Comparison of cumulative survival rates among patients with IMPROVEDD_VTE (≥2) + IMPROVE_BRS (≥7) (high risk) prediction score subgroup; p-value < 0.003.