Abstract

Background: Severe acute respiratory syndrome from coronavirus-2 (SARS-CoV-2) has been associated with an increased risk of venous thromboembolism (VTE). Different anticoagulation protocols have been applied in several studies in the absence of clear evidence. A reliable deep venous thrombosis (DVT) indicator in critical patients with SARS-CoV-2 could guide the anticoagulation treatment; however, it has not yet been identified, and clinical applicability of the most common markers is debatable. The aim of our study was to determine the actual incidence of DVT in critically ill SARS-CoV-2 patients and to find a reliable tool to identify patients who might benefit from therapeutic-intensity anticoagulation.Methods: From March 1, 2020 to May 31, 2020, all patients admitted to the intensive care unit (ICU) for SARS-CoV-2 at Ospedale Regionale di Locarno, Locarno, Switzerland, were prospectively enrolled and screened daily with ultrasound for DVT. Following international consensus, a higher-intensity thromboprophylaxis was administered to all patients who were not at increased risk for bleeding. Sepsis-induced coagulopathy (SIC) and sequential organ failure assessment (SOFA) scores were calculated and time-to-DVT event in a COX proportional-hazard regression model was performed. A receiver operating characteristic (ROC) curve was used to determine sensitivity and specificity and the Youden's Index to establish the best threshold.Results: A total of 96 patients were enrolled. Deep venous thrombosis was detected in 37% of patients. Sepsis-induced coagulopathy and SOFA scores were both correlated to DVT. A SIC score of 1 vs. ≥2 showed a close association with DVT, with sensitivity, specificity, and positive and negative predictive values of 90.0, 48.1, and 49.1, and 89.7%, respectively. Most significantly though, a SOFA score of 1 or 2 points was shown to be the most accurate value in predicting the absence of DVT, indicating no need for therapeutic-intensity anticoagulation. Its sensitivity, specificity, and positive and negative predictive values were 87.9, 100, and 100, and 93.7%, respectively. The D-dimer test showed lower sensitivity and specificity whereas platelet count and aPTT were not found to be correlated to DVT.Conclusions: Patients with SOFA scores of 1 or 2 are at low risk of developing DVT and do not require therapeutic-intensity anticoagulation. Conversely, patients with scores ≥3 are at high risk of developing DVT.

Highlights

  • The link between a severe inflammatory state and coagulopathy has been established [1]

  • With a sequential organ failure assessment (SOFA) score threshold ≥2 points, we found the test to have a sensitivity of 97.0% and a specificity of 93.3%, while with a threshold ≥3 points the sensitivity was 87.9% and specificity 100%

  • The danger associated with hypercoagulability in patients with severe SARS-Co-V2 has been observed repeatedly and is well-accepted, three fundamental questions remain uncertain: What is the real incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) in this subset of patients?; Which prophylactic and anticoagulation strategies should be applied?; and Which are the most reliable markers that allow detection of patients who may benefit from anticoagulation treatment while avoiding overtreatment in patients at very low risk of developing venous thromboembolism (VTE)?

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Summary

Introduction

The link between a severe inflammatory state and coagulopathy has been established [1]. Venous thromboembolism has been associated with unfavorable outcomes, with some reports describing up to 40% mortality [5] This is why several different anticoagulation protocols have been suggested in a widespread effort among scientists worldwide [6, 7]. Despite widespread use of regular and higher-intensity thromboprophylaxis in severe cases in the later phases of the pandemic, a high incidence of thrombotic events was still observed [4, 10,11,12]. This suggests that there may be a subgroup of critical SARS-Co-V2 patients who might benefit from therapeutic-intensity anticoagulation before the onset of thrombotic complications. The aim of our study was to determine the actual incidence of DVT in critically ill SARS-CoV-2 patients and to find a reliable tool to identify patients who might benefit from therapeutic-intensity anticoagulation

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