key: cord-0875141-dzv57ucq authors: Zhang, Pu; Qu, Yali; Tu, Jie; Cao, Wen; Hai, Ning; Li, Shuo; Qu, Peng; Lv, Chaoyang; Guo, Ruijun title: Applicability of bedside ultrasonography for the diagnosis of deep venous thrombosis in patients with COVID‐19 and treatment with low molecular weight heparin date: 2020-08-05 journal: J Clin Ultrasound DOI: 10.1002/jcu.22898 sha: 6affc99ff401eeabb99b0fac3003438b352793fd doc_id: 875141 cord_uid: dzv57ucq PURPOSE: The aim of this study was to evaluate the applicability of bedside ultrasonography for the diagnosis of deep venous thrombosis (DVT) in patients infected with corona virus disease 2019 (COVID‐19) with and without treatment with low molecular weight heparin (LMWH). METHODS: We retrospectively analyzed the records of deceased and surviving patients in whom ultrasonography detected or not a DVT, and in whom LMWH was or not prescribed. RESULTS: The incidence of DVT is higher in the deceased (33/35) than in the surviving (22/46) patients. LMWH was administered in a larger proportion of surviving (18/22) than of deceased (18/33) patients. D‐dimer concentrations decreased in patients who received LMWH in both groups. CONCLUSIONS: There was a high incidence of DVT in patients who succumbed to COVID‐19. Bedside ultrasonography can detect the presence of DVT as early as possible and help assessing the risk of venous thromboembolism, allowing early and reasonable use of LMWH. Our study was conducted in accordance with the principles of the Declaration of Helsinki. The locally appointed ethics committee has approved the research protocol, and informed consent has been obtained from all subjects. Diagnosis of COVID-19 was based on a positive nucleic acid test of SARE-CoV-2, according to the Diagnosis and Treatment Plan of Novel Coronavirus Pneumonia (trial version 7th) issued by the National Health Commission of the People's Republic of China. 7 severity was assessed according to the following clinical classification: (a) light type: mild clinical symptoms, no pneumonia on imaging; (b) common type: fever, respiratory symptoms, pneumonia on imaging; (c) severe type: respiratory distress with respiratory rate ≥30/ min and/or oxygen saturation ≤93% at rest and/or partial arterial pressure of oxygen/fraction of inspired oxygen ≤300 mm Hg (40 kPa); and (d) critical type: respiratory failure requiring mechanical ventilation and/or shock and/or other organ failure and admission to intensive care unit (ICU). We performed the retrospective analysis of 81 severe and critical COVID-19 patients who had had an ultrasonographic examination performed in the ICU of Wuhan Jinyintan Hospital from January 1, 2020 to March 5, 2020. The total number of patients on ICU during the same time was 108. At the end-point date of March 5, 2020, the patients were divided into two groups: those who had succumbed to COVID-19, and the surviving patients. We did not report underlying diseases, since they have been reported to be absent in 47% of deceased patients 8 . SPSS 20.0 statistical software (IBM, New York, NY) was used for statistical analysis. Categorical data were expressed as number (percentage) and χ 2 test was used for comparisons. Continuous variables were expressed as mean ± SD and compared with paired student's t-test. A P value <.05 was accepted as statistically significant. There was no difference in clinical data between deceased and surviving patients (Table 1 ). There were deceased 35 patients, among whom 33 had DVT of whom 18 received LMWH. There were 46 surviving patients, among whom 22 had DVT of whom 18 received LMWH. The incidence of DVT was higher in deceased than in surviving patients (P < .001). The proportion of DVT patients who did not receive LMWH was greater among deceased than among surviving patients (P < .034). DVT was detected 2.5 ± 1.5 days after admission and LMWH administrating started 4.5 ± 1.5 days after admission in the whole population sample. D-dimer values were normally and similarly distributed in both groups. The concentration of D-dimer in the group of deceased patients with DVT treated with LMWH was 36.2 ± 4.5 and 23.9 ± 3.6 mg/L, respectively, before and after treatment (P < .05). In the group of surviving patients with DVT treated with LMWH, it was 28.4 ± 5.6 and 14.7 ± 3.0 mg/L, respectively, before and after treatment (P < .05) ( Table 2 ). The main clinical manifestations of COVID-19 are fever, fatigue, and dry cough. Pneumonia of varying degrees may appear if the condition deteriorates. A considerable number of patients suffer from respiratory distress, with some requiring admission to the ICU due to respiratory or another other organ failure. Some patients suffer from a sudden deterioration, with significant increases in D-dimer values, and an increased risk of sudden death. Therefore, a rapid clinical alarm regarding the risk of venous thromboembolism using bedside ultrasonography is essential. In the present study, DVT was present in a notably greater number of patients who succumbed to COVID-19 than patients who survived. Most COVID-19 patients (98%) have fever, 9 which can lead to hemoconcentration and increased blood viscosity. Additionally, patients with severe disease end up restricted to their beds, often with multiple organ failure and blood coagulation dysfunction. If D-dimer levels increase and a DVT is detected, medical therapy is prescribed according to the patient's coagulation status and other organ functions. LMWH usage is routine at a dosage of 5000u subcutaneous injection every 12 hours, adjusted using dynamic assessment. We observed a higher proportion of patients who did not receive LMWH among those who deceased (Tables 3). These patients were mostly in critical condition and anticoagulants might have been contraindicated due to hepatic, renal, cardiac, or coagulation dysfunction. If DVT was detected early by bedside ultrasonography, that is, before deterioration that could contraindicate anticoagulation therapy shown that thrombi in the pulmonary arteriole can occur before pulmonary congestion, edema, hemorrhage, and hyaline membrane formation. When ARDS does occur, the alveolar-capillary permeability increases first, then alveolar epithelial damage is caused by microthrombotic embolism, 11 promoting the aggregation and adhesion of neutrophils, 12 and finally, pulmonary fibrosis develops. Therefore, the pathological setting of ARDS is the mutual promotion between a hypercoagulable status and an inflammatory reaction. LMWH has the advantages of long half-life, high bioavailability, strong anticoagulant effect, and few adverse reactions, and is safer and more effective than unfractionated heparin. On the one hand, LMWH plays an antithrombotic role through a significant anti-Xa and anti-IIa factors, improves coagulation disorders, reduces the damage to vascular endothelial cells caused by thrombosis, 13, 14 promotes the synthesis of endothelial cells and release of tissue factor pathway inhibitors, and enhances fibrinolysis, while having little impact on platelet function and rarely causing bleeding. On the other hand, LMWH also blocks the NF-κB pathway and inhibits the activation of the p38 MARK signal transduction pathway through factor X, thus blocking the release of inflammatory mediators and inhibiting neutrophil chemotaxis and phagocytosis. [15] [16] [17] Therefore, LMWH has both anticoagulant and anti-inflammatory effects. 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