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Vol. 21.
(March - April 2021)
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Vol. 21.
(March - April 2021)
Original article
DOI: 10.1016/j.aohep.2020.10.002
Open Access
Aminotransferases disorders associated with venous thromboembolic events in patients infected with COVID-19
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Amer Hamadéa,
Corresponding author
hamadea@ghrmsa.fr

Corresponding author.
, Bastien Woehla, Marjolaine Talbota, Naouel Bensalaha, Pierre Michela, Golnaz Obringera, Michèle Lehn-Hogga, Nathalie Buschenriedera, Mahdi Issab, Jonathan Touscha, Dominique Stephanc, Lucas Jamberta
a Service de Médecine Vasculaire, GHRMSA, Hôpital Emile Muller, 20, Rue du Dr Laennec, 68051 Mulhouse, France
b Service de Chirurgie Digestive, GHRMSA, Hôpital Emile Muller, Mulhouse, France
c Service d’Hypertension et de Maladies Vasculaires, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
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Tables (6)
Table 1. Lung Parenchyma Lesions on Chest CT : Recommendation of French Society of Thoracic Imaging.
Table 2. Patient Characteristics.
Table 3. 10 patients (21.7%) of the cohort wit VTE.
Table 4. 8 patients(17.4%) Patients Transferred to ICU.
Table 5. 3 patients (6.5%) Patients died.
Table 6. Follow-up Patients D15- D 30.
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Abstract
Introduction and objectives

Since the outbreak of the COVID-19 pandemic, increasing evidence suggests that infected patients present a high incidence of venous thromboembolic (VTE) events and elevated aminotransferases (AT).The objective of this work was to evaluate the incidence of aminotransferases disorders in patients infected with COVID-19 and to manage the VTE events associated with elevated AT.

Patients or Materials and methods

We report a retrospective study of 46 patients admitted for COVID-19 infection. Venous duplex ultrasound of lower limbs was performed in all patients at Day 0 and Day 5. All patients had antithrombotic-prophylaxis upon admission using low molecular weight heparin with Enoxaparin. Demographics, comorbidities and laboratory parameters were collected and analyzed.

Results

Elevated AT were reported in 28 patients (61%). 10 had acute VTE events of which eight (17.4%) had aminotransferases disorders. They had been treated with curative Enoxaparin. After a follow-up of 15 and/or 30 days, six of them were controlled, and treated with direct oral anticoagulant (DOACs) after normalization of aminotransferases.

Conclusions

The incidence of aminotransferases disorders associated with acute VTE events in patients infected with COVID-19 is significant. The use of DOACs appear pertinent in these patients. Monitoring of the liver balance should therefore be considered at a distance from the acute episode in the perspective of DOACs relay.

Keywords:
COVID-19
Venous thromboembolism
Aminotransferases disorders
Direct oral anticoagulant
Liver disorders
Elevated AST and ALT
Full Text
1Introduction

COVID-19 spread in the East of France after a religious meeting in Mulhouse, which gathered about 2000 people from February 17th to 24th 2020. From March 2nd, our hospital had to face a massive inflow of patients presenting acute respiratory failure [1].The largest study on COVID-19 to date showed that the prevalence of elevated aminotransferases (AT) in people faring worst was at least double that of others [2].We further noted that there is a potential link between venous thromboembolic (VTE) events and COVID-19 infection [3]. Before initiating treatment with an oral direct anticoagulant (DOACs), liver function should be assessed. The objective of this work was to evaluate the incidence of aminotransferases disorders in patients hospitalized in a conventional unit infected with COVID-19 and to manage the VTE events associated with elevated AT.

2Materials and methods

This monocentric retrospective study was approved by the local ethics committee. We had oral consent from our patients for the various practical tests and for all the data provided for this study following the principles outlines in the declaration to Helsinki. From March 2nd to April 11, 46 patients with COVID- 19 infection with mean age (67 ± 12 years) were hospitalized in our unit. 24 (52%) were women. The diagnostics of COVID-19 pneumonia was evaluated by a retrotranscriptase polymerase chain reaction (RT-PCR) of the samples taken with a nasopharyngeal swab. For the patients who were RT-PCR negative, the diagnostics of COVID-19 infection was confirmed by the clinical signs of the infection and the Computed Tomography (CT) following the recommendations of French Society of Thoracic Imaging [3] (Table 1).

Table 1.

Lung Parenchyma Lesions on Chest CT : Recommendation of French Society of Thoracic Imaging.

Chest CT Severity  Extent of Lesions % 
Stage 1 Minimal  < 10 
Stage 2 Moderate  10−25 
Stage 3 Extended  25−50 
Stage 4 Severe  50−75 
Stage 5 Critical  > 75 

CT without concentration iodine contrast. In patients with COVID-19 we show a characteristic lung parenchyma lesions : ground glass and crazy paving pattern opacity. These lesions are classified in 5 stages.

Complete venous duplex ultrasound (DU) was performed at Day (D) 0 and D 5 by the team of Vascular Medicine. The calf, popliteal, femoral, great and small saphenous veins were explored using the ultrasound machine Samsung HS50.When it was possible we examined iliac veins and inferior vena cava. The main criteria for a positive diagnosis of venous thrombosis were venous incompressibility under the cross-section probe and the direct visualization of the thrombus. The secondary criteria was the absence of the Doppler flow in the vein. DVT was classified as distal (below the popliteal vein) or proximal (popliteal or above popliteal veins. The DU was carried out according to a strict protocol in order to protect the examiner.

Demographics, comorbidities characteristics were collected and laboratory parameters were automatically extracted from our heath information system.

All hospitalized patients had anticoagulation treatment on admission. Classic prophylactic anticoagulation treatment (PAT) is defined by the administration of standard doses of low molecular weight heparin (LMWH) (4000 IU of Enoxaparin every 24 h for patients with a weight less than 100 kg or 6000 IU every 24 h for patients with a weight greater than 100 kg). The patients with a history of VTE had been treated with therapeutic anticoagulation using subcutaneous Enoxaparin (100 UI/12 h).

Qualitative and quantitative variables were analyzed using means or medians, percentages and standard deviations. Univariate analysis were performed, Mann-Whitney and Fisher tests were used to establish the correlation between the variables. P values less than 0.05 were considered to indicate statistical significance.

3Results

COVID-19 false negative test results can be seen in patients infected [4].PCR was positive in 37 patients (80%), in nine (20%) COVID-19 infection was confirmed with a chest CT showing a characteristical lung parenchyma lesions : bilateral peripheral ground- glass opacities (Fig. 1).

Fig. 1.

Lung parenchyma lesions in COVID-19: Patient with COVID-19 infection who presented lung parenchyma lesions on chest CT without iodine contrast, stage (extended lesions 50-75 % of lung parenchyma: bilateral peripheral ground-glass opacities: classification of the French Society of Thoracic Imaging.

(0.18MB).

Upon admission, we observed elevated C-reactive protein (CRP) (mean 83.3 ± 61.8 mg/l) in 39 patients (84.8%), 29 % had lymphopenia (mean 1.28 ± 1.39 × 10.9/l), 28 % with anemia (mean Hemoglobin 12.7 ± 2.05 g/dl). In our cohort, the activated partial thromblastine time was 1.09 ± 0.298, prothrombin time was 78.3 ± 13.9 %), and glomerular filtration (GF) rate was 78.6 ± 30.mil/min.D-dimer levels and white blood cells rate were significantly associated with VTE events (7317 ± 9550 in the group with VTE versus 1779 ± 2941 ng/ml p = 0.021 and 11.2 ± 4.15 versus 6.83 ± 3.52 × 10.9/L p < 0.01).

Biological cholestasis was observed in 10 patients (21.7%). Patient characteristics are summarized in the Table 2.

Table 2.

Patient Characteristics.

variable  Toatal 46 patients  36 NO VTE  10 VTE  P value 
Age (years)  67.2 ± 12.0  67.1 ± 12.1  67.6 ± 12.4  0.79 
F (n,%)M (n,%)  24 (52%)22 (48%)  20 (56%)16 (44%)  4 (40%)6 (60%)  0.48 
AST (  50.3 ± 34.1  50.4 ± 34.7  50.1 ± 33.7  0.94 
ALT (<61UI/L)  50.3 ± 34.1  48.9 ± 31.5  91.5 ± 71.0  0.16 
Total Biluribin (1−17um/L)  9.90 ± 4.01  10.1 ± 4.41  9.40 ± 2.84 
D-dimer (<500 ng/mL)  2914 ± 5362  1779 ± 2941  7315 ± 9550  0.021 
GammaGT (15−85 UI/L)  136 ± 152  128 ± 155  173 ± 145  0.41 
Alkaline phosphatase (45−117 UI/L)  149 ± 206  159 ± 230  114 ± 70.7  0.71 
CRP (0−3 mg/L)  83.3 ± 61.8  69.7 ± 53.1  110 ± 72.8  0.11 
GF >90 ml/min)  78.6 ± 30.0  78.1 ± 31.1  80.7 ± 26.5 
BMI (kg/m227.9 ± 4.14  27.8 ± 4.03  28.3 ± 4.74  0.72 
aPTT (0.86−1.20)  1.09 ± 0.298  1.09 ± 0.236  1.10 ± 0.456  0.19 
NT-proBNP (<194 pg/mL)  2388 ± 5361)  2879 ± 5927  483 ± 480  0.52 
CPK (26−192 UI/L)  124 ± 83.3)  134 ± 83.3  46.5 ± 19.1  0.079 
Hemoglobin (13.5−16.9 g/dL)  12.7 ± 2.05  12.5 ± 1.87  13.2 ± 2.78  0.23 
LDH (57−241 UI/L)  360 ± 151  361 ± 159  356 ± 134 
Lymphocyes (1.26−3.35 × 10.9/L)  1.28 ± 1.39  1.28 ± 1.57  1.27 ± 0.475  0.16 
Platelets (166−308 × 10.9/L)  280 ± 108  280 ± 108  301 ± 87.1  0.36 
WBC (3.91−10.9 × 10.9/L)  7.85 ± 4.08)  6.83 ± 3.52  11.2 ± 4.15  <0.01 
Prothrombin time %  78.3 ± 13.9  78.3 ± 15.0)  78.4 ± 10.7  0.91 
HomeICUFollow-up careDeath  8 (18%)4 (11%)3(6.5%)  22(63%)6(17%)4(11%)2(8.6%)  7 (70%)2(20%)0 (0%)1(10%)  0.87 
Hypertension  25 (54.3%)  22(5.5%)  3(30%)   
Diabetes  7 (15.2%)  7(19.4%)  0(0%)   
Dyslipidemia  11 (24%)  10 (27.8%)  1(10%)   
Digestive sypmtoms  4 (8.7%)  3 (8.3%)  1 (10%)   
History/liver diseases (n,%)  0 (0%)  0(%)  0(%)   
Smoking  10 (21.7%)  10 (27.8%)  0(0%)   
Lymphopenia  29 (63%)  24(67%)  5(50%)   
Active cancer  0 (0%)  0 (0%)  0 (0%)   
History of cancer (n,%)  3 (6.5%)  3 (8.3%)  0(0%)   
History of VTE (n,%)  3 (6.5%)  2(5.5%)  1(10%)   
Chronic Renal Failure  5 (8.7%)  5 (13.9%)  0(0%)   
Haemodialysis  2(4.3%)  2(5.6%)  0(0%)   
Sleep Apnea Syndrome  6 (13%)  4 (11%)  2(20%)   
Septicaemia  0 (0%)  0 (0%)  0 (0%)   

. BMI = Body mass index. CRP = C-reactive protein. LDH = Lactic aciddehydrogenase. ICU = Intensive Care Unit. NT-proBNP = N-terminal prohormone brain natriuretic peptide. aPTT = Activated partial thromblastine time. WBC = White blood cells. CPK = creatine phosphokinase.

Six patients had pulmonary CT angiogram for suspicion of pulmonary embolism (PE) of them three (50%) with acute PE. We reported one primary PE and two associated with proximal deep venous thrombosis of lower limb (DVT).

DU showed acute DVT in nine patients (19.5%) of whom two was diagnosed at D 5 despite PAT. Six were proximal (67%) and three (33%) distal (Table 3).In six patients, DVT was without signs and symptoms, two had pain and leg edema (Table 3).

Table 3.

10 patients (21.7%) of the cohort wit VTE.

  P1  P2  P3  P4  P5  P6  P7  P8  P9  P10 
Age (years)  56  70  72  69  67  79  74  81  79  58 
Sex 
DVT  DIST  DIST  PROX  PROX  PROX  NON  PROX  PPROX  DIST  PROX 
PE  NO  NO  Lobar  NO  NO  Lobar  Lobar  CT ND  CT N D  CT ND 
D-dimer (<500 ng/mL)  4631  1337  25,000  19,889  700  4179  7261  N D  N D  6821 
AST (<37 UI/L)  55  115  29  47  30  106  59  47  78  58 
ALT (<61 UI/L)  23  190  37  171  25  174  72  88  44  102 
Total Bilirubin (1−17um/L)  13  11 
GammaGT(15−85 UI/L)  384  286  95  -----  308  21  N D  402  102 
Alkaline Phosphatase 45−117 UI/L  84  126  62  253  61  88  56  N D  319  105 
aPTT (0.86−1.20)  0.83  1.13  1.08  0.85  1.03  1.36  1.07  1.05  1.21  1.11 
PT %  75  76  76  62  84  65  82  57  84  87 
GF(> 90 mL/min)  104  97  92  33  90  55  61  63  65  95 
Platelets (166−308 × 10.9/L)  249  478  249  318  208  311  180  689  251  364 
Treatment  T.LMWH  T.LMWH  T.LMWH  T.LMWH  T.LMWH  T.LMWH  T.LMWH  T.LMWH  T.LMWH  T.LMWH 
ICU  NO  Day 2  NO  Day 1  NO  NO  NO  NO  NO  NO 
Death  NO  NO  NO  NO  NO  Day 6  NO  NO  NO  NO 
Bleeding  NO  NO  NO  NO  NO  NO  NO  NO  NO  NO 

T.LMWH = Therapeutic lower molecular weight heparin. Total Bil = Total Bilirubin. DIST = distal. PROX = Proximal CT = Computed tomography. ND =not done. PT = Prothrombin time. P = Patient.

We observed elevated AT in 28 patients (68.3%),11 of them (24%) had hepatic impairment with AST twice normal (normal <37 UI/). In five (11%) ALT was twice normal (normal < 61 UI/L). Of the 10 patients with VTE, eight (80%) had elevated AT. AST > 74 UI/L was reported in three patients (37.5%) (Fig. 2) and four (50%) had ALT > 120 UI/L. (Fig. 3). Total Bilirubin rate was normal in all patients (mean 9.90 ± 4.01 um/l).

Fig. 2.

AST disorders in the cohort (46 patients) and in the patients with VTE (10 patients) AST UI/L, normal < 37 UI/L.

(0.13MB).
Fig. 3.

ALT disorders in the cohort (46 patients) and in the patients with VTE (10 patients) ALT UI/L, normal< 61 UI/L.

(0.14MB).

Four patients (8.7%) described digestive symptomatology (abdominal pain and nausea). None of our patients had history of liver diseases, two had history of VTE. The management consisted of a bi-antibiotic therapy with Cefotaxime and Azithromycin /IV, paracetamol and oxygen therapy. The patients without acute VTE received PAT, those with acute VTE had a therapeutic anticoagulation with Enoxaparin (100 UI/12 h); however, no bleeding tendency was noted (no bruise, hematoma, digestive bleeding or epistaxis were detected). During hospitalization the evolution was marked by a stability of liver enzymes without aggravation after the initiation of the different therapies.

Eight patients (17.4%) were transferred to the Intensive Care Unit (ICU) for acute respiratory failure. Elevated platelets rate was significantly associated with the transfer (mean326 ± 69.0 versus 270 ± 113 × 10.9/L, p = 0.046) (Table 4).

Table 4.

8 patients(17.4%) Patients Transferred to ICU.

Variable  NO ICU n = 38  ICU n = 8  P value 
Age (years)  68.4 ± 12.3  61.5 ± 9.12  0.15 
ALT (<61 UI/L)  56.7 ± 44.7  65.2 ± 53.2  0.67 
AST (<37UI/L)  52.3 ± 35.6)  52.2 ± 32.5  0.73 
Total Biluribin (1−17um/L)  9.79 ± 3.97  9.79 ± 3.97  0.77 
GammaGT (15−85 UI/L)  116 ± 131)  276 ± 227  0.06 
Alkaline phosphatase (45−117 UI/L)    192 ± 132  0.12 
D-dimer (<500 ng/mL)  2885 ± 5066  3522 ± 6647  0.91 
VTE (n,%)  8(21%)  2(25%) 
GF (>90 ml/min)  78.0 ± 27.9  81.8 ± 40.7  0.14 
BMI (kg/m227.5 (±4.34)  29.6 (±2.76)  0.13 
CPK (26−192 UI/L)  143 (±91.1)  76.6 (±25.7)  0.17 
LDH (57−241 UI/L)  374 (±136)  325 (±194)  0.41 
Hemoglobulin (13.5−16.9 g/dL)  12.9 (±1.96)  11.7 (±2.38  0.086 
Lymphocytes (1.26−3.35 × 10.9/L)  1.31 (±1.53)  1.15 (±0.522)  0.68 
NT-proBNP (<194 pg/mL)  2731 (±5945)  1056 (±1400)  0.97 
Platelets (166−308 × 10.9/L)  270 (±113)  326 (±69.0)  0.046 
Bleeding (n,%)  0 (0%)  0 (0%)   

Three patients died (6.5%). The age (mean 83.3 ± 6.66 versus 65.5 ± 10.9 years, p value 0.017), AST (mean 125 ± 21.9 versus 84.2 ± 69.4 UI/L p < 0.01), GF rate (mean 35.2 ± 17.8 versus 82.9 ± 27.6 mL/min p < 0.01), white blood cells (mean 12.3 ± 3.13 versus7.52 ± 3.97 × 10.9/l, p = 0.048) and N-terminal prohormone brain natriuretic peptide rate (mean 8665 ± 7169 versus 1865 (±4960) pg/mL, p = 0.025) were significantly associated with death. The threepatients indeed died in the conventional unit after cardio-respiratory failure (Table 5).

Table 5.

3 patients (6.5%) Patients died.

  SURVIVED n = 43 (91.3%)  DIED n = 3 (8.7%)  P value 
Age  65.5 ± 10.9  83.3 ± 6.66  0.017 
ALT (<61 UI/L)  55.7 ± 43.3  106 ± 65.6)  0.097 
AST (< 37 IU/L)  84.2 ± 69.4  125 ± 21.9  <0.01 
Total Biluribin (17um/L)  9.89 ± 4.16  8.50 ± 2.12  0.85 
GammaGT (15−85 UI/L)  140 ± 155  128 ± 158  0.87 
Alkaline phosphatase (45−117 UI/L)  156 ± 218  107 ± 29.8  0.33 
d-dimer (<500 ng/mL)  3118 ± 5596  2060 ± 1594  0.72 
VTE (n,%)  9(21.4%)  1(33%)  0.54 
GF (>90 ml/min)  82.9 ± 27.6  35.2 ± 17.8  <0.01 
BMI (kg/m228.1 ± 4.11  27.9 ± 4.14  0.71 
WBC (3.91−10.9 × 10.9/L  7.52 ± 3.97  12.3 ± 3.13  0.048 
Lymphocytes (1.263.35 × 10.9/L)  1.05 ± 0.514  4.32 ± 4.54  0.082 
Platelets (166−308 × 10.9/L)  281 ± 111  272 ± 76.7  0.96 
NT-proBNP (<194 pg/mL)  1865 (±4960)  8665 ± 7169  0.025 
LDH (57-241 UI/L)  366 ± 157  304 ± 79.9  0.59 
Hemoglobulin (13.5-16.9 g/dL)  12.8 ± 1.97  10.8 ± 3.03  0.3 
Prothombin Time (%)  78.0 ± 13.9  82.7 ± 15.3  0.5 
CPK (26-192 UI/L)  124 ± 83.3  96.5 ± 47.4  0.75 
Bleeding (n,%)  0 (0%)  0 (%)   
  DeadP1  DeadP2  DeadP3 
Age (years)  79  80  92 
GF (>90 ml/min)  55  12  34 
WBC (3.91−10.9 × 10.9/L)  10.56  15.92  10.43 
AST (< 37 UI/L)  115  120  149 
NT-proBNP (<194 pg/mL)  1319  15,643  9032 
VTE  Lobar PE  NO  NO 

After their discharge, the patients with VTE were treated at home with therapeutic Enoxaparin (100 UI/12 h), and those without VTE with PAT for 14 days.

With follow-up of 15 and 30 days, we controlled six patients (75%) who had VTE with elevated AT. A treatment with curative DOACs was initiated after normalization of the aminotransferases at Day 15 in fourpatients, in two DAOCs was started at Day 30 (Table 6).

Table 6.

Follow-up Patients D15- D 30.

Variable  P 1  P 7  P 9  P 8  P2  P10 
Age (years)  56  74  79  81  70  58 
Sex 
AST D0 UI/L  55  74  78  80  70  58 
ALT D 0 UI/L  22  59  44  47  115  102 
DVT  D5 distal  D0 Proximal  D0 Distal  D0 Proximal  D0 Distal  D0 Proximal 
PE  NO  LOBAR  PCTA ND  PCTA ND  NO  PCTA ND 
Transfer ICU  NO  NO  NO  NO  D2 after admission  NO 
Death  NO  NO  NO  NO  NO  NO 
AST D15  18  30  19  39  50  52 
ALT D15  45  17  51  100  85 
AST D30  -------  ------  -------  ----  22  22 
ALT D30  -------  -------  --------  ------  60  66 
Bleeding  NO  NO  NO  NO  NO  NO 
DOACs  D15  D15  D15  D15  D30  D30 

PCTA ND = Pulmonary CT angiogram not done.

At D30 after their discharge, 12 patients who had elevated AT without VTE were checked. In 10 patients, liver enzymes were normal.

4Discussion

Thrombosis associated with acute viral infection has been described in the literature. The incidence of thrombosis among hospitalized patients with acute cytomegalovirus (CMV) infection has been studied once by Atzmony L et al. [5]; they retrospectively studied the incidence of DVT as among 140 consecutive patients with acute CMV infection, the incidence of DVT was 2.9%.. In our cohort infected with COVID-19, the prevalence of DVT at Day 0 was 9.7%. A relationship between VTE has been reported in patients with COVID-19 pneumonia.

Cui S. et al. [3] described 25 % of DVT in 81 patients hospitalized in ICU with COVID-19 pneumonia with elevated D-dimer levels. Middeldrop S. et al. [6] reported 20% of VTE events in 198 patients with COVID-19 pneumonia (38% in ICU) during follow-up of 7 days. 21.7 % of our patients had acute VTE with follow-up of 5 days (1 primary PE and 9 DVT).

The significant increase of D-dimer in severe COVID-19 patients is a good index for identifying high-risk groups of VTE. The patients need PTA and in some cases curative anticoagulant treatment [3]. In our study, D-dimer levels were significantly associated with VTE and all the patients had PTA upon admission.

Many viral infections provoke aminotransferases disorders, viral hepatitis in the first place [7]. Other viruses can also disrupt liver function such as CMV [8]. Elevated AT was also observed in respiratory tropism viruses such as Middle East Respiratory Syndrome-Cov [9] and severe acute respiratory syndrome-Cov (SARS) [10].The pathophysiology of the new SARS-Cov-2 virus is still poorly understood but it is admitted that there are forms with digestive symptomatology [11]. In our population,four patients (8.7%) of 46 had digestive signs and symptoms.

Review of the Chinese studies covering 8 studies for a total of 1,628 patients, showed rates ranging from 16.1% to 53.1% of elevated TA during infection with SARS-Cov-2 [12]. Aminotransferases disorders were observed in our cohort in 28 patients (61 %) of them 24% had AST twice normal and in 11% the ALT.

DOACs are indicated in the treatment of thromboembolic events. However, some precautions should be taken before considering their use, especially in cirrhotic patients, cancer, «extreme» weights (≤60 and > 100 kg) [13].Rarely DOACs can indeed cause liver disorders even in patients without particular risk [14]. The patients with significant hepatic impairment (aminotransferases and bilirubin double) normal) were excluded from studies with DOACs. In the presence of significant hepatic impairment and according to the Child-Pugh classification, DOACs may be used with caution [15].We were facing a new pathology, the oral treatment with warfarin was also likely to be compromised [16]. For this reason, we preferred to treat all patients with VTE who had elevated AT with therapeutic LMWH until the standardization of the biological balance sheet.

Patients infected with COVID-19 have an excessive inflammation with a cytokine storm [17], elevated CRP in our population (84.8%) could be related to the inflammatory response.

Our study is limited due to the very small number of patients; the significance of elevated AT and VTE events associated with these disorders may have been influenced by this limited cohort. COVID-19 infection is frequently complicated by elevated AT and VTE. The use of DOACs in the acute VTE in these patients does not appear pertinent. Monitoring of the liver balance should therefore be considered at a distance from the acute episode in the perspective of DOACs relay.

The patients with COVID-19 pneumonia have a profound hypercoagulable state, and complicating venous thrombotic events are common. COVID-19 infection fulfil the three criteria of the Virchow triad among hypercoagulability, endothelial dysfunction [18] and stasis. Hospitalized COVID-19 patients require an early administration of PTA with LMWH as part of their treatment. Based on these findings, these patients also require a follow-up with vein ultrasonography. DU is a quick, easy and non invasive exam.AbbreviationsVTEVenous thromboembolismATAminotransferasesASTAspartate aminotransferaseDOACsDirect oral anticoagulant CPKCreatine Phosphokinase DVTDeep venous thrombosisPEPulmonary EmbolismLMWHLower molecular weight heparinPATProphylactic anticoagulation treatmentDUDuplex ultrasoundGFGlomerular filtrationCRPC-reactive proteinRT-PCRTranscriptase polymerase chain reactionALTAlanine aminotransferaseCTComputed tomographyICUIntensive care unitCMVCytomegalovirusSARSSevere acute respiratory syndromeDDay

AbbreviationsVTE

Venous thromboembolism

AT

Aminotransferases

AST

Aspartate aminotransferase

DOACs

Direct oral anticoagulant

CPK

Creatine Phosphokinase

DVT

Deep venous thrombosis

PE

Pulmonary Embolism

LMWH

Lower molecular weight heparin

PAT

Prophylactic anticoagulation treatment

DU

Duplex ultrasound

GF

Glomerular filtration

CRP

C-reactive protein

RT-PCR

Transcriptase polymerase chain reaction

ALT

Alanine aminotransferase

CT

Computed tomography

ICU

Intensive care unit

CMV

Cytomegalovirus

SARS

Severe acute respiratory syndrome

D

Day

Sources of funding

None.

Conflicts of interest

The authors declare that there is no conflict of interest for this publication.

Acknowledgements

The authors would like to thank Mrs. Floralie GALLION and Mrs. Céline LAPIERRE to their precious help in the data collection

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