key: cord-0714695-7zviroif
authors: Tsaplin, S.; Schastlivtsev, I.; Lobastov, K.; Zhuravlev, S.; Barinov, V.; Caprini, J.
title: The validation of the original and modified Caprini score in COVID-19 patients
date: 2020-06-23
journal: nan
DOI: 10.1101/2020.06.22.20137075
sha: 0baaf797f1c89d4754398ebeda66436adfdf3648
doc_id: 714695
cord_uid: 7zviroif

Objective. The study aimed to validate the original Caprini score and its modifications considering coronavirus disease (COVID-19) as a severe prothrombotic condition in patients admitted to the hospital with confirmed infection. Methods. The relevant data were extracted from the electronic medical records with the implemented Caprini score and were evaluated retrospectively. The score was calculated twice: by the physician at the admission and by the investigator at discharge or after death. The second calculation at discharge, considered additional risk factors that occurred during inpatient treatment. Besides the original Caprini score (a version of 2005), the modified version added the elevation of D-dimer and specific scores for COVID-19 as follows: 2 points for asymptomatic, 3 points for symptomatic and 5 points for symptomatic infection with positive D-dimer, were evaluated in a retrospective manner. The primary endpoint was symptomatic venous thromboembolism (VTE) confirmed by appropriate imaging testing or dissection. The secondary endpoint included the unfavorable outcome as a combination of symptomatic VTE, admission to the intensive care unit, the requirement for invasive mechanical ventilation, and death. The association of eight different versions of the Caprini score with outcomes was evaluated. Results. Totally 168 patients (83 males and 85 females at the age of 58.3{+/-}12.7 years old) were admitted to the hospital between April 30 and May 29, 2020, and were discharged or died up to the time of data analysis. The original Caprini score varied between 2-12 (5.4{+/-}1.8) at the admission and between 2-15 (5.9{+/-}2.5) at discharge or death. The presence of the virus increased these scores and resulted in an increased score with the maximal value for those including COVID-19 points (10.0{+/-}3.0). Patients received prophylactic (2.4%), intermediate (76.8%), or therapeutic (20.8%) doses of enoxaparin. Despite this, the symptomatic VTE was detected in 11 (6.5%) and unfavorable outcomes in 31 (18.5%) patients. The Caprini score of all eight versions demonstrated a significant association with VTE with the highest predictability for the original scale when assessed at discharge. Supplementation of the original score by elevated D-dimer improved predictability only at the admission. Four versions of the Caprini score calculated at the admission had a significant correlation with the unfavorable outcome with the minor advantages of specific COVID-19 points. Conclusion. The study identified a significant correlation between the Caprini score and the risk of VTE or unfavorable outcomes in COVID-19 patients. All models, including specific COVID-19 scores, showed high predictability with minor differences.

Coronavirus disease (COVID-19) is a highly infectious disease caused by the SARS-CoV-2 virus leading to the development of severe pneumonia and acute respiratory distress syndrome (ARDS). The infection has appeared in Wuhan, Hubei Province, China, in December of 2019, and has been spread globally. 1 The high prevalence of venous thromboembolism (VTE), including deep vein thrombosis (DVT), pulmonary embolism (PE), and pulmonary artery (PA) thrombosis, among the inpatients and critically ill patients, have been reported since the beginning of the pandemic. [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] The overall duplex ultrasound scan (DUS) detected the presence of DVT in 46% of the patients in the general ward and up to 79% of the patients in the intensive care unit (ICU). 10, 11 Proven PE using contrast computed tomography (CT) scan was observed in 30% of all COVID-19 patients. 8 The evidence of small and mid-sized PA thrombosis and microthrombi in alveolar capillaries was found in most of the deceased patients in parallel with the occlusion of big branches of PA in 9-33% of dissections. 12-16 Considering the high incidence of thrombotic complications in COVID-19, most of the current guidelines suggest routine pahrmacoprophylaxis using low-molecularweight heparin (LMWH) or unfractionated heparin (UFH) for patients admitted to the hospital. 17-21 Some publications support the intensification of anticoagulation (intermediate to therapeutic doses of heparin) in subjects at individually highest risk for VTE including critical illness, obesity, and high level of D-dimer. 17, 19, 20 The tools mentioned in these publications for VTE risk assessment include: the Caprini score, Padua score, and IMPROVE VTE score. [18] [19] [20] The Padua score was assessed in two papers without a clear correlation with VTE events. 22, 23 To the best of our knowledge, the Caprini and IMPROVE VTE scores have not been validated in COVID-19 patients.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 23, 2020. . https://doi.org/10.1101/2020. 06.22.20137075 doi: medRxiv preprint To cover this gap, we decided to perform the current study aimed to validate the original Caprini score and its modified version considering COVID-19 as a severe prothrombotic condition in patients admitted to the hospital with confirmed SARS-CoV-2 infection. We also tested the influence of several levels of D-dimer combined with the original Caprini score to improve the identification of patients at the highest risk of VTE.

This study is a single-center retrospective analysis of prospectively collected data became mandatory for assessment. The EMRs were extracted on May 30, 2020, when all COVID-19 patients were discharged, and the hospital turned back to the standard care.

The initial Caprini score was calculated by the physician at the time of patients admission. It did not take into account some risk factors related to inpatient treatment (bed rest for >72 hours, central venous catheter, acquired thrombophilia, etc.). Standard coagulation testing, including the level of D-dimer, prothrombin time (PT), activated partial thromboplastin time (APTT), was performed in all admitted patients but was not considered within the primary assessment of Caprini score. The reason being at the time of admission, the blood test results were not known by the initial examiner. In Russia, the indication for inpatient treatment for adults is a moderate to severe disease according to the locally adopted criteria with respiratory rate >22 per min or SpO 2 <93% with room air, a mild illness in subjects over 65 years old with significant co-morbidities (chronic heart failure, diabetes mellitus, chronic obstructive pulmonary disease [COPD]), and pregnancy. We decided that . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted June 23, 2020. all patients with moderate to severe illness and/or representing specific signs of pneumonia on a chest CT scan should receive one Caprini point for pneumonia at the admission as well as one additional score for medical illness with bed rest (Table I) .

The final score was assessed by the two investigators via EMR after patients' discharge or death. The additional risk factors related to inpatient treatment were evaluated. Also, the elevated D-dimer at admission was assessed as "acquired" thrombophilia from the block of 3 scores. We used a liberal or strict approach in the assessment of D-dimer and achieved two different versions of the Caprini score. In the liberal version, we put an additional 3 points for any patient who had elevated D-dimer over the upper limit of normal (ULN: >0,55 mg/L) at the admission. Within the strict version, only patients with D-dimer >3 times ULN (>1,5 mg/L) received the additional 3 points. Due to the coronavirus pandemic, one of the authors (JA Caprini) proposed using a modified score for COVID-19 patients. It adds 2 points for COVID-19 patients with asymptomatic disease, 3 points for those with symptomatic illness, and 5 points for symptomatic patients with a positive D-dimer. This modification also was used for the retrospective analysis. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted June 23, 2020. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted June 23, 2020. Caprini score with current sensitivity and specificity was extracted from the coordinates of ROC curves. The analysis was performed using SPSS version 26 software package (IBM Corp, Armonk, NY). The value of p<0.05 was considered statistically significant.

A total of 168 patients were admitted to the hospital between April 30 and May 29, 2020. Up to the time of data extraction, everybody was discharged or died, and every EMR was eligible for analysis. The number of males and females was equivalent (83 and 85, respectively). The age varied between 21 and 86 (mean of 58.3±12.7) years old. COVID-19 diagnosis was confirmed with polymerase chain reaction on nasopharyngeal swabs of 140 patients (83%); 28 (17%) despite the negative result had a typical pattern of viral pneumonia . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted June 23, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 23, 2020. The risk factor distribution by the Caprini score is represented in Table I . By the original scale, the score ranged from 2 to 12 (mean of 5.4±1.8) as calculated at the admission and between 2 and 15 (mean of 5.9±2.5) as calculated at discharge or death. Among all modifications, the highest score was observed with Caprini[COVID-19] version followed by

, and the original version. All scores significantly increased when they were measured at the end of hospitalization (Table II) .

The symptomatic VTE was detected in 11 of 168 (6.5%; 95% CI, 3.7-11.3%) patients including catheter-related venous thrombosis of upper limbs in 3 (1.8%; 95% CI, 0.6-5.1%) cases; isolated DVT in 2 (1.2%; 95% CI, 0.3-4.3%) cases; combination of DVT and PE in 1 (0.6%; 95% CI, 0.1-3.3%) case, and isolated PE in 5 (3.0%; 95% CI, 1.3-6.8%) cases. Of three DVT, two affected the distal veins, and one -the proximal veins. Thrombosis of calf muscle veins was the only one of these leg clots associated with PE. Of six pulmonary embolism, five were fatal and confirmed by autopsy; the last one was confirmed by CTPA. The statistically significant association with symptomatic VTE was observed for all versions of the Caprini score calculated either at the admission or discharge or death (p<0.001, Figures 1 and 2) . The high predictability was confirmed by the single-factor . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 23, 2020. . https://doi.org/10.1101/2020.06.22.20137075 doi: medRxiv preprint 1 1 logistic regression analysis (Table III) (Table III, 

The Caprini score is the most validated risk assessment tool for VTE that was evaluated in about 5 million medical and surgical patients worldwide. [35] [36] [37] The previous study showed . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 23, 2020. improved predictability when the results of viscoelastic measurements supplemented the original score. 38 However, it has not been validated in patients infected by SARS-CoV-2 to date. Despite this, the American Venous Forum has already recommended using the Caprini score for VTE risk assessment at admission and discharge. 19 They referenced the original Caprini score in their recommendations. The score of ≥ 8 was suggested as an indication for the intensification of pharmacological prophylaxis in the hospital and extended prophylaxis after discharge. Our study is the first to use a COVID-19 modified Caprini score, and compare it to the original score. We also tested some theoretical score modifications based on the D-dimer level. At the same time, our study shows that an original score of (Table IV) .

Interestingly, the incidence of VTE and mortality rate in our study appeared to be lower than previously reported for the general ward. 4 The study was limited by a retrospective character, small sample size, absence of the total instrumental screening for VTE, and lack of follow-up after discharge. Despite these disadvantages, it may be essential to improve VTE risk stratification in COVID-19 patients.

The study identified a direct correlation between the Caprini score and the risk of VTE or unfavorable outcomes in COVID-19 patients. The score of . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 23, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 23, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 23, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 23, 2020. ULN -upper limit of normal . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 23, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 23, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 23, 2020. . https://doi.org/10.1101/2020.06.22.20137075 doi: medRxiv preprint 6 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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The copyright holder for this preprint this version posted June 23, 2020. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

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