Blood Res 2021; 56(4):
Published online December 31, 2021
https://doi.org/10.5045/br.2021.2021131
© The Korean Society of Hematology
Correspondence to : Maryam Sadat Mirenayat, M.D.
ChronicRespiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran 19839-63113, Iran
E-mail: mirenayat_m@yahoo.com
*This study was supported by Isfahan University of Medical Sciences.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background
Since the emergence of coronavirus disease 2019 (COVID-19), various clinical manifestations ranging from asymptomatic to severe, life-threatening courses have been presented. It is well known that COVID-19 patients are at an increased risk of pulmonary thromboembolism (PTE) development; however, the associated demographic, medical, and clinical factors for developing PTE remain unknown. The current study aimed to assess the characteristics of patients with PTE.
Methods
This case-control study was derived from an ongoing population-based investigation of hospitalized patients with COVID-19 pneumonia. The case group included 99 patients with PTE confirmed by computed tomography pulmonary angiography (CTPA), and the controls (N=132) were age-matched patients selected from the PTE-suspected patients with a negative CTPA. The demographic, medical, and clinical characteristics of the study population were entered into the study checklist and compared. A logistic regression test was used to determine the factors associated with PTE development.
Results
Among the 13,099 admitted patients, 690 (5.26%) were suspected of having PTE according to their clinical manifestations. CTPA was performed for suspected cases, and PTE was confirmed in 132 patients (19.13%). Logistic regression assessments revealed that male gender (OR, 2.39; 95%CI, 1.38‒4.13), decreased oxygen saturation (OR, 2.33; 95%CI, 1.27‒4.26), and lower hemoglobin (OR, 0.83, 0.95), and albumin (OR, 0.31; 95%CI, 0.18‒0.53) levels were associated with PTE development.
Conclusion
PTE was confirmed in one-fifth of suspected patients who underwent CTPA imaging. Male sex, decreased oxygen saturation, and lower levels of hemoglobin and albumin were independent predictors of PTE in patients with COVID-19 pneumonia.
Keywords COVID-19, Pulmonary embolism, Computed tomography angiography, Coronavirus
Blood Res 2021; 56(4): 293-300
Published online December 31, 2021 https://doi.org/10.5045/br.2021.2021131
Copyright © The Korean Society of Hematology.
Somayeh Sadeghi1,2, Maryam Nasirian1,3, Elaheh Keivany4,5, Peiman Nasri6,7, Maryam Sadat Mirenayat8
1Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, 2Acquired Immunodeficiency Research Center, Al-Zahra Hospital, Isfahan University of Medical Sciences, 3Epidemiology and Biostatistics Department, Health School, Isfahan University of Medical Sciences, 4Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, 5Department of Pulmonology, Isfahan University of Medical Sciences, 6Metabolic Liver Disease Research Center, Isfahan University of Medical Sciences, 7Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, 8Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Correspondence to:Maryam Sadat Mirenayat, M.D.
ChronicRespiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran 19839-63113, Iran
E-mail: mirenayat_m@yahoo.com
*This study was supported by Isfahan University of Medical Sciences.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background
Since the emergence of coronavirus disease 2019 (COVID-19), various clinical manifestations ranging from asymptomatic to severe, life-threatening courses have been presented. It is well known that COVID-19 patients are at an increased risk of pulmonary thromboembolism (PTE) development; however, the associated demographic, medical, and clinical factors for developing PTE remain unknown. The current study aimed to assess the characteristics of patients with PTE.
Methods
This case-control study was derived from an ongoing population-based investigation of hospitalized patients with COVID-19 pneumonia. The case group included 99 patients with PTE confirmed by computed tomography pulmonary angiography (CTPA), and the controls (N=132) were age-matched patients selected from the PTE-suspected patients with a negative CTPA. The demographic, medical, and clinical characteristics of the study population were entered into the study checklist and compared. A logistic regression test was used to determine the factors associated with PTE development.
Results
Among the 13,099 admitted patients, 690 (5.26%) were suspected of having PTE according to their clinical manifestations. CTPA was performed for suspected cases, and PTE was confirmed in 132 patients (19.13%). Logistic regression assessments revealed that male gender (OR, 2.39; 95%CI, 1.38‒4.13), decreased oxygen saturation (OR, 2.33; 95%CI, 1.27‒4.26), and lower hemoglobin (OR, 0.83, 0.95), and albumin (OR, 0.31; 95%CI, 0.18‒0.53) levels were associated with PTE development.
Conclusion
PTE was confirmed in one-fifth of suspected patients who underwent CTPA imaging. Male sex, decreased oxygen saturation, and lower levels of hemoglobin and albumin were independent predictors of PTE in patients with COVID-19 pneumonia.
Keywords: COVID-19, Pulmonary embolism, Computed tomography angiography, Coronavirus
Table 1 . Demographic, clinical, and laboratory characteristics of the studied population..
No PTE (N=132) | PTE (N=99) | ||
---|---|---|---|
Age (yr), mean (SD) | 58.0 (17.9) | 59.0 (17.6) | 0.665 |
Gender-male, N (%) | 63 (47.7) | 68 (68.7) | 0.001a) |
Comorbidities, N (%) | |||
Diabetes mellitus | 22 (16.7) | 19 (19.2) | 0.619 |
Chronic obstructive pulmonary disease | 8 (6.1) | 2 (2.0) | 0.135 |
End-stage renal disease | 0 (0) | 3 (3.0) | - |
Malignancy | 3 (3.0) | 3 (3.0) | 1.000 |
Cerebrovascular accident | 7 (5.3) | 6 (6.1) | 0.805 |
Ischemic heart disease | 15 (11.4) | 20 (20.2) | 0.064 |
Previous history of pulmonary thromboembolism | 1 (0.76) | 1 (1.0) | 0.838 |
Having the least of one comorbidity | 48 (36.4) | 38 (38.4) | 0.753 |
Current smoking, N (%) | 10 (7.6) | 12 (12.1) | 0.244 |
History of medications, N/N (%) | |||
None | 31/103 (30.1) | 66/94 (70.2) | <0.0001a) |
Aspirin | 13/102 (12.8) | 20/94 (21.3) | 0.111 |
Clopidogrel | 0/131 (0) | 1/99 (1.0) | 0.249 |
Anticoagulant prophylaxis | 2/132 (1.52) | 3/99 (3.0) | 0.434 |
Therapeutic anticoagulant | 0/132 (0) | 2/99 (2.0) | 0.156 |
On admission clinical presentations | |||
Systolic blood pressure, mean (SD) | 127.1 (23.6) | 124.1 (17.8) | 0.297 |
Systolic blood pressure <90 mmHg, N (%) | 3 (2.3) | 1 (1.0) | 0.637 |
Diastolic blood pressure, mean (SD) | 77.8 (15.8) | 78.8 (13.1) | 0.624 |
Diastolic blood pressure <60 mmHg, N (%) | 3 (2.3) | 1 (1.0) | 0.637 |
Pulse rate per minute, mean (SD) | 92.3 (18.6) | 94.7 (18.0) | 0.332 |
Pulse rate >100 per minute, N (%) | 33 (25.0) | 33 (33.3) | 0.165 |
Respiratory rate per minute-mean (SD) | 24.5 (6.4) | 24.6 (5.7) | 0.838 |
Respiratory rate >30 per minute, N (%) | 15 (11.4) | 13 (13.1) | 0.684 |
O2 saturation (%), mean (SD) | 86.1 (8.2) | 81.8 (10.9) | 0.001a) |
O2 saturation t <90%, N (%) | 83 (62.9) | 79 (79.8) | 0.005a) |
O2 saturation 90–93%, N(%) | 25 (18.9) | 9 (9.1) | 0.037a) |
O2 saturation >93%, N(%) | 24 (18.2) | 11 (11.1) | 0.138 |
Clinical presentations three days before CT-scan, N (%) | |||
Relative bed rest | 75 (56.8) | 34 (40.5) | 0.019a) |
Complete bed rest | 77 (58.3) | 63 (75.0) | 0.012a) |
On admission laboratory characteristics, mean (SD) | |||
Neutrophil count (per mL) | 6,042 (4,100) | 7,851 (4,016) | 0.001a) |
Lymphocyte count (per mL) | 1,239 (1,015) | 1,048 (1,016) | 0.161 |
Platelet ×103 (per mL) | 193.9 (95.7) | 216.3 (94.4) | 0.905 |
Neutrophil-to-lymphocyte ratio | 6.9 (6.9) | 10.3 (8.1) | 0.001a) |
International normalized ratio | 1.23 (0.56) | 1.27 (0.43) | 0.544 |
Hemoglobin (mg/dL) | 13.3 (1.9) | 12.6 (2.3) | 0.006a) |
Ferritin (μg/L) | 814.7 (582.5) | 817.2 (554.7) | 0.978 |
Fibrinogen degradation products (μg/mL) | 25.8 (8.9) | 26.2 (5.8) | 0.871 |
Fibrinogen (mg/dL) | 331.7 (111.4) | 278.3(106.5) | 0.040a) |
Prothrombin time (s) | 13.8 (5.5) | 14.1 (4.4) | 0.721 |
Partial thromboplastin time (s) | 37.2 (15.7) | 32.4 (8.2) | 0.010a) |
Albumin (g/dL) | 3.64 (0.63) | 3.25 (0.52) | <0.0001a) |
Troponin (ng/mL) | 68.2 (232.8) | 230.0 (495.1) | 0.019a) |
D-dimer (μg/mL) | 2,869 (3,285) | 4,775 (3,641) | 0.001a) |
C-reactive protein (mg/L) | 67.6 (46.3) | 85.2 (45.4) | 0.006a) |
Lactate dehydrogenase (IU/L) | 794.2 (385.1) | 1,016.6 (527.4) | 0.001a) |
Maximum laboratory characteristics-Median (IQR) | |||
D-dimer (μg/mL) | 1,971 (817–4,732) | 3,550 (2,259–8,191) | <0.0001a) |
C-reactive protein (mg/L) | 77 (54–111) | 98 (60–125) | 0.034a) |
Lactate dehydrogenase (IU/L) | 803 (629–1,215) | 1,020 (683–1,380) | 0.017a) |
Maximum increase compared to admission time, mean (min–max) | |||
D-dimer (μg/mL) | 575.9 (0–8,909) | 359.7 (0–9,363) | 0.050 |
C-reactive protein (mg/L) | 11.0 (0–102) | 5.0 (0–86) | 0.032a) |
Lactate dehydrogenase (IU/L) | 188.6 (0–2,242) | 114.3 (0–2,644) | 0.206 |
a)Chi2/exact test for categorical variable, independent T-test or Wilcoxon rank-sum test for continuous variable were significant if
Abbreviation: PTE, pulmonary thromboembolism..
Table 2 . Hospital-related characteristics of the studied population..
No PTE | PTE | ||
---|---|---|---|
Prescribed Drugs | N=131 | N=84 | - |
Hydroxychloroquine | 61 (46.6) | 20 (23.8) | 0.001a) |
Antibiotic | 118 (9.1) | 74 (88.1) | 0.647 |
Remdesivir | 23 (17.6) | 14 (16.7) | 0.866 |
Interferon | 18 (13.8) | 4 (4.8) | 0.034a) |
Favipiravir | 2 (1.53) | 1 (1.20) | 0.845 |
Corticosteroid | 87 (66.4) | 68 (81.0) | 0.020a) |
Kaletra | 13 (9.1) | 7 (8.3) | 0.695 |
Unknown | 1 (0.75) | 15 (15.1) | |
Anticoagulation prior to PTE diagnosis, N (%) | N=130 | N=84 | - |
None | 34 (26.2) | 38 (45.2) | 0.004a) |
Prophylactic doses | 71 (54.6) | 27 (32.1) | 0.001a) |
Intermediate doses | 6 (4.6) | 8 (9.5) | 0.156 |
Therapeutic doses | 19 (14.6) | 11 (13.1) | 0.754 |
Unknown | 2 (1.5) | 15 (15.1) | |
Side effects of anticoagulants, N (%) | N=132 | N=84 | - |
GI-bleeding | 6 (4.6) | 6/84 (7.2) | 0.389 |
Hemoptysis | 8 (6.1) | 5/84 (6.0) | 0.0001a) |
Hematuria | 2 (1.5) | 3/84 (3.6) | 0.327 |
Other | 2 (1.5) | 3/84 (3.6) | 0.327 |
Missing | 0 (0) | 15 (15.1) | |
Disease severitya), N (%) | 13 (9.9) | 10 (10.1) | 0.949 |
Hospitalization outcome, N (%) | N=132 | N=99 | - |
Intensive care unit admission | 59 (44.7) | 47 (47.5) | 0.675 |
Non-invasive ventilation | 12 (9.1) | 25 (25.3) | 0.001a) |
Intubation | 18 (13.6) | 19 (19.2) | 0.255 |
Discharge | 124 (93.9) | 81 (81.8) | 0.004a) |
Death | 8 (6.1) | 18 (18.2) | |
Interval times-day, median (IQR) | N=132 | N=99 | - |
Symptom to admission | 7 (4–10) | 7 (4–14) | 0.467 |
Symptom to computed tomography, scan | 13 (7–17) | 14 (6–20) | 0.841 |
Admission to computed tomography, scan | 2 (0–7) | 4 (3–8) | 0.607 |
Admission to intensive care unit | 2 (0–5) | 3 (1–6) | 0.247 |
Admission to discharged | 9 (5–14) | 10 (7–19) | 0.033a) |
Admission to dead | 13 (12–21) | 8 (13.5–30) | 0.837 |
a)Chi2/exact test for categorical variable, independent T-test or Wilcoxon rank-sum test for continuous variable were significant if
Abbreviation: PTE, pulmonary thromboembolism..
Table 3 . The effect of PTE on hospitalization outcomes..
ICU admission | NIV | Intubation | Dead | Time from admission to | |||
---|---|---|---|---|---|---|---|
Discharge | Death | ||||||
OR/exp(Beta)a)(95% CI) | Crude | 1.11 (0.66–1.88) | 3.37 (1.60–7.12)b) | 1.50 (0.74–3.04) | 3.44 (1.43–8.20)b) | 9.42 (0.36–245) | 8.73 (0.002– 302) |
Adjustedb) | 1.09 (0.64–1.86) | 3.40 (1.59–7.25)b) | 1.48 (0.73–3.02) | 3.41 (1.41–8.28)b) | 4.25 (0.001–271.9) | 9.86 (0.39–249.3) |
a)Binary logistic regression was used to estimate crude and adjusted odds ratio for categorical variables, and linear logistic regression was used to estimate crude and adjusted exponential beta for time to death and discharge. b)Adjusted for severity, age, have at least one underlying disease.
Abbreviations: CI, confidence interval; ICU, intensive care unit; NIV, non-invasive ventilation; OR, odds ratio..
Table 4 . Logistic regression analysis of factors associated with PTE..
OR (95% CI)c) | ||
---|---|---|
Crude | Adjustedb) | |
Age | 1.00 (0.98–1.01) | - |
Gender-male | 2.40 (1.39–4.14)d) | 2.39 (1.38–4.13)d) |
On admission clinical presentations | ||
O2 saturation percentage | 0.95 (0.92–0.98)d) | - |
O2 saturation <93% | 2.33 (1.27–4.26)d) | - |
Hemoglobin | 0.83 (0.73–0.95)d) | 0.83 (0.73–0.95)d) |
Fibrinogen | 0.99 (0.98–0.99)d) | 0.99 (0.99–1.00) |
Albumin | 0.32 (0.18–0.53)d) | 0.31 (0.18–0.55)d) |
NLR | 1.07 (1.02–1.11)d) | 1.07 (1.02–1.12) |
Troponin | 1.00 (1.00–1.00)d) | 1.01 (1.00–1.01)d) |
D-dimer | 1.00 (1.00–1.00)d) | 1.00 (1.00–1.00)d) |
CRP | 1.00 (1.00–1.01)d) | 1.00 (1.00–1.01)d) |
LDH | 1.00 (1.00–1.00)d) | 1.00 (1.00–1.00)d) |
Maximum laboratory characteristics | ||
D-dimer | 1.00 (1.00–1.00)d) | 1.00 (1.00–1.00)d) |
CRP | 1.01 (0.99–1.01) | 1.01 (0.99–1.01) |
LDH | 1.00 (0.99–1.00) | 1.00 (0.99–1.00) |
Maximum increase compared to admission time | ||
D-dimer | 0.99 (0.99–1.00) | 0.99 (0.99–1.00) |
CRP | 0.98 (0.96–0.99)d) | 0.98 (0.96–0.99)d) |
LDH | 0.99 (0.99–1.00) | 0.99 (0.99–1.00) |
Disease severitya) | 1.03 (0.43–2.5) | - |
At least have one underlying disease | 1.09 (0.63–1.86) | 1.05 (0.61–1.85) |
Hemoptysis | 0.98 (0.30–3.10) | 1.01 (0.30–3.34) |
a)Disease severity defined as O2 sat<90, respiratory rate>30. b)Adjusted by age and severity. c)Binary logistic regression was used to estimate crude and adjusted odds ratio. d)
Abbreviations: CRP, C reactive protein; LDH, lactate dehydrogenase; NLR, neutrophil lymphocyte ratio..
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