|
 |
| ORIGINAL ARTICLE |
|
| Year : 2023 | Volume
: 22
| Issue : 3 | Page : 286-292 |
|
|
Does follow-up D-dimer level help in predicting oxygenation status, ventilatory support requirement, lung fibrosis, and thromboembolic events in coronavirus disease 2019 pneumonia? A prospective observational study in a tertiary care setting in India
Shital Patil1, Abhijit Acharya2, Gajanan Gondhali3, Ganesh Narwade1
1 Department of Pulmonary Medicine, MIMSR Medical College, Latur, Maharashtra, India
2 Department of Pathology, MIMSR Medical College, Latur, Maharashtra, India
3 Department of Internal Medicine, MIMSR Medical College, Latur, Maharashtra, India
| Date of Submission | 18-Mar-2022 |
| Date of Decision | 16-Oct-2022 |
| Date of Acceptance | 04-Jan-2023 |
| Date of Web Publication | 4-Jul-2023 |
Correspondence Address:
Shital Patil
Department of Pulmonary Medicine, MIMSR Medical College, Latur, Maharashtra
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/aam.aam_47_22
 Abstract | | |
Introduction: Coronavirus disease 2019 (COVID-19) pneumonia is a heterogeneous disease with variable effects on lung parenchyma, airways, and vasculature, leading to long-term effects on lung functions. Materials and Methods: This multicentric, prospective, observational, and interventional study included 1000 COVID-19 cases confirmed with reverse transcription–polymerase chain reaction. All cases were assessed with high-resolution computed tomography thorax, oxygen saturation, inflammatory marker as D-dimer at the entry point, and follow-up. Age, gender, comorbidity, use of bilevel positive airway pressure/noninvasive ventilation (BiPAP/NIV), and outcome as with or without lung fibrosis as per CT severity were key observations. In selected cases, we have performed lower limb venous Doppler and computed tomography (CT) pulmonary angiography to rule out deep-vein thrombosis (DVT) or pulmonary thromboembolism (PTE) respectively. Statistical analysis is performed by using Chi-square test. Observations and Analysis: Age (<50 and >50 years) and gender (male vs. female) has a significant association with D-dimer level (P < 0.00001 and P < 0.010, respectively). CT severity score at the entry point with the D-dimer level has a significant correlation (P < 0.00001). The D-dimer level has a significant association with the duration of illness before hospitalization (P < 0.00001). Comorbidities have a significant association with D-dimer levels (P < 0.00001). D-dimer level has a significant association with oxygen saturation (P < 0.00001). BIPAP/NIV requirement has a significant association with the D-dimer level (P < 0.00001). Timing of BIPAP/NIV requirement during hospitalization has a significant association with D-dimer level (P < 0.00001). Follow-up D-dimer titer during hospitalization as compared to normal and abnormal to entry point level has a significant association with post-COVID lung fibrosis, DVT, and PTE (P < 0.00001). Conclusions: D-dimer has documented a very crucial role in COVID-19 pneumonia in predicting the severity of illness and assessing response to treatment during hospitalization, and follow-up titers have a significant role in step-up or step-down interventions in a critical care setting.
Résumé
Introducción: La neumonía por enfermedad por coronavirus 2019 (COVID 19) es una enfermedad heterogénea con efectos variables sobre el parénquima pulmonar, las vías respiratorias y la vasculatura, lo que lleva a efectos a largo plazo sobre las funciones pulmonares. Materiales y métodos: este estudio multicéntrico, prospectivo, observacional e intervencionista incluyó 1000 casos de COVID 19 confirmados con reacción en cadena de la polimerasa con transcriptasa inversa. Todos los casos fueron evaluados con tomografía computarizada de tórax de alta resolución, saturación de oxígeno, marcador inflamatorio como dímero D en el punto de entrada y seguimiento. La edad, el sexo, la comorbilidad, el uso de presión positiva en las vías respiratorias de dos niveles/ventilación no invasiva (BiPAP/NIV) y el resultado con o sin fibrosis pulmonar según la gravedad de la TC fueron observaciones clave. En casos seleccionados, hemos realizado Doppler venoso de miembros inferiores y angiografía pulmonar por tomografía computarizada (TC) para descartar trombosis venosa profunda (TVP) o tromboembolismo pulmonar (TEP) respectivamente. El análisis estadístico se realiza utilizando la prueba de Chi cuadrado. Observaciones y análisis: la edad (50 años) y el sexo (hombre vs. mujer) tienen una asociación significativa con el nivel de dímero D (P < 0,00001 y P < 0,010, respectivamente). La puntuación de gravedad de la TC en el punto de entrada con el nivel de dímero D tiene una correlación significativa (P < 0,00001). El nivel de dímero D tiene una asociación significativa con la duración de la enfermedad antes de la hospitalización (P < 0,00001). Las comorbilidades tienen una asociación significativa con los niveles de dímero D (P < 0,00001). El nivel de dímero D tiene una asociación significativa con la saturación de oxígeno (P < 0,00001). El requerimiento de BIPAP/NIV tiene una asociación significativa con el nivel de dímero D (P < 0.00001). El momento del requerimiento de BIPAP/NIV durante la hospitalización tiene una asociación significativa con el nivel de dímero D (P < 0.00001). El título de dímero D de seguimiento durante la hospitalización en comparación con el nivel normal y anormal al punto de entrada tiene una asociación significativa con la fibrosis pulmonar, la TVP y la TEP posteriores a la COVID (P < 0,00001). Conclusiones: el dímero D ha documentado un papel muy importante en la neumonía por COVID 19 para predecir la gravedad de la enfermedad y evaluar la respuesta al tratamiento durante la hospitalización, y los títulos de seguimiento tienen un papel importante en las intervenciones de aumento o reducción en un entorno de cuidados críticos.
Mots-clés: Palabras clave: enfermedad por coronavirus 2019, neumonía, dímero D, trombosis venosa profunda, marcador inflamatorio, fibrosis pulmonar, embolia pulmonar
Keywords: Coronavirus disease 2019 pneumonia, D-dimer, deep-vein thrombosis, inflammatory marker, lung fibrosis, pulmonary embolism
How to cite this article:
Patil S, Acharya A, Gondhali G, Narwade G. Does follow-up D-dimer level help in predicting oxygenation status, ventilatory support requirement, lung fibrosis, and thromboembolic events in coronavirus disease 2019 pneumonia? A prospective observational study in a tertiary care setting in India. Ann Afr Med 2023;22:286-92 |
How to cite this URL:
Patil S, Acharya A, Gondhali G, Narwade G. Does follow-up D-dimer level help in predicting oxygenation status, ventilatory support requirement, lung fibrosis, and thromboembolic events in coronavirus disease 2019 pneumonia? A prospective observational study in a tertiary care setting in India. Ann Afr Med [serial online] 2023 [cited 2023 Sep 26];22:286-92. Available from: https://www.annalsafrmed.org/text.asp?2023/22/3/286/380157 |
| Introduction | |  |
The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), originally emerged from China, has documented 274,628,461 confirmed cases and 5,358,978 deaths globally, and 34,752,164 confirmed cases and 478,007 deaths in India.[1] The International Federation of Clinical Chemistry and Laboratory Medicine Task Force on COVID-19 has been established to synthesize up-to-date information on the epidemiology, pathogenesis, and laboratory diagnosis and monitoring of COVID-19, as well as to develop practical recommendations on the use of molecular, serological, and biochemical tests in disease diagnosis and management.[2],[3]
COVID-19 pneumonia is a heterogeneous disease with variable effects on lung parenchyma, airways, and vasculature, leading to long-term effects on lung functions. Although lung is the primary target organ involved in COVID-19, many patients were shown pulmonary and extrapulmonary manifestations of diseases variably during the first and second waves, which occurred as resultant pathophysiological effects of immune activation pathway and direct virus-induced lung damage. In COVID-19 pneumonia, pathophysiology constitutes different pathways such as immune activation, inflammatory, thrombogenic, and direct viral affection to lungs and extrapulmonary tissues. COVID-19, the pandemic disease caused by infection with the novel virus, SARS-CoV-2, can now be added to the already extensive list of conditions that may be associated with elevated D-dimer. The discovery that D-dimer may be elevated in COVID-19 was first reported by physicians in Wuhan, China, where the epidemic started. A study of 191 patients with COVID-19, who were hospitalized in Wuhan during January 2020 at the outset of the pandemic, revealed that D-dimer was elevated in many of these patients, and the magnitude of the elevation was greatest in those who did not survive.[4]
Fibrin degradation products are a highly heterogeneous group of soluble fragments that appear in the circulation as a result of two simultaneous physiological processes: (1) coagulation, resulting in the conversion of soluble fibrinogen into insoluble stabilized fibrin by the enzymes thrombin and factor XIIIa, and (2) fibrinolysis, resulting in the dissolution of the fibrin clot by the enzyme plasmin. The D-dimer fragment is the terminal product of this process.[5] A number of subsequent studies conducted around the world have confirmed that D-dimer is elevated in those with severe COVID-19 and highest in those who are most critically ill and those who do not survive. Much COVID-19 research over the past months has been directed at understanding the significance of D-dimer elevation and the COVID-19-related coagulopathy that is presumed responsible for the elevation.[4]
D-dimer has been extensively investigated for the diagnosis, monitoring, and treatment of venous thromboembolism for which it is used routinely.[6] D-dimer levels are also elevated in conditions of chronic inflammation, such as active malignancy, rheumatoid arthritis, sickle cell disease, and asthma.[7] In the setting of COVID-19, D-dimer has been reported to be higher in subjects who are critically ill or those who expire.[4],[8],[9],[10],[11]
In the present study, we have utilized D-dimer as a basic marker in laboratory panel workup in all COVID patients and analyzed as “core marker” for assessment of coagulation status with other markers of inflammation: interleukin (IL)-6, C-reactive protein (CRP), and ferritin during follow-up in all admitted patients to assess response to therapy and predictor of post-COVID fibrosis, which can be promptly evaluated and treated to have successful treatment outcome.
| Materials and Methods | | |
This multicentric, prospective, and observational study conducted from July 2020 to May 2021, in MIMSR Medical College and Venkatesh Hospital, Latur, India, included 1000 COVID-19 cases confirmed with reverse transcription–polymerase chain reaction (RT-PCR), to find out the role of D-dimer in predicting the severity of illness, assessing response to therapy and outcome as post-COVID fibrosis, and predicting deep-vein thrombosis (DVT)/pulmonary thromboembolism (PTE) in COVID-19 pneumonia cases admitted in the critical care unit. A total of 1000 cases were enrolled in the study after IRB approval and written informed consent of the patient.
Inclusion criteria
COVID-19 patients, confirmed with RT-PCR, above the age of 18 years, hospitalized in the study centers, including those with comorbidities, and irrespective of severity and oxygen saturation, were included in the study.
Exclusion criteria
Those not willing to give consent, not able to perform D-dimer, and not willing to remain in follow-up were excluded from the study.
All study cases were undergone following assessment before enrolling in the study:
- COVID-19 RT-PCR test performed in all cases, if the first test results were negative and radiological features clearly documenting pneumonia, we have repeated the RT-PCR test and enrolled all cases with positive COVID-19 RT-PCR test
- High-resolution computed tomography (HRCT) thorax to assess the severity of lung involvement, and categorized as mild if the score <7, moderated if the score 8–15, and severe if the score >15 or 15–25
- Clinical assessment – vital parameters such as heart rate, oxygen saturation, respiratory rate, blood pressure, and documentation of respiratory adventitious sounds
- Laboratory parameters – complete blood counts, liver functions, blood sugar level, renal functions, and electrocardiogram
- Viral inflammatory markers such as D-dimer, CRP, and IL-6 assessed at the entry point and repeated whenever required during the course of the illness. Normal and abnormal parameter readings were considered as per pathological laboratory standards
- Entry point D-dimer titer was utilized as an assessment tool of the severity of illness with clinical parameters
- If D-dimer analysis was normal at the entry point, then D-dimer titer was repeated on the day of discharge from the hospital or done during hospitalization if the clinical course deteriorates
- If D-dimer analysis was abnormal at the entry point, we repeated on every 72 h as follow-up to assess the severity, progression of illness, and also titer level utilized to assess response to medical treatment
- In selected cases, with abnormal D-dimer or persistent tachycardia, subjected to lower limb venous Doppler to rule out DVT, and or CT pulmonary angiography to rule out PTE
- Follow-up HRCT thorax was done after 12 weeks or 3 months of discharge from the hospital for analysis of post-COVID lung fibrosis in selected cases with abnormal D-dimer level at discharge and required bilevel-positive airway pressure (BIPAP)/noninvasive ventilation (NIV) during hospitalization and cases required oxygen supplementation at home.
D-dimer titer assessment
Normal values: 70–470 mg/dL.
- Interpretation of results
- Normal: D-dimer value up to 470 mg/L
- Positive: Value above 470 mg/dL
- Significant: Two-fold raised D-dimer level
- Highly significant: Four-fold raised D-dimer level
- Follow-up significance: Values raised or decreased in 2-to-4-fold change.
The statistical analysis was performed using the Chi-squared test. Significant values of Chi-squared were seen from the probability table for different degrees of freedom required. P value was considered statistically significant if it was below 0.05 and highly significant in the case if it was < 0.001.
| Results | | |
In the present study of 1000 COVID 19 by COVID 19 RT PCR positive pneumonia cases, in age and gender distribution; males were 65% (650/1000) and females were 35% (350/1000) & age >50 were 60% (600/1000), and age <50 were 40% (400/1000) cases.
CT severity score at the entry point with D-dimer level has a significant correlation in COVID-19 pneumonia cases (P < 0.00001) [Table 1]. | Table 1: Correlation of computed tomography severity (at entry point) and D-dimer in coronavirus disease 2019 cases (n=1000)
Click here to view |
D-dimer level has a significant association with the duration of illness (Doi) in COVID-19 pneumonia cases (P < 0.00001) [Table 2]. | Table 2: Duration of illness at entry point during hospitalization and D-dimer level in coronavirus disease 2019 pneumonia cases (n=1000)
Click here to view |
A significant association between D-dimer and COVID-19 pneumonia has been documented with variables such as age, gender, diabetes mellitus, ischemic heart disease (IHD), hypertension, chronic obstructive pulmonary disease (COPD), and obesity (P < 0.00001) [Table 3]. | Table 3: Other variables and D-dimer level in coronavirus disease 2019 pneumonia cases (n=1000)
Click here to view |
D-dimer level has a significant association with oxygen saturation in COVID-19 pneumonia cases (P < 0.00001) [Table 4]. | Table 4: Oxygen saturation at entry point and D-dimer level in coronavirus disease 2019 pneumonia cases (n=1000)
Click here to view |
BIPAP/NIV requirement during the course of COVID-19 pneumonia in a critical care setting has a significant association with D-dimer level (P < 0.00001) [Table 5]. | Table 5: Correlation of bilevel-positive airway pressure use with D-dimer level in coronavirus disease 2019 pneumonia cases (n=1000)
Click here to view |
Timing of BIPAP/NIV requirement during the course of COVID-19 pneumonia in a critical care setting has a significant association with D-dimer level (P < 0.00001) [Table 6]. | Table 6: Bilevel-positive airway pressure/noninvasive ventilation initiation time at entry point and D-dimer level coronavirus disease 2019 pneumonia cases (n=600)
Click here to view |
Follow-up D-dimer titer during hospitalization as compared to entry point abnormal D-dimer has a significant association in post-COVID lung fibrosis (P < 0.00001) [Table 7]. | Table 7: Abnormal D-dimer level at entry point (n=680) and follow-up and its correlation with post-COVID lung fibrosis
Click here to view |
Follow-up D-dimer titer during hospitalization as compared to entry point normal D-dimer has a significant association in post-COVID lung fibrosis (P < 0.00001) [Table 8]. | Table 8: Normal D-dimer level (n=320) at entry point and follow-up and its correlation with post-COVID lung fibrosis
Click here to view |
Follow-up D-dimer titer during hospitalization as compared to entry point abnormal D-dimer has a significant association in the presence of DVT (P < 0.00001) [Table 9]. | Table 9: Abnormal D-dimer level at entry point (n=680) and its correlation with follow-up titer with deep-vein thrombosis
Click here to view |
Follow-up D-dimer titer during hospitalization as compared to entry point normal D-dimer has a significant association with PTE (P < 0.00001) [Table 10]. | Table 10: Normal D-dimer level (n=320) at the entry point and its correlation with follow-up titer with pulmonary thromboembolism
Click here to view |
| Discussion | | |
Correlation of computed tomography severity (at entry point) and D-dimer in coronavirus disease 2019 cases
In the present study, CT severity score at the entry point with D-dimer level has a significant correlation in COVID-19 pneumonia cases, scores <8, 8–15, and >15 documented normal and abnormal D-dimer levels as in 190/110, 90/210, and 40/360, respectively, of total 1000 study cases (P < 0.00001). We observed that CT severity is the best visual assessment and indirect marker of inflammation which can be collaborated with D-dimer, and as the CT severity score increases, the D-dimer level also increases, which is a marker of coagulation abnormality. Numerous studies[12],[13],[14],[15],[16],[17],[18],[19] have documented similar observations.
Duration of illness at entry point during hospitalization and D-dimer level in coronavirus disease 2019 pneumonia cases (n = 1000)
In the present study, D-dimer level has a significant association with Doi in COVID-19 pneumonia cases, Doi <7 days, 8–15 days, and >15 days of onset of symptoms documented normal and abnormal D-dimer levels in 30/310, 160/300, and 130/70 cases, respectively (P < 0.00001). Doi has direct correlation with D-dimer level i.e., as Doi increases resulted in an increase in inflammatory surge leading to abnormal coagulation cascade and rise in D-Dimer level. Studies by various authors[13],[14],[15],[16],[17],[19],[20],[21],[22],[23],[24],[25] have documented similar observations. We have also documented that entry point abnormal D-dimer with other inflammatory markers such as CRP and IL-6 with Doi more than a week or 7 days is a predictor of prolonged hospital stay with the requirement of ventilatory requirement in the intensive care unit. A similar observation has been documented in various studies.[20],[21],[22],[23],[24]
Correlation of bilevel-positive airway pressure use with D-dimer level in coronavirus disease 2019 pneumonia cases (n = 1000)
In the present study, BIPAP/NIV requirement during the course of COVID 19 pneumonia in a critical care setting has a significant association with D dimer level. (P < 0.00001) Total 155/320 cases with normal D-Dimer and 445/680 cases with abnormal D-Dimer cases required BIPAP/NIV during hospitalization. We have documented a positive correlation with hypoxia and resulting in need of ventilatory support during hospitalization with abnormal D-dimer level. Similarly, various authors[13],[19],[20],[21],[22],[23],[24] have observed that abnormal or high D-dimer is a predictor of poor outcomes and these patients require aggressive interventions such as BIPAP/NIV, mechanical ventilation, or extracorporeal membrane oxygenation in due course and persistent high level denotes higher chances of mortality.
Correlation of oxygen saturation at the entry point and D-dimer level in coronavirus disease 2019 pneumonia cases (n = 1000)
In the present study, D-dimer level has a significant association with oxygen saturation in COVID-19 pneumonia cases; cases with oxygen saturation >90%, 75%–90%, and <75% were observed as normal and abnormal D-dimer levels in 110/100, 150/340, and 60/240 cases, respectively (P < 0.00001). We have documented a positive correlation with hypoxia at the entry point during hospitalization and abnormal D-dimer level, which is similar to studies by various authors.[13],[19] Low oxygen saturation or hypoxia is an independent predictor of poor outcomes in COVID-19 pneumonia, as hypoxia is the trigger for deranged coagulation secondary to an increase in hypoxia-inducible transcription factor, which will increase D-dimer level. Numerous studies[20],[21],[22],[23],[24] have documented similar observations.
Correlation of bilevel-positive airway pressure/noninvasive ventilation initiation time at entry point and D-dimer level coronavirus disease 2019 pneumonia cases (n = 600)
In present study, Timing of BIPAP/NIV requirement during course of covid-19 pneumonia in critical care setting has significant association with abnormal and four-fold rise in D-Dimer level. [p<0.00001] Total 70/180 cases at entry point or <1 day, 160/310 cases during 3-7 days of hospitalization, and 80/100 cases after >7 days of hospitalization required BIPAP/NIV with four-fold raised D-dimer level. We have documented a positive correlation with hypoxia and resulting in the need of ventilatory support during hospitalization with abnormal D-dimer level. Cases with high D-dimer would have required BIPAP/NIV early as compared with normal to slightly raised D-dimer levels, which is in correlation with studies[13],[14],[15],[16],[17],[18],[19] that documented similar observations.
Other important observations in this study
Correlation of abnormal D-dimer level at the entry point (n = 680) and follow-up and its correlation with post-COVID lung fibrosis, deep-vein thrombosis, and pulmonary thromboembolism
In the present study, radiological outcome as post covid lung fibrosis has significant association with four-fold rise in follow up D dimer titer during hospitalization in cases with abnormal D-Dimer titer at entry point. (P < 0.00001) Total 40/210 & 170/210 post covid lung fibrosis cases were having abnormal and four-fold rise in D-Dimer titer respectively. Total 360/470 & 110/470 cases were having no radiological sequelae with abnormal and four-fold rise in D-Dimer titer respectively. In the present study, coagulation abnormality such as DVT has significant association with four-fold rise in follow up D dimer titer during hospitalization in cases with abnormal D-Dimer titer at entry point. (P < 0.00001) Total 40/210 & 170/210 DVT cases were having abnormal and four-fold rise in D-Dimer titer respectively. Total 360/470 & 110/470 cases were having normal venous doppler with abnormal and four-fold rise in D-Dimer titer respectively. We have observed that ongoing inflammation is the key for the rise of D-dimer level irrespective of CT severity score as mild cases were also having a significant rise in D-dimer level as compared to advanced CT severity; thus, it will help in predicting the progression of disease in due course during hospitalization and aggressive steps to be taken during the management of these cases. Numerous studies[19],[26],[27],[28],[29],[30] have documented similar risks of poor outcome and adverse lung outcome as increased D-dimer is an indication of severe inflammatory response and resulted in lung fibrosis in follow-up of survivors of COVID-19 pneumonia.
Correlation of normal D-dimer level (n = 320) at the entry point and follow-up and its correlation with post-COVID lung fibrosis, deep-vein thrombosis, and pulmonary thromboembolism
In the present study, radiological outcome as post covid lung fibrosis has significant association with four-fold rise in follow up D dimer titer during hospitalization in cases with normal or less than four-fold D-Dimer titer at entry point. (P < 0.00001) Total 5/40 & 35/40 post covid lung fibrosis cases were having normal or less than four-fold D-Dimer titer at entry point and sequential four-fold rise in D-Dimer titer respectively. Total 115/280 & 165/280 cases were having no radiological sequelae with normal or less than four-fold D-Dimer titer at entry point and serial four-fold rise in D-Dimer titer respectively. In this study, a small fraction of nonsevere patients evolved and progressed to severe illness during two weeks of symptom onset. These cases having propensity of progression can be earliest picked up by doing serial or follow up D-dimer titers. Therefore, health-care institutions should also pay close attention to mild patients, identify progressors early, and provide appropriate treatment to reduce mortality. In the present study, coagulation abnormality such as Pulmonary embolism has significant association with four-fold rise in follow up D dimer titer during hospitalization in cases with normal or less than four-fold D-Dimer titer at entry point. (P < 0.00001) Total 5/40 & 35/40 Pulmonary embolism cases were having normal or less than four-fold D-Dimer titer at entry point and sequential four-fold rise in D-Dimer titer respectively. Total 115/280 & 165/280 cases were having normal pulmonary angiography with normal or less than four-fold D-Dimer titer at entry point and serial four-fold rise in D-Dimer titer respectively. Authors in various studies[13],[14],[16],[18],[19],[20],[21],[22],[23],[24] have documented similar observations.
Correlation of other variables and D-dimer level in coronavirus disease 2019 pneumonia cases
In the present study, the age of patients, i.e., <50 years and >50 years, has a significant association in COVID-19 cases with normal and abnormal D-dimer levels (P < 0.00001). We have also documented significant association between gender, respiratory symptoms, and haematological parameters such as neutrophil to lymphocyte ratio with normal and abnormal D dimer levels in COVID-19 pneumonia cases. (P < 0.010). Studies by various authors[13],[14],[15],[16],[17],[18],[19],[25],[26],[27],[28],[29],[30],[31] have documented similar observations.
In the present study, comorbidities such as diabetes mellitus, COPD, hypertension, IHD, and obesity have documented a significant association in COVID-19 cases with normal and abnormal D-dimer levels at the entry point (P < 0.00001). Numerous studies[13],[14],[15],[16],[17],[18],[19],[25],[26],[27],[28],[29],[30],[31] have documented similar observations.
| Conclusions | | |
D-dimer is an easily available and universally acceptable inflammatory marker, which has documented a very crucial role in COVID-19 pneumonia in predicting the severity of illness, and assessing response to treatment during hospitalization. D-dimer has an important role during interventions in the intensive care unit, as follow-up titers have a significant role in step-up or step-down interventions in a critical care setting. Correlating D-dimer with variables such as Doi, oxygenation status, and timing of BIPAP/NIV at the entry point is important to have a satisfactory treatment outcome.
Sequential D-dimer titer during follow up has a crucial role in predicting course during hospitalization and guided treatment in these cases with high risk of progression of COVID-19 pneumonia. We have documented a proportionate number of mild COVID-19 cases as per CT Severity with initial normal D-Dimer have progressed to critical illness during the second week of hospitalization and these cases were earliest picked up by follow up D-dimer titers with other inflammatory markers. We recommend follow up titers in all hospitalized cases which will guide timely interventions with successful treatment outcomes. D-dimer follow-up titer can help in predicting the progression of COVID pneumonia, and assessing the risk of post-COVID lung fibrosis.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | |
| 2. | Lippi G, Plebani M. The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks. Clin Chem Lab Med 2020;58:1063-9.  |
| 3. | Bohn MK, Lippi G, Horvath A, Sethi S, Koch D, Ferrari M, et al. Molecular, serological, and biochemical diagnosis and monitoring of COVID-19: IFCC taskforce evaluation of the latest evidence. Clin Chem Lab Med 2020;58:1037-52. |
| 4. | Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020;395:1054-62. |
| 5. | Dempfle CE. Validation, calibration, and specificity of quantitative D-dimer assays. Semin Vasc Med 2005;5:315-20. |
| 6. | Bockenstedt P. D-dimer in venous thromboembolism. N Engl J Med 2003;349:1203-4. |
| 7. | Kabrhel C, Mark Courtney D, Camargo CA Jr., Plewa MC, Nordenholz KE, Moore CL, et al. Factors associated with positive D-dimer results in patients evaluated for pulmonary embolism. Acad Emerg Med 2010;17:589-97. |
| 8. | Levi M, Thachil J, Iba T, Levy JH. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol 2020;7:e438-40. |
| 9. | Shah S, Shah K, Patel SB, Patel FS, Osman M, Velagapudi P, et al. Elevated D-dimer levels are associated with increased risk of mortality in coronavirus disease 2019: a systematic review and meta-analysis. Cardiol Rev 2020;28:295-302. |
| 10. | Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 2020;18:844-7. |
| 11. | Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: Retrospective study. BMJ 2020;368:m1091. |
| 12. | Scherer PM, Chen DL. Imaging pulmonary inflammation. J Nucl Med 2016;57:1764-70. |
| 13. | Wang L, Yang L, Bai L, Huang Z, Peng Y. Association between D-dimer level and chest CT severity score in patients with SARS-COV-2 pneumonia. Sci Rep 2021;11:11636. |
| 14. | Saeed GA, Gaba W, Shah A, Al Helali AA, Raidullah E, Al Ali AB, et al. Correlation between chest CT severity scores and the clinical parameters of adult patients with COVID-19 pneumonia. Radiol Res Pract 2021;2021:669767. |
| 15. | Inamdar AV. Correlation of chest CT severity score with D-dimer levels in patients with COVID-19. Eur Heart J 2021;42:ehab724.1285. |
| 16. | Jesenak M, Brndiarova M, Urbancikova I, Rennerova Z, Vojtkova J, Bobcakova A, et al. Immune parameters and COVID-19 infection – Associations with clinical severity and disease prognosis. Front Cell Infect Microbiol 2020;10:364. |
| 17. | Mohamed IA, Hasan HA, Abdel-Tawab M. CT characteristics and laboratory findings of COVID-19 pneumonia in relation to patient outcome. Egypt J Radiol Nucl Med 2021;52:28. |
| 18. | Berger JS, Kunichoff D, Adhikari S, Ahuja T, Amoroso N, Aphinyanaphongs Y, et al. Prevalence and outcomes of D-dimer elevation in hospitalized patients with COVID-19. Arterioscler Thromb Vasc Biol 2020;40:2539-47. |
| 19. | Gopala Krishna BS, Pranay Krishna P, Ravi Sankar V, Raghu K, Siva Kumar A, Srikanth M, et al. Laboratory markers versus Ct severity score in predicting mortality in Covid 19. Eur J Mol Clin Med 2021;7:1824-31. |
| 20. | Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20. |
| 21. | Yang W, Cao Q, Qin L, Wang X, Cheng Z, Pan A, et al. Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): A multi-center study in Wenzhou city, Zhejiang, China. J Infect 2020;80:388-93. |
| 22. | Yuan J, Zou R, Zeng L, Kou S, Lan J, Li X, et al. The correlation between viral clearance and biochemical outcomes of 94 COVID-19 infected discharged patients. Inflamm Res 2020;69:599-606. |
| 23. | Yang AP, Liu JP, Tao WQ, Li HM. The diagnostic and predictive role of NLR, d-NLR and PLR in COVID-19 patients. Int Immunopharmacol 2020;84:106504. |
| 24. | Shoenfeld Y. Corona (COVID-19) time musings: Our involvement in COVID-19 pathogenesis, diagnosis, treatment and vaccine planning. Autoimmun Rev 2020;19:102538. |
| 25. | Poudel A, Poudel Y, Adhikari A, Aryal BB, Dangol D, Bajracharya T, et al. D-dimer as a biomarker for assessment of COVID-19 prognosis: D-dimer levels on admission and its role in predicting disease outcome in hospitalized patients with COVID-19. PLoS One 2021;16:e0256744. |
| 26. | Zhang L, Yan X, Fan Q, Liu H, Liu X, Liu Z, et al. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J Thromb Haemost 2020;18:1324-9. |
| 27. | Soni M, Gopalakrishnan R, Vaishya R, Prabu P. D-dimer level is a useful predictor for mortality in patients with COVID-19: Analysis of 483 cases. Diabetes Metab Syndr 2020;14:2245-9. |
| 28. | Naymagon L, Zubizarreta N, Feld J, van Gerwen M, Alsen M, Thibaud S, et al. Admission D-dimer levels, D-dimer trends, and outcomes in COVID-19. Thromb Res 2020;196:99-105. |
| 29. | Oualim S, Abdeladim S, Ouarradi AE, Bensahi I, Hafid S, Naitlho A, et al. Elevated levels of D-dimer in patients with COVID-19: Prognosis value. Pan Afr Med J 2020;35:105. |
| 30. | Peiró ÓM, Carrasquer A, Sánchez-Gimenez R, Lal-Trehan N, Del-Moral-Ronda V, Bonet G, et al. Biomarkers and short-term prognosis in COVID-19. Biomarkers 2021;26:119-26. |
| 31. | He X, Yao F, Chen J, Wang Y, Fang X, Lin X, et al. The poor prognosis and influencing factors of high D-dimer levels for COVID-19 patients. Sci Rep 2021;11:1830. |
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10]
|
