Purpose: This study investigated the D-dimer level on admission as a significant predictor of outcomes for COVID-19 patients. Setting: This cross-sectional study was conducted among purposively selected RT-PCR-positive 52 COVID-19 patients in the Intensive Care Unit at Bangabandhu Sheikh Mujib Medical University in Dhaka, Bangladesh, between July 2020 and June 2021. Methodology: The analysis was done using SPSS software version 24. Continuous variables were analyzed for inferential statistics using the Mann-Whitney U and Kruskal-Wallis tests. Pearson's correlation analysis was done on D-dimer and many hematological and biochemical markers in COVID-19 patients. Primary and secondaryoutcome: The primary outcome was in-hospital mortality, and secondary outcomes included a comparison between D-dimer levels and chances of mortality. Results: The mean±SD of the patient's age was 58.09±10.01 years (34-88 years), with 42 (80.8%) being over 50 years old and the majority of them were male 30 (57.7%). A maximum 36 (69.2%) patients fell into the severe COVID-19 category; 36 (69.2%) of the total patients died after 28 days of admission. On admission, D-dimer levels were more significant in death patients compared to those who survived (7.96±7.40 vs 0.98±1.88 µg/mL, p <0.001). Conclusions: On admission, D-dimer levels are strong predictors of COVID-19 severity and death. However, experimental research is needed to explore the actual scenario. Strengths and Limitations: This was a study to predict mortality among COVID-19 patients. Long-term follow-up was not undertaken because it was outside the study's scope, and the D-dimer's half-lifewas around 8 hours. It was a single-centered study. Data Availability Statement: Datasets prepared during and analyzed during the current study are available from the corresponding author upon reasonable request.
D-dimer, a substance produced when blood clots break down, is involved in the clotting and inflammation in people with COVID-19. High D-dimer levels are linked to more severe COVID-19 and worse outcomes [1]. Patients with D-dimer levels over 1000 ng/ml have a 20 times higher risk of dying compared to those with lower levels. However, the main reason behind increased clotting in COVID-19 patients has not been fully discovered. D-dimer is commonly used in medical practice to rule out deep vein and lung blood clots with confirmation of widespread blood clotting. Most people with severe blood clots have high D-dimer levels. D-dimer levels can be high in both normal and abnormal situations, such as during pregnancy, cancer, inflammation, and after surgery [2].High D-dimer levels have been found to strongly predict death in COVID-19 patients in intensive care units (ICUs) in Bangladesh. These high levels are strongly linked to more severe illness and a greater risk of dying. Studies indicated that D-Dimer levels ≥376 ng/mL significantly increase mortality risk by 22.4 times, with a sensitivity of 82.6% and specificity of 82.5%. A D-Dimer cutoff of ≥308 ng/mL is associated with severe disease, enhancing the risk of complications [3].
A study found that D-dimer levels above 1415 ng/mL reported a high likelihood of receiving invasive mechanical ventilation [4]. Another study also found a strong link between D-dimer levels and the severity of COVID-19 and clinical symptoms like cough, joint pain, and muscle pain. To predict survival, the optimal D-dimer cutoff point was <1059 µg/L, with a sensitivity of 75.44% and a specificity of 58.70%. For predicting disease severity, the cutoff point was <2244 µg/L, with an 85.9% sensitivity and a 30.4% specificity [5].Monitoring D-Dimer levels can inform clinical decisions regarding mechanical ventilation and potential anticoagulant therapy, as thrombotic events are prevalent in severe cases.D-Dimer levels are a reliable predictive tool, with studies showing that higher levels correlate with longer ICU stays and increased mortality [6].
A recent study showed that COVID-19 increases the risk of complications like deep vein thrombosis (DVT), venous thromboembolism (VTE), and pulmonary embolism (PE) by up to 25%. The excessive inflammation triggered by severe lung injury in COVID-19 can lead to VTE due to factors such as cytokine storm, endothelial and macrophage activation, DIC, immobilization, and hypoxia. D-dimer levels can effectively predict severe and fatal COVID-19 cases. Moreover, complicated clinical outcomes such as all-cause mortality, ICU hospitalization, ventilation, or acute respiratory distress syndrome (ARDS) [7]. COVID-linked fatalities are connected mainly to increased blood clotting and a heightened risk of blood clot events in the veins, leading to clot-related inflammation in severe cases. Consequently, blood clotting markers could signal the seriousness of the disease and the likelihood of death and assist in determining patient prioritization, treatment approaches, and prognosis monitoring [8].
A study showed that D-dimer levels could predict outcomes in COVID-19 patients. They studied 1643 patients in China, including 691 with high D-dimer levels. Most of these patients had symptoms like fever, dry cough, and issues with breathing, digestion, or the nervous system. They found that 12% patients had too few lymphocytes, while 32.1% had too many of them. Patients with raised D-dimer levels have a higher probability of death and stay in the hospital for an average of 20 days. Elevated D-dimer levels could potentially be an early sign of severe illness and a higher risk of death.Tang et al. studied 183 severe COVID-19 patients and found that non-survivors had significantly higher D-dimer and FDP levels [9]. Poudelet al.also suggested that D-dimer levels greater than 2.0µg/mL could effectively predict in-hospital mortality in COVID-19 patients [10]. The predictive importance and ideal threshold value of D-dimer levels upon admission to reliably predict outcomes have yet to be determined, indicating a need for more study in this field. As a result, this study aimed to investigate D-dimer levels as a predictor of survival of COVID-19 patients [11]. However, more information is needed about the sensitivity and specificity of D-dimer as a predictor of outcomes, particularly when compared to other predictive criteria in our specific situation. Elevated D-dimer levels in COVID-19 patients might be attributed to the body's reaction to viral infections and endothelial cell failure, which causes greater clotting. D-dimer has been shown to have a 77% predictive value for severity and a 75% predictive value for death in COVID-19, with specificity of 71% and 83%, respectively. This study investigated the D-dimer level on admission as a significant predictor of outcomes for COVID-19 patients.
Study Design This cross-sectional study was conducted among 52 RT-PCR-positive COVID-19 patients in the Bangabandhu Sheikh Mujib Medical University Intensive Care Unit from July 2020 to June 2021. The objective was to determine the outcomes of COVID-19 patients concerning D-dimer level on admission. Patients older than 18 years and willing to participate were included purposively in the study. RT-PCR-positive COVID-19 patients who had pregnancy, active cancer &significant surgery, and trauma within the last 30 days were excluded from the study. After describing the detailed purpose and procedure of the study to the patients or their attendant’s, informed written consent was obtained from each patient or their accompanying attendant. Data was collected through face-to-face interviews using a pre-tested, observation-based, peer-reviewed, semi-structured questionnaire and checklist. Socio-demographic data with detailed history of the participants' clinical manifestations and comorbidities, which were recorded for each respondent in a separate questionnaire. After maintaining proper personal protective equipment, optimum relevant physical examinations were performed. Patients' blood samples were collected for CBC, CRP, D-dimer, ALT, AST, Serum urea, Serum creatinine, and Serum ferritin. D–dimer level was detected by standard procedure on the first day of admission by SYSMAX CS-1600 analyzer in the fibrinogen equivalent unit (FEU), and other investigations were performed in the Department of Hematology, Department of Biochemistry BSMMU. Clinical, Hematological, and biochemical information were recorded on separate checklists. The severity of COVID-19 was categorized according to the WHO classification. All patients were treated according to protocol of the National Guideline of Bangladesh. Discharge criteria were two negative reports of RT-PCR at 24 hours apart. Patients were categorized as mild illness, moderate, severe, and critical. Statistical Analysis After collecting the necessary data, it was extensively reviewed for inconsistencies before being edited, coded, and categorized. The data were then tabulated using SPSS software version 24. Descriptive statistics for numerical data included mean, median, and standard deviation, while frequencies and percentages were used for categorical data. Continuous variables were evaluated using the Mann-Whitney U and Kruskal-Wallis tests. Pearson's correlation analysis was also done on D-dimer and many hematological and biochemical indicators in COVID-19 patients. The statistical significance criterion was established at 95% confidence. A p-value of less than 0.05 was judged statistically significant. Ethical Implication Patients and significant families were properly informed about the study's scope and limitations. It was conveyed to them that there would be no bodily or social danger to the volunteers and that they may withdraw from the research at any time. Every stage of the investigation was conducted using proper safety procedures. The patient provided informed written consent.The participants received no inducement to participate in the study. Written approval was also obtained from the relevant department where the study was conducted. BSMMU's Institutional Review Board (IRB) provided ethical approval for the current study. Memo-BSMMU/2020/9137, dated 17/10/20.