Discussion
This study aimed to show whether MPV and D-Dimer values could be used early in determining coagulopathy and thrombosis that may occur in the early period in Covid-19 patients. In this way, the rapid implementation of treatment options for coagulopathy and thrombosis in the early period without clinical deterioration will prevent complications that may occur. Our results showed that D-Dimer was significantly higher in the deceased group than in the living group. However, no significant differences were observed between the WBC of the deceased group and living groups.
Although MPV is known as a marker for infectious and inflammatory diseases, its association with Covid-19 disease remains unknown and conflicting results have been reported. Zhong et al. showed in their study that higher MPV levels could be associated with a higher risk of pneumonia in Covid-19 patients. In another study, Lippi et al. examined the relationship between MPV and the severity of Covid-19 disease and concluded that MPV was significantly associated with disease severity and mortality in Covid-19 patients. Guner et al. studied the role of MPV and D-Dimer in predicting disease severity in a study of children with Covid-19 (13-15). Their results showed that D-Dimer was the strongest predictor of hospitalization and disease severity among the studied parameters. However, they found no association between MPV and the severity of Covid-19 disease. Aktas et al. examined the MPV role in predicting the prognosis of Covid-19 disease (16). They found no association between MPV levels and mortality and prognosis in Covid-19 patients. The results of our study were consistent with these findings and showed no significant association between MPV and mortality in Covid-19 patients. The reason for this discrepancy in the results may be hematological influencing factors or comorbidities that require further study.
Another finding in this study was the importance of the D-Dimer marker in predicting disease severity and mortality in Covid-19 patients. D-Dimer is one of the products of fibrin degradation in the body that can be measured in the blood. With the increase of the fibrin lysis process in coagulation disorders, the amount of this product in the blood will also increase and indicate the severity of the disease. In Covid-19 disease, coagulation cascade activity is increased by several mechanisms that are still under investigation, leading to an increase in the amount of D-dimer in patients’ blood. According to studies, an increase in D-Dimer in patients’ blood worsen the patient’s condition. Our results are consistent with these findings (17,18).
Low D-Dimer concentrations can be used to diagnose vascular thrombotic such as pulmonary embolism and Deep Vein Thrombosis (DVT). In other words, increasing the amount of D-Dimer indicates the activity of the coagulation process followed by fibrinolysis (19). The incidence of thrombotic events is one in a thousand people in adults, and risk factors such as infections and inflammatory diseases are involved in this occurrence. Before the Covid-19 pandemic, an increase in D-Dimer in influenza was reported as a pulmonary infection activating the coagulation system (20).
In Covid-19, D-Dimer increases in parallel with CRP, and unlike the classic DIC due to bacterial infection, there is a slight increase in PT and PTT and moderate thrombocytopenia in Covid-19 patients (Platelets ≈ 100x10^9/L). Several studies in Wuhan, China, have shown that an increase in D-Dimer in Covid-19 patients is associated with increased mortality (21-23). Although anticoagulants were not commonly used in these studies, observations suggest that patients receiving anticoagulants indicate lower D-Dimer levels (24).
There is still no agreement among researchers on using D-Dimer values in the management and monitoring of Covid-19 patients. Based on experience in Covid-19 patients, a D-Dimer value of cut-off > 1µg/ml can indicate high risk and poor outcome for the patient. There is no agreement on how to measure D-Dimer and how to function based on the results obtained from its values for receiving anticoagulants in hospitalized patients (23). The D-Dimer level is directly related to the severity of the disease, the area of lung involvement identified on CT, and the oxygen index. Our results are consistent with these findings, in which the median and mean level of D-Dimer was significantly higher in patients who did not survive (25).
The specific mechanisms associated with systemic inflammatory responses in Covid-19 infection are not well understood. In Covid-19, misalignment of the coagulation and anticoagulation cascades leads to worsening of the pathological complications of the lung (19). In influenza, pathogenicity occurs by increasing virus replication, stimulating the immune system, and deviating the immune system, including cellular and protein components. Covid-19 pathogenesis includes extensive alveolar lesion with fibrinous cellular exudate, destruction of squamous lung cells and hyaline membrane formation, pulmonary edema, infiltration of mononuclear inflammatory cells with predominant lymphocytes, similar to what is seen in SARS and MERS (17,18). Increased D-Dimer value indicates increased fibrinolysis and increased burden of Covid-19 infection. Extensive anticoagulant therapy is directly associated with reduced mortality, especially in patients who breathe mechanically (26,27).
New Guidelines published by the IFCC emphasize the considering D-Dimer in Covid-19 patients. Studies on SARS‑CoV‑2 have shown a strong association between disease severity and D-Dimer outcome in Covid-19 patients so that in very severe cases, Disseminated Intravascular Coagulation (DIC) can occur (23). In one study, an increase in the amount of D-Dimer was considered a predictor of the development and exacerbation of respiratory distress in Covid-19, which may be due to the development of pulmonary embolism, especially in severe cases of Covid-19. Wuhan studies showed that Covid-19 patients with D-Dimer ≥ 2.0 µg/ml have a higher mortality rate than lower doses (28).
In terms of risk factors, studies to date have shown that age, gender, and days of hospitalization are not associated with an increased risk of Pulmonary Embolism (PE). Patients who show higher levels of D-Dimer are more likely to develop PE in the next three days. Studies have shown that in severe Covid-19 pneumonia, the risk of developing PE is associated with increased D-dimer levels. The potential link between Covid-19 and vascular embolism is still unclear. It is also shown that mortality in patients with D-Dimer levels higher than 1µg/ml will be higher (17,18).
In one study, comparative studies between bacterial pneumonia and Covid-19 patients showed an increased D-Dimer level in both diseases, but in Covid-19, the increase was much higher. In patients with Covid-19, coagulation system activity increases due to raised blood viscosity after fever and excessive sweating. Risk factors such as long-term hospitalization, old age, and obesity also increase the thrombosis risk. These increase D-Dimer and increase the need for anticoagulants. As inflammation decreases and the patient recovers, the level of D-Dimer decreases in most patients, while in some of these patients, the amount of D-Dimer remains high, contrary to expectations. This justifies the continued use of anticoagulants in these patients to prevent venous thrombosis (29).
In conclusion, our findings in line with previous findings highlight the significant association of D-Dimer in patients with severe Covid-19 and the importance of monitoring it in patients to prevent exacerbation of the disease by anticoagulants. Our results also did not show any significant relationship between the mortality of Covid-19 patients and their MPV levels. Various studies have reported this relationship with different results, which indicates the influence of other factors on this parameter and requires more detailed studies. One of the limitations of this study was the lack of consideration for BMI and common comorbidities affecting hematological parameters. Future studies should consider additional parameters related to hematological factors to elucidate further the association of MPV with Covid-19 severity and mortality.