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.