Discussion
D-dimer is a biomarker of fibrin degradation that can be measured in
plasma. D-Dimer content of normal human plasma is very low, but is
increased relating to thrombosis.
Plasma D-Dimer level has high sensitivity in the diagnosis of VTE, but
with modest specificity. It can be confused by numerous
pathophysiological events, such as inflammation, malignancy, pregnancy,
myocardial infarction, DIC, aortic dissection, and liver and kidney
dysfunction10.
In our study, we report the levels of D-Dimer spread around
1.37-2.89mg/L in the stage of low-flow oxygen in COVID-19, may be caused
by inflammation, and (or) thrombosis, or other factors. An obvious
increasing trend can be found at the D-Dimer levels while the condition
of the patient deteriorated further. Moreover, risk of aggravation of
COVID-19 with D-Dimer>3mg/L is more than 15 times than those
D-Dimer≤3mg/L. Though lack multi-factor regression analysis, other
researchers have reported similar associations. Guan and Tang reported
the significant increase with D-Dimer in COVID-19
death11. Wu found D-Dimer was a risk factors
associated with the development of acute respiratory distress syndrome
(ARDS) and progression from ARDS to death12. Despite
the reason is various and complicated for D-Dimer abnormalities in
COVID-19, disease aggravation accompanied by increased plasma D-Dimer
levels. It is conceivable that D-Dimer may be an effective parameter to
assess the degree of illness.
Whether the D-Dimer abnormalities
were directly responsible for VTE cannot be determined, as its modest
specificity. The high infectivity and pathogenicity of SARS-CoV-2 limit
the routine screening of VTE by Doppler studies of lower limb veins and
pulmonary artery CTA. Diagnosis should be decided according to the
peculiar circumstances and available related tests of the patients, and
how to consider D-Dimer abnormalities in perspective may provide new
ideas for identifying VTE. Inflammatory reactions can activate the
coagulation system, but some differences were found in Zhou’s research
that elevated D-dimer levels occurred earlier than that of inflammatory
factor, suggesting that the very high D-dimer levels observed in
COVID-19 patients are not only secondary to systemic inflammation, but
also reflect true thrombotic disease, possibly induced by cellular
activation that is triggered by the virus13-14. In
addition, a study reported that the incidence of VTE in severe COVID-19
patients in the Intensive Care Unit (ICU) was 25%4.
Besides, 30% patients had acute
pulmonary embolus when pulmonary CT angiograms performed for COVID-19
patients showed in a study of France with 106
patients15. In a cohort study of Wang forecasted that
40% of COVID-19 patients had a high risk of VTE16.
Unlike SARS-CoV, small vessel thrombosis was found not only in pulmonary
but also in multiple organs after SARS-CoV-2 infection in
humans13. Based on a comprehensive analysis of these
consequences, it was hypothesized
that D-Dimer abnormalities and VTE
in COVID-19 had a close relationship. It should be noted that, in one
interesting study, plasmin may cleave a newly inserted furin site in the
S protein of SARS-CoV-2, extracellularly, which increases its
infectivity and virulence17. Elevated plasmin is a
shared feature in people with underlying medical conditions, including
hypertension, diabetes, cardiovascular disease, cerebrovascular disease,
and chronic renal illness. Those people are susceptible to SARS-CoV-2
infection, their elevated plasmin was responsible for D-Dimer
abnormalities.
In addition to its assessment of risk and diagnostic use, D-Dimer has
been proposed to guide anticoagulant therapy gradually. Tang et
al18 showed that the
prophylactic anticoagulation
regimen can reduce the COVID-19 patient mortality when D-Dimer levels
greater than six times of the
normal upper limit value. What is more, Lin et al19suggested beginning prophylactic anticoagulation regimen once D-Dimer up
to four times of the normal. Larger prospective studies are to be
required to support the D-Dimer value can become guidelines on
anticoagulant therapy in the
future, but now its severity of the abnormal value and rate of the
significant change can provide a basis and direction for clinical
treatment. In our present study, in patients on anticoagulant therapy,
the recovery was quick of those plasma D-Dimer≤3mg/L when
anticoagulant therapy was
initiated than that of plasma D-Dimer>3mg/L. Nevertheless, their
hospital stays had no significant difference, it may be related to our
discharge criteria that the condition was significantly alleviated and
nucleic acid tests were negative. Viral infection is a self-limiting
disease, the anticoagulant role of LMWH may alleviate the illness but
does not have a prominent antiviral function.
However, due to the limited number of cases included in our study,
especially hard to collect the matched no anticoagulant therapy
patients, we could not perform further and more conceivable analysis.
Through the analysis of D-Dimer changes at different stages of illness
and its function to suggest much more benefits could be made at
early-stage anticoagulation therapy in severe COVID-19, the guidance of
D-Dimer should not be ignored and should be studied further.