D-dimer in COVID-19
As COVID-19 continues to swipe around the world, rapid diagnosis as well as prognosis and treatment of the COVID-19 patients has become an equally important topic among clinicians. Recently scientists have discovered that COVID-19 has a host cell receptor, Angiotensin Converting Enzyme II or ACE2. With the help of ACE2, COVID-19 invades the human body rapidly by reproducing on its own at a massive rate, destroying normal cell, tissue and microvascular system, ﬁnally causing acute lung injury, multiple organ failure[2-4], and intravascular coagulation which occurs in 71.4% of patients who died from COVID-19. It is widely known that D-dimer is a signiﬁcant bio-marker which correlates with hypercoagulability. More clinical studies have also revealed the relationship between D-dimer and COVID-19.
As published on Jama by Zhi Yong’s Group, in the patients’ death(non-survivor) group of novel coronavirus pneumonia, the D-dimer level initially increased as the disease developed, until the 7th day when the D-dimer level broke through the normal range, and ﬁnally plateaued at a high level [Figure 1 A]. In comparison, the survivor group remained within the normal range consistently. Another article published in the Lancet also claims that there is a close correlation between the D-dimer level and the mortality rate of victims [Figure 1 B]. The same conclusion was also drawn in Shah’ s research, which utilized a systematic meta-analysis method (including results from 18 articles and a total of 3,682 patients) to draw the forest plots [Figure 1 C, D]. To sum up, whether in severe or dead COVID-19 patients, the D-dimer level was higher than that which was found in non-severe or surviving patients.
Figure 1: Correlation between D-dimer and COVID-19
Application of D-dimer in COVID-19 Prognosis
According to the study by Zhang’s group, D-dimer among all parameters tested in patients with COVID-19 had the highest C-index, which indicates that it has the highest prediction coincidence rate in routine lab testing methods [Figure 3 A]. In addition, they also found the 2 μg/ml of D-dimer could be the cut-oﬀ value of mortality risk of COVID-19, as DD > 2 μg/ml the survival probability will decrease dramatically [Figure 2 B]. Consequently, they based the evaluation of this value and manifested that when 2 μg/ml was set as the cut-oﬀ value, 92.3% of sensitivity and 83.3% of speciﬁcity is the optimum in all groups [Figure 2 C].
There has been evidence regarding an increased incidence of venous thromboembolic events (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients with severe COVID-19 infection, and D-dimer can also be used as a monitoring indicator of VTE and PE with a cut-oﬀ value of 0.55 μg/ml. Furthermore, Yao not only found that patients with over 2 μg/ml D-dimer needed intensive care and early intervention, but suggested a cut-oﬀ value of 1 μg/ml could help doctors identify patients with a poor prognosis .
Figure 2: Numberic Results of D-Dimer by Zhang’s Group
In conclusion, D-dimer has enormous clinical values in the treatment and prognosis of COVID-19 as a sensitive monitoring index. In consideration of disordered coagulation micro-environment in patients infected with COVID-19 or at high risk of VTE induced by reduced activity, increased bed time, or in people being quarantined for hospitalization, testing of D-dimer on a regular basis is necessary for rapid monitoring of disease treatment. While a cut-oﬀ value of over 2 ug/ml has been proved by many researchers monitoring patients’ treatment, laboratories are still advised to set their own standard so the variation in demographics can be taken into account.
Mindray’s Coagulation D-dimer Solution
Mindray’s auto-coagulation analyzers C3100 & C3510 are equipped with both classic mechanical and optical detection mechanisms. The mechanical methodology is insensitive to interference from icteric, lipemic, chylus and hemolytic samples. Moreover, the patented VRIM(VLin-Rate Integrative Method) algorithm has also been developed to combine “Two Point End Method” at a low D-dimer concentration together with “Rate Method” at a higher level [Figure 3]. This has enabled a much wider linearity range of D-dimer results compared with other models on the market [Figure 4].
Patented VRIM Algorithm
Figure 3: Mindray’s patented VRIM Algorithm for D-dimer testing
|Brand B||Two Point End||0.15~3.7|
|Brand C||Two Point End||0.22~3.0|
Figure 4: Comparison of Linearity Range (without dilution) between Mindray and other brands
In addition, Mindray’ s coagulation solution to D-dimer testing is less susceptible to common interferents. As is shown in [Figure 5], when the serum samples are added with bilirubin, hemoglobin, triglycerides and rheumatoid factors at respective concentration, D-dimer results remain at constant levels as before. The Comparison study with Sysmex CS5100 has also shown a good correlation with R2> 97% with interferents added.
|Bilirubin (40 mg/dL)||2.43||2.38|
|Hemoglobin (200 mg/dL)||2.31||2.36|
|Triglycerides (1800 mg/dL)||2.39||2.25|
|Rheumatoid Factor (1300 lU/mL)||1.54||1.55|
Comparison Study when DD<20µg/ml with Interferent
Figure 5: Comparison study with interferents
Mindray’ s D-dimer coagulation reagents are all manufactured in a bottled liquid state which are ready to use [Figure 6], while the majority of coagulation testing kits are made into powder. Simply by opening the cap and loading D-dimer reagents onto the analyzer, preparation can be set up rapidly with ease on Mindray’s coagulation analyzers.
Figure 6: Mindray’s D-dimer coagulation reagents
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