Elevated D-Dimer Levels in COVID-19 Patients

March 8, 2021
DdimerCOVID

D-dimer is the primary breakdown fragment of fibrin and is routinely used as a biomarker of fibrinolysis and coagulation [1]. Healthy individuals have low levels of circulating D-dimer, whereas elevated levels are frequently found in conditions associated with chronic inflammation and thrombosis [1]. Given that widespread microthrombi have been observed in multiple organ systems in patients with COVID-19, many recent studies have focused on the role of D-dimer in determining disease outcomes [1]. 

Elevated D-dimer levels have been linked to several adverse events, including thrombosis, critical illness, acute kidney injury, and all-cause mortality [1]. Patients with severe COVID-19 have a higher level of D-dimer than those with a mild infection [3]. A D-dimer level greater than 0.5 μg/ml is associated with severe infection in patients with COVID-19 [3]. Higher in-hospital mortality is associated with D-dimer levels greater than 3 μg/ml [3]. Markedly elevated D-dimer has also been linked to 28-day mortality in COVD-19 patients [3].  

The D-dimer test is commonly used in clinical practice to exclude a diagnosis of deep vein thrombosis (DVT), pulmonary embolism (PE), or disseminated intravascular coagulation (DIC) [2]. Elevated D-dimer levels indicate increased risk of abnormal blood clotting and are found in almost all patients with severe DVT [2,3]. A rise in D-dimer levels has also been associated with a higher mortality rate in community-acquired pneumonia [3]. The amount of D-dimer in the body can be measured using various commercial kits based on a monoclonal antibody [2]. The sensitivity of these D-dimer test kits ranges between 93% and 95% [2]. 

COVID-19 predisposes patients to thrombotic disease, both in venous and arterial circulation, due to excessive inflammation, platelet activation, endothelial dysfunction, and stasis [4]. Patients with COVID-19 infection are up to 25% more likely to experience thrombosis [2]. Elevated D-dimer levels are associated with the disease progression of COVID-19 and increased incidence of coagulopathy [3]. The levels of D-dimer in patients with COVID-19 admitted to the ICU has been reported to be significantly increased [3]. Patients with COVID-19 infections in the ICU are often preemptively treated with therapeutic anticoagulation in order to prevent future thrombotic events [5]. A 2020 study examined the incidence of thrombotic complications in 184 COVID-19 patients admitted to the ICU [5]. The results showed a 31% incidence of thrombotic complications, with PE ranking as the most frequent thrombotic complication [5]. 

There is also evidence to suggest that D-dimer may not only be a biomarker of hypercoagulability but also may participate in pathogenesis [1]. Fibrin degradation products have a direct procoagulant effect by inducing acute pulmonary dysfunction [1]. They also increase platelet aggregation, prostaglandin synthesis, complement activation, and initiation of chemotaxis and neutropenia [1]. Underlying conditions such as diabetes, cancer, stroke, and pregnancy may trigger an increase in D-dimer levels in COVID-19 patients [6]. 

 One of the most consistent hemostatic abnormalities associated with COVID-19 is increased D-dimer levels [4]. Although the cause of this elevation is uncertain, new data has indicated that a 3- to 4-fold rise in D-dimer levels is associated with poorer prognosis [4,6]. When treating patients with COVID-19, physicians should be aware of D-dimer level status and vigilant to signs of thrombotic complications [5]. 

References 

  1. Berger, J., Kunichoff, D., Adhikari, S. et al. (2020). Prevalence and Outcomes of D-Dimer Elevation in Hospitalized Patients With COVID-19. Arteriosclerosis, Thrombosis, And Vascular Biology, 40(10), 2539-2547. doi:10.1161/atvbaha.120.314872 
  1. Rostami, M., & Mansouritorghabeh, H. (2020). D-dimer level in COVID-19 infection: a systematic review. Expert Review of Hematology, 13(11), 1265-1275. doi:10.1080/17474086.2020.1831383 
  1. Yu, H., Qin, C., Chen, M. et al. (2020). D-dimer level is associated with the severity of COVID-19. Thrombosis Research, 195, 219-225. doi:10.1016/j.thromres.2020.07.047 
  1. Demelo-Rodríguez, P., Cervilla-Muñoz, E., Ordieres-Ortega, L. et al. (2020). Incidence of asymptomatic deep vein thrombosis in patients with COVID-19 pneumonia and elevated D-dimer levels. Thrombosis Research, 192, 23-26. doi:10.1016/j.thromres.2020.05.018 
  1. Klok, F., Kruip, M., van der Meer, N. et al. (2020). Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thrombosis Research, 191, 145-147. doi:10.1016/j.thromres.2020.04.013 
  1. Yao, Y., Cao, J., Wang, Q. et al. (2020). D-dimer as a biomarker for disease severity and mortality in COVID-19 patients: a case control study. Journal of Intensive Care, 8(1). doi:10.1186/s40560-020-00466-z 

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