Low D-Dimer concentrations can be used to exclude venous thrombic events (VTE) such as deep vein thrombosis of the leg (DVT), pulmonary embolism (PE), or disseminated intravascular coagulation (DIC). On the other hand, increased D-Dimer levels indicate the activation of coagulation and following fibrinolytic processes demanding for further diagnostic and therapeutic approaches. (1)
The recently published IFFC Guidelines on COVID-19 strongly suggest D-Dimer testing in patients with COVID-19. (2) Studies show increased D-Dimer concentrations in severe cases of the disease compared to mild cases and healthy or non-COVID patients. (3,4) Finally, D-Dimer on admission was above the reference range in non-survivors in a study by Pan et al. (5)
The initial laboratory findings of international data from nearly 28 thousand COVID-19 patients showed the most significant abnormalities in D-dimer and CRP. Elevated D-Dimer concentrations were consistently observed among all institutions. The average values of hospitalized patients increased with severity and ongoing hospitalization in agreement to earlier studies from China. (6)
In a study by Zhang et al. including 241 COVID-19 patients (57 severe) and over 220 healthy or non-COVID patients, severely ill COVID-19 patients presented with abnormal platelet parameters as well as abnormal coagulation parameters, such as increased D-Dimer. The authors observed increased platelet activity, especially when SARS-CoV-2-RNA was detectable in the bloodstream. (4)
Platelets play a significant role in hemostasis and thrombosis, but they are also part of innate and adaptive immunity. They carry inflammatory molecules, cytokines, and chemokines and express pathogen recognition receptors. Aside from their effects on pathogens, they can be targeted by pathogens as well. Especially viral infections can cause platelet activation and trigger disseminated intravascular coagulopathy and clotting. (7, 8)
Platelets express angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), which are crucial for SARS-CoV-2 cell entry. Zhang et al. showed a dose-dependent activation of platelets and a decrease of platelet ACE2. In their study, SARS-CoV-2 stimulated the release of coagulation factors V and XIII and inflammatory factors such as cytokines. Further experiments indicated the activation of the mitogen-activated protein kinase (MAPK) pathway in platelets to mediate potentiating role on the activity of platelets. The findings propose SARS-CoV-2 mediated activation of platelets and their prothrombotic function may be responsible for thrombotic events in COVID-19 that come along with increased D Dimer values. (4)
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References:
1. Thomas L, editor. Labor und Diagnose: Indikation und Bewertung von Laborbefunden für die medizinische Diagnostik. 6. Aufl. Frankfurt/Main: TH-Books-Verl.-Ges; 2005.
2. IFCC Information Guide on COVID-19 [Internet]. IFCC Information Guide on COVID-19. 2020. Available from: www.ifcc.org/ifcc-news/2020-03-26-ifcc-information-guide-on-covid-19/
3. Song J-W, Zhang C, Fan X, Meng F-P, Xu Z, Xia P, et al. Immunological and inflammatory profiles in mild and severe cases of COVID-19. Nat Commun. 2020;11:3410.
4. Zhang S, Liu Y, Wang X, Yang L, Li H, Wang Y, et al. SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19. J Hematol Oncol. 2020;13:120.
5. Pan F, Zheng C, Ye T, Li L, Liu D, Li L, et al. Different computed tomography patterns of Coronavirus Disease 2019 (COVID-19) between survivors and non-survivors. Sci Rep. 2020;10:11336.
6. Brat GA, Weber GM, Gehlenborg N, Avillach P, Palmer NP, Chiovato L, et al. International electronic health record-derived COVID-19 clinical course profiles: the 4CE consortium. npj Digit Med. 2020;3:109.
7. Assinger A. Platelets and Infection – An Emerging Role of Platelets in Viral Infection. Front Immunol [Internet]. 2014 [cited 2020 Oct 7];5. Available from: journal.frontiersin.org/article/10.3389/fimmu.2014.00649/abstract
8. Li C, Li J, Ni H. Crosstalk Between Platelets and Microbial Pathogens. Front Immunol. 2020;11:1962.
Andreas Bäcker