Pulmonary thrombosis in 2019‐nCoV pneumonia?

Last February, the Journal of Thrombosis and Haemostasis published a retrospective study of 138 patients admitted to Tongji Hospital in Wuhan, China, for novel coronavirus (2019‐nCoV) pneumonia.¹

The purpose of this study was to describe the characteristics of coagulative tests in these patients. At admission, the deceased patients showed higher levels of D‐dimer and fibrin degradation products other than significantly prolonged prothrombin time (PT) than survivors. International Society on Thrombosis and Haemostasis (ISTH) criteria for disseminated intravascular coagulation (DIC) were present in 71.4% of non‐survivors and in 0.6% of survivors. The total mortality rate was 11.5%.

The authors suggested an activation of blood coagulation with secondary fibrinolysis. However, they reported only laboratory findings of DIC but no bleeding was mentioned, indicating that there was not an overt DIC.

Our hypothesis is that the abnormal laboratory findings could be an expression of a local DIC, ie, a pulmonary vascular thrombosis with subsequent activation of fibrinolysis. The concept of pulmonary thrombosis has been recently proposed for conditions such as pneumonia, asthma, and chronic obstructive pulmonary disease.² It is known that viral diseases such as those from EBOLA and cytomegaloviruses can induce DIC.3., 4. Therefore, it is not surprising that 2019‐nCoV could be capable of doing the same.

The development of DIC is due to the activation of cytokine‐producing monocytes, such as interleukin 6 and tumor necrosis factor, which in turn induce activation of the endothelial cells and tissue factor that triggers the blood coagulation cascade.⁵ The activation of blood coagulation is essential in counteracting viral infections along with the immune system trapping viruses by forming a fibrin network, thus limiting their dissemination.⁶ However, a massive inflammatory and coagulative response is dangerous because it can lead to a local thrombosis in the lungs.⁷

Acute respiratory distress syndrome (ARDS) has been described in approximately 40% of 201 patients with 2019‐nCoV pneumonia⁸ and it was crucial in increasing the risk of death. ARDS may be associated with pulmonary vascular microthrombosis.⁹

Thus, a different interpretation of the results obtained by Tang et al¹ may be advanced.

It could be possible that pulmonary thrombosis may further complicate the course of 2019‐nCoV pneumonia. It could induce a prothrombotic endothelial dysfunction, which may cause a severe acute inflammation via complement and cytokine release and a blood coagulation activation with vascular microthrombosis that induces a local consumption coagulopathy, ie a DIC, resulting in ARDS (Figure 1 ).

Figure 1.

A drawing to illustrate a possible mechanism inducing pulmonary thrombosis. After nCoV infection monocytes and released cytokines can provoke interstitial inflammation, endothelial damage, and blood coagulation activation. Tissue factor is crucial in that it can be either exposed by monocytes, damaged endothelial cells or activated by the cytokines’ burden. The final result may be thrombin production and consequent alveolar and capillary thrombosis. C, cytokines; DEC, damaged endothelial cells; M, monocyte; nCoV, novel coronavirus; P, pneumocyte; TF, tissue factor; Th, thrombin

What may this suggest? It could be useful to combine drugs to reduce the inflammatory cytokine potential with anticoagulant treatment. Low molecular weight heparin or fondaparinux may be helpful by limiting the vicious circle of inflammation‐blood coagulation activation‐inflammation, thus improving the severely impaired gas exchange in these patients. In particular, fondaparinux was effective in reducing sepsis derived coagulopathy in an animal model¹⁰ further affirming the concept that coagulation and inflammation are closely linked.

AUTHOR CONTRIBUTIONS

All the authors contributed to write the draft of the manuscript.

CONFLICT OF INTEREST

The authors have no conflict of interest to declare.