Biogenesis aberration: One of the mechanisms of thrombocytopenia in COVID-19

Cuiting Shan; Feng Yu; Xuemei Deng; Li Ni; Xuming Luo; Jialin Li; Si Cai; Mian Huang; Xiongbiao Wang

doi:10.3389/fphys.2023.1100997

Biogenesis aberration: One of the mechanisms of thrombocytopenia in COVID-19

Front Physiol. 2023 Mar 20:14:1100997. doi: 10.3389/fphys.2023.1100997. eCollection 2023.

Authors

Cuiting Shan¹, Feng Yu², Xuemei Deng³, Li Ni², Xuming Luo¹, Jialin Li¹, Si Cai¹, Mian Huang³, Xiongbiao Wang¹

Affiliations

¹ Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
² Shanghai Putuo District People's Hospital, Shanghai, China.
³ Department of Neurology, Wuhan Third Hospital, China and Tongren Hospital of Wuhan University, Wuhan, Hubei, China.

Abstract

Background: The pathogenesis of COVID-19, including thrombocytopenia, has not been fully clarified. The lungs are a major organ of platelet production and thrombocytopenia induced by severe COVID-19 was proposed. Methods: the change of platelet level was analysed with clinical parameters in 95 hospitalized COVID-19 patients in Wuhan Third Hospital. The production of platelets in the lungs was explored in an ARDS rat model. Results: The level of platelets was negatively correlated with disease severity and was recovered with disease improvement. The non-survivors were accompanied by lower levels of platelet. The odds ratio (OR) of the valley level of the platelet count (PLTlow) was greater than 1, suggesting that PLTlow could be a death exposure factor. The platelet/lymphocyte ratio (PLR) was positively associated with severity of COVID-19, and the platelet/lymphocyte ratio threshold of 248.5 was best correlated with death risk (sensitivity 0.641 and specificity 0.815). To demonstrate the possible biogenesis aberration of platelet in lungs, an LPS-induced ARDS rat model was applied. Lower level of platelet in peripheral and less production of platelet from lungs in ARDS were demonstrated. Though megakaryocyte (MK) number in ARDS lungs is higher than controls, the immature platelet fraction (IPF) in postpulmonary blood is still at the same level as prepulmonary in ARDS rat, indicating that ARDS rats generated fewer platelets in lungs. Conclusion: Our data suggested that COVID-19-induced severe lung inflammation may impair platelet production in the lung. Thrombocytopenia may be mainly caused by platelet consumption for multiorgan thrombosis; however, biogenesis aberration of platelet in the lung induced by diffuse interstitial pulmonary damage cannot be ruled out.

Keywords: ARDS; COVID-19; IPF; platelet; platelet production.

Grants and funding

This work was supported by the Plan of Clinical Specialty Construction in Shanghai Putuo District Health System (2020tszk02), the Scientific and Technological Innovation 2030: Major Project of New Generation Artificial Intelligence (No. 2018AAA0100300), Shanghai Natural Science Foundation (20ZR1450400).