Low arterial oxygen partial pressure induces pulmonary thrombocytopenia in patients and a mouse model.

BACKGROUND

Recent basic studies demonstrate that the lung is a primary organ of platelet biogenesis. However, whether the pathophysiological state of the lung affect the platelets is little known. We aim to investigate the incidence of thrombocytopenia in patients with pulmonary infection (PIN) and risk factors associated with pulmonary thrombocytopenia.

METHODS

In total, 11,941 patients with pulmonary infection (PIN) were enrolled, and patients with other three infectious diseases were collected as controls. The incidence of thrombocytopenia was compared, and the risk factors associated with thrombocytopenia in PIN patients were investigated by multivariate analysis. To explore the mechanism of thrombocytopenia, hypoxic model was constructed. Blood platelet counts from the angular vein (PLTs), left ventricle (PLTpost) and right ventricle (PLTpre) were determined. Megakaryocytes identified by anti-CD41 antibody were detected through flow cytometry and immunofluorescence.

RESULTS

The incidence of thrombocytopenia in PIN was higher than that in other three infectious diseases (9.8% vs. 6.4% ~ 5.0%, P < 0.001). Low arterial oxygen partial pressure (PaO2) was an important risk factor for thrombocytopenia (OR = 0.88; P < 0.001). In a hypoxic mouse model, PLTs decreased (518.38 ± 127.92 vs 840.75 ± 77.30, P < 0.05), which showed that low PaO2 induced thrombocytopenia. The difference between the PLTpost and PLTpre (∆PLTpost-pre), representing the production of platelets in the lungs, was significantly attenuated in hypoxic mice when compared with normoxic mice (F = 25.47, P < 0.05). Additionally, proportions of CD41-positive megakaryocytes in the lungs, marrow, spleen all decreased in hypoxic mice.

CONCLUSION

There is a high incidence for thrombocytopenia in PIN patients. Low PaO2-induced thrombocytopenia is associated with impaired generation of platelet in the lungs.