Close Association Between Platelet Biogenesis and Alveolarization of the Developing Lung

Chen, Xueyu; Zhong, Junyan; Han, Dongshan; Yao, Fang; Zhao, Jie; Wagenaar, Gerry T. M.; Yang, Chuanzhong; Walther, Frans J.

doi:10.3389/fped.2021.625031

Cited by 3 publications

(6 citation statements)

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“…Recently, the concept that megakaryopoiesis occurs in the lung parenchyma with significant contribution of the lungs in platelet biogenesis has emerged (74)(75)(76). There is a close association between platelet biogenesis and alveolarization of the lung (77,78), and hypoxia-induced thrombocytopenia associated with reduction of lung megakaryocytes and impaired generation of platelets in the lungs (79). The SARS-CoV-2 virus elicited up-regulation of megakaryocyte progenitors and elevated circulating megakaryocytes in blood in severe COVID-19 (80,81), hypothetically through infection of early megakaryocyte progenitors.…”

Section: Platelet Changesmentioning

confidence: 99%

Meta-Analysis and Systematic Review of Coagulation Disbalances in COVID-19: 41 Studies and 17,601 Patients

Len

Iskakova

Sautbayeva

et al. 2022

Front. Cardiovasc. Med.

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IntroductionCoagulation parameters are important determinants for COVID-19 infection. We conducted meta-analysis to assess the association between early hemostatic parameters and infection severity.MethodsElectronic search was made for papers that addressed clinical characteristics of COVID-19 patients and disease severity. Results were filtered using exclusion and inclusion criteria and then pooled into a meta-analysis to estimate the standardized mean difference (SMD) with 95% confidence interval (CI) for D-dimers, fibrinogen, prothrombin time, platelet count (PLT), activated partial thromboplastin time. To explore the heterogeneity and robustness of our fundings, sensitivity and subgroup analyses were conducted. Publication bias was assessed with contour-enhanced funnel plots and Egger's test by linear regression. Coagulation parameters data from retrospective cohort study of 451 patients with COVID-19 at National Research Center for Cardiac Surgery were included in meta-analysis of published studies.ResultsOverall, 41 original studies (17,601 patients) on SARS-CoV-2 were included. For the two groups of patients, stratified by severity, we identified that D-dimers, fibrinogen, activated partial thromboplastin time, and prothrombin time were significantly higher in the severe group [SMD 0.6985 with 95%CI (0.5155; 0.8815); SMD 0.661 with 95%CI (0.3387; 0.9833); SMD 0.2683 with 95%CI (0.1357; 0.4009); SMD 0.284 with 95%CI (0.1472; 0.4208)]. In contrast, PLT was significantly lower in patients with more severe cases of COVID-19 [SMD −0.1684 with 95%CI (−0.2826; −0.0542)]. Neither the analysis by the leave-one-out method nor the influence diagnostic have identified studies that solely cause significant change in the effect size estimates. Subgroup analysis showed no significant difference between articles originated from different countries but revealed that severity assessment criteria might have influence over estimated effect sizes for platelets and D-dimers. Contour-enhanced funnel plots and the Egger's test for D-dimers and fibrinogen revealed significant asymmetry that might be a sign of publication bias.ConclusionsThe hemostatic laboratory parameters, with exception of platelets, are significantly elevated in patients with severe COVID-19. The two variables with strongest association to disease severity were D-dimers and fibrinogen levels. Future research should aim outside conventional coagulation tests and include analysis of clotting formation and platelet/platelet progenitors characteristics.

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Section: Platelet Changesmentioning

confidence: 99%

Meta-Analysis and Systematic Review of Coagulation Disbalances in COVID-19: 41 Studies and 17,601 Patients

Len

Iskakova

Sautbayeva

et al. 2022

Front. Cardiovasc. Med.

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“…This increase in platelet biogenesis stabilizes at approximately day 20 of life in rats, which coincides with the process of postnatal alveolarization. These findings suggest a role for platelets in alveolarization in the developing lung ( 12 ). Furthermore, we also observed impaired platelet biogenesis in both BPD infants and rats with experimental BPD ( 12 ).…”

Section: Introductionmentioning

confidence: 75%

“…We have previously shown that platelets are reduced in infants and rats with BPD ( 12 ). In this study, we demonstrated that platelet depletion in mice led to alveolar simplification with enlarged alveoli, similar to experimental BPD ( Figures 2E,F ).…”

Section: Resultsmentioning

confidence: 99%

“…Tissue sections were further processed with HRP conjugated anti-mouse/rabbit secondary antibody (#ab6728 or #ab6721, Abcam, Cambridge, MA; diluted 1: 1,000), visualized using the chromogenic substrate NovaRed as recommended by the manufacturer (#SK-4800, Vector, Burlingame, CA, United States), and counterstained briefly with hematoxylin. Mean linear intercept (MLI) was used to assess alveolar development, as previously described ( 12 ). At least 1,000 alveoli per animal were measured.…”

Section: Methodsmentioning

confidence: 99%

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Platelets are indispensable for alveolar development in neonatal mice

et al. 2022

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Previous studies suggest that platelets are involved in fetal and adult lung development, but their role in postnatal lung development especially after premature birth is elusive. There is an urgent need to scrutinize this topic because the incidence of bronchopulmonary dysplasia (BPD), a chronic lung disease after premature birth, remains high. We have previously shown impaired platelet biogenesis in infants and rats with BPD. In this study, we investigated the role of anti-CD41 antibody-induced platelet depletion during normal postnatal lung development and thrombopoietin (TPO)-induced platelet biogenesis in mice with experimental BPD. We demonstrate that platelet deficient mice develop a BPD-like phenotype, characterized by enlarged alveoli and vascular remodeling of the small pulmonary arteries, resulting in pulmonary arterial hypertension (PAH)-induced right ventricular hypertrophy (RVH). Vascular remodeling was potentially caused by endothelial dysfunction demonstrated by elevated von Willebrand factor (vWF) concentration in plasma and reduced vWF staining in lung tissue with platelet depletion. Furthermore, TPO-induced platelet biogenesis in mice with experimental BPD improved alveolar simplification and ameliorated vascular remodeling. These findings demonstrate that platelets are indispensable for normal postnatal lung development and attenuation of BPD, probably by maintaining endothelial function.

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“…In line with this finding, Sallmon et al ( 9) also reported an increase in platelet count after the first course of cyclooxygenase inhibitor (COXI) cycle in both success and failed ductus closure. This could be partially attributed to the physiological increase of platelet count in the postnatal life of premature infants (32). Furthermore, ibuprofen might interfere with platelet function as the authors and other researchers suggested (9,33).…”

Section: Discussionmentioning

confidence: 95%

Platelet Count Might Be Associated With the Closure of Hemodynamically Significant Patent Ductus Arteriosus

Zhong

Lin

et al. 2021

Front. Pediatr.

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Background: Platelet-rich thrombosis leads to the occlusion of arteries. Whether the association between platelet count and closure of hemodynamically significant patent ductus arteriosus (hsPDA) exists remains inconclusive. Given that neonatal platelet count is significantly affected by infection, this study aims to evaluate the association of platelet parameters before ibuprofen treatment with the closure of hsPDA in very low birth weight (VLBW) infants without concurrent infection.Methods: A retrospective study was conducted at the NICU of Shenzhen Maternity and Child Healthcare Hospital from January 2016 to August 2020. VLBW infants diagnosed with hsPDA, treated with oral ibuprofen and without concurrent infection were included in this study. The platelet parameters were retrieved from the whole-blood test routinely performed within 24 h before starting treatment of oral ibuprofen. A multiple regression model was built to evaluate the association between platelet parameters before ibuprofen treatment and successful closure of hsPDA.Results: A total of 129 premature infants with hsPDA were analyzed in this study. After oral ibuprofen treatment, successful closure of hsPDA was achieved in 70 (54.3%) infants. The gestational age at birth and birth weight in infants with successful or failed closure of hsPDA after ibuprofen treatment were 28.3 vs. 27.6 weeks (p = 0.016) and 1,120 vs. 960 g (p = 0.043), respectively. The rate of mechanical ventilation in infants with successful closure of hsPDA was significantly lower compared to those with failed closure of hsPDA, 31.4 vs. 54.2%, p = 0.014. The platelet count in infants with successful closure of hsPDA after ibuprofen treatment was significantly higher compared to those with failed closure of hsPDA, 212 vs. 183 (in a unit of 109/L), respectively (p = 0.024). Multivariate logistic regression analysis showed that a higher platelet count (≥181 × 109/L) before ibuprofen treatment was independently associated with successful closure of hsPDA [odds ratio 2.556, 95% confidence interval (1.101–5.932), p = 0.029].Conclusion: The findings in this study suggest that a higher platelet count before oral ibuprofen treatment may predict the probability of successful closure of hsPDA in VLBW infants.

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Close Association Between Platelet Biogenesis and Alveolarization of the Developing Lung

Cited by 3 publications

References 24 publications

Meta-Analysis and Systematic Review of Coagulation Disbalances in COVID-19: 41 Studies and 17,601 Patients

Meta-Analysis and Systematic Review of Coagulation Disbalances in COVID-19: 41 Studies and 17,601 Patients

Platelets are indispensable for alveolar development in neonatal mice

Platelet Count Might Be Associated With the Closure of Hemodynamically Significant Patent Ductus Arteriosus

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