Platelet Counts and Patent Ductus Arteriosus in Preterm Infants: An Updated Systematic Review and Meta-Analysis

González-Luis, Gema E.; Ghiradello, Stefano; Bas-Suárez, Pilar; Cavallaro, Giacomo; Mosca, Fabio; Clyman, Ronald I.; Villamor, Eduardo

doi:10.3389/fped.2020.613766

Cited by 8 publications

(11 citation statements)

References 67 publications

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“…Furthermore, a higher platelet count (≥181 × 10 9 /L) before ibuprofen treatment was found to be independently associated with the closure of hsPDA in VLBW infants without concurrent infection. Since Echtler et al (16) first reported that platelets are crucial for ductus arteriosus closure in mice and premature infants, several studies also analyzed the association between low platelet and the patency of ductus arteriosus in preterm infants, yielding conflicting findings (8,(17)(18)(19)(20). Building up the complexity studies investigating whether platelet level affects the closure of PDA after pharmacotherapeutic agents also reported conflicting findings.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…The methodology of this study is based on that of earlier studies of our group on risk factors for PDA [ 27 , 28 , 29 , 30 ]. The study was performed and reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) and meta-analysis of observational studies in epidemiology (MOOSE) guidelines [ 15 ].…”

Section: Methodsmentioning

confidence: 99%

“…As in our previous meta-analyses [ 27 , 28 , 29 , 30 ], the studies were divided according to the way they considered small ductal shunts [ 27 , 28 , 29 , 30 ]. Studies comparing small + large PDA vs. closed DA were classified as reporting on “any PDA.” Studies comparing large PDA vs. small PDA + closed DA were classified as reporting on “hemodynamically significant PDA” (hsPDA).…”

Section: Methodsmentioning

confidence: 99%

Sex Differences in Patent Ductus Arteriosus Incidence and Response to Pharmacological Treatment in Preterm Infants: A Systematic Review, Meta-Analysis and Meta-Regression

Borges-Lujan

González-Luis

Roosen

et al. 2022

JPM

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A widely accepted concept in perinatal medicine is that boys are more susceptible than girls to complications of prematurity. However, whether this ‘male disadvantage of prematurity’ also involves persistent patent ductus arteriosus (PDA) has been scarcely investigated. Our aim was to conduct a systematic review and meta-analysis on studies addressing sex differences in the risk of developing PDA among preterm infants. We also investigated whether the response to pharmacological treatment of PDA differs between boys and girls. PubMed/Medline and Embase databases were searched. The random-effects male/female risk ratio (RR) and 95% confidence interval (CI) were calculated. We included 146 studies (357,781 infants). Meta-analysis could not demonstrate sex differences in risk of developing any PDA (37 studies, RR 1.03, 95% CI 0.97 to 1.08), hemodynamically significant PDA (81 studies, RR 1.00, 95% CI 0.97 to 1.02), or in the rate of response to pharmacological treatment (45 studies, RR 1.01, 95% CI 0.98 to 1.04). Subgroup analysis and meta-regression showed that the absence of sex differences was maintained over the years and in different geographic settings. In conclusion, both the incidence of PDA in preterm infants and the response rate to pharmacological treatment of PDA are not different between preterm boys and girls.

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“…In summary, the aforementioned studies (and recent metaanalyses) on platelet indices and PDA have revealed inconsistent or even conflicting results, which were probably, at least in part, due to differences in study designs, treatment protocols, and the definition of hsPDA (28,34). Furthermore, hematologic indices might be affected by several conditions, such as inflammation, hypoxia and/or volume status, and thus likely represent surrogate markers of neonatal well-being rather than being specific indicators of PDA/hsPDA, e.g., higher PDW values are thought to reflect altered platelet function/activation (35).…”

Section: Platelet Indices and Pdamentioning

confidence: 99%

“…However, it should be noted, that most studies were retrospective in nature, and thus, even the positive studies cannot conclude on any causality as relevant confounding factors might have been missed by the analyses. In addition, the remarkable heterogeneity in study design (selection criteria, genetic background, and timing of platelet counts), diagnostic protocols (timing of echocardiography and criteria used to define hemodynamic significance), and differences in treatment approaches (timing, dosage, and application route) may have influenced the comparability of the available studies (18,26,28).…”

Section: The Effects Of Thrombocytopenia and Platelet Transfusions Onmentioning

confidence: 99%

Current Controversy on Platelets and Patent Ductus Arteriosus Closure in Preterm Infants

et al. 2021

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Platelets are critically involved in murine patent ductus arteriosus (PDA) closure. To date, the clinical significance of these findings in human preterm infants with PDA is still controversial. We discuss the available study data on the role of platelets for PDA closure in preterm infants: Several mostly retrospective studies have yielded conflicting results on whether thrombocytopenia contributes to failed spontaneous ductal closure. The same applies to investigations on the role of thrombocytopenia as a risk factor for unsuccessful ductus arteriosus closure by pharmacological treatment with cyclooxygenase inhibitors. Nonetheless, recent meta-analyses have concluded that thrombocytopenia constitutes an independent risk factor for both failed spontaneous and pharmacological PDA closure in preterm infants. However, the available investigations differ in regard to patient characteristics, diagnostic strategies, and treatment protocols. Several studies suggest that impaired platelet function rather than platelet number is critically involved in failure of ductus arteriosus closure in the preterm infant. A recent randomized-controlled trial on platelet transfusions in preterm infants with PDA failed to show any benefit for liberal vs. restrictive transfusion thresholds on PDA closure rates. Importantly, liberal transfusions were associated with an increased rate of intraventricular hemorrhage, and thus should be avoided. In conclusion, the available evidence suggests that thrombocytopenia and platelet dysfunction contribute to failure of spontaneous and pharmacological PDA closure in preterm infants. However, these platelet effects on PDA seem to be of only moderate clinical significance. Furthermore, platelet transfusions in thrombocytopenic preterm infants in order to facilitate PDA closure appear to cause more harm than good.

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Platelet Counts and Patent Ductus Arteriosus in Preterm Infants: An Updated Systematic Review and Meta-Analysis

Cited by 8 publications

References 67 publications

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

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

Sex Differences in Patent Ductus Arteriosus Incidence and Response to Pharmacological Treatment in Preterm Infants: A Systematic Review, Meta-Analysis and Meta-Regression

Current Controversy on Platelets and Patent Ductus Arteriosus Closure in Preterm Infants

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