Perinatal factors affecting platelet parameters in late preterm and term neonates

Hayato Go; Hitoshi Ohto; Kenneth E. Nollet; Nozomi Kashiwabara; Mina Chishiki; Masato Hoshino; Kei Ogasawara; Yukihiko Kawasaki; Nobuo Momoi; Mitsuaki Hosoya

doi:10.1371/journal.pone.0242539

Abstract

Platelets parameters including platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) are associated with various physiological and pathological functions in various disease. However, few studies have addressed whether perinatal factors may be associated with platelet parameters at birth in a large cohort of late preterm and term neonates. The aim of this study to investigate perinatal factors affecting platelet parameters in late preterm and term neonates. We retrospectively investigated platelet parameters including PLT, PCT, MPV, and PDW on the first day of life in 142 late preterm and 258 term neonates admitted to our NICU from 2006 through 2020. PLT, MPV, PCT, PDW on Day 0 did not significantly differ between the two groups. In term neonates, multivariate analysis revealed that PCT correlated with being small for gestational age (SGA) (β = -0.168, P = 0.006), pregnancy induced hypertension (PIH) (β = -0.135, P = 0.026) and male sex (β = -0.185, P = 0.002). PLT was associated with SGA (β = -0.186, P = 0.002), PIH (β = -0.137, P = 0.024) and male sex (β = -0.166, P = 0.006). In late preterm neonates, multivariate analysis revealed that PLT were associated with PIH, whereas no factors associated with PDW and MPV were found. In all patients studied, chorioamnionitis (CAM) was significantly associated with MPV (CAM = 10.3 fL vs. no CAM = 9.7 fL, P<0.001). Multivariate analysis showed that SGA, male sex and PIH were associated with PCT and PLT. This study demonstrates that different maternal and neonatal complications affect platelet parameters in late preterm and term neonates.

Citation: Go H, Ohto H, Nollet KE, Kashiwabara N, Chishiki M, Hoshino M, et al. (2020) Perinatal factors affecting platelet parameters in late preterm and term neonates. PLoS ONE 15(11): e0242539. https://doi.org/10.1371/journal.pone.0242539

Editor: Kelli K. Ryckman, Univesity of Iowa, UNITED STATES

Received: December 5, 2019; Accepted: November 4, 2020; Published: November 19, 2020

Copyright: © 2020 Go et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting information files.

Funding: This research proceeded without the benefit of grant money or any other external financial support. Accordingly, funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Introduction

Platelets parameters including platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) are associated with various physiological and pathological functions in various disease [1–3]. Platelet production is a complex process arising from the proliferation and differentiation of megakaryocytes under the stimulating influence of thrombopoietin. Platelet function in premature neonates is immature. Previous research indicated that low birth weight infants were at almost 2.5-fold increased risk for thrombocytopenia [4]. On the other hand, MPV, PDW, PCT are associated with neonatal disease such as sepsis, fungal infection and intraventricular hemorrhage [5–8]. Among extremely low birth weight neonates born to mothers with preeclampsia, the MPV/platelet count (PLT) ratio at birth significantly correlated with mortality [9]. Also, changes of PDW during the neonatal period were associated with thrombocytopenia and with neonatal sepsis in very low birth weight infants [10]. We previously reported that higher MPV correlates with mortality among those born at < 32weeks’ gestation [11].

On the other hand, Alicja et al reported decreased PCT and PLT in late preterm neonates compared with term neonates [12]. However, few studies have addressed whether perinatal factors may be associated with platelet parameters (PCT, PLT, MPV and PDW) at birth in a large cohort of late preterm and term neonates. Recently, some studies have been associated maternal complication such as premature rupture of membranes (PROM), chorioamnionitis (CAM), and pregnancy induced hypertension (PIH) were associated with platelet parameters [13–15]. Therefore, we hypothesized that platelet parameters such as MPV, PCT and PDW could be affected by perinatal factors. The objective of this study was to investigate the factors affecting platelet parameters at birth in late preterm and term neonates.

Materials and methods

Study design and population

This retrospective, single center, cohort study examined records from 2006 through 2020 at the neonatal intensive care unit (NICU) of Fukushima Medical University Hospital. The study protocol was approved by our institutional review board, The Ethics Committee of Fukushima Medical University, Fukushima, Japan. After deliberation, the board decided that no written consent was needed. Of 1789 neonates admitted to our NICU between January 2006 and Mar 2020, there were 400 born at term or late preterm (weeks 35–36). Late preterm neonates and full term neonates numbered 142 and 258, respectively (Fig 1). Exclusion criteria were congenital anomalies, neonatal alloimmune thrombocytopenia, and neonates not tested within 12 hours of birth.

Download:

Fig 1. Flowchart showing enrollment of study subjects.

https://doi.org/10.1371/journal.pone.0242539.g001

Platelet parameter measurements

Blood samples were collected through peripheral venipuncture to measure PLT, PCT, MPV and PDW of each newborn. Complete blood counts were measured using a Sysmex CS-5100 coagulation analyzer (Sysmex, Kobe, Japan) on admission.

Prenatal and postnatal risk factors

Platelet parameters were compared with demographic variables including gender, birth weight (BW), and gestational age (GA). Furthermore, we considered pregnancy-induced hypertension (PIH), chorioamnionitis (CAM, defined clinically, with histopathological confirmation in pre-term placentas) [16]. premature rupture of membranes (PROM), and placental abruption (PA) as possible prenatal risk factors, and small for gestational age (SGA), respiratory distress syndrome (RDS), and Apgar scores as possibly associated with platelet parameters. Infants whose birth weight and height were below the 10^th percentile of the normal curve at each GA were classified as SGA.

Statistical analysis

Platelet parameters from medical records were rendered into median and interquartile range (IQR) as non-normally distributed continuous variables. Differences in categorical variables and continuous variables were assessed for significance using Chi-square and Mann–Whitney U test. Likewise, correlations between BW, GA, and Apgar scores versus platelet parameters were also investigated using Spearman’s rank correlation (r) with P < 0.05 considered to be statistically significant. Moreover, the variables at P < 0.05 in univariate analysis were entered into a multiple regression analysis to identify independent prognostic factors.

Data analysis was performed with SPSS for Mac, release 25.0 (SPSS, Chicago, IL) and Prism 8 (GraphPad Software, San Diego, CA).

Results

Table 1 shows platelet parameters in late preterm and term neonates. There are no significant differences in platelet parameters between late preterm and term neonates. The median of sampling time was 82 min as shown in Fig 2. Fig 3A and 3B show no significant correlation between BW, GA and PLT. Likewise, Fig 3C and 3D show no significant correlation between BW, GA and PCT in late preterm and term neonates.

Download:

Fig 2. Peripheral blood sampling time distribution.

https://doi.org/10.1371/journal.pone.0242539.g002

Download:

Fig 3. Correlation between platelet count, plateletcrit, GA, and BW.

R is Spearman’s correlation coefficient.

https://doi.org/10.1371/journal.pone.0242539.g003

Download:

Table 1. Platelet parameters in late preterm and term neonates.

https://doi.org/10.1371/journal.pone.0242539.t001

Tables 2 and 3 outline the results of univariate and multivariate analyses for the correlation between perinatal factors and platelet parameters in preterm and term neonates, respectively.

Download:

Table 2. Factors affecting platelet parameters in term neonates.

https://doi.org/10.1371/journal.pone.0242539.t002

Download:

Table 3. Factors affecting platelet parameters in late preterm neonates.

https://doi.org/10.1371/journal.pone.0242539.t003

As shown in Table 2, in term neonates, MPV was associated with CAM (CAM = 10.4 fL vs. no CAM = 9.7 fL, P = 0.005). Furthermore, PCT was associated with male sex (male = 0.24% vs. female = 0.27%, P = 0.005), SGA (SGA = 0.23% vs. no SGA = 0.26%, P = 0.024) and PIH (PIH = 0.19% vs. no PIH = 0.50%, P = 0.009), respectively. PLT was also associated with male sex (male = 25.9×10³/μL vs. female = 28.8×10³/μL, P = 0.009), SGA (SGA = 24.8×10³/μL vs. no SGA = 26.7×10³/μL, P = 0.023) and PIH (PIH = 17.4×10³/μL vs. no PIH = 26.5×10³/μL, P = 0.007), respectively. Multivariate analysis revealed that PCT correlated with male sex (β = -0.185, P = 0.002), SGA (β = -0.168, P = 0.006) and PIH (β = -0.135, P = 0.026). PLT was associated with male sex (β = -0.166, P = 0.006), SGA (β = -0.186, P = 0.002) and PIH (β = -0.137, P = 0.024).

As shown in Table 3, univariate analysis revealed that MPV was correlated with PROM in late preterm neonates (PROM = 10.1 fL vs. no PROM = 9.8 fL, P = 0.044). Multivariate analysis associated PLT with PIH (β = -0.194, P = 0.023), whereas no associations with PCT were found in late preterm neonates.

When all patients were studied, multivariate analysis showed that SGA, male sex and PIH were associated with PCT and PLT (S1 Table). Furthermore, MPV was significantly associated with CAM (CAM = 10.3 fL vs. no CAM = 9.7 fL, P = 0.001) and male sex (male = 9.7 fL vs. female = 9.9 fL, P = 0.011).

Next, we compared the differences of platelet parameters, sex and PIH between SGA and not SGA (S2 Table). S2 Table showed that SGA was significantly associated with PIH in preterm neonates. Furthermore, PCT and PLT were significantly decreased in SGA neonates compared with not SGA neonates. All data pertaining to our analyses are contained within the S1 Text.

Discussion

This large cohort showed no differences in platelet parameters at birth between late preterm and term neonates. Previous reports indicated that PLT and PCT were lower in late preterm neonates compared with term neonates [12, 17]. Furthermore, they suggested that GA was significantly correlated with PLT, however, in our study, GA did not correlate with PLT [12]. Instead, there was positive correlation between BW and PLT in late preterm neonates by univariate analysis. These differences may be due to differences in sample size and time of sampling. Other research included 129 neonates: 58 late preterm and 71 full term. Moreover, they found that PLT measured using cord blood was associated with GA and BW in late preterm and term neonates. In our study, we used venous blood at admission to NICU. The mean time of sampling in this study was just under 2 hours after birth.

This study also demonstrates that various maternal and neonatal factors affect platelet parameters in late preterm and term neonates. Especially, late preterm and term SGA neonates had lower PLT and PCT compared with not SGA neonates as previously described [18, 19]. Lower PLT in SGA indicates the immaturity of thrombopoiesis [20, 21]. Roberts suggested that reduced platelet production was characteristic of preterm neonates and they had fewer circulating megakaryocytes [22]. Another study reported that plasma thrombopoietin concentrations were low in thrombocytopenic newborns, indicative of inadequate up-regulation of TPO production [23]. Platelets are produced in the fetal liver, with production transferred to bone marrow in the third trimester [24]. The liver is one of the first organs to be affected by growth restriction. Furthermore, in this study, PIH was associated with lower PLT and PCT. Moreover, PIH is also a significant risk factor for SGA in this study as previously reported. Maternal PIH can result in neonatal thrombocytopenia [13, 25]. However, the pathogenesis of thrombocytopenia among infants born to mothers with PIH remain unknown. One potential mechanism is that maternal hypertension and resultant fetal hypoxia affects megakaryocyte proliferation [13, 26].

The present study suggested that CAM was associated with MPV in term neonates. However, PROM is not associated with MPV as in a previous study [27]. Recently, a retrospective study has reported significant correlation between MPV and intrauterine infection in neonates with thrombocytopenia and leukopenia at birth [23, 28]. Since CAM was indicative of intrauterine infection, our results are consonant with previous studies. Furthermore, PDW in SGA neonates did not differ from those of not SGA neonates. This result agrees with a previous study [29]. Recently, elevated PDW was associated with poor prognosis of various conditions such as carcinoma and cardiovascular disease [1, 30, 31]. Although, Patrick et al reported that high MPV and PDW showed high specificity in neonates with late sepsis [32], there are no late sepsis cases in this study.

Another important finding of the present study concerns PLT differences by sex. Although there are few reports about the relationships between PLT and sex in neonates, a previous study reported that school-age females had higher PLT than their male counterparts [33]. However, the mechanisms responsible for PLT differences by sex are unknown.

Our study has several limitations. First, we used samples of venous blood on admission. The timing of samples might affect platelet parameters. Second, we could not investigate the relationship between platelet parameters and sepsis because few of our preterm infants had sepsis at birth and we did not investigate changes of platelet parameters during the postnatal period. Some studies associated sepsis with elevated MPV in neonates during the postnatal period [32, 34]. Third, Apgar score was not associated with lower PLT in late preterm and term neonates in this study. Some studies previously showed that low Apgar score at 5 minutes was related to thrombocytopenia [35, 36]. Mario et al showed that SGA, low Apgar score at 5 minutes, cesarean delivery and lower gestational age were risk factors for thrombocytopenia in preterm deliveries between 27 and 35 weeks of gestation [35]. In murine models, it is known that hypoxia affects megakaryocyte progenitors and induces thrombocytopenia [37, 38]. Castle et al reported that severe hypoxia significantly shortened the survival of platelets in a murine model [39]. In this study, there were too few subjects with severe birth asphyxia to make any inferences. Since very low birth weight neonatal platelets were markedly less reactive than adult platelets to ADP/epinephrine, further study to investigate the relationship between severe birth asphyxia requiring epinephrine and PLT reactivity is needed [40]. Finally, the subjects of term neonates admitted to our NICU in this study have various diseases such as transient tachypnea of newborn, pneumothorax and RDS or hypoglycemia or birth asphyxia. Although RDS is not associated with platelet indices in this study, these term neonates strictly differ from healthy term neonates.

In summary, this study demonstrates that various maternal and neonatal factors affect platelet parameters in late preterm and term neonates. In particular, SGA male sex, and PIH were associated with lower PLT and PCT in late preterm and term neonates. Furthermore, CAM was significantly associated with MPV. Thus, this study demonstrates that different maternal and neonatal complications affect platelet parameters in late preterm and term neonates.

Supporting information

S1 Table. Factors affecting platelet parameters in late preterm and term neonates.

https://doi.org/10.1371/journal.pone.0242539.s001

(DOCX)

S2 Table. Platelet parameters in SGA and not neonates.

https://doi.org/10.1371/journal.pone.0242539.s002

(DOCX)

S1 Text. This study’s data set.

https://doi.org/10.1371/journal.pone.0242539.s003

(XLSX)

Acknowledgments

We would like to thank Kyohei Miyazaki, Kenichi Sato, Hajime Maeda, and Maki Sato for their productive discussions and comments on the manuscript, as well as for their technical help.

References

1. Martin JF, Kristensen SD, Mathur A, Grove EL, Choudry FA. The causal role of megakaryocyte-platelet hyperactivity in acute coronary syndromes. Nat Rev Cardiol. 2012;9(11):658–70.
- View Article
- Google Scholar
2. Han L, Liu X, Li H, Zou J, Yang Z, Han J, et al. Blood coagulation parameters and platelet indices: changes in normal and preeclamptic pregnancies and predictive values for preeclampsia. PLoS One. 2014;9(2): e114488. pmid:25464515
- View Article
- PubMed/NCBI
- Google Scholar
3. Coban E, Adanir H, Bilgin D. The association of mean platelet volume levels with hypertensive retinopathy. Platelets. 2008;19(2):115–8. pmid:17852776
- View Article
- PubMed/NCBI
- Google Scholar
4. Roberts I, Murray NA. Neonatal thrombocytopenia: causes and management. Arch Dis Child Neonatal Ed. 2003;88: F359–364. pmid:12937037
- View Article
- PubMed/NCBI
- Google Scholar
5. Catal F, Tayman C, Tonbul A, Akca H, Kara S, Tatli MM, et al. Mean platelet volume (MPV) may simply predict the severity of sepsis in pretem infants. Clin Lab. 2014;60(7):1193–200. pmid:25134389
- View Article
- PubMed/NCBI
- Google Scholar
6. ZhaO D, Qiu G, Luo Z, Zhang Y. Platelet parameters and (1,3)-β-D-gulcan as a diagnostic and prognostic marker of invasive fungal disease in preterm infants. PLoS One. 2015;10(4):e0123907. pmid:25874376
- View Article
- PubMed/NCBI
- Google Scholar
7. Aydemir C, Aydemir H, Kokturk F, Kulah C, Mungan AG. The cut-off levels of procalcitonin and C-reactive protein and the kinetics of mean platelet volume in preterm neonates with sepsis. BMC Pediatr. 2018;18(1):253. pmid:30068303
- View Article
- PubMed/NCBI
- Google Scholar
8. Mitsiakos G, Papathanasiou AE, Kyriakidis I, Karagianni P, Tsepis K, Tzimou I, et al. Intraventricular Hemorrhage and Platelet indices in Extremely Premature Neonates. J Pediatr Hematol Oncol. 2016;38(7):533–538. pmid:27849673
- View Article
- PubMed/NCBI
- Google Scholar
9. Aksoy HT, Güzoğlu N, Eras Z, Canpolat FE, Uraş N. Mean platelet volume/count and mortality in extremely low birth weight infants of preeclamptic mothers. Clin Invest Med. 2018;41(3):E130–135. pmid:30315748
- View Article
- PubMed/NCBI
- Google Scholar
10. Kim JY, Yoon J, Lim CS, Choi BM, Yoon SY. Clinical significance of platelet-associated hematological parameters as an early supplementary diagnostic tool for sepsis in thrombocytopenic very-low-birth-weight infants. Platelets. 2015;26(7):620–6. pmid:25275826
- View Article
- PubMed/NCBI
- Google Scholar
11. Go H, Ohto H, Kenneth N, Takano S, Kashiwabara N, Chisiki M, et al. Using Platelet Parameters to Anticipate Morbidity and Mortality Among Preterm Neonates: A Retrospective Study. Front Pediatr. 2020;8:90. pmid:32232019
- View Article
- PubMed/NCBI
- Google Scholar
12. Alicja W, Agnieszka P, Piotr L, Slawomir R, Barbara KW, Milena D, et al. Platelet indices in late preterm newborns. J Matern Fetal Neonatal Med. 2017; 30(14):1699–1703. pmid:27628188
- View Article
- PubMed/NCBI
- Google Scholar
13. Backes CH, Markham K, Moorehead P, Cordero L, Nankervis CA, Giannone PJ. Maternal preeclampsia and neonatal outcomes. J Pregnancy 2011; 214365. pmid:21547086
- View Article
- PubMed/NCBI
- Google Scholar
14. Thalor N, Singh K, Pujani M, Chauhan V, Agarwal C, Ahuja R. A correlation between platelet indices and preeclampsia. Hematol Transfus Cell Ther. 2019;41(2)129–133. pmid:31084762
- View Article
- PubMed/NCBI
- Google Scholar
15. Ekin A, Gezer C, Kulhan G, Avci ME, Taner CE. Can platelet count and mean platelet volume during the first trimester of pregnancy predict preterm premature rupture of membrenes? J Obstet Gynaecol Res. 2015;41(1):23–28. pmid:25130327
- View Article
- PubMed/NCBI
- Google Scholar
16. Tita AT, Andrew WW. Diagnosis and management of clinical chorioamnionitis. Clinics in Perinatology. 2010;37(2):339–354. pmid:20569811
- View Article
- PubMed/NCBI
- Google Scholar
17. Wasiluk A, Osada J, Dabrowska M, Szczepański M, Jasinska E. Does prematurity affect platelet indices? Adv Med Sci. 2009; 54(2):253–5. pmid:19808160
- View Article
- PubMed/NCBI
- Google Scholar
18. Christensen RD, Baer VL, Henry E, Snow GL, Butler A, Sola-Visner MC. Thrombocytopenia in Small-for-Gestational-Age Infants. Pediatrics. 2015; 135(2):e361–70.
- View Article
- Google Scholar
19. Wasiluk A, Mantur M, Kemona H, Szczepański M, Jasińska E, Milewski R. Thrombopoiesis in small for gestational age newborns. Platelets. 2009;20(7):520–524. pmid:19852692
- View Article
- PubMed/NCBI
- Google Scholar
20. Fustolo-Gunnink SF, Vlug RD, Smits-Wintjens VE, Heckman EJ, Te Pas AB, Fijnvandaraat K, et al. Early-Onset Thrombocytopenia in Small-For-Gestational-Age Neonates: A retrospective Cohort Study. PLoS One. 2016; 11(5):e0154853. pmid:27177157
- View Article
- PubMed/NCBI
- Google Scholar
21. Lee E, Lim Z, Malhotra A. Thrombocytopenia in well small for gestational age neonates. Blood Coagul Fibrinolysis. 2019. 30(3):104–110. pmid:30864963
- View Article
- PubMed/NCBI
- Google Scholar
22. Murray NA, Watts TL, Roberts IA. Endogenous thrombopoietin levels and effect of recombinant human thrombopoietin on megakaryocyte precursors in term and preterm babies. Pediatr Res. 1998; 43:148–151. pmid:9432127
- View Article
- PubMed/NCBI
- Google Scholar
23. Watts TL, Murray NA, Roberts IA. Thrombopoietin has a primary role in the regulation of platelet production in preterm babies. Pediatr Res. 1999; 46(1):28–32. pmid:10400130
- View Article
- PubMed/NCBI
- Google Scholar
24. Maruyama H, Shinozuka M, Kondoh Y, Akahori Y, Matsuda M, Inoue S, et al. Thrombocytopenia in Preterm Infants with Intrauterine Growth Restriction. Acta Med. Okayama, 2008:62(5):313–317. pmid:18985091
- View Article
- PubMed/NCBI
- Google Scholar
25. Brazy J. E., Grimm J. K., and Little V. A. Neonatal manifestations of severe maternal hypertension occurring before the thirty-sixth week of pregnancy. J Pediatr. 1982; 100(2):265–271. pmid:7057337
- View Article
- PubMed/NCBI
- Google Scholar
26. Weiner C. P. and Williamson R. A. Evaluation of severe growth retardation using cordocentesis—hematologic and metabolic alterations by etiology. Obstet Gynecol.1989; 73(2): 225–229. pmid:2536145
- View Article
- PubMed/NCBI
- Google Scholar
27. Ekin A, Gezer C, Kulhan G, Avcı ME, Taner CE. Can platelet count and mean platelet volume during the first trimester of pregnancy predict preterm premature rupture of membranes? J Obstet Gynaecol Res. 2015; 41(1);23–28. pmid:25130327
- View Article
- PubMed/NCBI
- Google Scholar
28. Chen CY, Essien MD, Johnson AJ, Lee GT, Chou FS. Use of mean platelet volume in the assessment of intrauterine infection in newborns with thrombocytopenia and leukopenia at birth. J Matern Fetal Neonatal Med. 2019; 1–7. pmid:30983434
- View Article
- PubMed/NCBI
- Google Scholar
29. Wasiluk A, Mantur M, Kenoma H, Szczepański M, Jasińska E, Milewski R. Platelet indices in SGA newborns. Adv Med Sci. 2011. 20(7):520–524. pmid:21940264
- View Article
- PubMed/NCBI
- Google Scholar
30. Zuo X, Kong W, Feng L, Zhang H, Meng X, Chen W. Elevated platelet distribution width predicts poor prognosis in hepatocellular carcinoma. Cancer Biomark. 2019;24(3):307–313. pmid:30829614
- View Article
- PubMed/NCBI
- Google Scholar
31. Xie X, Zeng X, Cao S, Hu X, Shi Q, Li D, et al. Elevated pretreatment platelet distribution width and platelet count predict poor prognosis in nasopharyngeal carcinoma. Oncotarget. 2017:8(62):106089–106097. pmid:29285316
- View Article
- PubMed/NCBI
- Google Scholar
32. Patrick CH, Lazarchick J. The effect of bacteremia on automated platelet measurements in neonates. 1990; 93(3):391–4.
- View Article
- Google Scholar
33. Taylor ME, Holland CV, Spencer R, Jackson JF, O’Connor GI, O’Donnell JR. Haematological reference ranges for schoolchildren. Clin Lab Haematol. 1997;19(1):1–15. pmid:9146941
- View Article
- PubMed/NCBI
- Google Scholar
34. Hanaganahalli SB,Sreeram S, Bompada M, Kuppannagari SK, Suresh PK, Philipose CS. Is MPV a Predictive Marker for Neonatal Sepsis? A Pilot Study. J Pediatr Hematol Oncol. 2018; 40(7):548–552. pmid:30080755
- View Article
- PubMed/NCBI
- Google Scholar
35. Beiner ME, Simchen MJ, Sivan E, Chetrit A, Kuint J, Schiff E. Risk factors for neonatal thrombocytopenia in preterm infants. Am J Perinatol. 2003; 20(1):49–54. pmid:12638081
- View Article
- PubMed/NCBI
- Google Scholar
36. Nadkarni J, Patne SK, Kispotta R. Hypoxia as a predisposing factor for the development of early onset neonatal thrombocytopenia. J Clin Neonatol. 2012; 1(3):131–134. pmid:24027708
- View Article
- PubMed/NCBI
- Google Scholar
37. Cremer M, Weimann A, Schmalisch G, Hammer H, Bührer C, Dame C. Immature platelet values indicate impaired megakaryopoietic activity in neonatal early-onset thrombocytopenia. Thromb Haemost. 2010; 103:1016–1021. pmid:20216981
- View Article
- PubMed/NCBI
- Google Scholar
38. Saxonhouse MA, Rimsza LM, Stevens G, Jouei N, Christensen RD, Sola MC. Effects of hypoxia on megakaryocyte progenitors obtained from the umbilical cord blood of term and preterm neonates. Biol Neonate. 2006; 89:104–108. pmid:16192692
- View Article
- PubMed/NCBI
- Google Scholar
39. Castle V, Coates G, Mitchell LG, O’Brodovich H, Andrew M. The effect of hypoxia on platelet survival and site of sequestration in the newborn rabbits. Thromb Haemost. 1988; 59(1):45–48.
- View Article
- Google Scholar
40. Rajasekhar D, Barnard MR, Bednarek FJ, Michelson AD. Platelet hyporeactivity in very low birth weight neonates. Thromb Haemost. 1997;77(5):1002–1007. pmid:9184418
- View Article
- PubMed/NCBI
- Google Scholar

[ref1] 1. Martin JF, Kristensen SD, Mathur A, Grove EL, Choudry FA. The causal role of megakaryocyte-platelet hyperactivity in acute coronary syndromes. Nat Rev Cardiol. 2012;9(11):658–70.
View Article
Google Scholar

[2] View Article

[3] Google Scholar

[ref2] 2. Han L, Liu X, Li H, Zou J, Yang Z, Han J, et al. Blood coagulation parameters and platelet indices: changes in normal and preeclamptic pregnancies and predictive values for preeclampsia. PLoS One. 2014;9(2): e114488. pmid:25464515
View Article
PubMed/NCBI
Google Scholar

[5] View Article

[6] PubMed/NCBI

[7] Google Scholar

[ref3] 3. Coban E, Adanir H, Bilgin D. The association of mean platelet volume levels with hypertensive retinopathy. Platelets. 2008;19(2):115–8. pmid:17852776
View Article
PubMed/NCBI
Google Scholar

[9] View Article

[10] PubMed/NCBI

[11] Google Scholar

[ref4] 4. Roberts I, Murray NA. Neonatal thrombocytopenia: causes and management. Arch Dis Child Neonatal Ed. 2003;88: F359–364. pmid:12937037
View Article
PubMed/NCBI
Google Scholar

[13] View Article

[14] PubMed/NCBI

[15] Google Scholar

[ref5] 5. Catal F, Tayman C, Tonbul A, Akca H, Kara S, Tatli MM, et al. Mean platelet volume (MPV) may simply predict the severity of sepsis in pretem infants. Clin Lab. 2014;60(7):1193–200. pmid:25134389
View Article
PubMed/NCBI
Google Scholar

[17] View Article

[18] PubMed/NCBI

[19] Google Scholar

[ref6] 6. ZhaO D, Qiu G, Luo Z, Zhang Y. Platelet parameters and (1,3)-β-D-gulcan as a diagnostic and prognostic marker of invasive fungal disease in preterm infants. PLoS One. 2015;10(4):e0123907. pmid:25874376
View Article
PubMed/NCBI
Google Scholar

[21] View Article

[22] PubMed/NCBI

[23] Google Scholar

[ref7] 7. Aydemir C, Aydemir H, Kokturk F, Kulah C, Mungan AG. The cut-off levels of procalcitonin and C-reactive protein and the kinetics of mean platelet volume in preterm neonates with sepsis. BMC Pediatr. 2018;18(1):253. pmid:30068303
View Article
PubMed/NCBI
Google Scholar

[25] View Article

[26] PubMed/NCBI

[27] Google Scholar

[ref8] 8. Mitsiakos G, Papathanasiou AE, Kyriakidis I, Karagianni P, Tsepis K, Tzimou I, et al. Intraventricular Hemorrhage and Platelet indices in Extremely Premature Neonates. J Pediatr Hematol Oncol. 2016;38(7):533–538. pmid:27849673
View Article
PubMed/NCBI
Google Scholar

[29] View Article

[30] PubMed/NCBI

[31] Google Scholar

[ref9] 9. Aksoy HT, Güzoğlu N, Eras Z, Canpolat FE, Uraş N. Mean platelet volume/count and mortality in extremely low birth weight infants of preeclamptic mothers. Clin Invest Med. 2018;41(3):E130–135. pmid:30315748
View Article
PubMed/NCBI
Google Scholar

[33] View Article

[34] PubMed/NCBI

[35] Google Scholar

[ref10] 10. Kim JY, Yoon J, Lim CS, Choi BM, Yoon SY. Clinical significance of platelet-associated hematological parameters as an early supplementary diagnostic tool for sepsis in thrombocytopenic very-low-birth-weight infants. Platelets. 2015;26(7):620–6. pmid:25275826
View Article
PubMed/NCBI
Google Scholar

[37] View Article

[38] PubMed/NCBI

[39] Google Scholar

[ref11] 11. Go H, Ohto H, Kenneth N, Takano S, Kashiwabara N, Chisiki M, et al. Using Platelet Parameters to Anticipate Morbidity and Mortality Among Preterm Neonates: A Retrospective Study. Front Pediatr. 2020;8:90. pmid:32232019
View Article
PubMed/NCBI
Google Scholar

[41] View Article

[42] PubMed/NCBI

[43] Google Scholar

[ref12] 12. Alicja W, Agnieszka P, Piotr L, Slawomir R, Barbara KW, Milena D, et al. Platelet indices in late preterm newborns. J Matern Fetal Neonatal Med. 2017; 30(14):1699–1703. pmid:27628188
View Article
PubMed/NCBI
Google Scholar

[45] View Article

[46] PubMed/NCBI

[47] Google Scholar

[ref13] 13. Backes CH, Markham K, Moorehead P, Cordero L, Nankervis CA, Giannone PJ. Maternal preeclampsia and neonatal outcomes. J Pregnancy 2011; 214365. pmid:21547086
View Article
PubMed/NCBI
Google Scholar

[49] View Article

[50] PubMed/NCBI

[51] Google Scholar

[ref14] 14. Thalor N, Singh K, Pujani M, Chauhan V, Agarwal C, Ahuja R. A correlation between platelet indices and preeclampsia. Hematol Transfus Cell Ther. 2019;41(2)129–133. pmid:31084762
View Article
PubMed/NCBI
Google Scholar

[53] View Article

[54] PubMed/NCBI

[55] Google Scholar

[ref15] 15. Ekin A, Gezer C, Kulhan G, Avci ME, Taner CE. Can platelet count and mean platelet volume during the first trimester of pregnancy predict preterm premature rupture of membrenes? J Obstet Gynaecol Res. 2015;41(1):23–28. pmid:25130327
View Article
PubMed/NCBI
Google Scholar

[57] View Article

[58] PubMed/NCBI

[59] Google Scholar

[ref16] 16. Tita AT, Andrew WW. Diagnosis and management of clinical chorioamnionitis. Clinics in Perinatology. 2010;37(2):339–354. pmid:20569811
View Article
PubMed/NCBI
Google Scholar

[61] View Article

[62] PubMed/NCBI

[63] Google Scholar

[ref17] 17. Wasiluk A, Osada J, Dabrowska M, Szczepański M, Jasinska E. Does prematurity affect platelet indices? Adv Med Sci. 2009; 54(2):253–5. pmid:19808160
View Article
PubMed/NCBI
Google Scholar

[65] View Article

[66] PubMed/NCBI

[67] Google Scholar

[ref18] 18. Christensen RD, Baer VL, Henry E, Snow GL, Butler A, Sola-Visner MC. Thrombocytopenia in Small-for-Gestational-Age Infants. Pediatrics. 2015; 135(2):e361–70.
View Article
Google Scholar

[69] View Article

[70] Google Scholar

[ref19] 19. Wasiluk A, Mantur M, Kemona H, Szczepański M, Jasińska E, Milewski R. Thrombopoiesis in small for gestational age newborns. Platelets. 2009;20(7):520–524. pmid:19852692
View Article
PubMed/NCBI
Google Scholar

[72] View Article

[73] PubMed/NCBI

[74] Google Scholar

[ref20] 20. Fustolo-Gunnink SF, Vlug RD, Smits-Wintjens VE, Heckman EJ, Te Pas AB, Fijnvandaraat K, et al. Early-Onset Thrombocytopenia in Small-For-Gestational-Age Neonates: A retrospective Cohort Study. PLoS One. 2016; 11(5):e0154853. pmid:27177157
View Article
PubMed/NCBI
Google Scholar

[76] View Article

[77] PubMed/NCBI

[78] Google Scholar

[ref21] 21. Lee E, Lim Z, Malhotra A. Thrombocytopenia in well small for gestational age neonates. Blood Coagul Fibrinolysis. 2019. 30(3):104–110. pmid:30864963
View Article
PubMed/NCBI
Google Scholar

[80] View Article

[81] PubMed/NCBI

[82] Google Scholar

[ref22] 22. Murray NA, Watts TL, Roberts IA. Endogenous thrombopoietin levels and effect of recombinant human thrombopoietin on megakaryocyte precursors in term and preterm babies. Pediatr Res. 1998; 43:148–151. pmid:9432127
View Article
PubMed/NCBI
Google Scholar

[84] View Article

[85] PubMed/NCBI

[86] Google Scholar

[ref23] 23. Watts TL, Murray NA, Roberts IA. Thrombopoietin has a primary role in the regulation of platelet production in preterm babies. Pediatr Res. 1999; 46(1):28–32. pmid:10400130
View Article
PubMed/NCBI
Google Scholar

[88] View Article

[89] PubMed/NCBI

[90] Google Scholar

[ref24] 24. Maruyama H, Shinozuka M, Kondoh Y, Akahori Y, Matsuda M, Inoue S, et al. Thrombocytopenia in Preterm Infants with Intrauterine Growth Restriction. Acta Med. Okayama, 2008:62(5):313–317. pmid:18985091
View Article
PubMed/NCBI
Google Scholar

[92] View Article

[93] PubMed/NCBI

[94] Google Scholar

[ref25] 25. Brazy J. E., Grimm J. K., and Little V. A. Neonatal manifestations of severe maternal hypertension occurring before the thirty-sixth week of pregnancy. J Pediatr. 1982; 100(2):265–271. pmid:7057337
View Article
PubMed/NCBI
Google Scholar

[96] View Article

[97] PubMed/NCBI

[98] Google Scholar

[ref26] 26. Weiner C. P. and Williamson R. A. Evaluation of severe growth retardation using cordocentesis—hematologic and metabolic alterations by etiology. Obstet Gynecol.1989; 73(2): 225–229. pmid:2536145
View Article
PubMed/NCBI
Google Scholar

[100] View Article

[101] PubMed/NCBI

[102] Google Scholar

[ref27] 27. Ekin A, Gezer C, Kulhan G, Avcı ME, Taner CE. Can platelet count and mean platelet volume during the first trimester of pregnancy predict preterm premature rupture of membranes? J Obstet Gynaecol Res. 2015; 41(1);23–28. pmid:25130327
View Article
PubMed/NCBI
Google Scholar

[104] View Article

[105] PubMed/NCBI

[106] Google Scholar

[ref28] 28. Chen CY, Essien MD, Johnson AJ, Lee GT, Chou FS. Use of mean platelet volume in the assessment of intrauterine infection in newborns with thrombocytopenia and leukopenia at birth. J Matern Fetal Neonatal Med. 2019; 1–7. pmid:30983434
View Article
PubMed/NCBI
Google Scholar

[108] View Article

[109] PubMed/NCBI

[110] Google Scholar

[ref29] 29. Wasiluk A, Mantur M, Kenoma H, Szczepański M, Jasińska E, Milewski R. Platelet indices in SGA newborns. Adv Med Sci. 2011. 20(7):520–524. pmid:21940264
View Article
PubMed/NCBI
Google Scholar

[112] View Article

[113] PubMed/NCBI

[114] Google Scholar

[ref30] 30. Zuo X, Kong W, Feng L, Zhang H, Meng X, Chen W. Elevated platelet distribution width predicts poor prognosis in hepatocellular carcinoma. Cancer Biomark. 2019;24(3):307–313. pmid:30829614
View Article
PubMed/NCBI
Google Scholar

[116] View Article

[117] PubMed/NCBI

[118] Google Scholar

[ref31] 31. Xie X, Zeng X, Cao S, Hu X, Shi Q, Li D, et al. Elevated pretreatment platelet distribution width and platelet count predict poor prognosis in nasopharyngeal carcinoma. Oncotarget. 2017:8(62):106089–106097. pmid:29285316
View Article
PubMed/NCBI
Google Scholar

[120] View Article

[121] PubMed/NCBI

[122] Google Scholar

[ref32] 32. Patrick CH, Lazarchick J. The effect of bacteremia on automated platelet measurements in neonates. 1990; 93(3):391–4.
View Article
Google Scholar

[124] View Article

[125] Google Scholar

[ref33] 33. Taylor ME, Holland CV, Spencer R, Jackson JF, O’Connor GI, O’Donnell JR. Haematological reference ranges for schoolchildren. Clin Lab Haematol. 1997;19(1):1–15. pmid:9146941
View Article
PubMed/NCBI
Google Scholar

[127] View Article

[128] PubMed/NCBI

[129] Google Scholar

[ref34] 34. Hanaganahalli SB,Sreeram S, Bompada M, Kuppannagari SK, Suresh PK, Philipose CS. Is MPV a Predictive Marker for Neonatal Sepsis? A Pilot Study. J Pediatr Hematol Oncol. 2018; 40(7):548–552. pmid:30080755
View Article
PubMed/NCBI
Google Scholar

[131] View Article

[132] PubMed/NCBI

[133] Google Scholar

[ref35] 35. Beiner ME, Simchen MJ, Sivan E, Chetrit A, Kuint J, Schiff E. Risk factors for neonatal thrombocytopenia in preterm infants. Am J Perinatol. 2003; 20(1):49–54. pmid:12638081
View Article
PubMed/NCBI
Google Scholar

[135] View Article

[136] PubMed/NCBI

[137] Google Scholar

[ref36] 36. Nadkarni J, Patne SK, Kispotta R. Hypoxia as a predisposing factor for the development of early onset neonatal thrombocytopenia. J Clin Neonatol. 2012; 1(3):131–134. pmid:24027708
View Article
PubMed/NCBI
Google Scholar

[139] View Article

[140] PubMed/NCBI

[141] Google Scholar

[ref37] 37. Cremer M, Weimann A, Schmalisch G, Hammer H, Bührer C, Dame C. Immature platelet values indicate impaired megakaryopoietic activity in neonatal early-onset thrombocytopenia. Thromb Haemost. 2010; 103:1016–1021. pmid:20216981
View Article
PubMed/NCBI
Google Scholar

[143] View Article

[144] PubMed/NCBI

[145] Google Scholar

[ref38] 38. Saxonhouse MA, Rimsza LM, Stevens G, Jouei N, Christensen RD, Sola MC. Effects of hypoxia on megakaryocyte progenitors obtained from the umbilical cord blood of term and preterm neonates. Biol Neonate. 2006; 89:104–108. pmid:16192692
View Article
PubMed/NCBI
Google Scholar

[147] View Article

[148] PubMed/NCBI

[149] Google Scholar

[ref39] 39. Castle V, Coates G, Mitchell LG, O’Brodovich H, Andrew M. The effect of hypoxia on platelet survival and site of sequestration in the newborn rabbits. Thromb Haemost. 1988; 59(1):45–48.
View Article
Google Scholar

[151] View Article

[152] Google Scholar

[ref40] 40. Rajasekhar D, Barnard MR, Bednarek FJ, Michelson AD. Platelet hyporeactivity in very low birth weight neonates. Thromb Haemost. 1997;77(5):1002–1007. pmid:9184418
View Article
PubMed/NCBI
Google Scholar

[154] View Article

[155] PubMed/NCBI

[156] Google Scholar

Figures

Abstract

Introduction

Materials and methods

Study design and population

Platelet parameter measurements

Prenatal and postnatal risk factors

Statistical analysis

Results

Discussion

Supporting information

S1 Table. Factors affecting platelet parameters in late preterm and term neonates.

S2 Table. Platelet parameters in SGA and not neonates.

S1 Text. This study’s data set.

Acknowledgments

References