Platelet Indices: Universally Available Clinical Adjunct for Diagnosing Necrotizing Enterocolitis

Abstract

Objective Platelet function parameters can be predictive of several adult diseases and their severity. However, few studies report on the association between platelet indices and neonatal diseases, specifically necrotizing enterocolitis (NEC). The objective of this study is to investigate whether platelet indices are associated with NEC diagnosis and NEC-related mortality.

Study Design We retrospectively examined records from infants admitted to the neonatal intensive care unit with a diagnosis of NEC, verified by the presence of pneumatosis on X-ray or pathology at surgery. We compared them with an age-matched group of prematures without NEC. We investigated platelet count, mean platelet volume (MPV), platelet distribution width and red cell distribution width to platelet ratio (RPR) and delta platelets from birth to the time of NEC diagnosis or day of life 14 in the control group.

Results Sixty-nine infants with NEC and 78 control infants were studied. Basic sociodemographic data were similar in both groups. All platelet parameters measured—except for MPV—were significantly associated with NEC diagnosis. Although MPV was not associated with the diagnosis of NEC (p = 0.800), it was significantly associated with NEC-related mortality (p < 0.001). Only total platelet count and RPR were significantly associated with both NEC diagnosis (p < 0.0001) and mortality (p = 0.04 and 0.01, respectively). On multivariable analysis only the change in platelet count from birth to time of diagnosis remained significant.

Conclusion While not definitive, this study demonstrates that these routinely available, inexpensive, and easily calculated platelet indices can provide a clinical adjunct in the often-elusive attempts to definitively diagnose NEC in preterm neonates.

Key Points

• Platelet indices were associated with NEC diagnosis.

• MPV was predictive of NEC-related mortality.

• Delta platelet count from birth was significantly related to NEC diagnosis.

Keywords

necrotizing enterocolitis - platelet indices - preterm neonates

• References

• 1 Neu J, Walker WA. Necrotizing enterocolitis. N Engl J Med 2011; 364 (03) 255-264
• 2 Patel RM, Kandefer S, Walsh MC. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Causes and timing of death in extremely premature infants from 2000 through 2011. N Engl J Med 2015; 372 (04) 331-340
• 3 Vancamelbeke M, Vermeire S. The intestinal barrier: a fundamental role in health and disease. Expert Rev Gastroenterol Hepatol 2017; 11 (09) 821-834
• 4 Song R, Subbarao GC, Maheshwari A. Haematological abnormalities in neonatal necrotizing enterocolitis. J Matern Fetal Neonatal Med 2012; 25 (04, suppl 4): 22-25
• 5 Ye S, Zhang Y, Zhang C, Xu D. Are platelet volume indices related to mortality in hospitalized children on mechanical ventilation?. J Int Med Res 2018; 46 (03) 1197-1208
• 6 Zheng YG, Yang T, Xiong CM. et al. Platelet distribution width and mean platelet volume in idiopathic pulmonary arterial hypertension. Heart Lung Circ 2015; 24 (06) 566-572
• 7 Cui MM, Li N, Liu X. et al. Platelet distribution width correlates with prognosis of non-small cell lung cancer. Sci Rep 2017; 7 (01) 3456
• 8 Cekmez F, Tanju IA, Canpolat FE. et al. Mean platelet volume in very preterm infants: a predictor of morbidities?. Eur Rev Med Pharmacol Sci 2013; 17: 134-137
• 9 Okur N, Buyuktiryaki M, Uras N. et al. Platelet mass index in very preterm infants: can it be used as a parameter for neonatal morbidities?. J Matern Fetal Neonatal Med 2016; 29 (19) 3218-3222
• 10 Mohsen L, Akmal DM, Ghonaim EKE, Riad NM. Role of mean platelet volume and ischemia modified albumin in evaluation of oxidative stress and its association with postnatal complications in infants of diabetic mothers. J Matern Fetal Neonatal Med 2018; 31 (14) 1819-1823
• 11 Pradella P, Bonetto S, Turchetto S. et al. Platelet production and destruction in liver cirrhosis. J Hepatol 2011; 54 (05) 894-900
• 12 Dani C, Poggi C, Barp J, Berti E, Fontanelli G. Mean platelet volume and risk of bronchopulmonary dysplasia and intraventricular hemorrhage in extremely preterm infants. Am J Perinatol 2011; 28 (07) 551-556
• 13 Go H, Ohto H, Nollet KE. et al. Using platelet parameters to anticipate morbidity and mortality among preterm neonates: a retrospective study. Front Pediatr 2020; 8: 90
• 14 Tao Y, Dong Y, Lu CW, Yang W. Mean platelet volume in retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol 2015; 253 (11) 2047-2048
• 15 Grevsen AK, Hviid CVB, Hansen AK, Hvas A-M. The role of platelets in premature neonates with intraventricular hemorrhage: a systematic review and meta-analysis. Semin Thromb Hemost 2020; 46 (03) 366-378
• 16 Wang J, Wang Z, Zhang M, Lou Z, Deng J, Li Q. Diagnostic value of mean platelet volume for neonatal sepsis: a systematic review and meta-analysis. Medicine (Baltimore) 2020; 99 (32) e21649
• 17 Kim JY, Yoon J, Lim CS, Choi BM, Yoon S-Y. 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 (07) 620-626
• 18 Kannar V, Deepthi A, Kumar MLH, Junjegowda K, Mariyappa N. Effect of gestational age, prematurity and birth asphyxia on platelet indices in neonates. J Clin Neonatol 2014; 3: 144
• 19 Golwala ZM, Shah H, Gupta N, Sreenivas V, Puliyel JM. Mean platelet volume (MPV), platelet distribution width (PDW), platelet count and plateletcrit (PCT) as predictors of in-hospital paediatric mortality: a case-control study. Afr Health Sci 2016; 16 (02) 356-362
• 20 Peng F, Li Z, Yi C. et al. Platelet index levels and cardiovascular mortality in incident peritoneal dialysis patients: a cohort study. Platelets 2017; 28 (06) 576-584
• 21 Tian C, Song J, He D, Wu J, Sun Z, Sun Z. Predictive value of mean platelet volume/platelet count for prognosis in acute myocardial infarction. Int Heart J 2018; 59 (02) 286-292
• 22 Gorelik O, Tzur I, Barchel D. et al. A rise in mean platelet volume during hospitalization for community-acquired pneumonia predicts poor prognosis: a retrospective observational cohort study. BMC Pulm Med 2017; 17 (01) 137
• 23 Guler Kazanci E, Buyuktiryaki M, Unsal H, Tayman C. Useful platelet indices for the diagnosis and follow-up of patent ductus arteriosus. Am J Perinatol 2019; 36 (14) 1521-1527
• 24 Ververidis M, Kiely EM, Spitz L, Drake DP, Eaton S, Pierro A. The clinical significance of thrombocytopenia in neonates with necrotizing enterocolitis. J Pediatr Surg 2001; 36 (05) 799-803
• 25 Ragazzi S, Pierro A, Peters M, Fasoli L, Eaton S. Early full blood count and severity of disease in neonates with necrotizing enterocolitis. Pediatr Surg Int 2003; 19 (05) 376-379
• 26 Patel CC. Hematologic abnormalities in acute necrotizing enterocolitis. Pediatr Clin North Am 1977; 24 (03) 579-584
• 27 Maheshwari A. Role of platelets in neonatal necrotizing enterocolitis. Pediatr Res 2021; 89 (05) 1087-1093
• 28 Hutter Jr JJ, Hathaway WE, Wayne ER. Hematologic abnormalities in severe neonatal necrotizing enterocolitis. J Pediatr 1976; 88 (06) 1026-1031
• 29 Kenton AB, O'Donovan D, Cass DL. et al. Severe thrombocytopenia predicts outcome in neonates with necrotizing enterocolitis. J Perinatol 2005; 25 (01) 14-20
• 30 Guida JD, Kunig AM, Leef KH, McKenzie SE, Paul DA. Platelet count and sepsis in very low birth weight neonates: is there an organism-specific response?. Pediatrics 2003; 111 (6 pt 1): 1411-1415
• 31 Yildiz A, Yigit A, Benli AR. The prognostic role of platelet to lymphocyte ratio and mean platelet volume in critically ill patients. Eur Rev Med Pharmacol Sci 2018; 22 (08) 2246-2252
• 32 Gao Y, Li Y, Yu X. et al. The impact of various platelet indices as prognostic markers of septic shock. PLoS One 2014; 9 (08) e103761
• 33 Kim CH, Kim SJ, Lee MJ. et al. An increase in mean platelet volume from baseline is associated with mortality in patients with severe sepsis or septic shock. PLoS One 2015; 10 (03) e0119437
• 34 Lippi G, Filippozzi L, Montagnana M. et al. Clinical usefulness of measuring red blood cell distribution width on admission in patients with acute coronary syndromes. Clin Chem Lab Med 2009; 47 (03) 353-357
• 35 Spell DW, Jones Jr. DV, Harper WF, David Bessman J. The value of a complete blood count in predicting cancer of the colon. Cancer Detect Prev 2004; 28 (01) 37-42
• 36 Chen PC, Sung FC, Chien KL, Hsu HC, Su TC, Lee YT. Red blood cell distribution width and risk of cardiovascular events and mortality in a community cohort in Taiwan. Am J Epidemiol 2010; 171 (02) 214-220
• 37 Patel KV, Ferrucci L, Ershler WB, Longo DL, Guralnik JM. Red blood cell distribution width and the risk of death in middle-aged and older adults. Arch Intern Med 2009; 169 (05) 515-523
• 38 Horne BD. A changing focus on the red cell distribution width: why does it predict mortality and other adverse medical outcomes?. Cardiology 2012; 122 (04) 213-215
• 39 Bojakowski K, Dzabic M, Kurzejamska E. et al. A high red blood cell distribution width predicts failure of arteriovenous fistula. PLoS One 2012; 7 (05) e36482
• 40 Chen B, Ye B, Zhang J, Ying L, Chen Y. RDW to platelet ratio: a novel noninvasive index for predicting hepatic fibrosis and cirrhosis in chronic hepatitis B. PLoS One 2013; 8 (07) e68780
• 41 Nagula P, Karumuri S, Otikunta AN, Yerrabandi SRV. Correlation of red blood cell distribution width with the severity of coronary artery disease-a single center study. Indian Heart J 2017; 69 (06) 757-761
• 42 Salvagno GL, Sanchis-Gomar F, Picanza A, Lippi G. Red blood cell distribution width: a simple parameter with multiple clinical applications. Crit Rev Clin Lab Sci 2015; 52 (02) 86-105
• 43 Garofoli F, Ciardelli L, Mazzucchelli I. et al. The red cell distribution width (RDW): value and role in preterm, IUGR (intrauterine growth restricted), full-term infants. Hematology 2014; 19 (06) 365-369
• 44 Olukman O, Ozdemir R, Karadeniz C, Calkavur S, Mese T, Vergin C. Is there a relationship between platelet parameters and patency of ductus arteriosus in preterm infants?. Blood Coagul Fibrinolysis 2017; 28 (01) 8-13
• 45 Demir N, Peker E, Ece İ, Ağengin K, Bulan KA, Tuncer O. Is platelet mass a more significant indicator than platelet count of closure of patent ductus arteriosus?. J Matern Fetal Neonatal Med 2016; 29 (12) 1915-1918
• 46 Sallmon H, Weber SC, Hüning B. et al. Thrombocytopenia in the first 24 hours after birth and incidence of patent ductus arteriosus. Pediatrics 2012; 130 (03) e623-e630
• 47 Kahvecioglu D, Erdeve O, Akduman H. et al. Influence of platelet count, platelet mass index, and platelet function on the spontaneous closure of ductus arteriosus in the prematurity. Pediatr Neonatol 2018; 59 (01) 53-57
• 48 Özer Bekmez B, Tayman C, Büyüktiryaki M, Çetinkaya AK, Çakır U, Derme T. A promising, novel index in the diagnosis and follow-up of patent ductus arteriosus: red cell distribution width-to-platelet ratio. J Clin Lab Anal 2018; 32 (09) e22616