Download PDF
Am J Perinatol 2022; 29(14): 1519-1523
DOI: 10.1055/a-1724-3433
Short Communication

Does Early Neonatal Thrombocytopenia Affect Ductal Therapeutic Response to Acetaminophen in Preterm Neonates?

Alona Bin-Nun
1   Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel
2   Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
,
Rawan Abu-Omar
1   Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel
,
Irina Shchors
1   Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel
,
Francis Mimouni
1   Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel
3   Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
,
Cathy Hammerman 
1   Department of Neonatology, Shaare Zedek Medical Center, Jerusalem, Israel
2   Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
› Author Affiliations Funding None.
› Further Information
Also available at
    Permissions and Reprints

Abstract

Objective Perinatal thrombocytopenia has been shown to affect responsiveness to therapeutic ductal closure with cyclooxygenase (COX) inhibitors. This has not been studied in responsiveness to acetaminophen, which has less effect on platelet function. The objective of this study was to evaluate whether thrombocytopenia affects ductal responsiveness to acetaminophen.

Study Design This study was a retrospective review of preterm neonates <1,500 g. Echocardiograms were performed within the first week of life; if ductal status was found to be hemodynamically significant, infants were treated with acetaminophen.

Results We studied 254 infants. Fifty-seven of these (22%) had a hemodynamically significant patent ductus arteriosus (hsPDA) and were treated with acetaminophen. Forty (70%) of those treated responded with ductal closure after one to two courses of acetaminophen. Seventeen infants were considered nonresponsive, requiring the addition of ibuprofen and/or surgical ligation. Sixty seven of the 254 infants (26%) developed moderate thrombocytopenia (platelets <100,000) within the first 10 days of life, more within the hsPDA group (54 vs. 18% p < 0.001); however, no differences in platelet-related parameters were observed between those who did and did not respond to acetaminophen treatment when comparing infants with hsPDA. Twenty-six of the 67 thrombocytopenic infants were already thrombocytopenic prior to acetaminophen treatment, and 19 of these 26 (73%) with pretreatment thrombocytopenia responded to acetaminophen treatment—with the overall response rate of 70%.

Conclusions This study is the first to document that, in contrast to the COX inhibitors, there is no association between early neonatal thrombocytopenia and ductal therapeutic responsiveness to acetaminophen.

Key Points

  • Perinatal thrombocytopenia affects ductal closure with COX inhibitors.

  • In contrast to the COX inhibitors, acetaminophen responsiveness is not affected by thrombocytopenia.

  • Acetaminophen can be recommended to close hsPDA in the presence of thrombocytopenia.

Keywords

acetaminophen - thrombocytopenia - patent ductus arteriosus - preterm neonate


Publication History

Received: 08 June 2021

Accepted: 15 December 2021

Accepted Manuscript online:
17 December 2021

Article published online:
11 January 2022

© 2022. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Echtler K, Stark K, Lorenz M. et al. Platelets contribute to postnatal occlusion of the ductus arteriosus. Nat Med 2010; 16 (01) 75-82
    CrossrefPubMedSearch in Google Scholar
  • 2 Clyman R, Chemtob S. Vessel remodeling in the newborn: platelets fill the gap. Nat Med 2010; 16 (01) 33-35
    CrossrefPubMedSearch in Google Scholar
  • 3 Sallmon H, Timme N, Atasay B. et al. Current controversy on platelets and patent ductus arteriosus closure in preterm infants. Front Pediatr 2021; 9: 612242
    CrossrefPubMedSearch in Google Scholar
  • 4 Mitra S, Chan AK, Paes BA. Thrombosis and Hemostasis in Newborns (THIN) Group. The association of platelets with failed patent ductus arteriosus closure after a primary course of indomethacin or ibuprofen: a systematic review and meta-analysis. J Matern Fetal Neonatal Med 2017; 30 (02) 127-133
    CrossrefPubMedSearch in Google Scholar
  • 5 Boo NY, Mohd-Amin I, Bilkis AA, Yong-Junina F. Predictors of failed closure of patent ductus arteriosus with indomethacin. Singapore Med J 2006; 47 (09) 763-768
    PubMedSearch in Google Scholar
  • 6 Mitra S, Wahab MG. Indomethacin dose-interruption and maternal chorioamnionitis are risk factors for indomethacin treatment failure in preterm infants with patent ductus arteriosus. J Clin Neonatol 2015; 4: 250-255
    CrossrefPubMedSearch in Google Scholar
  • 7 Ahamed MF, Verma P, Lee S. et al. Predictors of successful closure of patent ductus arteriosus with indomethacin. J Perinatol 2015; 35 (09) 729-734
    CrossrefPubMedSearch in Google Scholar
  • 8 Shah NA, Hills NK, Waleh N. et al. Relationship between circulating platelet counts and ductus arteriosus patency after indomethacin treatment. J Pediatr 2011; 158 (06) 919-923.e1 , 2
    CrossrefPubMedSearch in Google Scholar
  • 9 Alyamac Dizdar E, Ozdemir R, Sari FN. et al. Low platelet count is associated with ductus arteriosus patency in preterm newborns. Early Hum Dev 2012; 88 (10) 813-816
    CrossrefPubMedSearch in Google Scholar
  • 10 Schena F, Ciarmoli E, Ghirardello M, Groppo M, Lonati A, Mosca F. A low platelet count is associated with treatment failure in preterm infants treated with ibuprofen for patent ductus arteriosus (PDA). Pediatr Res 2010; 68: 118-119
    CrossrefPubMedSearch in Google Scholar
  • 11 Dani C, Poggi C, Fontanelli G. Relationship between platelet count and volume and spontaneous and pharmacological closure of ductus arteriosus in preterm infants. Am J Perinatol 2013; 30 (05) 359-364
    PubMedSearch in Google Scholar
  • 12 Bas-Suárez MP, González-Luis GE, Saavedra P, Villamor E. Platelet counts in the first seven days of life and patent ductus arteriosus in preterm very low-birth-weight infants. Neonatology 2014; 106 (03) 188-194
    CrossrefPubMedSearch in Google Scholar
  • 13 Manalastas M, Zaheer F, Nicoski P, Weiss MG, Amin S. Acetaminophen therapy for persistent patent ductus arteriosus. Neoreviews 2021; 22 (05) e320-e331
    CrossrefPubMedSearch in Google Scholar
  • 14 Meena V, Meena DS, Rathore PS, Chaudhary S, Soni JP. Comparison of the efficacy and safety of indomethacin, ibuprofen, and paracetamol in the closure of patent ductus arteriosus in preterm neonates—a randomized controlled trial. Ann Pediatr Cardiol 2020; 13 (02) 130-135
    CrossrefPubMedSearch in Google Scholar
  • 15 El-Mashad AE, El-Mahdy H, El Amrousy D, Elgendy M. Comparative study of the efficacy and safety of paracetamol, ibuprofen, and indomethacin in closure of patent ductus arteriosus in preterm neonates. Eur J Pediatr 2017; 176 (02) 233-240
    CrossrefPubMedSearch in Google Scholar
  • 16 Graham GG, Davies MJ, Day RO, Mohamudally A, Scott KF. The modern pharmacology of paracetamol: therapeutic actions, mechanism of action, metabolism, toxicity and recent pharmacological findings. Inflammopharmacology 2013; 21 (03) 201-232
    Search in Google Scholar
  • 17 Kulkarni VV, Dutta S, Sundaram V, Saini SS. Preterm thrombocytopenia and delay of ductus arteriosus closure. Pediatrics 2016; 138 (04) e20161627
    CrossrefPubMedSearch in Google Scholar
  • 18 Simon SR, van Zogchel L, Bas-Suárez MP, Cavallaro G, Clyman RI, Villamor E. Platelet counts and patent ductus arteriosus in preterm infants: a systematic review and meta-analysis. Neonatology 2015; 108 (02) 143-151
    CrossrefPubMedSearch in Google Scholar
  • 19 González-Luis G, Ghiradello S, Bas-Suárez P. et al. Platelet counts and patent ductus arteriosus in preterm infants: an updated systematic review and meta-analysis. Front Pediatr 2021; 8: 613766
    CrossrefPubMedSearch in Google Scholar
  • 20 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
    CrossrefPubMedSearch in Google Scholar
  • 21 Murphy DP, Lee HC, Payton KS, Powers RJ. Platelet count and associated morbidities in VLBW infants with pharmacologically treated patent ductus arteriosus. J Matern Fetal Neonatal Med 2016; 29 (13) 2045-2048
    CrossrefPubMedSearch in Google Scholar
  • 22 Sallmon H, Weber SC, Dirks J. et al. Association between platelet counts before and during pharmacological therapy for patent ductus arteriosus and treatment failure in preterm infants. Front Pediatr 2018; 6: 41
    CrossrefPubMedSearch in Google Scholar
  • 23 Schafer AI. Effects of nonsteroidal antiinflammatory drugs on platelet function and systemic hemostasis. J Clin Pharmacol 1995; 35 (03) 209-219
    CrossrefPubMedSearch in Google Scholar
  • 24 Munsterhjelm E, Munsterhjelm NM, Niemi TT, Ylikorkala O, Neuvonen PJ, Rosenberg PH. Dose-dependent inhibition of platelet function by acetaminophen in healthy volunteers. Anesthesiology 2005; 103 (04) 712-717
    CrossrefPubMedSearch in Google Scholar