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Ibuprofen lysine administration to neonates with a patent ductus arteriosus: effect on platelet plug formation assessed by in vivo and in vitro measurements

Journal of Perinatology volume 29, pages 39–43 (2009)Cite this article

Abstract

Objective

Ibuprofen might have advantages over indomethacin, when used to effectuate closure of a neonate's patent ductus arteriosus (PDA). Several previous studies indicate that platelet plug formation is impaired after administration of indomethacin, but it is not clear whether a similar impairment occurs following ibuprofen dosing.

Study Design

We performed template bleeding times and PFA-100 tests (platelet function analyzer) on 20 neonates who had a PDA, before and again at various preset intervals following ibuprofen dosing.

Result

Patients ranged from 23 to 40 weeks gestation and weighed 511 to 2566 g. Their first dose of ibuprofen was administered at 72 h (18 to 363 h) after birth (median, range). None of the subjects had clinical bleeding problems noted during the days they received ibuprofen dosing. The template bleeding times before dosing ranged from 135 to 450 s. Repeat tests were performed in groups of four, at 2 h, 4 to 6 h, 12 to 18 h, 24 h after the first dose, and at 2 h after the third dose of ibuprofen. No changes in bleeding times were detected. (P=0.299) A PFA-100 time was performed on all 20 patients before and again after the ibuprofen administration. However, 3 of the 40 tests were unsuccessful, because of microclots in the blood sample (n=1) or failure of the analyzer for an unspecified reason (n=2). Before the dosing the PFA-100 time ranged from 52 to 300 s. A paired t-test showed a slight but statistically significant lengthening in PFA-100 time after the ibuprofen administration (P=0.019). The correlation between the bleeding time and the PFA-100 was poor (R2=0.212, P=0.576).

Conclusion

On the basis of our present studies, we speculate that ibuprofen lysine administration to neonates with a PDA, when used according to the manufacturer's recommendations, has little adverse effect on platelet plug formation. This information might be a factor to consider when deciding whether to select indomethacin or ibuprofen for PDA closure.

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References

  1. Jim WT, Chiu NC, Chen MR, Hung HY, Kao HA, Hsu CH et al. Cerebral hemodynamic change and intraventricular hemorrhage in very low birth weight infants with patent ductus arteriosus. Ultrasound Med Biol 2005; 31: 197–202.

    Article  Google Scholar 

  2. Gibbs NM, Weightman WM, Thackray NM, Michalopoulos N, Weidmann C . The effects of recent aspirin ingestion on platelet function in cardiac surgical patients. J Cardiothorac Vasc Anesth 2001; 15: 55–59.

    Article  CAS  Google Scholar 

  3. Del Vecchio A, Sola MC . Performing and interpreting the bleeding time in the neonatal intensive care unit. Clin Perinatol 2000; 27: 643–654.

    Article  CAS  Google Scholar 

  4. Del Vecchio A . Use of the bleeding time in the neonatal intensive care unit. Acta Paediatr Suppl 2002; 91: 82–86.

    Article  CAS  Google Scholar 

  5. Barradas MA, Jeremy JY, Mikhailidis DP, Dandona P . The effect of tiaprofenic acid and indomethacin administration of human platelet function. Inflammation Res 1989; 26: 386–390.

    CAS  Google Scholar 

  6. Corazza MS, Davis RF, Merritt TA, Bejar R, Cvetnic W . Prolonged bleeding time in preterm infants receiving indomethacin for patent ductus arteriosus. J Pediatr 1984; 105: 292–296.

    Article  CAS  Google Scholar 

  7. Bolisetty S, Patole S, Koh G, Stalewski H, Whitehall J . Neonatal acute haemorrhagic gastritis and antenatal exposure to indomethacin for tocolysis. ANZ J Surg 2001; 71: 122–123.

    Article  CAS  Google Scholar 

  8. Chirico G, Gasparoni MC, Rondini G . Exchange transfusion for indomethacin-induced hemorrhagic complication in the neonate. J Pediatr 1985; 107: 312.

    Article  CAS  Google Scholar 

  9. Aranda JV, Thomas R . Systematic review: intravenous Ibuprofen in preterm newborns. Semin Perinatol 2006; 30: 114–120.

    Article  CAS  Google Scholar 

  10. Sola MC, Edwards TJ, Del Vecchio A, Suttner D, Hutson AD, Christensen RD . A low hematocrit prolongs the bleeding time of very low birth-weight infants in the first week of life. J Perinatol 2001; 21: 368–371.

    Article  CAS  Google Scholar 

  11. Sola MC, Christensen RD . Developmental aspects of platelets and disorders of platelets in the neonatal period. In: Christensen RD (ed). Hematologic Problems of the Neonate. WB Saunders Co: Philadelphia, 2000, p 276.

    Google Scholar 

  12. Feusner JH . Normal and abnormal bleeding times in neonates and young children utilizing a fully standardized template technic. Am J Clin Pathol 1980; 74: 73–77.

    Article  CAS  Google Scholar 

  13. Andrew M, Castle V, Mitchell L, Paes B . Modified bleeding time in the infant. Am J Hematol 1989; 30: 190–191.

    Article  CAS  Google Scholar 

  14. Borzini P, Laxxaro A, Mazzucco L, Papili F . The in-vitro bleeding time for the screening of platelet function in the newborn: assessment of a normal reference range. Eur J Pediatr 2001; 160: 199–200.

    Article  CAS  Google Scholar 

  15. Israels SJ, Cheang T, McMillan-Ward EM, Cheang M . Evaluation of primary hemostasis in neonates with a new in vitro platelet function analyzer. J Pediatr 2001; 138: 116–119.

    Article  CAS  Google Scholar 

  16. Boudewijns M, Raes M, Peeters V, Mewis A, Cartuvvels R, Magerman K et al. Evaluation of platelet function on cord blood in 80 healthy term neonates using the Platelet Function Analyser (PFA-100); shorter in vitro bleeding times in neonates than adults. Eur J Pediatr 2003; 162: 212–213.

    Article  Google Scholar 

  17. Del Vecchio A, Latini G, Henry E, Christensen RD . Template bleeding times of 240 neonates born at 24 to 41weeks gestation. J Perinatol 2008; 28: 427–431.

    Article  CAS  Google Scholar 

  18. Perneby C, Wallén NH, Hofman-Bang C, Tornvall P, Ivert T, Li N et al. Effect of clopidogrel treatment on stress-induced platelet activation and myocardial ischemia in aspirin-treated patients with stable coronary artery disease. Thromb Haemost 2007; 98: 1316–1322.

    Article  CAS  Google Scholar 

  19. Knijff-Dutmer EA, Kalsbeek-Batenburg EM, Koerts J, van de Laar MA . Platelet function is inhibited by non-selective non-steroidal anti-inflammatory drugs but not by cyclo-oxygenase-2-selective inhibitors in patients with rheumatoid arthritis. Rheumatology (Oxford) 2002; 41: 458–461.

    Article  CAS  Google Scholar 

  20. Hermes-DeSantis ER, Clyman RI . Patent ductus arteriosus: pathophysiology and management. J Perinatol 2006; 26 (Suppl 1): S14–S18.

    Article  Google Scholar 

  21. Aranda JV, Varvarigou A, Beharry K, Bansal R, Bardin C, Modanlou H et al. Pharmacokinetics and protein binding of intravenous ibuprofen in the premature newborn infants. Acta Paediatr 1997; 86: 289–293.

    Article  CAS  Google Scholar 

  22. Shah U, Ma AD . Tests of platelet function. Curr Opin Hematol 2007; 14: 432–437.

    Article  Google Scholar 

  23. Israels SJ, Cheang T, McMillan-Ward EM, Cheang M . Evaluation of primary hemostasis in neonates with a new in vitro platelet function analyzer. J Pediatr 2001; 138: 116–119.

    Article  CAS  Google Scholar 

  24. Roschitz B, Sudi K, Köstenberger M, Muntean W . Shorter PFA-100 closure times in neonates than in adults: role of red cells, white cells, platelets and von Willebrand factor. Acta Paediatr 2001; 90: 664–670.

    Article  CAS  Google Scholar 

  25. Boudewijns M, Raes M, Peeters V, Mewis A, Cartuyvels R, Magerman K et al. Evaluation of platelet function on cord blood in 80 healthy term neonates using the Platelet Function Analyser (PFA-100); shorter in vitro bleeding times in neonates than adults. Eur J Pediatr 2003; 162: 212–213.

    Article  Google Scholar 

  26. Fass RJ, Copelan EA, Brandt JT, Moeschberger ML, Ashton JJ . Platelet-mediated bleeding caused by broad-spectrum penicillins. J Infect Dis 1987; 155: 1242–1248.

    Article  CAS  Google Scholar 

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Acknowledgements

Assisted by an unrestricted educational grant from Ovation Pharmaceuticals.

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Authors and Affiliations

  1. Intermountain Healthcare, McKay-Dee Hospital Center, Ogden, UT, USA

    M J Sheffield, N Schmutz, D K Lambert & R D Christensen

  2. The Institute for Healthcare Delivery Research, Salt Lake City, UT, USA

    E Henry

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  1. M J Sheffield
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  2. N Schmutz
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  4. E Henry
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Correspondence to M J Sheffield.

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Sheffield, M., Schmutz, N., Lambert, D. et al. Ibuprofen lysine administration to neonates with a patent ductus arteriosus: effect on platelet plug formation assessed by in vivo and in vitro measurements. J Perinatol 29, 39–43 (2009). https://doi.org/10.1038/jp.2008.122

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