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Semin Thromb Hemost 2020; 46(03): 366-378
DOI: 10.1055/s-0039-3402687
Review Article

The Role of Platelets in Premature Neonates with Intraventricular Hemorrhage: A Systematic Review and Meta-Analysis

Alexander K. Grevsen
1   Thrombosis and Haemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
,
Claus V. B. Hviid
1   Thrombosis and Haemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
,
Anne K. Hansen
2   Neonatal Intensive Care Unit, Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
,
Anne-Mette Hvas
1   Thrombosis and Haemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
3   Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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Abstract

Intraventricular hemorrhage (IVH) affects up to 22% of extremely low birth weight neonates. Impaired coagulation might contribute to the pathogenesis of IVH. The aims of this study were to summarize the current knowledge on the role of platelet indices in premature neonates with IVH and to provide an overview of secondary hemostasis parameters as well as fibrinolysis in premature neonates with IVH. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases PubMed, Embase, Scopus, and Web of Science were searched on March 7, 2019, without time restrictions. In total, 30 studies were included. Most studies investigated the significance of platelet counts and/or mean platelet volume (MPV). The meta-analysis showed that at day 1 of life, neither platelet count nor MPV differed significantly between neonates with or without IVH (standardized mean difference [SMD]: –0.15 × 109/L, 95% confidence interval [CI]: –0.37 to 0.07 and SMD: 0.22 fl, 95% CI: –0.07 to 0.51, respectively). However, platelet counts < 100 × 109/L were associated with an increased risk of IVH. Secondary hemostasis parameters did not differ between neonates with and without IVH. Fibrinolysis was only sparsely investigated. In conclusion, platelet counts < 100 × 109/L were associated with an increased risk of IVH in premature neonates. The impact of secondary hemostasis was only sparsely investigated but seemed to be minor, and the role of fibrinolysis in IVH in premature neonates needs further research. Whether reduced platelet function is associated with an increased risk of IVH in premature neonates remains to be investigated.

Keywords

intraventricular hemorrhage - premature neonates - platelet - blood coagulation tests - fibrinolysis


Publication History

Publication Date:
20 December 2019 (online)

© 2020. Thieme. All rights reserved.

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  • References

  • 1 Ancel PY, Goffinet F, Kuhn P. et al; EPIPAGE-2 Writing Group. Survival and morbidity of preterm children born at 22 through 34 weeks' gestation in France in 2011: results of the EPIPAGE-2 cohort study. JAMA Pediatr 2015; 169 (03) 230-238
    CrossrefPubMedGoogle Scholar
  • 2 Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 1978; 92 (04) 529-534
    Google Scholar
  • 3 Mukerji A, Shah V, Shah PS. Periventricular/intraventricular hemorrhage and neurodevelopmental outcomes: a meta-analysis. Pediatrics 2015; 136 (06) 1132-1143
    CrossrefPubMedGoogle Scholar
  • 4 Hambleton G, Wigglesworth JS. Origin of intraventricular haemorrhage in the preterm infant. Arch Dis Child 1976; 51 (09) 651-659
    CrossrefPubMedGoogle Scholar
  • 5 Volpe JJ, Inder TE, Darras BT. et al. Volpe's Neurology of the Newborn. 6th ed. Philadelphia, PA: Elsevier; 2017
    Google Scholar
  • 6 Perlman JM, McMenamin JB, Volpe JJ. Fluctuating cerebral blood-flow velocity in respiratory-distress syndrome. Relation to the development of intraventricular hemorrhage. N Engl J Med 1983; 309 (04) 204-209
    CrossrefPubMedGoogle Scholar
  • 7 Kuperman AA, Brenner B, Kenet G. Intraventricular haemorrhage in preterm infants--can we improve outcome by addressing coagulation?. J Matern Fetal Neonatal Med 2015; 28 (01, Suppl 1): 2265-2267
    CrossrefPubMedGoogle Scholar
  • 8 Andrew M, Paes B, Milner R. et al. Development of the human coagulation system in the healthy premature infant. Blood 1988; 72 (05) 1651-1657
    CrossrefPubMedGoogle Scholar
  • 9 Neary E, McCallion N, Kevane B. et al. Coagulation indices in very preterm infants from cord blood and postnatal samples. J Thromb Haemost 2015; 13 (11) 2021-2030
    CrossrefPubMedGoogle Scholar
  • 10 Duppré P, Sauer H, Giannopoulou EZ. et al. Cellular and humoral coagulation profiles and occurrence of IVH in VLBW and ELWB infants. Early Hum Dev 2015; 91 (12) 695-700
    CrossrefPubMedGoogle Scholar
  • 11 Piotrowski A, Dabrowska-Wojciak I, Mikinka M. et al. Coagulation abnormalities and severe intraventricular hemorrhage in extremely low birth weight infants. J Matern Fetal Neonatal Med 2010; 23 (07) 601-606
    CrossrefPubMedGoogle Scholar
  • 12 Wiedmeier SE, Henry E, Sola-Visner MC, Christensen RD. Platelet reference ranges for neonates, defined using data from over 47,000 patients in a multihospital healthcare system. J Perinatol 2009; 29 (02) 130-136
    CrossrefPubMedGoogle Scholar
  • 13 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
    CrossrefPubMedGoogle Scholar
  • 14 Mitsiakos G, Papathanasiou AE, Kyriakidis I. et al. intraventricular hemorrhage and platelet indices in extremely premature neonates. J Pediatr Hematol Oncol 2016; 38 (07) 533-538
    CrossrefPubMedGoogle Scholar
  • 15 Mosayebi Z, Sepidarkish M, Nikseresht Z, Sharifi M, Sagheb S, Nariman S. Mean platelet volume as a marker of intraventricular hemorrhage in very premature infants. Iran J Pediatr 2017; 27 (02) e8322
    CrossrefPubMedGoogle Scholar
  • 16 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 (01) 134-137
    PubMedGoogle Scholar
  • 17 PRISMA guidelines - the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Accessed 2018 at: http://prisma-statement.org/
    PubMedGoogle Scholar
  • 18 Higgins J, Green S. eds. Cochrane Handbook for Systematic Reviews of Interventions. Chichester: John Wiley & Sons; 2011
    PubMedGoogle Scholar
  • 19 Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327 (7414): 557-560
    Google Scholar
  • 20 Thanhaeuser M, Binder C, Derhaschnig U. et al. Can sequential coagulation monitoring predict major haemorrhage in extremely low birth weight infants?. Thromb Haemost 2018; 118 (07) 1185-1193
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Kaveh M, Kamrani K, Akhbari S. The evaluation of mean platelet volume in neonates with intraventricular hemorrhage and sepsis. Iran J Ped Hematol Oncol 2018; 8 (04) 221-227
    PubMedGoogle Scholar
  • 22 Szpecht D, Gadzinowski J, Seremak-Mrozikiewicz A, Kurzawińska G, Drews K, Szymankiewicz M. The role of FV 1691G>A, FII 20210G>A mutations and MTHFR 677C>T; 1298A>C and 103G>T FXIII gene polymorphisms in pathogenesis of intraventricular hemorrhage in infants born before 32 weeks of gestation. Childs Nerv Syst 2017; 33 (07) 1201-1208
    CrossrefPubMedGoogle Scholar
  • 23 Radicioni M, Bruni A, Bini V, Villa A, Ferri C. Thromboelastographic profiles of the premature infants with and without intracranial hemorrhage at birth: a pilot study. J Matern Fetal Neonatal Med 2015; 28 (15) 1779-1783
    CrossrefPubMedGoogle Scholar
  • 24 Schreiner C, Suter S, Watzka M. et al. Genetic variants of the vitamin K dependent coagulation system and intraventricular hemorrhage in preterm infants. BMC Pediatr 2014; 14: 219
    CrossrefPubMedGoogle Scholar
  • 25 Christensen RD, Baer VL, Lambert DK, Henry E, Ilstrup SJ, Bennett ST. Reference intervals for common coagulation tests of preterm infants (CME). Transfusion 2014; 54 (03) 627-632 , quiz 626
    CrossrefPubMedGoogle Scholar
  • 26 Hussein N, Helaly N, Ghany E, Anis S. Relationship between Mean platelet volume and bronchopulmonary dysplasia and intraventricular hemorrhage in very low birth weight neonates. J Am Sci 2012; 8 (05) 2012
    PubMedGoogle Scholar
  • 27 Zisk JL, Mackley A, Christensen RD, Paul DA. Is a small platelet mass associated with intraventricular hemorrhage in very low-birth-weight infants?. J Perinatol 2011; 31 (12) 776-779
    CrossrefPubMedGoogle Scholar
  • 28 Ryckman KK, Dagle JM, Kelsey K, Momany AM, Murray JC. Replication of genetic associations in the inflammation, complement, and coagulation pathways with intraventricular hemorrhage in LBW preterm neonates. Pediatr Res 2011; 70 (01) 90-95
    CrossrefPubMedGoogle Scholar
  • 29 Ramenghi LA, Fumagalli M, Groppo M. et al. Germinal matrix hemorrhage: intraventricular hemorrhage in very-low-birth-weight infants: the independent role of inherited thrombophilia. Stroke 2011; 42 (07) 1889-1893
    CrossrefPubMedGoogle Scholar
  • 30 Strauss T, Levy-Shraga Y, Ravid B. et al. Clot formation of neonates tested by thromboelastography correlates with gestational age. Thromb Haemost 2010; 103 (02) 344-350
    Article in Thieme ConnectPubMedGoogle Scholar
  • 31 Salonvaara M, Riikonen P, Kekomäki R. et al. Intraventricular haemorrhage in very-low-birthweight preterm infants: association with low prothrombin activity at birth. Acta Paediatr 2005; 94 (06) 807-811
    CrossrefPubMedGoogle Scholar
  • 32 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 (01) 49-54
    Article in Thieme ConnectPubMedGoogle Scholar
  • 33 Kahn DJ, Richardson DK, Billett HH. Association of thrombocytopenia and delivery method with intraventricular hemorrhage among very-low-birth-weight infants. Am J Obstet Gynecol 2002; 186 (01) 109-116
    CrossrefPubMedGoogle Scholar
  • 34 Baschat AA, Gembruch U, Viscardi RM, Gortner L, Harman CR. Antenatal prediction of intraventricular hemorrhage in fetal growth restriction: what is the role of Doppler?. Ultrasound Obstet Gynecol 2002; 19 (04) 334-339
    CrossrefPubMedGoogle Scholar
  • 35 Chen JP, Lorch V. Intraventricular haemorrhage in preterm infants: evidence of suppressed fibrinolysis. Blood Coagul Fibrinolysis 1996; 7 (03) 289-294
    CrossrefPubMedGoogle Scholar
  • 36 Lupton BA, Hill A, Whitfield MF, Carter CJ, Wadsworth LD, Roland EH. Reduced platelet count as a risk factor for intraventricular hemorrhage. Am J Dis Child 1988; 142 (11) 1222-1224
    PubMedGoogle Scholar
  • 37 Amato M, Fauchere JC, Hermann Jr U. Coagulation abnormalities in low birth weight infants with peri-intraventricular hemorrhage. Neuropediatrics 1988; 19 (03) 154-157
    Article in Thieme ConnectPubMedGoogle Scholar
  • 38 Van de Bor M, Briet E, Van Bel F, Ruys JH. Hemostasis and periventricular-intraventricular hemorrhage of the newborn. Am J Dis Child 1986; 140 (11) 1131-1134
    PubMedGoogle Scholar
  • 39 McDonald MM, Johnson ML, Rumack CM. et al. Role of coagulopathy in newborn intracranial hemorrhage. Pediatrics 1984; 74 (01) 26-31
    CrossrefPubMedGoogle Scholar
  • 40 Beverley DW, Chance GW, Inwood MJ, Schaus M, O'Keefe B. Intraventricular haemorrhage and haemostasis defects. Arch Dis Child 1984; 59 (05) 444-448
    CrossrefPubMedGoogle Scholar
  • 41 Thorburn RJ, Lipscomb AP, Stewart AL, Reynolds EO, Hope PL. Timing and antecedents of periventricular haemorrhage and of cerebral atrophy in very preterm infants. Early Hum Dev 1982; 7 (03) 221-238
    CrossrefPubMedGoogle Scholar
  • 42 Andrew M, Castle V, Saigal S, Carter C, Kelton JG. Clinical impact of neonatal thrombocytopenia. J Pediatr 1987; 110 (03) 457-464
    CrossrefPubMedGoogle Scholar
  • 43 Garg SK, Amorosi EL, Karpatkin S. Use of the megathrombocyte as an index of megakaryocyte number. N Engl J Med 1971; 284 (01) 11-17
    CrossrefPubMedGoogle Scholar
  • 44 Risson DC, Davies MW, Williams BA. Review of neonatal alloimmune thrombocytopenia. J Paediatr Child Health 2012; 48 (09) 816-822
    CrossrefPubMedGoogle Scholar
  • 45 Curley A, Stanworth SJ, New H. A randomized trial of neonatal platelet transfusion thresholds [Reply]. N Engl J Med 2019; 380 (16) 1584-1585
    CrossrefPubMedGoogle Scholar
  • 46 Al-Abdi SY, Al-Aamri MA. A systematic review and meta-analysis of the timing of early intraventricular hemorrhage in preterm neonates: clinical and research implications. J Clin Neonatol 2014; 3 (02) 76-88
    CrossrefPubMedGoogle Scholar
  • 47 Larsen JB, Hvas AM. Predictive value of whole blood and plasma coagulation tests for intra- and postoperative bleeding risk: a systematic review. Semin Thromb Hemost 2017; 43 (07) 772-805
    Article in Thieme ConnectPubMedGoogle Scholar