Impaired Platelet Function in Neonates Born to Mothers with Diabetes or Hypertension During Pregnancy

Abstract

Objective: In a recent pilot study, platelet function of 4 neonates born to mothers with pregnancy-induced hypertension (PIH) was found to display lower platelet adhesion compared to healthy neonates. The present study aimed at confirming and validating these findings.

Study Design: Platelet adhesion was measured using a Cone Platelet Analyzer (CPA). The platelet function in the cord blood of 35 term infants born to mothers with PIH or gestational diabetes (GD) was compared with the platelet function of 196 infants born to healthy mothers. All neonates were monitored for perinatal complications until hospital discharge.

Results: Neonates born to mothers with PIH and with GD displayed poorer platelet function, with decreased platelet surface coverage as tested by CPA (control group 8.53±3.81%; PIH: 5.9±3.91%, p=0.003; GD: 6.64±3.64%, p=0.005). No association was found between CPA values and post-natal complications.

Conclusions: Maternal PIH or GD is associated with impaired platelet function in neonates. The clinical impact of these findings is yet to be studied.

Zusammenfassung

Hintergrund: Wir haben in einer Pilotstudie zeigen können, dass die Thrombozytenadhäsion bei 4 Neugeborenen vom Müttern mit gesichertem Schwangerschaftshochdruck (SH) im Vergleich zu Neugeborenen gesunder Mütter deutlich reduziert war. Ziel der vorliegenden Studie war es, diese Ergebnisse mit einem kontrollierten Studienansatz zu überprüfen und zu validieren.

Methode: Die Thrombozytenadhäsion aus Nabelschnurblut wurde bei 35 Neugeborenen von Müttern mit SH oder Schwangerschaftsdiabetes (SD) im Vergleich zu 196 Neugeborenen gesunder Mütter im Cone-Plättchen-Analyzer (CPA) bestimmt. Alle Neugeborenen wurden bis zur Krankenhausentlassung nachbeobachtet.

Ergebnisse: Säuglinge von Müttern mit SH oder SD zeigten eine signifikant schlechtere Thrombozytenadhäsion (SH: 5,9±3,91, p=0,003; SD: 6,64±3,64%; p=0,005) als Neugeborene gesunder Mütter (8,53±3,81%). Wir konnten keinen Zusammenhang zwischen Plättchenadhäsion mit postpartalen Komplikationen finden.

Schlussfolgerung: Mütterlicher SH oder SD ist mit einer reduzierten Thrombozytenadhäsion bei Neugeborenen assoziiert. Die klinische Relevanz dieser Beobachtung bedarf weiterer Studien.

Key words

neonates - platelet function - Cone and Platelet Analyzer (CPA) - diabetes - pregnancy induced hypertension (PIH)

Schlüsselwörter

Neugeborene - Cone Platelet Analyzer (CPA) - Diabetes - Schwangerschaftshochdruck

References

• 1 Andrew M, Paes B, Milner M. Development of human coagulation system in healthy premature infant.  Blood. 1988;  72 1651-1657
• 2 Andrew M, Paes B, Milner M. Development of human coagulation system in the full term infant.  Blood. 1987;  70 165-172
• 3 Bednarek FJ, Bean S, Barnard MR. et al . The platelet hyporeactivity of extremely low birth weight neonates is age-dependent.  Thromb Res.. 2009;  124 42-45
• 4 Bhat YR, Cherian CS. Neonatal thrombocytopenia associated with maternal pregnancy induced hypertension.  Indian J Pediatr.. 2008;  75 473-571
• 5 Colwell JA, Nesto RW. The platelet in diabetes: focus on prevention of ischemic events.  Diabetes Care.. 2003;  26 2181-2188
• 6 Christensen RD, Henry E, Wiedmeier SE. et al . Thrombocytopenia among extremely low birth weight neonates: data from a multihospital healthcare system.  J Perinatol.. 2006;  26 348-353
• 7 Dardik R, Kaufmann Y, Savion N. et al . Platelets mediate tumor cell adhesion to the subendothelium under flow conditions: Involvement of platelet GPIIbIIIa and tumor cell integrins.  Int J Cancer. 1997;  70 201-207
• 8 Del Vecchio A, Latini G, Henry E. et al . Template bleeding time of 240 neonates born at 24 to 41 weeks gestation.  J Perinatol. 2008;  28 427-423
• 9 El Haouari M, Rosado JA. Platelet function in hypertension.  Blood Cells Mol Dis. 2009;  42 38-43
• 10 Finkelstein Y, Shenkman B, Sirota L. et al . Whole blood platelet deposition on extracellular matrix under flow conditions in preterm neonatal sepsis.  Eur J Ped. 2002;  161 270-274
• 11 Harlow FH, Brown MA, Brighton TA. et al . Platelet activation in the hypertensive disorders of pregnancy.  Am J Obstet Gynecol. 2002;  187 688-695
• 12 Hezard N, Potron G, Schlegel N. et al . Unexpected persistence of platelet hyporeactivity beyond the neonatal period: a flow cytometric study in neonates, infants and older children.  Thromb Haemost. 2003;  90 116-123
• 13 Kenet G, Lubetsky A, Shenkman B. et al . Cone and platelet analyzer CPA: A new test for prediction of bleeding among thrombocytopenic patients.  Br J Haematol. 1998;  101 255-259
• 14 Knobler H, Savion N, Shenkman B. et al . Shear-induced platelet adhesion and aggregation on subendothelium are increased in diabetic patients.  Thromb Res. 1998;  90 181-190
• 15 Kudolo GB, Koopmans SJ, Haywood JR. et al . J Lipid Chronic hyperinsulinemia inhibits platelet-activating factor (PAF) biosynthesis in the rat kidney.  Mediat Cell Signal. 1997;  16 23-37
• 16 Kuhne T, Ryan G, Blanchette V. et al . Platelet surface glycoproteins in healthy and preeclamptic mothers and their newborn infants.  Pediatr Res. 1996;  40 876-880
• 17 Levy-Shraga Y, Maayan-Metzger A, Lubetsky A. et al . Platelet function of newborns as tested by the Cone and Platelet analyser correlates with gestational age.  Acta Haematol. 2006;  115 152-156
• 18 Linder N, Shenkman B, Levin E. et al . Deposition of whole blood platelet on extracellular matrix under flow conditions in preterm infants.  Arch Dis Chil. 2002;  86 127-130
• 19 Mankin P, Marngos J, Akhand M. et al . Impaired platelet dense granules release in neonate.  J Pediatr Hematol Oncol. 2000;  22 143-147
• 20 Monagle P, Barnes C, Ignjatovic V. et al . Developmental haemostasis.  Impact for clinical haemostasis laboratories.  Thromb Haemost. 2006;  95 362-372
• 21 Nathan and Oski's Hematology of infancy and childhood, 6th edition.  2003; 
• 22 Rajasekhar D, Barnard M, Francis J. et al . Platelet hyporeactivity in very low birth weight neonates.  Thromb haemost. 1997;  77 1002-1007
• 23 Rajasekhar D, Kestin A, Bednarek F. Neonatal platelets are less reactive than adult platelets to physiological agonists in whole blood.  Thromb Haemost. 1994;  72 957-963
• 24 Saxonhouse MA, Sola MC. Platelet function in term and preterm neonates.  Clin Perinatol. 2004;  31 15-18
• 25 Shenkman B, Einav Y, Salomon O. et al . Testing agonist-induced platelet aggregation by the Impact-R Cone and platelet analyzer CPA.  Platelets. 2008;  19 440-446
• 26 Shenkman B, Savion N, Tamarin I. et al . Testing of platelet deposition on polystyrene surface under flow conditions by cone and platelet analyzer: the role of platelet activation, fibrinogen and von Willebrand factor.  Throm Res. 2000;  99 353-361
• 27 Shi B, Yin C, Guo H. et al . Influence of intensive insulin therapy on the intestinal microcirculatory dysfunction in rats with sepsis.  Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2009;  21 492-494
• 28 Simak J, Holada K, Janota J. et al . Surface expression of major membrane glycoproteins on resting and TRAP-activated neonatal platelets.  Pediatr Res. 1999;  46 445-449
• 29 Varon D, Dardik R, Shenkman B. et al . A new method for quantitative analysis of whole blood platelet interaction with extracellular matrix under flow conditions.  Throm Res. 1997;  85 283-294
• 30 Wiedmeier SE, Henry E, Sola-Visner MC. et al . Platelet reference ranges for neonates, defined using data from over 47 000 patients in a multihospital healthcare system.  J Perinatol. 2009;  29 130-136

Correspondence