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Neuropediatrics 2006; 37(2): 67-71
DOI: 10.1055/s-2006-923980
Original Article

Georg Thieme Verlag KG Stuttgart · New York

Increased Prevalence of Glycoprotein IIb/IIIa Leu33Pro Polymorphism in Term Infants with Grade I Intracranial Haemorrhage

V. Havasi1 , K. Komlósi1 , J. Bene1 , 2 , B. Melegh1
  • 1Department of Medical Genetics and Child Development, University of Pécs, Pécs, Hungary
  • 2MTA‐PTE Clinical Genetics Research Group of Hungarian Academy of Sciences at University of Pécs, Pécs, Hungary
Further Information

Publication History

Received: June 14, 2005

Accepted after Revision: February 9, 2006

Publication Date:
14 June 2006 (online)

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Abstract

The prevalence rates of the platelet glycoprotein IIb/IIIa Leu33Pro allele (PLA2), and factor V G1691A Leiden mutation were determined in 109 appropriate for gestational age neonates with grade I intraventricular haemorrhage (IVH) and in 118 IVH-free control infants. The PLA2 allele frequency was 16.4 % in the group of full-term infants with grade I IVH, while it was 9.5 % in the relevant controls (p < 0.005); there was no difference in the PLA allele frequencies on comparing the IVH affected (8.34 %) and unaffected (9.2 %) premature infants. By contrast, the factor V Leiden allele frequency was increased only in the subgroup of premature infants with grade I IVH as compared with the appropriate premature controls (9.25 % vs. 3.34 %, respectively, p < 0.005). These data suggest that besides the factor V Leiden mutation, the PLA2 allele, which has already been suggested to have a role in neonatal alloimmune thrombocytopenia and certain subtypes of adult stroke, can have significance in the development of the events of IVH.

Key words

Increased prevalence of PLA2 - intraventricular haemorrhage - factor V Leiden

References

  • 1 Alberts M J. Stroke genetics update.  Stroke. 2003;  34 342-344
    CrossrefPubMedGoogle Scholar
  • 2 Aronis S, Bouza H, Pergantou H, Kapsimalis Z, Platokouki H, Xanthou M. Prothrombotic factors in neonates with cerebral thrombosis and intraventricular hemorrhage.  Acta Paediatr Suppl. 2002;  91 87-91
    CrossrefPubMedGoogle Scholar
  • 3 Birchall J E, Murphy M F, Kaplan C, Kroll H. European collaborative study of the antenatal management of feto-maternal alloimmune thrombocytopenia.  Br J Haematol. 2003;  122 275-288
    CrossrefPubMedGoogle Scholar
  • 4 Blickman J G, Jaramillo D, Cleveland R H. Neonatal cranial ultrasonography.  Curr Probl Diagn Radiol. 1991;  20 91-119
    PubMedGoogle Scholar
  • 5 Carter A M, Catto A J, Bamford J M, Grant P J. Platelet GP IIIa PlA and GP Ib variable number tandem repeat polymorphisms and markers of platelet activation in acute stroke.  Arterioscler Thromb Vasc Biol. 1998;  18 1124-1131
    PubMedGoogle Scholar
  • 6 Davoren A, Curtis B R, Aster R H, McFarland J G. Human platelet antigen-specific alloantibodies implicated in 1162 cases of neonatal alloimmune thrombocytopenia.  Transfusion. 2004;  44 1220-1225
    CrossrefPubMedGoogle Scholar
  • 7 Erhardt E, Stankovics J, Molnar D, Adamovich K, Melegh B. High prevalence of factor V Leiden mutation in mothers of premature neonates.  Biol Neonate. 2000;  78 145-146
    CrossrefPubMedGoogle Scholar
  • 8 Feng D, Lindpaintner K, Larson M G. et al . Increased platelet aggregability associated with platelet GPIIIa PlA2 polymorphism: the Framingham Offspring Study.  Arterioscler Thromb Vasc Biol. 1999;  19 1142-1147
    CrossrefPubMedGoogle Scholar
  • 9 Fullard J F. The role of the platelet glycoprotein IIb/IIIa in thrombosis and haemostasis.  Curr Pharm Des. 2004;  10 1567-1576
    CrossrefPubMedGoogle Scholar
  • 10 Gopel W, Fehlau K, Kohl M, Schultz C, Moller J. HPA‐1 carrier status and thrombocytopenia in preterm infants with a birth weight below 1500 grams.  J Perinat Med. 2002;  30 176-178
    CrossrefPubMedGoogle Scholar
  • 11 Gopel W, Gortner L, Kohlmann T, Schultz C, Moller J. Low prevalence of large intraventricular haemorrhage in very low birth weight infants carrying the factor V Leiden or prothrombin G20210A mutation.  Acta Paediatr. 2001;  90 1021-1024
    CrossrefPubMedGoogle Scholar
  • 12 Herman J H, Jumbelic M I, Ancona R J, Kickler T S. In utero cerebral hemorrhage in alloimmune thrombocytopenia.  Am J Pediatr Hematol Oncol. 1986;  8 312-317
    PubMedGoogle Scholar
  • 13 Humphries S E, Morgan L. Genetic risk factors for stroke and carotid atherosclerosis: insights into pathophysiology from candidate gene approaches.  Lancet Neurol. 2004;  3 227-235
    PubMedGoogle Scholar
  • 14 Israels S J, Rand M L, Michelson A D. Neonatal platelet function.  Semin Thromb Hemost. 2003;  29 363-372
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Kenet G, Maayan-Metzger A, Rosenberg N. et al . Thrombophilia does not increase risk for neonatal complications in preterm infants.  Thromb Haemost. 2003;  90 823-828
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Komlosi K, Havasi V, Bene J. et al . Increased prevalence of factor V Leiden mutation in premature but not in full-term infants with grade I intracranial haemorrhage.  Biol Neonate. 2004;  87 56-59
    PubMedGoogle Scholar
  • 17 Lee R. Factor V Leiden: a clinical review.  Am J Med Sci. 2001;  322 88-102
    PubMedGoogle Scholar
  • 18 Linder N, Haskin O, Levit O. et al . Risk factors for intraventricular hemorrhage in very low birth weight premature infants: a retrospective case-control study.  Pediatrics. 2003;  111 e590-e595
    CrossrefPubMedGoogle Scholar
  • 19 Melegh B, Stankovics J, Kis A. et al . Increased prevalence of factor V Leiden mutation in neonatal intracranial haemorrhage [letter].  Eur J Pediatr. 1998;  157 261
    PubMedGoogle Scholar
  • 20 Michelson A D. Platelet function in the newborn.  Semin Thromb Hemost. 1998;  24 507-512
    PubMedGoogle Scholar
  • 21 Michelson A D, Furman M I, Goldschmidt-Clermont P. et al . Platelet GP IIIa Pl(A) polymorphisms display different sensitivities to agonists.  Circulation. 2000;  101 1013-1018
    PubMedGoogle Scholar
  • 22 Newman P J, Derbes R S, Aster R H. The human platelet alloantigens, PlA1 and PlA2, are associated with a leucine33/proline33 amino acid polymorphism in membrane glycoprotein IIIa, and are distinguishable by DNA typing.  J Clin Invest. 1989;  83 1778-1781
    CrossrefPubMedGoogle Scholar
  • 23 Osborn D A, Evans N, Kluckow M. Hemodynamic and antecedent risk factors of early and late periventricular/intraventricular hemorrhage in premature infants.  Pediatrics. 2003;  112 33-39
    CrossrefPubMedGoogle Scholar
  • 24 Perlman J M. White matter injury in the preterm infant: an important determination of abnormal neurodevelopment outcome.  Early Hum Dev. 1998;  53 99-120
    CrossrefPubMedGoogle Scholar
  • 25 Petaja J, Hiltunen L, Fellman V. Increased risk of intraventricular hemorrhage in preterm infants with thrombophilia.  Pediatr Res. 2001;  49 643-646
    PubMedGoogle Scholar
  • 26 Rayment R, Birchall J, Yarranton H. et al . Neonatal alloimmune thrombocytopenia.  BMJ. 2003;  327 331-332
    CrossrefPubMedGoogle Scholar
  • 27 Sajid M, Vijayan K V, Souza S, Bray P F. PlA polymorphism of integrin beta 3 differentially modulates cellular migration on extracellular matrix proteins.  Arterioscler Thromb Vasc Biol. 2002;  22 1984-1989
    PubMedGoogle Scholar
  • 28 Sosa M E. Alloimmune thrombocytopenia in the fetus: current management theories.  J Perinat Neonatal Nurs. 2003;  17 181-189
    PubMedGoogle Scholar
  • 29 Szolnoki Z, Somogyvari F, Kondacs A. et al . Increased prevalence of platelet glycoprotein IIb/IIIa PLA2 allele in ischaemic stroke associated with large vessel pathology.  Thromb Res. 2003;  109 265-269
    CrossrefPubMedGoogle Scholar
  • 30 Szolnoki Z, Somogyvari F, Szolics M, Szabo M, Fodor L. Common genetic mutations as possible aetiological factors in stroke.  Eur Neurol. 2001;  45 119-120
    CrossrefPubMedGoogle Scholar
  • 31 Undas A, Brummel K, Musial J, Mann K G, Szczeklik A. Pl(A2) polymorphism of beta(3) integrins is associated with enhanced thrombin generation and impaired antithrombotic action of aspirin at the site of microvascular injury.  Circulation. 2001;  104 2666-2672
    CrossrefPubMedGoogle Scholar
  • 32 Vijayan K V, Goldschmidt-Clermont P J, Roos C, Bray P F. The Pl(A2) polymorphism of integrin beta(3) enhances outside-in signaling and adhesive functions.  J Clin Invest. 2000;  105 793-802
    PubMedGoogle Scholar
  • 33 Vohr B R, Allan W C, Westerveld M. et al . School-age outcomes of very low birth weight infants in the indomethacin intraventricular hemorrhage prevention trial.  Pediatrics. 2003;  111 e340-e346
    CrossrefPubMedGoogle Scholar
  • 34 Weiss E J, Bray P F, Tayback M. et al . A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis.  N Engl J Med. 1996;  334 1090-1094
    CrossrefPubMedGoogle Scholar

Professor, M.D., Ph.D., D.Sc. Béla Melegh

Department of Medical Genetics and Child Development
University of Pécs

Szigeti u. 12

7624 Pécs

Hungary

Email: bela.melegh@aok.pte.hu

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