Diagnostic and Therapeutic Considerations on Inherited Platelet Disorders in Neonates and Children

Abstract

Inherited disorders of platelets constitute a group of rare diseases that give rise to bleeding syndromes of variety severity, with more severe cases being first diagnosed during infancy and childhood. To appropriate diagnose a platelet function disorder during early childhood the knowledge of the physiological characteristics of platelets in the paediatric population is mandatory. Apart from thrombocytopenia which is quite common in neonates and children the present overview is aimed to focus on inherited platelet function disorders. Furthermore, knowledge on platelet maturation and reference values according to age are given, and a diagnostic strategy specifically adapted to a pediatric population is presented on the bases of plasmatic and molecular laboratory methodologies. Finally, therapeutic approaches are briefly summarized (antifibrinolytic agents, Desmopressin, HLA-matched platelets, recombinant factor VIIa).

Zusammenfassung

Angeborene Störungen der Plättchenfunktion sind selten und können durch eine unterschiedlich stark ausgeprägte Blutungsneigung klinisch auffällig werden. Schwere Störungen der Thrombozytenfunktion treten bereits im Säuglings- und Kindesalter auf. Um Störungen der Thrombozytenfunktion adäquat abklären zu können, ist die Kenntnis der altersabhängigen Plättchenphysiologie erforderlich. Neben den Ursachen für eine Thrombozytopenie, der häufigsten thrombozytären Störung im Kindesalter, fasst dieser Überblick entwicklungsbedingte Besonderheiten und altersabhängige Referenzwerte zusammen. Neben einem diagnostischen Algorithmus, basierend sowohl auf Untersuchungen im plättchenreichen Plasma als auch auf mole-kulargenetischer Ebene, werden die verfügbaren Therapieoptionen (Antifibrinolytika, Desmopressin, HLA-typisierte Thrombozytentransfusionen, rekombinanter Faktor VIIa) zusammengefasst.

Key Words

platelet function disorders - neonates - infants - children - developmental hemostasis - laboratory work-up

Schlüsselwörter

Thrombozytenfunktionsstörungen - Neugeborene - Säuglinge - Kinder - entwicklungsbedingte Besonderheiten - Vorgehen im Labor

Literatur

• 1 Arrondel C, Vodovar N, Knebelmann B. et al . Expression of the Nonmuscle Myosin Heavy Chain IIA in the human kidney and screening for MYH9 mutations in Epstein and Fechtner syndromes.  J Am Soc Nephrol. 2002;  13 63-74
• 2 Balduini CL, Iolascon A, Savoia A. Inherited thrombocytopenias : from genes to therapy.  Haematologica. 2002;  87 860-880
• 3 Bolton-Maggs PHB, Chalmers EA, Collins OPW. et al . A review of inherited platelet disorders with guidelines for their management on behalf of the UKHCDO.  Br J Haematol. 2006;  135 603-633
• 4 Coppola A, Di Minno G. Desmopressin in inherited disorders of platelet function.  Haemophilia. 2008;  14 (S1) 31-33
• 5 Federici AB, Canciani MT. Clinical and laboratory versus molecular markers for a correct classification of von Willebrand disease.  Haematologica. 2009;  94 610-615
• 6 Fujita H, Hashimoto Y, Russell S. et al . In vivo expression of murine platelet glycoprotein Ibalpha.  Blood. 1998;  92 488-495
• 7 Hézard 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
• 8 Hurtaud-Roux MF, Hezard N, Lefranc V. et al . Quantification of the major integrins and P-Selectin in neonatal platelets by flow cytometry.  A bicentric study. Thromb Haemost. 2001;  ISSN 0340-6245
• 9 Kühne 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
• 10 Kunishima S, Matsushita T, Kojima T. et al . Identification of six novel MYH9 mutations and genotype-phenotype relationships in autosomal dominant macrothrombocytopenia with leucocyte inclusions.  J Hum Genet. 2001;  46 722-729
• 11 Michelson AD, Rajasekhar D, Bednarek FJ. et al . Platelet and platelet-derived microparticle surface factor V/Va binding in whole blood: differences between neonates and adults.  Thromb Haemost. 2000;  84 689-694
• 12 Nurden AT, Nurden P, Bermejo E. et al . Phenotypic heterogeneity in the Gray Platelet Syndrome extends to the expression of TREM family member, TLT-1.  Thromb Haemost. 2008;  100 45-51
• 13 Nurden AT, Fiore M, Pillois X. et al . Genetic testing in the diagnostic evaluation of inherited platelet disorders.  Sem Thromb Hemost. 2009;  35 204-212
• 14 Rajasekhar D, Kestin AS, Bednarek FJ. et al . Neonatal platelets are less reactive than adult platelets to physiological agonists in whole blood.  Thromb Haemost. 1994;  72 957-963
• 15 Rajasekhar D, Barnard MR, Bednarek FJ. et al . Platelet hyporeactivity in very low birth weight neonates.  Thromb Haemost. 1997;  77 1002-1007
• 16 Rolf N, Knoefler R, Bugert P. et al . Clinical and laboratory phenotypes associated with the aspirin-like defect: a study in 17 unrelated families.  Br J Haematol. 2008;  144 416-424
• 17 Scharf RE. Erworbene Plättchenfunktionsstörungen. Pathogenese, Klassifikation, Häufigkeit, Diagnostik und Behandlung.  Haemostaseologie. 2008;  28 299-311
• 18 Seri M, Cusano R, Gangarossa S. et al . Mutations in MYH9 result in the May-Hegglin anomaly, and Fechtner and Sebastian syndromes. The May-Hegglin/Fechtner Syndrome Consortium.  Nat Genet. 2000;  26 103-105
• 19 Zieger B, Jenny A, Tsakiris DA. et al . A large Swiss family with Bernard-Soulier syndrome – Correlation phenotype and genotype.  Haemostaseologie. 2009;  29 161-167
• 20 Kosch A, Kehrel B, Nowak-Göttl U. et al . Thrombocytic alpha-delta-storage-pool-disease: shortening of bleeding time after infusion of 1-desamino-8-D-arginine vasopressin.  Klin Pädiatr. 1999;  211 198-200
• 21 Poon MC, D’Orion R, von Depka M. et al . Prophylactic and therapeutic recombinant factor VIIa administration to Glanzmann's thrombasthenia: results of an international survey.  J Thromb Haemost. 2004;  2 1093-1103
• 22 Almeida KM, Khair K, Hann I. et al . The use of recombinant factor VIIa in children with inherited platelet function disorders.  Br J Haematol. 2003;  121 477-481

Correspondence