Abstract

Objective: Patients with Noonan syndrome (NS), who may need various surgical interventions throughout their lives, need to be evaluated carefully in the preoperative period due to the risk of bleeding diathesis. There is a limited number of studies evaluating bleeding diathesis in patients with NS. In this study, we aimed to determine the frequency of bleeding diathesis in patients with NS and to evaluate the place of thromboelastography (TEG) in determining the risk of bleeding.

Method: In our study, bleeding score and coagulation test results obtained from the files of 12 patients with NS were evaluated.

Results: The most frequently detected factor deficiency is vWF deficiency (41%), followed by platelet dysfunction (33%). Two cases with a bleeding score of 2 or above were detected, and in one of them, both platelet dysfunction (response to epinephrine in platelet aggregometer, 7%) and vWF deficiency (vWF Ag: 20%), and in the other case, mild Factor VII deficiency (17%) were detected. TEG results of nine patients were normal. TEG abnormality was detected in three patients and 2 of them had bleeding phenotype.

Conclusion: As a result, although laboratory examinations in patients with NS often yield values consistent with bleeding diathesis, bleeding event does not occur in most patients. We suggest that with the use of the TEG method, the risk of bleeding can be predicted and unnecessary treatments can be prevented.

Keywords: bleeding disorders, laboratory test abnormalities, Noonan syndrome, thromboelastography

Copyright and license

Copyright © 2024 The author(s). This is an open-access article published by Aydın Pediatric Society under the terms of the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is properly cited.

How to cite

1.
Okur Acar S, Tahta N, Odaman Al I, Erdem M, Oymak Y, Gözmen S, et al. Evaluation of bleeding diathesis in patients with Noonan syndrome and comparison with thromboelastography (TEG) test results: A single center experience. Trends in Pediatrics. 2024;5(3):85-9. https://doi.org/10.59213/TP.2024.157

References

  1. Romano AA, Allanson JE, Dahlgren J, et al. Noonan syndrome: clinical features, diagnosis, and management guidelines. Pediatrics. 2010;126:746-59. https://doi.org/10.1542/peds.2009-3207 DOI: https://doi.org/10.1542/peds.2009-3207
  2. Zenker M, Edouard T, Blair JC, Cappa M. Noonan syndrome: improving recognition and diagnosis. Arch Dis Child. 2022;107:1073-8. https://doi.org/10.1136/archdischild-2021-322858 DOI: https://doi.org/10.1136/archdischild-2021-322858
  3. Nugent DJ, Romano AA, Sabharwal S, Cooper DL. Evaluation of bleeding disorders in patients with Noonan syndrome: a systematic review. J Blood Med. 2018;9:185-92. https://doi.org/10.2147/JBM.S164474 DOI: https://doi.org/10.2147/JBM.S164474
  4. Artoni A, Selicorni A, Passamonti SM, et al. Hemostatic abnormalities in Noonan syndrome. Pediatrics. 2014;133:e1299-304. https://doi.org/10.1542/peds.2013-3251 DOI: https://doi.org/10.1542/peds.2013-3251
  5. Lan J, Zeng T, Liu S, Lan J, Qian L. Noonan syndrome with RAF1 gene mutations in a newborn with cerebral haemorrhage. Eur J Med Res. 2022;27:146. https://doi.org/10.1186/s40001-022-00772-2 DOI: https://doi.org/10.1186/s40001-022-00772-2
  6. Linglart L, Gelb BD. Congenital heart defects in Noonan syndrome: Diagnosis, management, and treatment. Am J Med Genet C Semin Med Genet. 2020;184:73-80. https://doi.org/10.1002/ajmg.c.31765 DOI: https://doi.org/10.1002/ajmg.c.31765
  7. Turner AM. Noonan syndrome. J Paediatr Child Health. 2014;50:E14-20. https://doi.org/10.1111/j.1440-1754.2010.01970.x DOI: https://doi.org/10.1111/j.1440-1754.2010.01970.x
  8. Derbent M, Öncel Y, Tokel K, et al. Clinical and hematologic findings in Noonan syndrome patients with PTPN11 gene mutations. Am J Med Genet A. 2010;152A:2768-74. https://doi.org/10.1002/ajmg.a.33713 DOI: https://doi.org/10.1002/ajmg.a.33713
  9. Noonan JA. Hypertelorism with Turner phenotype. A new syndrome with associated congenital heart disease. Am J Dis Child. 1968;116:373-80. https://doi.org/10.1001/archpedi.1968.02100020377005 DOI: https://doi.org/10.1001/archpedi.1968.02100020377005
  10. Witt DR, McGillivray BC, Allanson JE, et al. Bleeding diathesis in Noonan syndrome: a common association. Am J Med Genet. 1988;31:305-17. https://doi.org/10.1002/ajmg.1320310208 DOI: https://doi.org/10.1002/ajmg.1320310208
  11. Stoffman JM, Mcnicol A, Zelinski T, Chodirker BN, Israels SJ. The association between SHP-2 mutations and platelet function in Noonan syndrome. Blood 2008;112:1239 https://doi.org/10.1182/blood.V112.11.1239.1239 DOI: https://doi.org/10.1182/blood.V112.11.1239.1239
  12. Perez Botero J, Ho TP, Rodriguez V, Khan SP, Pruthi RK, Patnaik MM. Coagulation abnormalities and haemostatic surgical outcomes in 142 patients with Noonan syndrome. Haemophilia. 2017;23:e237-40. https://doi.org/10.1111/hae.13225 DOI: https://doi.org/10.1111/hae.13225
  13. Morice A, Harroche A, Cairet P, Khonsari RH. Preoperative detailed coagulation tests are required in patients with Noonan syndrome. J Oral Maxillofac Surg. 2018;76:1553-8. https://doi.org/10.1016/j.joms.2017.12.012 DOI: https://doi.org/10.1016/j.joms.2017.12.012
  14. van der Burgt I. Noonan syndrome. Orphanet J Rare Dis. 2007;2:4. https://doi.org/10.1186/1750-1172-2-4 DOI: https://doi.org/10.1186/1750-1172-2-4
  15. Bowman M, Mundell G, Grabell J, et al. Generation and validation of the Condensed MCMDM-1VWD Bleeding Questionnaire for von Willebrand disease. J Thromb Haemost. 2008;6:2062-6. https://doi.org/10.1111/j.1538-7836.2008.03182.x DOI: https://doi.org/10.1111/j.1538-7836.2008.03182.x
  16. Toulon P, Berruyer M, Brionne-François M, et al. Age dependency for coagulation parameters in paediatric populations. Results of a multicentre study aimed at defining the age-specific reference ranges. Thromb Haemost. 2016;116:9-16. https://doi.org/10.1160/TH15-12-0964 DOI: https://doi.org/10.1160/TH15-12-0964
  17. Favaloro EJ. Utility of the PFA-100 for assessing bleeding disorders and monitoring therapy: a review of analytical variables, benefits and limitations. Haemophilia. 2001;7:170-9. https://doi.org/10.1046/j.1365-2516.2001.00486.x DOI: https://doi.org/10.1046/j.1365-2516.2001.00486.x
  18. Ng C, Motto DG, Di Paola J. Diagnostic approach to von Willebrand disease. Blood. 2015;125:2029-37. https://doi.org/10.1182/blood-2014-08-528398 DOI: https://doi.org/10.1182/blood-2014-08-528398
  19. Saeveraas SB, Seghatchian J, Sivertsen J, Hervig T. The use of thromboelastography (TEG) in massively bleeding patients at Haukeland University Hospital 2008-15. Transfus Apher Sci. 2019;58:117-21. https://doi.org/10.1016/j.transci.2018.12.017 DOI: https://doi.org/10.1016/j.transci.2018.12.017
  20. Hartert H. Blood clotting studies with Thrombus stressography; a new investigation procedure. Klin Wochenschr. 1948;26:577-83. https://doi.org/10.1007/BF01697545 DOI: https://doi.org/10.1007/BF01697545
  21. Hans GA, Besser MW. The place of viscoelastic testing in clinical practice. Br J Haematol. 2016;173:37-48. https://doi.org/10.1111/bjh.13930 DOI: https://doi.org/10.1111/bjh.13930
  22. Bruno L, Lenberg J, Le D, Dimmock D, Thornburg CD, Briggs B. Novel approach to improve the identification of the bleeding phenotype in Noonan syndrome and related RASopathies. J Pediatr. 2023;257:113323. https://doi.org/10.1016/j.jpeds.2022.12.036 DOI: https://doi.org/10.1016/j.jpeds.2022.12.036
  23. Barg AA, Yeshayahu Y, Avishai E, et al. Bleeding phenotype and hemostatic evaluation by thrombin generation in children with Noonan syndrome: a prospective study. Pediatr Blood Cancer. 2024;71:e30761. https://doi.org/10.1002/pbc.30761 DOI: https://doi.org/10.1002/pbc.30761
  24. Bertola DR, Carneiro JD, D'Amico EA, et al. Hematological findings in Noonan syndrome. Rev Hosp Clin Fac Med Sao Paulo. 2003;58:5-8. https://doi.org/10.1590/s0041-87812003000100002 DOI: https://doi.org/10.1590/S0041-87812003000100002
  25. Sharland M, Patton MA, Talbot S, Chitolie A, Bevan DH. Coagulation-factor deficiencies and abnormal bleeding in Noonan's syndrome. Lancet. 1992;339:19-21. https://doi.org/10.1016/0140-6736(92)90141-o DOI: https://doi.org/10.1016/0140-6736(92)90141-O
  26. Ruiz-Llobet A, Isola I, Gassiot S, et al. Platelet dysfunction in Noonan and 22q11.2 Deletion syndromes in childhood. Thromb Haemost. 2020;120:457-65. https://doi.org/10.1055/s-0040-1701239 DOI: https://doi.org/10.1055/s-0040-1701239