Journal of Thrombosis and Thrombolysis

, Volume 32, Issue 4, pp 474–477 | Cite as

Thrombotic events in MYH9 gene-related autosomal macrothrombocytopenias (old May–Hegglin, Sebastian, Fechtner and Epstein syndromes)

  • Girolami AntonioEmail author
  • Vettore Silvia
  • Bonamigo Emanuela
  • Fabris Fabrizio


Congenital macrothrombocytopenia are a group of disorders which may be due to mutations in the MYH9 gene. This gene linked to chromosome 22 encodes for the nonmuscle heavy chain IIA that is expressed in platelets and in other tissues. In the past these disorders were known as May–Hegglin anomaly, Sebastian, Fechtner and Epstein syndromes. The main common feature is the presence of thrombocytopenia with large platelets. The evaluation of all reported cases indicates that thrombotic events appear to occur only in patients with May Hegglin variants. Whether this is due to the higher prevalence of this variant as compared with the others or to a specific difference is still unknown. However, the occurrence of thrombotic events in only one of these conditions may be used as a new tentative differentiability feature.


MYH9 gene Macrothrombocytopenias Thrombosis 



This study was supported in part by the “Associazione Emofilia ed altre Coagulopatie delle Tre Venezie”.


  1. 1.
    Girolami A, Ruzzon E, Fabris F, Varvarikis C, Sartori R, Girolami B (2006) Myocardial infarction and other arterial occlusions in hemophilia a patients. A cardiological evaluation of all 42 cases reported in the literature. Acta Haematol 116:120–125PubMedCrossRefGoogle Scholar
  2. 2.
    Franchini M (2004) Thrombotic complications in patients with hereditary bleeding disorders. Thromb Haemost 92:298–304PubMedGoogle Scholar
  3. 3.
    Girolami A, Scandellari R, Zanon E, Sartori R, Girolami B (2006) Non-catheter associated venous thrombosis in hemophilia A, B. A critical review of all reported cases. J Thromb Thrombolysis 21:279–284PubMedCrossRefGoogle Scholar
  4. 4.
    Girolami A, Tezza F, Scapin M, Vettore S, Casonato A (2006) Arterial and venous thrombosis in patients with von Willebrand’s disease: a critical review of the literature. J Thromb Thrombolysis 21:175–178PubMedCrossRefGoogle Scholar
  5. 5.
    Mariani G, Herrmann FH, Schulman S, Batorova A, Wulff K, Etro D, Dolce A, Auerswald G, Astermark J, Schved JF, Ingerslev J, Bernardi F (2003) International factor VII deficiency study group. Thrombosis in inherited factor VII deficiency. J Thromb Haemost 1:2153–2158PubMedCrossRefGoogle Scholar
  6. 6.
    Girolami A, Ruzzon E, Tezza F, Scandellari R, Vettore S, Girolami B (2006) Arterial and venous thrombosis in rare congenital bleeding disorders: a critical review. Haemophilia 12:345–351PubMedCrossRefGoogle Scholar
  7. 7.
    Seri M, Pecci A, Di Bari F, Cusano R, Savino M, Panza E, Nigro A, Noris P, Gangarossa S, Rocca B, Gresele P, Bizzaro N, Malatesta P, Koivisto PA, Longo I, Musso R, Pecoraro C, Iolascon A, Magrini U, Rodriguez Soriano J, Renieri A, Ghiggeri GM, Ravazzolo R, Balduini CL, Savoia A (2003) MYH9-related disease: May–Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness. Medicine 82:203–215PubMedGoogle Scholar
  8. 8.
    McDunn S, Hartz W Jr, Ts’Ao C, Green D (1991) Coronary thrombosis in a patient with May–Hegglin anomaly. Am J Clin Pathol 95:715–718PubMedGoogle Scholar
  9. 9.
    Goto S, Kasahara H, Sakai H, Goto M, Ono M, Ikeda Y, Jorquera JI, Bravo MI, Handa S (1998) Functional compensation of the low platelet count by increased individual platelet size in a patient with May–Hegglin anomaly presenting with acute myocardial infarction. Int J Cardiol 64:171–177PubMedCrossRefGoogle Scholar
  10. 10.
    Everlien M, Knoch K, Farah I, Greve H (2001) Koronare bypassoperation bei May–Hegglin-anomalie. Dtsch med Wochenschr 126:47–49PubMedCrossRefGoogle Scholar
  11. 11.
    Varbella F, Bongioanni S, Gagnor A, Nannini C, La Brocca A, Badalì A, Conte MR (2005) Infarto miocardico acuto trattato con angioplastica primaria in una rara forma di piastrinopenia ereditaria: anomalia di May–Hegglin. Caso clinico e revisione della letteratura. Italian Heart J Suppl 6:214–217Google Scholar
  12. 12.
    Nishiyama Y, Akaishi J, Katsumata T, Katsura K, Katayama Y (2008) Cerebral infarction in a patient with macrothrombocytopenia with leukocyte inclusions (MTCP, May–Hegglin anomaly/Sebastian syndrome). J Nippon Med Sch 75:228–232CrossRefGoogle Scholar
  13. 13.
    Heller PG, Pecci A, Glembotsky AC, Savoia A, Negro FD, Balduini CL, Molinas FC (2006) Unexplained recurrent venous thrombosis in a patient with MYH9-related disease. Platelets 17:274–275PubMedCrossRefGoogle Scholar
  14. 14.
    Fabris F, Scandellari R, Vettore S, Scapin M, Bizzaro N, Randi ML (2010) Intriguing outcome of JAK2V617F mutation seen in a patient with MYH9-related hereditary macrothrombocytopenia. Thromb Haemost 104:858–859PubMedCrossRefGoogle Scholar
  15. 15.
    Kunishima S, Yoshinari M, Nishio H, Ida K, Miura T, Matsushita T, Hamaguchi M, Saito H (2007) Haematological characteristics of MYH9 disorders due to MYH9 R702 mutations. Eur J Haematol 78:220–226PubMedCrossRefGoogle Scholar
  16. 16.
    Balderramo DC, Ricchi BN, Marun SG, Scaliter G, Alonso M (2003) Sebastian syndrome: report of the first case in a south American family. Haematologica 88:74–77Google Scholar
  17. 17.
    Epstein CJ, Sahud MA, Piel CF, Goodman JR, Bernfield MR, Kushner JH, Ablin AR (1972) Hereditary macrothrombocytopathia, nephritis and deafness. Am J Med 52:299–310PubMedCrossRefGoogle Scholar
  18. 18.
    Peterson LC, Rao KV, Crosson JT, White JG (1985) Fechtner syndrome—a variant of Alport’s syndrome with leukocyte inclusions and macrothrombocytopenia. Blood 65:397–406PubMedGoogle Scholar
  19. 19.
    Greinacher A, Nieuwenhuis HK, White JG (1990) Sebastian platelet syndrome: a new variant of hereditary macrothrombocytopenia with leukocyte inclusions. Blut 61:282–288PubMedCrossRefGoogle Scholar
  20. 20.
    Young G, Luban NL, White JG (1999) Sebastian syndrome: case report and review of the literature. Rev Am J Hematol 61:62–65CrossRefGoogle Scholar
  21. 21.
    Chen Z, Shivdasani RA (2009) Regulation of platelet biogenesis: insights from the May–Hegglin anomaly and other MYH9-related disorders. J Thromb Haemost 7(Suppl 1):272–276PubMedCrossRefGoogle Scholar
  22. 22.
    Rhee HY, Choi HY, Kim SB, Shin WC (2010) Recurrent ischemic stroke in a patient with idiopathic thrombocytopenic purpura. J Thromb Thrombolysis 30:229–232PubMedCrossRefGoogle Scholar
  23. 23.
    Fuchi T, Kondo T, Sase K, Takahashi M (1999) Primary percutaneous transluminal coronary angioplasty performed for acute myocardial infarction in a patient with idiopathic thrombocytopenic purpura. Jpn Circ J 63:133–136PubMedCrossRefGoogle Scholar
  24. 24.
    Eleftheriadis T, Antoniadi G, Akritidou A, Kasimatis E, Apostolidis G, Pashalidou S, Salmas M, Liakopoulos V, Barboutis K (2008) A case report of recurrent vascular access thrombosis in a hemodialysis patient reveals combined acquired and inherited thrombophilia. Ther Apher Dial 12:190–192PubMedCrossRefGoogle Scholar
  25. 25.
    van der Loop FT, Heidet L, Timmer ED, van den Bosch BJ, Leinonen A, Antignac C, Jefferson JA, Maxwell AP, Monnens LA, Schröder CH, Smeets HJ (2000) Autosomal dominant Alport syndrome caused by a COL4A3 splice site mutation. Kidney Int 58:1870–1875PubMedCrossRefGoogle Scholar
  26. 26.
    McCarthy PA, Maino DM (2000) Alport syndrome: a review. Clin Eye Vis Care 12:139–150PubMedCrossRefGoogle Scholar
  27. 27.
    Nurden P, Nurden AT (2008) Congenital disorders associated with platelet dysfunctions. Thromb Haemost 99:253–263 ReviewPubMedGoogle Scholar
  28. 28.
    Balduini CL, Pecci A, Savoia A (2011) Recent advances in the understanding and management of MYH9-related inherited thrombocytopenias. Br J Haematol 154(2):161–174. doi: 10.1111/j.1365-2141.2011.08716.x PubMedCrossRefGoogle Scholar
  29. 29.
    Phillips R, Richards M (2007) Venous thrombosis in Glanzmann’s thrombasthenia. Haemophilia 13:758–759PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Girolami Antonio
    • 1
    Email author
  • Vettore Silvia
    • 1
  • Bonamigo Emanuela
    • 1
  • Fabris Fabrizio
    • 1
  1. 1.Department of Medical and Surgical SciencesUniversity of Padua Medical SchoolPaduaItaly

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