International Journal of Hematology

, Volume 78, Issue 4, pp 329–334 | Cite as

Dominant β-Thalassemia with Hemoglobin Hradec Kralove: Enhanced Hemolysis in the Spleen

  • Shouichi Ohga
  • Akihiko Nomura
  • Hidetoshi Takada
  • Junko Kato
  • Hiroshi Ideguchi
  • Yukio Hattori
  • Masahiro Suda
  • Sachiyo Suita
  • Toshiro Hara
Review Article


We describe a 6-year-old girl and her mother with dominant β-thalassemia due to hemoglobin Hradec Kralove (Hb HK). Both patients presented microcytic anemia, jaundice, splenomegaly, cholelithiasis, and recurrent hemolytic bouts. Osmotic resistance tests using saline and coiled planet centrifugation revealed the increased fragility of the red cell membrane. On the other hand, the glycerol lysing time was prolonged, and results of the isopropanol test were weakly positive. Despite mimicking the features of hereditary spherocytosis, the results of the genetic analyses verified the second reported family with Hb HK (codon 115,\(G\underset{\raise0.3em\hbox{$\smash{\scriptscriptstyle-}$}}{C} C[Ala] \to G\underset{\raise0.3em\hbox{$\smash{\scriptscriptstyle-}$}}{A} C[Asp]\)). Splenectomy was effective for the amelioration of hemolysis. Of 7 reported patients with Hb variants at β-globin codon 115 (Hb Madrid and Hb HK), 5 underwent splenectomy. Because of the variable augmentation of extramedullary hemolysis in dominant β-thalassemias, genotyping is necessary for determining the clinical indication of splenectomy.

Key words

Dominant β-thalassemia Hemoglobin Hradec Kralove Red cell fragility Splenectomy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Forget BG. The β-thalassemias. In: Steinberg MH, Forget BG, Higgs DR, Nagel RL, eds.Disorders of Hemoglobin, Genetics, Pathophysiology, and Clinical Management. Cambridge, UK: Cambridge University Press; 2001;231–388.Google Scholar
  2. 2.
    Olivieri NF. The beta-thalassemias.N Engl J Med. 1999;341:99–109.CrossRefPubMedGoogle Scholar
  3. 3.
    Adams JG 3rd, Coleman MB. Structural hemoglobin variants that produce the phenotype of thalassemia.Semin Hematol. 1990;27:229–238.PubMedGoogle Scholar
  4. 4.
    Thein SL. Dominant beta thalassaemia: molecular basis and pathophysiology.Br J Haematol. 1992;80:273–277.CrossRefPubMedGoogle Scholar
  5. 5.
    Kazazian HH Jr, Orkin SH, Boehm CD, et al. Characterization of a spontaneous mutation to a beta-thalassemia allele.Am J Hum Genet. 1986;38:860–867.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Ohba Y. Unstable hemoglobins.Hemoglobin. 1990;14:353–388.CrossRefPubMedGoogle Scholar
  7. 7.
    Thein SL. Is it dominantly inherited beta thalassaemia or just a beta-chain variant that is highly unstable?Br J Haematol. 1999;107:12–21.CrossRefPubMedGoogle Scholar
  8. 8.
    Advani R, Sorenson S, Shinar E, Lande W, Rachmilewitz E, Schrier SL. Characterization and comparison of the red blood cell membrane damage in severe human alpha- and beta-thalassemia.Blood. 1992;79:1058–1063.PubMedGoogle Scholar
  9. 9.
    Wakamatsu C, Ichinose M, Manabe J, et al. Molecular basis of betathalassemia in Japan: heterogeneity and origins of mutations.Acta Haematol. 1994;91:136–143.CrossRefPubMedGoogle Scholar
  10. 10.
    Chifu Y, Nakashima H, Hara T, Yokota E, Imamura T. Betathalassemia major resulting from a compound heterozygosity for the beta-globin gene mutation: further evidence for multiple origin and migration of the thalassemia gene.Hum Genet. 1992;89:343–346.PubMedGoogle Scholar
  11. 11.
    Kitajima K, Shibata S. Coiled planet centrifugation and its application to the observation of altered membrane properties of erythrocytes in hepatobiliary disorders.J Lab Clin Med. 1975;85:855–864.Google Scholar
  12. 12.
    Outeirino J, Casey R, White JM, Lehmann H. Haemoglobin Madrid beta 115 (G17) alanine?proline: an unstable variant associated with haemolytic anaemia.Acta Haematol. 1974;52:53–60.CrossRefPubMedGoogle Scholar
  13. 13.
    Divoky V, Svobodova M, Indrak K, Chrobak L, Molchanova TP, Huisman TH. Hb Hradec Kralove (Hb HK) or alpha 2 beta 2 115(G17)Ala?Asp, a severely unstable hemoglobin variant resulting in a dominant beta-thalassemia trait in a Czech family.Hemoglobin. 1993;17:319–328.CrossRefPubMedGoogle Scholar
  14. 14.
    Molchanova TP, Postnikov YuV, Wilson JB, et al. Hb Madrid or alpha 2 beta (2)115 (G17)Ala?Pro in a black teenager.Hemoglobin. 1993;17:251–254.CrossRefPubMedGoogle Scholar
  15. 15.
    Maehara T, Tsukamoto N, Nojima Y, et al. Enhanced haemolysis with beta-thalassaemia trait due to the unstable beta chain variant, Hb Gunma, accompanied by hereditary elliptocytosis due to protein 4.1 deficiency in a Japanese family.Br J Haematol. 2002;117:193–197.CrossRefPubMedGoogle Scholar
  16. 16.
    Honig GR, Shamsuddin M, Zaizov R, Steinherz M, Solar I, Kirschmann C. Hemoglobin Petah Tikva (alpha 110 ala replaced by asp): a new unstable variant with alpha-thalassemia-like expression.Blood. 1981;57:705–711.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Kazazian HH Jr, Dowling CE, Hurwitz RL, Coleman M, Stopeck A, Adams JG 3rd. Dominant thalassemia-like phenotypes associated with mutations in exon 3 of the beta-globin gene.Blood. 1992;79:3014–3018.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Beris P, Miescher PA, Diaz-Chico JC, et al. Inclusion body betathalassemia trait in a Swiss family is caused by an abnormal hemoglobin (Geneva) with an altered and extended beta chain carboxyterminus due to a modification in codon beta 114.Blood. 1998;72:801–805.Google Scholar
  19. 19.
    Fucharoen S, Fucharoen G, Fukumaki Y, et al. Three-base deletion in exon 3 of the beta-globin gene produced a novel variant (beta Gunma) with a thalassemia-like phenotype.Blood. 1990;76:1894–1896.PubMedGoogle Scholar
  20. 20.
    Fucharoen S, Kobayashi Y, Fucharoen G, et al. A single nucleotide deletion in codon 123 of the beta-globin gene causes an inclusion body beta-thalassaemia trait: a novel elongated globin chain beta Makabe.Br J Haematol. 1990;75:393–399.CrossRefPubMedGoogle Scholar
  21. 21.
    Giordano PC, Harteveld CL, Michiels JJ, et al. Phenotype variability of the dominant beta-thalassemia induced in four Dutch families by the rare cd121 (G?T) mutation.Ann Hematol. 1998;77:249–255.CrossRefPubMedGoogle Scholar
  22. 22.
    Van Weel M, Harteveld CL, Bernini LF, Brouwers TM, Giordano PC. The second case of dominant beta-thalassemia induced by the codon 127 (CAG?TAG) described as a de novo mutation in a Dutch boy.Hemoglobin. 1999;23:389–393.CrossRefPubMedGoogle Scholar
  23. 23.
    Hall GW, Thein S. Nonsense codon mutations in the terminal exon of the beta-globin gene are not associated with a reduction in betamRNA accumulation: a mechanism for the phenotype of dominant beta-thalassemia.Blood. 1994;83:2031–2037.PubMedGoogle Scholar
  24. 24.
    Ho PJ, Hall GW, Watt S, et al. Unusually severe heterozygous betathalassemia: evidence for an interacting gene affecting globin translation.Blood. 1998;92:3428–3435.PubMedGoogle Scholar
  25. 25.
    Eldor A, Durst R, Hy-Am E, et al. A chronic hypercoagulable state in patients with beta-thalassaemia major is already present in childhood.Br J Haematol. 1999;107:739–746.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Eldor A, Rachmilewitz EA. The hypercoagulable state in thalassemia.Blood. 2002;99:36–43.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2003

Authors and Affiliations

  • Shouichi Ohga
    • 1
  • Akihiko Nomura
    • 1
  • Hidetoshi Takada
    • 1
  • Junko Kato
    • 4
  • Hiroshi Ideguchi
    • 4
  • Yukio Hattori
    • 5
  • Masahiro Suda
    • 3
  • Sachiyo Suita
    • 2
  • Toshiro Hara
    • 1
  1. 1.Department of PediatricsGraduate School of Medical Sciences, Kyushu UniversityFukuokaJapan
  2. 2.Department of Pediatric SurgeryGraduate School of Medical Sciences, Kyushu UniversityFukuoka
  3. 3.Division of Clinical LaboratoriesGraduate School of Medical Sciences, Kyushu UniversityFukuoka
  4. 4.Department of Laboratory MedicineFukuoka UniversityFukuoka
  5. 5.Division of Clinical Laboratory SciencesFaculty of Health Sciences, Yamaguchi University School of MedicineYamaguchiJapan

Personalised recommendations