Skip to main content

Advertisement

SpringerLink
Log in

Increased endothelial activation in α-thalassemia disease

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

One complication of thalassemia is thromboembolism (TE), which is caused by an abnormal red blood cell surface, as well as endothelial and platelet activation. These findings are commonly observed in severe β-thalassemia. However, limited information on α-thalassemia exists. This study enrolled subjects with deletional and non-deletional α-thalassemia and normal controls (NC). Plasma and serum of subjects were tested for endothelial activation markers including thrombomodulin (TM), vascular cell adhesion molecule-1 (VCAM-1), and von Willebrand factor antigen as well as platelet activation markers including thromboxane B2 and platelet factor 4. A total of 179 subjects were enrolled: 29 in the deletional group (mean age 13.3 ± 4.4 years), 31 in the non-deletional group (mean age 12.9 ± 4.8 years), and 119 in the NC group (mean age 13.6 ± 3.0 years). Twenty nine percent of subjects in the non-deletional group received regular red blood cell transfusion and iron chelator administration. Serum ferritin level was higher in the non-deletional group than that in the deletional group. Multivariate analysis demonstrated that VCAM-1 and TM levels were increased significantly in α-thalassemia compared with NC group (816.8 ± 131.0 vs 593.9 ± 49.0 ng/ml, and 4.9 ± 0.7 vs 4.0 ± 0.4 ng/ml, P < 0.001 respectively). VCAM-1 and TM levels in the non-deletional group were significantly higher than that in the deletional group. The present study demonstrated endothelial activation in children with α-thalassemia disease, especially those in the non-deletional group, which might be one risk factor for TE in α-thalassemia disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

BMI:

Body mass index

β-TG:

β-Thromboglobulin

CBC:

Complete blood count

CECs:

Circulating endothelial cells

CS:

Hb constant spring

DNA:

Deoxyribonucleic acid

ELAM:

E-selectin

F1.2:

Prothrombin fragment 1 + 2

Hb:

Hemoglobin

HPLC:

High-performance liquid chromatography

ICAM-1:

Intercellular adhesion molecule-1

MCH:

Mean corpuscular hemoglobin

MCV:

Mean corpuscular volume

NC:

Normal controls

NTDT:

Non-transfusion dependent thalassemia

PF4:

Platelet factor 4

PS:

Hb Paksé

RBC:

Red blood cell

RDW:

Red cell distribution width

TAT:

Thrombin-antithrombin complex

TBX2:

Thromboxane B2

TDT:

Transfusion-dependent thalassemia

TE:

Thromboembolism

TM:

Thrombomodulin

VCAM-1:

Vascular cell adhesion molecule-1

VEGF:

Vascular endothelial growth factor

VWF:Ag:

Von Willebrand factor antigen

References

  1. Fucharoen S, Winichagoon P (1992) Thalassemia in Southeast Asia: problems and strategy for prevention and control. Southeast Asian J Trop Med Public Health 23:647–655

    CAS  PubMed  Google Scholar 

  2. Kohne E (2011) Hemoglobinopathies: clinical manifestations, diagnosis, and treatment. Dtsch Arztebl Int 108:532–540. https://doi.org/10.3238/arztebl.2011.0532

    Article  PubMed  PubMed Central  Google Scholar 

  3. Kelly N (2012) Thalassemia. Pediatr Rev 33:434–435. https://doi.org/10.1542/pir.339-434

    Article  PubMed  Google Scholar 

  4. Vichinsky EP (2005) Changing patterns of thalassemia worldwide. Ann N Y Acad Sci 1054:18–24. https://doi.org/10.1196/annals.1345.003

    Article  CAS  PubMed  Google Scholar 

  5. Williams TN, Weatherall DJ (2012) World distribution, population genetics, and health burden of the hemoglobinopathies. Cold Spring Harb Perspect Med 2:1–14. https://doi.org/10.1101/cshperspect.a011692

    Article  Google Scholar 

  6. Wasi P, Na-Nakorn S, Pootrakul S, Sookanek M, Disthasongchan P, Pornpatkul M, Pornpatkul M (1969) Alpha- and beta-thalassemia in Thailand. Ann N Y Acad Sci 165:60–82. https://doi.org/10.1111/j.1749-6632.1969.tb27777.x

    Article  CAS  PubMed  Google Scholar 

  7. Vichinsky E (2010) Complexity of alpha thalassemia: growing health problem with new approaches to screening, diagnosis, and therapy. Ann N Y Acad Sci 1202:180–187. https://doi.org/10.1111/j.1749-6632.2010.05572.x

    Article  PubMed  Google Scholar 

  8. Fucharoen S, Viprakasit V (2009) Hb H disease: clinical course and disease modifiers. Am Soc Hematol Educ Program 2009:26–34. https://doi.org/10.1182/asheducation-2009.1.26

    Article  Google Scholar 

  9. Vichinsky EP (2013) Clinical manifestations of α-thalassemia. Cold Spring Harb Perspect Med 3:1–10. https://doi.org/10.1101/cshperspect.a011742

    Article  CAS  Google Scholar 

  10. Laosombat V, Viprakasit V, Chotsampancharoen T, Wongchanchailert M, Khodchawan S, Chinchang W, Sattayasevana B (2009) Clinical features and molecular analysis in Thai patients with HbH disease. Ann Hematol 88:1185–1192. https://doi.org/10.1007/s00277-009-0743-5

    Article  CAS  PubMed  Google Scholar 

  11. Chui DH, Fucharoen S, Chan V (2003) Hemoglobin H disease: not necessarily a benign disorder. Blood 101:791–800. https://doi.org/10.1182/blood-2002-07-1975

    Article  CAS  PubMed  Google Scholar 

  12. Harteveld CL, Higgs DR (2010) α-Thalassaemia. Orphanet J Rare Dis 5:13. https://doi.org/10.1186/1750-1172-5-13

  13. Sirachainan N (2013) Thalassemia and the hypercoagulable state. Thromb Res 132:637–641. https://doi.org/10.1016/j.thromres.2013.09.029

    Article  CAS  PubMed  Google Scholar 

  14. Tso SC, Chan TK, Todd D (1982) Venous thrombosis in haemoglobin H disease after splenectomy. Aust NZ J Med 12:635–638. https://doi.org/10.1111/j.1445-5994.1982.tb02655.x

    Article  CAS  Google Scholar 

  15. Singer ST, Kim HY, Olivieri NF, Kwiatkowski JL, Coates TD, Carson S, Neufeld E, Cunningham MJ, Giardina PJ, Mueller BU, Quinn CT, Fung E, Vichinsky E, for the Thalassemia Clinical Research Network (2009) Hemoglobin H-constant spring in North America: an alpha thalassemia with frequent complications. Am J Hematol 84:759–761. https://doi.org/10.1002/ajh.21523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sun NA, Cheng P, Deng DH, Liu RR, Lai YR (2016) Analysis of the genetic variants associated with recurrent thromboembolism in a patient with hemoglobin H disease following splenectomy: a case report. Biomed Rep 5:23–26. https://doi.org/10.3892/br.2016.674

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Sonakul D, Fucharoen S (1992) Pulmonary thromboembolism in thalassemic patients. Southeast Asian J Trop Med Public Health 23:25–28

    PubMed  Google Scholar 

  18. Winichakoon P, Tantiworawit A, Rattanathammethee T, Hantrakool S, Chai-Adisaksopha C, Rattarittamrong E, Norasetthada L, Charoenkwan P (2015) Prevalence and risk factors for complications in patients with nontransfusion dependent alpha-and beta-thalassemia. Anemia 2015:793025. https://doi.org/10.1155/2015/793025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bunyaratvej A, Fucharoen S, Butthep P, Sae-ung N, Kamchonwongpaisan S, Khuhapinant A (1995) Alterations and pathology of thalassemic red cells: comparison between alpha-and beta-thalassemia. Southeast Asian J Trop Med Public Health 26:257–260

    PubMed  Google Scholar 

  20. Butthep P, Bunyaratvej A, Funahara Y, Kitaguchi H, Fucharoen S, Sato S, Bhamarapravati N (1995) Alterations in vascular endothelial cell-related plasma proteins in thalassaemic patients and their correlation with clinical symptoms. Thromb Haemost 74:1045–1049. https://doi.org/10.1055/s-0038-1649879

    Article  CAS  PubMed  Google Scholar 

  21. Carlos TM, Harlan JM (1994) Leukocyte-endothelial adhesion molecules. Blood 84:2068–2101

    CAS  PubMed  Google Scholar 

  22. Butthep P, Bunyaratvej A, Funahara Y, Kitaguchi H, Fucharoen S, Sato S, Bhamarapravati N (1997) Possible evidence of endothelial cell activation and disturbance in thalassemia: an in vitro study. Southeast Asian J Trop Med Public Health 28:141–148A

    PubMed  Google Scholar 

  23. Butthep P, Rummavas S, Wisedpanichkij R, Jindadamrongwech S, Fucharoen S, Bunyaratvej A (2002) Increased circulating activated endothelial cells, vascular endothelial growth factor, and tumor necrosis factor in thalassemia. Am J Hematol 70:100–106. https://doi.org/10.1002/ajh.10101

    Article  CAS  PubMed  Google Scholar 

  24. Chansai S, Fucharoen S, Fucharoen G, Jetsrisuparb A, Chumpia W (2018) Elevations of thrombotic biomarkers in hemoglobin H disease. Acta Haematol 139:47–51. https://doi.org/10.1159/000486157

    Article  CAS  PubMed  Google Scholar 

  25. Sirachainan N, Chuansumrit A, Kadegasem P, Sasanakul W, Wongwerawattanakoon P, Mahaklan L, Mahaklan L (2016) Normal hemostatic parameters in children and young adults with α-thalassemia diseases. Thromb Res 146:35–42. https://doi.org/10.1016/j.thromres.2016.08.024

    Article  CAS  PubMed  Google Scholar 

  26. Taher A, Vichinsky E, Musallam K, Cappellini MD, Viprakasit V, Weatherall D, editor (2013) Guidelines for the Management of Non Transfusion Dependent Thalassaemia (NTDT) [Internet]. Thalassaemia International Federation, Nicosia. Available from http://www.ncbi.nlm.nih.gov/books/NBK190453/. Accessed 4 April 2019

  27. Prasartkaew S, Bunyaratvej A, Fucharoen S, Wasi P (1986) Comparison of erythrocyte antioxidative enzyme activities between two types of haemoglobin H disease. J Clin Pathol 39:1299–1303. https://doi.org/10.1136/jcp.39.12.1299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Bunyaratvej A, Butthep P, Fucharoen S, Saw D (1992) Erythrocyte volume and haemoglobin concentration in haemoglobin H disease: discrimination between the two genotypes. Acta Haematol 87:1–5. https://doi.org/10.1159/000204704

    Article  CAS  PubMed  Google Scholar 

  29. Fucharoen S, Winichagoon P (2002) Thalassemia and abnormal hemoglobin. Int J Hematol 76:83–89. https://doi.org/10.1371/journal.pone.0108365

    Article  CAS  PubMed  Google Scholar 

  30. Boonsa S, Sanchaisuriya K, Fucharoen G, Wiangnon S, Jetsrisuparb A, Fucharoen S (2004) The diverse molecular basis and hematological features of Hb H and AE Bart’s diseases in Northeast Thailand. Acta Haematol 111:149–154. https://doi.org/10.1159/000076523

    Article  PubMed  Google Scholar 

  31. Bastyr EJ, Kadrofske MM, Vinik AI (1990) Platelet activity and phosphoinositide turnover increase with advancing age. Am J Med 88:601–606. https://doi.org/10.1016/00029343(90)90525-I

    Article  CAS  PubMed  Google Scholar 

  32. Trichero A, Marchetti M, Giaccherini C, Tartari CJ, Russo L, Falango A (2017) Platelet haemostatic properties in β-thalassemia: the effect of blood transfusion. Blood Transfus 15(5):413–421. https://doi.org/10.2450/2016.0033-16

    Article  Google Scholar 

  33. Steiner M, Anastasi J, Vitamin E (1976) An inhibitor of the platelet release reaction. J Clin Invest 57(3):732–737. https://doi.org/10.1172/JCI108331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

NC designed the study and reviewed the manuscript. PS performed the study and wrote the manuscript. AC, DS, and PW involved in the care of patients. PK performed the laboratory.

Funding

This work was supported by a Grant from the Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. We thank Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi District, Bangkok, 10400, Thailand

    Pankamol Sirivadhanakul, Ampaiwan Chuansumrit, Duantida Songdej, Praguywan Kadegasem & Nongnuch Sirachainan

  2. Department of Nursing, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

    Pakawan Wongwerawattanakoon

Authors
  1. Pankamol Sirivadhanakul
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ampaiwan Chuansumrit
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Duantida Songdej
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Praguywan Kadegasem
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pakawan Wongwerawattanakoon
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nongnuch Sirachainan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nongnuch Sirachainan.

Ethics declarations

Ethical approval for the study protocol was obtained from the Ethical Clearance Committee on Human Rights Related to Research to Research Involving Human Subjects, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Thailand (ID 12-59-09).

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sirivadhanakul, P., Chuansumrit, A., Songdej, D. et al. Increased endothelial activation in α-thalassemia disease. Ann Hematol 98, 1593–1602 (2019). https://doi.org/10.1007/s00277-019-03672-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-019-03672-4

Keywords

Search

Navigation