Evaluation of protein Z plasma level in beta-thalassemia major patients in Ahvaz city in Iran

Mohammad Taha Jalali, Abdorrahim Absalan, Alireza Mohseni, Gholam Abbas Kaydani, Zeinab Deris Zayeri

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Front. Biol. ›› 2017, Vol. 12 ›› Issue (6) : 442-447. DOI: 10.1007/s11515-017-1469-8
RESEARCH ARTICLE
RESEARCH ARTICLE

Evaluation of protein Z plasma level in beta-thalassemia major patients in Ahvaz city in Iran

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Abstract

OBJECTIVES: Thrombotic episodes occurred frequently in beta-thalassemia major (BTM) patients, leading to hypercoagulability of plasma. Protein Z (PZ) is a vitamin-K-dependent anti-coagulation factor that plays a role in the human homeostatic process. The objective of the current study is to investigate the distribution pattern of PZ plasma concentrations between BTM patients and the normal population in Ahvaz city, the center of Khuzestan province, southwest of Iran.

MATERIAL and METHODS: Forty confirmed BTM patients and 40 healthy volunteers were evaluated for complete blood count (CBC) indices and PZ plasma levels. CBC samples were measured using an automated cell counter, and PZ was assayed with an immunoassay method. Statistical analysis was conducted using SPSS software. The ROC curve and binary logistic regression estimated the sensitivity, specificity, and Odd’s ratio for PZ measurement.

RESULTS: The mean±SD of the PZ plasma level in normal individuals was 1.68±0.63 µg/mL, and in BTM patients, it was 1.10±0.52 µg/mL. This shows a significant reduction of PZ in BTM patients statistically (CI= 0.99; p<0.001). Further, the mean±SD of the PZ plasma levels in BTM patients who received washed red blood cells was not significantly different from that of patients undergoing packed red blood cell therapy (CI= 0.95; p = 0.320). The area under the curve (AUC) for PZ was 0.759 (p = 0.00). The cut-off value= 1.4 µg/mL of the PZ plasma level had at least 70% sensitivity and specificity in BTM patients.

DISCUSSION: Several epidemiologic studies have shown thromboembolism episodes in BTM patients. In the current study, PZ was reduced significantly in BTMs.

CONCLUSION: We noticed that BTMs have lower plasma PZ concentration might be predisposed to BTM.

Keywords

major beta-thalassemia / protein Z / thrombosis / immunoassay / anti-coagulation factor

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Mohammad Taha Jalali, Abdorrahim Absalan, Alireza Mohseni, Gholam Abbas Kaydani, Zeinab Deris Zayeri. Evaluation of protein Z plasma level in beta-thalassemia major patients in Ahvaz city in Iran. Front. Biol., 2017, 12(6): 442‒447 https://doi.org/10.1007/s11515-017-1469-8

References

[1]
Al-Shanqeeti A, van Hylckama Vlieg  A, Berntorp E ,  Rosendaal F R ,  Broze G J Jr  (2005). Protein Z and protein Z-dependent protease inhibitor.Determinants of levels and risk of venous thrombosis. Thromb Haemost, 93(3): 411–413
Pubmed
[2]
Alizadeh S, Bavarsad  M S, Dorgalaleh  A, Khatib Z K ,  Dargahi H ,  Nassiri N ,  Hamid F ,  Rahim F ,  Jaseb K ,  Saki N (2014). Frequency of beta-thalassemia or beta-hemoglobinopathycarriers simultaneously affected with alpha-thalassemia in Iran. Clin Lab, 60(6): 941–949
Pubmed
[3]
Borgna-Pignatti C, Rugolotto  S, De Stefano P ,  Piga A, Di Gregorio  F, Gamberini M R ,  Sabato V ,  Melevendi C ,  Cappellini M D ,  Verlato G  (1998). Survival and disease complications in thalassemia major. Ann N Y Acad Sci, 850(1): 227–231
CrossRef Pubmed Google scholar
[4]
Broze G J Jr ,  Miletich J P  (1984). Human Protein Z. J Clin Invest, 73(4): 933–938 160;
CrossRef Pubmed Google scholar
[5]
Cappellini M D ,  Robbiolo L ,  Bottasso B M ,  Coppola R ,  Fiorelli G ,  Mannucci A P  (2000). Venous thromboembolism and hypercoagulability in splenectomized patientswith thalassaemia intermedia. Br J Haematol, 111(2): 467–473
CrossRef Pubmed Google scholar
[6]
Cunningham M J ,  Macklin E A ,  Neufeld E J ,  Cohen A R , and the Thalassemia Clinical Research Network (2004). Complications of -thalassemia majorin North America. Blood, 104(1): 34–39 
CrossRef Pubmed Google scholar
[7]
Eldor A, Rachmilewitz  E A (2002). The hypercoagulable state in thalassemia. Blood, 99(1): 36–43160;
CrossRef Pubmed Google scholar
[8]
Elkhateeb M, Elmenshawy  I, Azzam H ,  Selim T ,  Abousamra N K ,  Elsharawy S  (2009). Plasma levels of protein Z and antiphospholipid protein antibodies in patientswith ischemic stroke. Egypt J Neurol PsychiatNeurosurg, 46(1): 11–17
[9]
Gillis S, Cappellini  M D, Goldfarb  A, Ciceri L ,  Fiorelli G ,  Rachmilewitz E A  (1999). Pulmonary thromboembolism in thalassemia intermedia patients. Haematologica, 84(10): 959–960
Pubmed
[10]
Gris J C, Quéré  I, Dechaud H ,  Mercier E ,  Pinçon C ,  Hoffet M ,  Vasse M ,  Marès P  (2002). High frequency of protein Z deficiency in patients withunexplained early fetal loss. Blood, 99(7): 2606–2608160;
CrossRef Pubmed Google scholar
[11]
Han X, Fiehler  R, Broze G J Jr  (2000). Characterization of the protein Z-dependent protease inhibitor. Blood, 96(9): 3049–3055
[12]
Han X, Huang  Z F, Fiehler  R, Broze G J Jr  (1999). The protein Z-dependent protease inhibitor is a serpin. Biochemistry, 38(34): 11073–11078 
CrossRef Pubmed Google scholar
[13]
Hassan T H, Elbehedy  R M, Youssef  D M, Amr  G E (2010). Protein C levels in beta-thalassemiamajor patients in the east Nile delta of Egypt. Hematol Oncol Stem Cell Ther, 3(2): 60–65 
CrossRef Pubmed Google scholar
[14]
Heeb M J, Paganini-Hill  A, Griffin J H ,  Fisher M  (2002). Low protein Z levels and risk of ischemic stroke: differences by diabetic status and gender. Blood Cells Mol Dis, 29(2): 139–144
CrossRef Pubmed Google scholar
[15]
Kemkes-Matthes B, Matthes  K J (1995). Protein Z deficiency: a new cause of bleeding tendency. Thromb Res, 79(1): 49–55
CrossRef Pubmed Google scholar
[16]
Kemkes-Matthes B, Nees  M, Kühnel G ,  Matzdorff A ,  Matthes K J (2002). Protein Z influences the prothrombotic phenotype inFactor V Leiden patients. Thromb Res, 106(4-5): 183–185 
CrossRef Pubmed Google scholar
[17]
Kuypers F A, de Jong  K (2004). The role of phosphatidylserine in recognition and removalof erythrocytes. Cell Mol Biol (Noisy-le-grand), 50(2): 147–158
Pubmed
[18]
Mendiratta S L ,  Mittal M ,  Naaz F, Singh  S, Anand S  (2017). Role of thalassemia screening in prevention and control of thalassemia-a5 year experience. Int J Reprod ContraceptObstet Gynecol, 5(9): 3107–3111
[19]
Michaeli J, Mittelman  M, Grisaru D ,  Rachmilewitz E A  (1992). Thromboembolic complications in beta thalassemia major. Acta Haematol, 87(1-2): 71–74
CrossRef Pubmed Google scholar
[20]
Miletich J P, Broze  G J J Jr (1987). Human plasma protein Z antigen: range in normal subjectsand effect of warfarin therapy. Blood, 69(6): 1580–1586
Pubmed
[21]
Moratelli S, De Sanctis  V, Gemmati D ,  Serino M L ,  Mari R, Gamberini  M R, Scapoli  G L (1998). Thrombotic risk in thalassemic patients. J Pediatr Endocrinol Metab, 11(Suppl 3): 915–921
Pubmed
[22]
Olivieri N F, Brittenham  G M (1997). Iron-chelating therapy and the treatment of thalassemia. Blood, 89(3): 739–761 
Pubmed
[23]
Pardos-Gea J, Ordi-Ros  J, Serrano S ,  Balada E ,  Nicolau I ,  Vilardell M  (2008). Protein Z levels and anti-protein Z antibodies in patients with arterial andvenous thrombosis. Thromb Res, 121(6): 727–734
CrossRef Pubmed Google scholar
[24]
Santacroce R, Sarno  M, Cappucci F ,  Sessa F ,  Colaizzo D ,  Brancaccio V ,  Grandone E ,  Margaglione M  (2006). Low protein Z levels and risk of occurrence of deep vein thrombosis. J Thromb Haemost, 4(11): 2417–2422
CrossRef Pubmed Google scholar
[25]
Schettini F, De Mattia  D, Arcamone G ,  Sabato V ,  Altomare M ,  Burattini M G ,  Fedele F ,  Compagnone A ,  Ciavarella G  (1987). Coagulation contact phase factors and inhibitors in -thalassemia major children. Pediatr Hematol Oncol, 4(3): 231–236
CrossRef Pubmed Google scholar
[26]
Singer S T, Kuypers  F A, Styles  L, Vichinsky E P ,  Foote D ,  Rosenfeld H  (2006). Pulmonary hypertension in thalassemia: association with platelet activation and hypercoagulablestate. Am J Hematol, 81(9): 670–675
CrossRef Pubmed Google scholar
[27]
Steinberg M H  (2001). Disorders of hemoglobin: genetics, pathophysiology, and clinical management. J R Soc Med, 94(11): 602–603
[28]
Vasse M, Guegan-Massardier  E, Borg J Y ,  Woimant F ,  Soria C  (2001). Frequency of protein Z deficiency in patients with ischaemic stroke. Lancet, 357(9260): 933–934 
CrossRef Pubmed Google scholar
[29]
Weatherall D J  (1976). Molecular pathology of the thalassemia disorders. West J Med, 124(5): 388–402 
Pubmed
[30]
Winichagoon P, Fucharoen  S, Wasi P  (1981). Increased circulating platelet aggregates in thalassaemia. Southeast Asian J Trop Med Public Health, 12(4): 556–560 
Pubmed
[31]
Yin Z F, Huang  Z F, Cui  J, Fiehler R ,  Lasky N ,  Ginsburg D ,  Broze G J Jr  (2000). Prothrombotic phenotype of protein Z deficiency. Proc Natl Acad Sci USA, 97(12): 6734–6738 
CrossRef Pubmed Google scholar

Acknowledgements

We thank Shafa Hospital’s staffwho worked with us, and patients who were involved in this study.This work was performed under a grant from Ahvaz Jundishapur Universityof Medical Sciences.

Compliance with ethics guidelines

The authors declare no conflict of interest. All proceduresperformed in studies involving human participants were in accordancewith the ethical standards of the institutional and/or national researchcommittee and with the 1964 Helsinki declaration and its later amendmentsor comparable ethical standards.

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2017 Higher Education Press and Springer-Verlag GmbH Germany, part of Springer Nature
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