Abstract
Background
A hypercoagulable state in sickle cell disease (SCD) and beta thalassemia has been established and thrombosis is an important aspect of the clinical spectrum of sickle cell disease. In a case-control study, the prevalence of factor V Leiden and prothrombin G20210A mutations were investigated among SCD patients from Southern Iran.
Methods
Patients comprised 60 individuals with SCD; of them 35 were with sickle cell anemia (SS) including 21 males and 14 females aged 17.2 ± 8.3 years, 15 were sickle cell trait (AS) consisted of nine males and six females aged 30 ± 15.4 years and 10 were sickle/β thalassemia (S/Thal) (three males and seven females) aged 24.6 ± 10.4 years. The control group were 126 apparently healthy individuals (50 males and 76 females) aged 20.1 ± 9.8 years. Genotyping was done by polymerase chain reaction restriction fragment-length polymorphism (PCR-RFLP) using Mnl I and Hind III for factor V Leiden and prothrombin G20210A, respectively.
Results
Heterozygous factor V Leiden mutation was found in five of 35 (14.3%) SS patients, two of 15 (13.3%) AS individuals, one (a sickle/β-zero thalassemia patient with IVSII.1 G→A mutation) of 10 S/Thal patients (10%), and two of 126 (1.6%) control subjects (P < 0.05). However, only one AS individual (6.7%) was found to be a carrier for prothrombin G20210A compared to five of 126 (4%) healthy individuals. Adjusted logistic regression analysis for the effects of age and sex was performed and a significant association was found between factor V Leiden mutation and sickle cell anemia with odds ratios (OR) of 6.5 (95% confidence intervals [CI] 1.19–35.33, P = 0.03) in SS patients. However, increased prevalence of the factor V Leiden in AS individuals and S/Thal patients was not statistically significant compared to controls (OR 3.84, 95% CI 0.49–29.9, P = 0.19 and OR 3.77, 95% CI 0.31–45.9, P = 0.29, respectively).
Conclusions
Our findings indicate a significant correlation between factor V Leiden and sickle cell anemia among Iranian patients. Association between venous thrombophilia and factor V Leiden mutation in Iranians with sickle cell anemia should be further studied.
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References
Almawi WY, Keleshian SH, Borgi L et al (2005) Varied prevalence of factor V G1691A (Leiden) and prothrombin G20210A single nucleotide polymorphisms among Arabs. J Thromb Thrombolys 20:163–168
Ataga KI, Orringer EP (2003) Hypercoagulability in sickle cell disease: a curious paradox. Am J Med 115:721–728
Rahimi Z, Merat A, Haghshenass M, Madani H, Rezaei M, Nagel RL (2006) Plasma lipids in Iranians with sickle cell disease: hypocholesterolemia in sickle cell anemia and increase of HDL-cholesterol in sickle cell trait. Clin Chim Acta 365:217–220
Habibzadeh F, Yadollahie M, Ayatollahie M, Haghshenass M (1999) The prevalence of sickle cell syndrome in south of Iran. Irn J Med Sci 24:32–34
Otrock ZK, Mahfouz RAR, Taher AT (2005) Should we screen Eastern Mediterranean sickle beta-thalassemia patients for inherited thrombophilia? J Thromb Haemost 3:599–600
Isma,eel H, Shamseddeen AW, Mahfouz R, Zeineh N, Jradi O, Taher A (2006) Screening for inherited thrombophilia might be warranted among Eastern Mediterranean sickle-beta-0-thalassemia patients. J Thromb Thrombolys 22:121–123
Andrade FL, Annichino-Bizzacchi JM, Saad STO, Costa FF, Arruda VR (1998) Prothrombin mutant, factor V Leiden, and thermolabile variant of methylenetetrahydrofolate reductase among patients with sickle cell disease in Brazil. Am J Hematol 59:46–50
Fawaz NA, Bashawery L, Al-Sheikh I, Qatari A, Al-Othman SS, Almawi WY (2004) Factor V-Leiden, prothrombin G20210A, and MTHFR C677T mutations among patients with sickle cell disease in Eastern Saudi Arabia. Am J Hematol 76:307–309
Fairbanks VF, Klee GG (1994) Biochemical aspects of hematology. In: Burtis CA, Ashwood ER (eds) Tietz text book of clinical chemistry. W.B.Saunders, Philadelphia, pp 2041–2042
Old JM, Higgs DR (1983) Gene analysis. In: Weatherall DJ (ed) Methods in hematology. The thalassemias, vol 6. Churchill Livingstone, London, pp 74–101
Cai SP, Wall J, Kan WY, Chehab FF (1994) Reverse dot blot probes for the screening of β-thalassemia mutations in Asian and American Blacks. Hum Mutat 3:59–63
Bertina RM, Koeleman BPC, Koster T et al (1994) Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 369:64–67
Poort SR, Rosendaal FR, Reitsma PH, Bertina RM (1996) A common genetic variation in the 3′-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 88:3698–3703
Zimmerman SA, Ware RE (1998) Inherited DNA mutations contributing to thrombotic complications in patients with sickle cell disease. Am J Hematol 59:267–272
Zeinali S, Duca F, Zarbakhsh B, Tagliabue L, Mannucci PM (2000) Thrombophilic Mutations in Iran. Thromb Haemost 83:351–352
Kahn JE, Veyssier-Belot C, Renier JL, de Mazancourt P, Peltier JY, de Raucourt E (2002) Recurrent thromboembolism in a patient with β-thalassemia major associated with double heterozygosity for factor V R506Q and prothrombin G20210A mutations. Blood Coagul Fibrin 13:461–463
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This work was financially supported by a grant from Kermanshah University of Medical Sciences, Kermanshah, Iran.
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Rahimi, Z., Vaisi-Raygani, A., Nagel, R.L. et al. Thrombophilic mutations among Southern Iranian patients with sickle cell disease: high prevalence of factor V Leiden. J Thromb Thrombolysis 25, 288–292 (2008). https://doi.org/10.1007/s11239-007-0069-x
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DOI: https://doi.org/10.1007/s11239-007-0069-x