Vascular thrombosis is an important pathophysiological aspect of sickle cell disease (SCD). This study aimed to investigate the prevalence and clinical impact of factor V Leiden G1691A (FVL) and prothrombin G20210A mutations among Palestinian sickle cell disease (SCD) patients.
A total of 117 SCD patients, including 59 patients with sickle cell anemia (SS), 33 patients with sickle β-thalassemia and 25 individuals with sickle cell trait (AS) were studied. The control group consisted of 118 healthy individuals. FVL and prothrombin G20210A mutations were determined by RFLP PCR.
Analysis of the clinical history of SCD patients revealed that seven patients have had vascular complications such as ischemic stroke or deep vein thrombosis. In SCD patients, the inheritance of the FVL mutation showed a significantly higher incidence of pain in joints, chest and abdomen as well as regular dependence on blood transfusion compared to SCD with the wild type. Age- and sex-adjusted logistic regression analysis revealed a significant association between FVL and sickle cell anemia with an odds ratio (OR) of 5.6 (95% confidence intervals [CI] of 1.91–39.4, P = 0.039) in SS patients. However, increased prevalence of the FVL in AS subjects and sickle β-thalassemia patients was not statistically significant compared to controls (OR 3.97, 95% CI 0.51–28.6, P = 0.17 and OR 3.59, 95% CI 0.35–41.6, P = 0.26, respectively). The distribution of prothrombin G20210A mutation among SCD patients compared to controls was not significantly different, thus our findings do not support an association of this mutation with SCD.
FVL was more prevalent among SS patients compared to controls and it was associated with higher incidence of disease complications among SCD patients.
Stuart MJ, Nagel RL. Sickle-cell disease. Lancet. 2004;346:1343–60. CrossRef
Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. 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. 1996;88(10):3698–703. PubMed
Wild BJ, Bain BJ. Investigation of abnormal hemoglobins and thalassemia. In: Bain BJ, Bates I, Laffan MA, Lewis SM, editors. Dacie and Lewis practical Haematology. 11th ed. London: Elsevier Churchill Livingstone; 2011. p. 301–32.
Kenneth IA, Eugene PO. Hypercoagulability in sickle cell disease: a curious paradox. Am J Med. 2003;115:721–8. CrossRef
Klaassen IL, van Ommen CH, Middeldorp S. Manifestations and clinical impact of pediatric inherited thrombophilia. Blood. 2015;25(7):1073–7. CrossRef
Pandey SK, Meena A, Kishor K, Mishra RM, Pandey S, Saxena R. Prevalence of factor V Leiden G1691A, MTHFR C677T, and prothrombin G20210A among Asian Indian sickle cell patients. Thromb Hemost. 2012;18(3):320–3.
Neto FM, Lourenco DM, Noguti MAE, Morelli VM, Gil ICP, Beltrao ACS, Figueiredo MS. The clinical impact of MTHFR polymorphism on the vascular complications of sickle cell disease. Braz J Med Biol Res. 2006;39:1291–5.
Mj K, Scher C, Rozans M, Michaels RK, Leissinger C, Krause J. Factor V Leiden is not responsible for stroke in patients with sickling disorders and is uncommon in African Americans with sickle cell disease. Am J Hematol. 1997;54:12–5. CrossRef
Rahimi Z, Raygani AV, Nagel RL, Muniz A. Thrombophilic mutations among southern Iranian patients with sickle cell disease: high prevalence of factor V Leiden. J Throm Thrombolys. 2008;25:288–92. CrossRef
De Stefano V, Finazzi G, Mannucci PM. Inherited thrombophilia: pathogenesis, clinical syndromes and management. Blood. 1996;87(9):3531–344. PubMed
Lane DA, Mannucci PM, Bauer KA, Bertina RM, Bochkov NP, Boulyjenkov V, et al. Inherited thrombophilia: part 1. Thromb Haemost. 1996;76(5):651–62. PubMed
Arruda VR, Annichino-Bizzachi JM, Goncalves MS, Costa FF. Prevalence of the prothrombin gene variant (20210A) in venous thrombosis and arterial disease. Thromb Haemost. 1997;78(6):1430–3. PubMed
Eid SS, Rihani G. Prevalence of factor V Leiden, prothrombin G20210A, and MTHFR C677T mutations in 200 healthy Jordanians. Clin Lab Sci. 2004;17(4):200–2. PubMed
Rosen E, Renbaum P, Heyd J, Levy-Lahad E. High frequency of factor V Leiden in a population of Israeli Arabs. Thromb Haemost. 1999;82(6):1768. PubMed
Almawi WY, Keleshian SH, Borgi L, Fawaz AN, Abboud N, Mitraoui N, et al. Varied prevalence of factor V G1691A (Leiden) and Prothrombin G20210A single nucleotide polymorphisms among Arabs. J Thromb Thrombolys. 2005;20(3):163–8. CrossRef
Zivelin A, Griffin JH, Xu X, Pabinger I, Samama M, Conard J, et al. A single genetic origin for a common Caucasian risk factor for venous thrombosis. Blood. 1997;89:397–402. PubMed
Atherosclerosis, Thrombosis, and Vascular Biology Italian Study Group. No evidence of association between prothrombotic gene polymorphisms and the development of acute myocardial infarction at a young age. Circulation. 2003;107:1117–22. CrossRef
- Factor V Leiden G1691A and prothrombin G20210A mutations among Palestinian patients with sickle cell disease
Mahmoud A. Srour
- BioMed Central
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