Thrombophilic mutations among Southern Iranian patients with sickle cell disease: high prevalence of factor V Leiden

J Thromb Thrombolysis. 2008 Jun;25(3):288-92. doi: 10.1007/s11239-007-0069-x. Epub 2007 Jul 11.

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/beta 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/beta-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Sickle Cell / blood
  • Anemia, Sickle Cell / ethnology
  • Anemia, Sickle Cell / genetics*
  • Blood Coagulation / genetics*
  • Case-Control Studies
  • Child
  • Factor V / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Heterozygote
  • Humans
  • Iran / epidemiology
  • Logistic Models
  • Male
  • Middle Aged
  • Mutation*
  • Odds Ratio
  • Polymorphism, Restriction Fragment Length
  • Prothrombin / genetics
  • Risk Assessment
  • Sickle Cell Trait / blood
  • Sickle Cell Trait / genetics
  • Thrombophilia / blood
  • Thrombophilia / ethnology
  • Thrombophilia / genetics*
  • beta-Thalassemia / blood
  • beta-Thalassemia / genetics

Substances

  • factor V Leiden
  • Factor V
  • Prothrombin