Factor V Leiden is not responsible for stroke in patients with sickling disorders and is uncommon in African Americans with sickle cell disease

Abstract

Cerebrovascular accidents in patients with sickle cell anemia are among the most devastating complications of the disease. It has recently been demonstrated that some patients have a hypercoagulable state on the basis of the presence of an abnormal factor V molecule, factor V Leiden. We undertook this study to evaluate the presence of factor V Leiden in sickle cell patients with stroke. Eighty-two patients with either Hgb SS, Hgb SC, or Hgb S(beta+)-thalassemia comprised the study population. Of the 82 patients in the study, 19 of them had a history of stroke. In our study population, none of the stroke patients possessed the factor V Leiden mutation. One of the non-stroke patients was a heterozygote for the mutation (P = 1.00). The overall frequency of the factor V Leiden allele in our population is 0.6%. The estimated prevalence for this mutation is reportedly between 3 and 7% in Caucasian populations. We conclude that the gene frequency for factor V Leiden is less common in Africa Americans with sickle cell disease. Furthermore, factor V Leiden does not appear to be responsible for the development of stroke in sickle cell patients.

Sickle Cell Disease in the Post Genomic Era: A Monogenic Disease with a Polygenic Phenotype

“…No association with cerebro-vascular disease was found when multiple coagulation factors were measured in children transfused for stroke, at risk for stroke and in untransfused controls 71–73. Polymorphisms in low-affinity Fc leucocyte receptors were not associated with stroke 64.…”

Gene interactions and stroke risk in children with sickle cell anemia

“…16 Other studies have reported no association with prothrombotic polymorphisms. [17][18][19][20][21][22] Because the etiology of stroke is most likely influenced by many genes, each with only modest effects, analysis of the combined effect of multiple genetic variants may prove more successful than evaluation of individual candidate genes. We previously examined the contribution of 36 candidate genes to stroke risk in SCA in a small pilot institutional study of children with and without MRI-documented cerebral infarction.…”

A 19-year-old man with sickle cell disease presenting with spinal infarction: a case report

“…From the available reports that have looked for an association between factor V Leiden and complications of sickle cell disease, there is no evidence of an obvious relationship [16,21,22]. Kahn et al studied a cohort of 82 patients with different sickle cell states, 19 of whom had had a stroke [21].…”

“…Kahn et al studied a cohort of 82 patients with different sickle cell states, 19 of whom had had a stroke [21]. Only one of the 82 was heterozygous for factor V Leiden (there were no homozygotes), and this was not a patient who had experienced a stroke, priapism or any other vascular-type disorder [21]. Andrade et al similarly examined a cohort of 73 patients with sickle cell disease in Brazil, of whom five had a stroke [16].…”