Researchers discovered that thrombophilic mutations can raise the risk of vascular complications in sickle cell disease (SCD), as published in Gene Reports.

“SCD is inherited either in homozygosity for the [sickle hemoglobin] gene (SS) or with another hemoglobin variant (compound heterozygosity), such as hemoglobin C (HbC) or β-thalassemia,” the authors of the study wrote. The most prominent pathology associated with SCD is the occurrence of vaso-occlusive crises. 

The researchers wanted to determine whether thrombophilic mutations influenced the risk of vascular complications and vaso-occlusive crises. In particular, they studied the thrombophilic variants Factor V Leiden (FVLG1691A), methylenetetrahydrofolate reductase (MTHFR) C677T, and prothrombin gene G20210A. 

Read more about SCD risk factors

The study was conducted with the participation of 82 patients with SCD and 70 healthy controls. The 82 patients were treated at the Hematology Clinic of Children’s Hospital at Cairo University in Egypt. Among the 82 patients, 53 were homozygous for the HbS gene and 29 had sickle β-thalassemia. A complete clinical and family history was subsequently obtained, and various tests for vascular complications were carried out.

All participants were genotyped for the thrombophilic variants under investigation. For patients who were positive for these thrombophilic variants, Sanger sequencing and real-time polymerase chain reaction-based single nucleotide polymorphisms genotyping assay were carried out.

In this study, 69 out of 82 patients experienced painful vaso-occlusive crises, representing 84.1% of patients. In addition, 9.7% of the patients with SCD had transient ischemic attacks, 9.7% had avascular necrosis of the femoral head, 6% had a stroke, and 14.6% had acute chest syndrome.

The results demonstrated that there was a statistically significant relationship between heterozygosity for the MTHFR C677T and FVLG1691A variants and a higher frequency of acute pain crises. The identification of the relationship between these 2 thrombophilic mutations and the increased risk of thrombotic complications has potentially important clinical implications. The screening of thrombophilic mutations in patients with SCD may allow physicians to introduce early prevention of vascular complications by prophylactic therapy.


Sokkar MF, Kamal L, Salama N, Hamdy M. Thrombophilic mutations and risk of vascular complications in sickle cell disease. Gene Reports. Published online March 16, 2022. doi:10.1016/j.genrep.2022.101595