Homocysteine elevation in sickle cell disease

Objective: Ischemic complications are common in patients with sickle cell d isease. Hyperhomocysteinemia is a risk factor for arteriosclerosis and veno us thrombosis, and given the propensity of patients with sickle cell diseas e to develop ischemic complications, we hypothesized that they might have e levated plasma homocysteine concentrations. Methods: Plasma concentrations of homocysteine, vitamin B12 and folate were measured in 49 adults with sickle cell disease and 16 normotensive Black c ontrols. All subjects with sickle cell disease had been prescribed folic ac id 1 mg by mouth daily. Results: The median plasma concentration of homocysteine of subjects with s ickle cell disease was approximately 1.5-fold higher than that of controls (p=0.0008). This difference persisted, even when subjects with renal insuff iciency were excluded. Plasma folate levels were 1.5-fold higher in subject s with sickle cell disease than in controls (p=0.0498). There was no signif icant difference in plasma vitamin B12 concentrations between the two group s. There was no difference in plasma homocysteine concentrations between tr ansfused and non-transfused sickle cell subjects. Conclusions: Patients with sickle cell disease have elevated plasma concent rations of homocysteine in spite of elevated plasma folate levels and vitam in B12 concentrations similar to those observed in controls. Based on these data, we hypothesize that the concentration of folate required to normaliz e plasma homocysteine levels in patients with sickle cell disease may be hi gher than that of normal controls and that patients with sickle cell diseas e have a higher nutritional requirement for folic acid than the general pop ulation.