Homocysteine is associated with severity of microvasculopathy in sickle cell disease patients

Abstract

Summary The pathophysiology of sickle cell disease (SCD) includes vasculopathy as well as anaemia. Elevated plasma homocysteine is a risk factor for vascular disease and may be associated with increased risk of vascular complications in SCD patients. In the present study, microvascular characteristics were assessed in the bulbar conjunctiva of 18 paediatric and 18 adult SCD patients, using the non‐invasive technique of computer‐assisted intravital microscopy. A vasculopathy severity index (SI) was computed to quantify the degree of microvasculopathy in each patient. Plasma homocysteine and several of its determinants [serum folate and vitamin B12, plasma pyridoxal‐5'‐phosphate (vitamin B6 status) and creatinine (kidney function)] were measured. Age was strongly correlated with microvasculopathy in the SCD patients, with the SI increasing about 0·1 unit per one‐year increase in age (P < 0·001). After adjusting for age, gender, B‐vitamin status and creatinine, homocysteine concentration was directly correlated with severity index (P < 0·05). Age and homocysteine concentration were independent predictors of microvasculopathy in SCD patients. It remains to be determined whether lowering homocysteine concentrations using appropriate B‐vitamin supplements (folate and vitamins B12 and B6) ‒ particularly if started early in life ‒ could ameliorate microvasculopathy and its associated complications in SCD patients.

Potential inflammatory targets in the integrative health care of patients with sickle cell disease

“…When compared with male patients, the female patients exhibited slightly higher tHCY concentrations (although within normal limits), which has also been reported in a previous study in patients with SCD aged 6-11 years (35). A previous meta-analysis indicated that elevated tHCY levels are linearly associated with physiological dysfunctions in a dose-dependent manner, with each 5-µmol/l increase in tHCY causing a 33.6% increase in the risk for major chronic diseases, such as CVD, cognitive decline, and endothelial dysfunction, contributing to all-cause mortality (27). It has been suggested that the administration of appropriate vitamin-B supplements during childhood could decrease the associated complications observed in SCD (27).…”

“…In patients with HbSS, CRP has been reported to be strongly and independently associated with increased mortality (26). It has been reported that in patients with SCD, age appears to be an independent predictor of microvasculopathy, and that the administration of appropriate vitamin B supplements during childhood could potentially decrease the associated complications observed (27). In the present study, when levels of tHCY were considered, almost all children with SCD (98.57%) exhibited normal concentrations, with 1.42% (n=1) of patients in the 11-16-years age group exhibiting concentration in the higher range.…”

Low vitamin B12 blood levels in sickle cell disease: Data from a large cohort study in Tanzania

“…30 Homocysteine is clinically relevant in SCD as it has been shown to increase the risk for VOC, microvasculopathy and furthermore the risk for cardiovascular disease and stroke in patients with SCD. [31][32][33] We observed that the vitamin B 12 tended to be lower in males as compared to females and moreover, males had higher homocysteine levels and lower folate levels as compared to females across all age groups (the gender difference in homocysteine levels was significant in the two adolescent subgroups). Furthermore, studies have shown that supplementation with folic acid can reduce elevated levels of homocysteine.…”

“…Given this, we were somewhat surprised that the concentrations of total homocysteine were within the reference range for the majority of our study cohort 30 . Homocysteine is clinically relevant in SCD as it has been shown to increase the risk for VOC, microvasculopathy and furthermore the risk for cardiovascular disease and stroke in patients with SCD 31–33 . We observed that the vitamin B 12 tended to be lower in males as compared to females and moreover, males had higher homocysteine levels and lower folate levels as compared to females across all age groups (the gender difference in homocysteine levels was significant in the two adolescent subgroups).…”

Microvasculopathy and biomarkers in sickle cell disease: the promise of non‐invasive real‐time in vivo tools

“…In fact, the presence of chronic kidney disease in patients with SCD is a risk factor for the development of pulmonary hypertension. 4 In this issue of the Brisith Journal of Haematology, Sammaron et al 8 show that homocysteine is directly correlated with the severity of microvasculopathy, as assessed in vivo through computer-assisted intravital microscopy (CAIM) in the bulbar conjunctiva of adults and children with SCD. The study shows that microvascular damage worsens with age.…”