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Endothelialized Microfluidics for Studying Microvascular Interactions in Hematologic Diseases
Published on: June 22, 2012
Homocysteine is associated with severity of microvasculopathy in sickle cell disease patients
Sandra L Samarron1, Joshua W Miller2, Anthony T Cheung1,3
1Department of Medical Pathology and Laboratory Medicine, University of California, Davis, CA, USA.
Insights
In sickle cell disease (SCD), both age and elevated plasma homocysteine are independent predictors of microvasculopathy. Early intervention with B-vitamins may help reduce vascular complications in SCD patients.
Area of Science:
- Hematology
- Vascular Biology
- Nutritional Science
Background:
- Sickle cell disease (SCD) pathophysiology involves anemia and vasculopathy.
- Elevated plasma homocysteine is a known vascular disease risk factor.
- Homocysteine may increase vascular complication risk in SCD patients.
Purpose of the Study:
- To assess microvascular characteristics in pediatric and adult SCD patients.
- To investigate the correlation between plasma homocysteine and microvasculopathy severity.
- To identify predictors of microvasculopathy in SCD.
Main Methods:
- Computer-assisted intravital microscopy of the bulbar conjunctiva.
- Quantification of microvasculopathy using a severity index (SI).
- Measurement of plasma homocysteine and its determinants (B vitamins, creatinine).
Main Results:
- Age strongly correlated with microvasculopathy (SI increased with age).
- Homocysteine concentration directly correlated with SI after adjusting for confounders.
- Age and homocysteine were independent predictors of microvasculopathy.
Conclusions:
- Microvasculopathy in SCD is associated with both age and homocysteine levels.
- Further research is needed to determine if lowering homocysteine with B-vitamins can mitigate SCD microvasculopathy.
- Early intervention with folate, B12, and B6 may be beneficial.
Abstract:
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.
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