Comparison of real-time microvascular abnormalities in pediatric and adult sickle cell anemia patients

Abstract

The conjunctival microcirculation in 14 pediatric and eight adult sickle cell anemia (SCA) patients was studied using computer-assisted intravital microscopy. The bulbar conjunctiva in SCA patients in both age groups exhibited a blanched/avascular appearance characterized by decreased vascularity. SCA patients from both age groups had many of the same abnormal morphometric [vessel diameter, vessel distribution, morphometry (shape), tortuosity, arteriole:venule (A:V) ratio, and hemosiderin deposits] and dynamic [vessel sludging/sludged flow, boxcar blood (trickled) flow, and abnormal flow velocity] abnormalities. A severity index (SI) was computed to quantify the degree of vasculopathy for comparison between groups. The severity of vasculopathy differed significantly between the pediatric and adult patients (SI: 4.2 ± 1.8 vs. 6.6 ± 2.4; P = 0.028), indicative of a lesser degree of overall severity in the pediatric patients. Specific abnormalities that were less prominent in the pediatric patients included abnormal vessel morphometry and tortuosity. Sludged flow, abnormal vessel distribution, abnormal A:V ratio, and boxcar flow appeared in high prevalence in both age groups. The results indicate that SCA microvascular abnormalities develop in childhood and the severity of vasculopathy likely progresses with age. Intervention and effective treatment/management modalities should target pediatric patients to ameliorate, slow down, or prevent progressive microvascular deterioration.

Figure 1

Figure 1A. A frame-captured image of the conjunctival microcirculation in a healthy non-SCA control subject [10, 11]. Optical magnification 4.5X; onscreen magnification 125X. This image illustrates a typical view of the conjunctival microcirculation in a healthy (non-SCA) control subject who has no history of any vascular disease. Note the even and orderly distribution of normal-sized arterioles, venules and capillaries in a richly vascularized network. Abbreviations: A = arteriole; V = venule. Figure 1B. A frame-captured image of the conjunctival microcirculation in a pediatric SCA patient (Patient #P-3; age 8y). Optical magnification 4.5X; onscreen magnification 125X. The SI of this patient is 3 and the microvascular abnormalities include only sludged blood flow (vessel sludging), boxcar (trickled) blood flow and abnormal A:V ratio. Overall, the vasculopathy observed is mild. Abbreviations: BC = boxcar (trickled) blood flow. Figure 1C. A frame-captured image of the conjunctival microcirculation in another pediatric SCA patient (Patient #P-8; age 15y). Optical magnification 4.5X; onscreen magnification 125X. Patient P-8 is 7 years older than the patient described in Figure 2. The microcirculation shows a greater level of vasculopathy, which includes abnormal vessel diameter, sludged blood flow, boxcar (trickled) blood flow, abnormal vessel distribution, hemosiderin deposit, and abnormal A:V ratio in this captured frame. The overall vasculopathy in this pediatric patient is severe, with an SI of 7 (compared with the SI of 3 in the pediatric patient described in Figure 2). Abbreviations: SF = sludged blood flow [stop-and-go pattern of blood flow as evidenced by area(s) of darker or uneven coloration within the vessel]; BC = boxcar (trickled) blood flow; AD = abnormal diameter (wide). Figure 1D. A frame-captured image of the conjunctival microcirculation in an adult SCA patient (Patient #A-7; age 58y). Optical magnification 4.5X; onscreen magnification 125X. The microvascular abnormalities in this adult patient include abnormal vessel diameter, pronounced vessel tortuosity, abnormal vessel distribution, abnormal A:V ratio, sludged (trickled) blood flow, boxcar flow pattern, damaged vessel, and hemosiderin deposits. Abbreviations: SF = sludged blood flow [stop-and-go pattern of blood flow as ecidenced by area(s) of darker or uneven coloration within the vessel]; BC = boxcar (trickled) blow flow; DV = damaged vessel; AD = abnormal diameter (wide); H = hemosiderin deposits; T = tortuosity.