Exchange transfusion therapy and its effects on real-time microcirculation in pediatric sickle cell anemia patients: an intravital microscopy study

Abstract

Periodic blood exchange transfusion is a treatment modality commonly used to manage pediatric sickle cell anemia at the University of California Davis Medical Center. The goal of exchange transfusion therapy is to ameliorate vasoocclusion and improve tissue perfusion by removing sickled red blood cells and introducing normal red blood cells. Using computer-assisted intravital microscopy, pretransfusion and posttransfusion microvascular characteristics were analyzed. In this study, the bulbar conjunctiva exhibited a "blanched" avascular appearance in all 6 pediatric sickle cell anemia patients before transfusion, indicative of tissue hypoperfusion and ischemia. Immediately after transfusion, substantial improvement in vascularization and tissue perfusion resulted, reflected by the enhanced appearance of capillaries and arterioles. In addition, a decrease in red cell velocity was observed. These observations provide evidence that exchange transfusion therapy is beneficial in ameliorating vasoocclusion and improving tissue perfusion. However, with the paradoxical posttransfusion decrease in red cell velocity presumably due to induced hyperviscosity from the large transfusion volume, blood flow is still impaired. This decreased velocity may thwart efforts to improve oxygen delivery through transfusion and may, to some extent, promote vasoocclusion instead. This paradoxical result warrants further investigation on the effects of transfusion volume and viscosity in the exchange transfusion process.

Conflict of interest statement

Disclosure: There is no conflict of interest disclosure for all authors.

Figures

Figure 1A–1F. Pre- and post-transfusion frame-captured images showing microvascular changes in the bulbar conjunctiva of pediatric SCA patients

Optical magnification, 4.5x; on-screen magnification, 125x. 1A. An image of the bulbar conjunctiva in a pediatric SCA patient (Patient #TF-2; age 8 years old). Note the characteristic “blanched” avascular appearance in the bulbar conjunctiva and a significantly diminished presence of arterioles and capillaries. The boxed area shows the presence of a typical venule with sludged blood flow in the patient. The parallel marker indicates the location where vessel diameter and red cell velocity were measured for comparison with 1B. 1B. An image of the same location of the bulbar conjunctiva in the patient immediately following transfusion, showing a significant post-transfusion decrease in venular diameter. In addition, a substantial increase in tissue perfusion is shown as indicated by the enhanced presence of capillaries and arterioles. 1C. An image of the bulbar conjunctiva in a second SCA patient (Patient #TF-3; age 5 years old). Again, note the “blanched” avascular appearance similar to the appearance in Patient #TF-2 in 1A. The two boxed areas and parallel markers indicate the locations where vessel diameters and red cell velocities were measured for comparison with 1D. 1D. An image of the same location in the bulbar conjunctiva shown in 1C immediately following transfusion. Note the significant decreases in vessel diameter in the two locations (indicated by the parallel markers) and a substantial improvement in tissue perfusion, 1E. An image of the bulbar conjunctiva in a third SCA patient (Patient #TF-5; age 15 years old). Again, note the “blanched” avascular appearance similar to the appearance in Patients #TF-2 and #TF-3. The boxed area and parallel marker indicate the location where measurements were made for comparison with 1F. 1F. An image on the same location in the bulbar conjunctiva shown in 1E immediately following transfusion. Again, note the significant decrease in vessel diameter and substantial improvement in tissue perfusion.

Figure 2. Pre- and post-transfusion measurements of the conjunctival vessel diameter in six pediatric SCA patients

Vessel diameter measurement for each patient and averaged (mean ± SD) vessel diameter measurement for all six patients combined. Note the significant change in post-transfusion vessel diameter measurements (p=0.015).

Figure 3. Pre- and post-transfusion red cell velocity measurements of the conjunctival vessels in six pediatric SCA patients

Red cell velocity measurements for each patient and averaged (mean ± SD) red cell velocity measurement for all six patients combined. Note the substantial change in post-transfusion velocity measurements, albeit not statistically significant (p=0.059).