In Patients with Sickle Cell Disease on Chronic Transfusion Therapy, Viscosity and Aggregation Are Increased After a Single Transfusion, Negatively Affecting Low Shear Rate Blood Flow
Authors: Detterich Jon , Alexy Tamas , Wenby Rosalinda B , Wood John C , Coates Thomas D. , Meiselman Herbert J 
Published: October 2019

Abstract
Abstract 1259
The ability for hemoglobin S to polymerize causes increased viscosity, decreased RBC deformability and increased RBC aggregation. Chronic transfusion therapy (CTT) in patients with sickle cell disease (SCD) decreases the percentage of hemoglobin S in the bloodstream. The hematocrit to viscosity ratio (HVR) has been used to estimate red cell oxygen transport effectiveness, a property of blood flow. There are undeniable benefits from CTT, however, there are patients on CTT who still suffer from acute crises. Acute hemorheologic changes after transfusion might contribute to these episodes. We hypothesize that viscosity and aggregation will increase post transfusion. Furthermore, we believe that these changes will result in lower oxygen transport effectiveness as measured by HVR.
To test this hypothesis we enrolled 26 patients on chronic transfusion therapy in a prospective study to evaluate blood viscosity and aggregation changes with transfusion. We measured both oxygenated and deoxygenated whole blood viscosity at shear rates from 1s−1 to 1000s−1 and RBC aggregation at native hematocrit using a Rheolog viscometer (Rheologics Co). We also obtained pre and post transfusion blood counts, chemistry panels and markers of inflammation and hemolysis.
14 females and 12 males were enrolled with one patient who was excluded due to incomplete data. The ages and reasons for starting transfusion were similar for male and female patients. As expected, transfusion resulted in significant increases of hemoglobin and hematocrit with a concomitant decrease of percent hemoglobin S and reticulocyte count. There was a trend toward decreased platelet count. Male patients had a significantly higher percent hemoglobin S, reticulocyte count, plasma free hemoglobin and platelet count compared to females. Viscosity increased significantly across all shear rates with transfusion and with deoxygenation. There was no sex difference in viscosity. Deoxygenation and transfusion increased the aggregation index. Change in viscosity positively correlated with increased hematocrit and aggregation index. There was no correlation of viscosity change with change in hemoglobin S, markers of inflammation or hemolysis.
Deoxygenation lowered HVR at all shear rates. HVR was significantly lower post transfusion at low shear rates of 1s−1, 2s−1 and 5s−1 (Figure 1). At mid to high shear rates there was no difference in HVR, although as the shear rate increased, the HVR curves crossed with apparently increasing improvement in HVR post transfusion at the highest shear rates. The significant decrease in HVR at low shear correlated with increased aggregation index but not increased hematocrit.
In this population of patients on CTT, blood viscosity and RBC aggregation increased post transfusion, thus predisposing them to impaired perfusion in low flow vascular beds. The decrease in HVR at low shear rates correlated with RBC aggregation, providing further evidence for post-transfusion risk of impaired perfusion. These results support our hypothesis and indicate potential adverse effects of transfusion on microvascular blood flow.Figure 1Figure 1.

Disclosures:
Wood: Novartis: Research Funding; Ferrokin Biosciences: Consultancy; Cooleys Anemia Foundation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.