Effect of Acute Transfusion on Cerebral Oxygenation in Patients with Sickle Cell Disease
Authors: Quarmyne Maa-Ohui , Figueroa Janet , McCracken Courtney , Quinn Charles T. , Brown Clark , Joiner Clinton H. 
Published: April 2021

Abstract
Introduction : The molecular abnormality in sickle hemoglobin (HbS) produces a unique cellular pathology characterized by fragile and rigid red blood cells which block the microcirculation, which, in concert with large vessel vasculopathy and the anemia of sickle cell disease (SCD), compromises oxygen delivery to the brain and other organs. Long-term, periodic transfusions are commonly used to prevent and ameliorate neurologic complications related to vasculopathy, particularly stroke. Despite widespread use of transfusions, little is known about the physiological effects on cerebral O2 delivery, which represents an integration of multiple, potentially opposing processes. While increased hematocrit improves O2 carrying capacity, the consequent elevation of blood viscosity has the potential to impede blood flow to cerebral tissue. Also, 2,3-BPG levels in stored blood are depleted, temporarily impairing O2 delivery. Advances in cerebral oximetry (using near infrared spectroscopy) provide an opportunity to address these issues directly to study cerebral oxygenation following transfusions in SCD. The FORE-SIGHT© cerebral oximeter (CAS Medical Systems) measures cerebral tissue hemoglobin saturation (SCTO2), a mixture of arterial and venous oxygen saturation (30:70) in a voxel of tissue near the gray-white junction in the frontal lobes. Using measured arterial Hb saturation (SaO2) by peripheral pulse oximetry and SCTO2 by cerebral oximetry, cerebral venous Hb saturation (SvO2) can be derived. Additionally, using a measured HbO2 affinity curve derived at the time of SCTO2 determination, SvO2 can be converted to venous oxygen tension, PvO2. PvO2 is in dynamic equilibrium with tissue oxygen tension and represents the best estimate of tissue oxygenation. The primary objective of this study was to use cerebral oximetry to assess and monitor cerebral tissue oxygenation following an elective pre-operative RBC transfusion.
Methods : This pilot prospective cohort study enrolled 12 patients with sickle cell anemia (SS, Sb0 thalassemia) in steady-state, who had elective, pre-operative transfusions. Patients who had received transfusion within 3 months or had known cerebral vasculopathy were excluded. Nine patients completed the planned 3 months of study follow up. Two patients were taken off study within a week of enrollment because of difficulties with cerebral oximetry measurements. One did not follow-up after 2 months of participation. Each patient had measurements of SCTO2 prior to the initiation of transfusion, continuously during transfusion, and at predetermined times points post-transfusion, for up to 3 months. Other parameters related to cerebral Hb oxygenation were also measured, including Hb, HbA, HbF, HbS, P50 and 2,3-BPG. The relationship between cerebral oxygenation with age and other predictors of oxygenation was assessed using linear mixed models. The first two post-transfusion measurements (within 96 hours) were compared against pre-transfusion measurements using Wilcoxon signed-rank tests.
Results : SCTO2 was significantly associated with age (p=0.02), Hb (p=0.01) and HbA % (p=0.03 (Table 1). Immediately post-transfusion, SCTO2, increased from median values of 58% to 68.5%, p 0.004 (Table 2). Arterial saturation (SaO2) was unchanged post-transfusion, thus the increase in SCTO2 resulted in an increased (calculated) venous saturation (SvO2). P50 fell post transfusion, as expected, and despite increased SvO2, PvO2 remained unchanged. Arterial and venous oxygen content (CaO2, CvO2) increased post transfusion as expected because Hb and SvO2 increased. However, the difference in arterial and venous oxygen content (CdO2 = CaO2 - CvO2) remained unchanged after transfusion. Similar trends in these parameters were observed in second measurements made up to 96 hours after transfusion (Table 2). Since oxygen delivery equals CdO2 × blood flow, cerebral oxygen delivery would only increase if blood flow were increased by transfusion, contrary to reports {Neurology. 1989 Mar;39(3):344-8; Stroke 25:2153-8, 1994}.
Conclusion: Although cerebral hemoglobin oxygen saturation (SCTO2) increased after acute transfusion, calculated tissue oxygen tension (PvO2) and apparent oxygen delivery (CdO2) remained unchanged, providing no evidence for acute improvement in cerebral oxygenation after transfusion in SCD.

Disclosures
Quinn: Global Blood Therapeutics: Research Funding.