Red Blood Cell Oxygen Transport Research Articles

Erythrapheresis Improves Blood Viscosity Compared to Manuel Procedure in Sickle Cell Disease

▪Blood transfusion is a cornerstone of the treatment in sickle cell disease (SCD). Guidelines and clinical trials indicate their use in several acute and chronic SCD manifestations such as cerebral vasculopathy prevention and acute chest syndrome. Two methods of blood exchange transfusion are available for physicians and patients: manual exchange transfusion (MET) and erythrapheresis, i.e. an automated exchange transfusion (AET). MET consists in a phlebotomy followed by a transfusion while erythrapheresis corresponds to the replacement of only sickle RBCs by healthy RBCs by controlling hematocrit. To our knowledge, no study has compared the impact of these two methods on blood viscosity and the ratio of hematocrit to blood viscosity (HVR); i.e., an index of red blood cell oxygen transport effectiveness (Alexy et al, 2006). Herein we aimed to compare those two procedures in term of biological parameters and blood viscosity, in order to offer new physiological parameters to guide the therapeutic management of SCD patients.This prospective, monocenter, observational study included sickle cell patients, ≥18 years old, treated by Blood Exchange Transfusion (BET) in our university hospital’s Adult Sickle-Cell Referral Center. The primary end point was the change in blood viscosity during the BET procedure. Secondary end-points included the change in HVR, blood viscosity and HVR at the end of the procedure. Blood viscosity was measured after full oxygenation of the blood, at native hematocrit and at a shear rate of 225 s-1using a cone/plate viscometer (Brookfield DVII+ with CPE40 spindle, Brookfield Engineering Labs, Natick, MA, USA) (Baskurt et al, 2009).This study was approved by the local Institutional Review Board. All patients gave their signed informed consent for the genetic studies in accordance with the Declaration of Helsinki. All data were rendered anonymous to protect patients' privacy and confidentiality.Twelve patients in AET group and 31 patients in MET group were included. Thirty-nine patients had a SS genotype, three patients had a S-β0 thalassemia genotype (2 AET, 1 MET) and one had a S-β+thalassemia genotype (AET). The proportion of hydroxyurea-treated patients was not different between the two groups (20/31 in MET group and 5/12 in the AET group; p=0.17). The BET indication was cerebral vasculopathy in 11/12 and vaso-occlusive crisis in 1/12 in the AET group. BET indications in the MET group were: frequent vaso-occlusive crisis (10/31), severe organ dysfunction or organ transplant (12/31), provisory hydroxyurea interruption due to pregnancy, breastfeeding, paternity desire (4/31) and leg ulcers (3/31).Differences between groups before BET were only a higher percentage of HbF in the MET group and a higher percentage of HbA in the AET group.Both AET and MET procedures decreased HbS level, leucocytes and platelets counts, and increased HbA level (p ranging from < 0.01 to < 0.001). The decrease in HbS (p < 0.001), HbF (p < 0.05), HbA2 (p < 0.05), leucocytes (p < 0.001) and platelets (p < 0.001) levels was higher in the AET than in the MET condition. MET caused a significant rise in hematocrit and hemoglobin (p < 0.001). In contrast, AET did not change hematocrit and induced a slight increase in hemoglobin (p < 0.05). The percentage of change in hemoglobin and hematocrit was higher in the MET than in the AET condition (p < 0.01 and p < 0.05, respectively). The median blood viscosity after AET was significantly lower (3.77 cP [3.78-4.25]) compared to before (4.47 cP [3.88-5.22 ]; (p=0.0001)), whereas there was no difference before (4 cP [3.7-4.25]) and after (4.15 cP [3.73-4.88]) BET in the MET group (p=0.11). The percentage of variation in blood viscosity between AET and MET was significantly different (p < 0.01). Both AET and MET significantly increased HVR (p < 0.001 and p < 0.01, respectively) and the percentage of variation was not significantly different between the two procedures (p = 0.138).Conclusion: Automated exchange transfusion and not manual exchange transfusion improved blood viscosity. This might be due to the control of hematocrit allowed by the automated procedure, while decreasing the HbS percentage. Automated exchange transfusion should be preferred in acute and chronic SCD manifestations to improve blood rheology. DisclosuresNo relevant conflicts of interest to declare.

Decreased Hematocrit-To-Viscosity Ratio and Increased Lactate Dehydrogenase Level in Patients with Sickle Cell Anemia and Recurrent Leg Ulcers

Leg ulcer is a disabling complication in patients with sickle cell anemia (SCA) but the exact pathophysiological mechanisms are unknown. The aim of this study was to identify the hematological and hemorheological alterations associated with recurrent leg ulcers. Sixty-two SCA patients who never experienced leg ulcers (ULC-) and 13 SCA patients with a positive history of recurrent leg ulcers (ULC+) - but with no leg ulcers at the time of the study – were recruited. All patients were in steady state condition. Blood was sampled to perform hematological, biochemical (hemolytic markers) and hemorheological analyses (blood viscosity, red blood cell deformability and aggregation properties). The hematocrit-to-viscosity ratio (HVR), which reflects the red blood cell oxygen transport efficiency, was calculated for each subject. Patients from the ULC+ group were older than patients from the ULC- group. Anemia (red blood cell count, hematocrit and hemoglobin levels) was more pronounced in the ULC+ group. Lactate dehydrogenase level was higher in the ULC+ group than in the ULC- group. Neither blood viscosity, nor RBC aggregation properties differed between the two groups. HVR was lower and RBC deformability tended to be reduced in the ULC+ group. Our study confirmed increased hemolytic rate and anemia in SCA patients with leg ulcers recurrence. Furthermore, our data suggest that although systemic blood viscosity is not a major factor involved in the pathophysiology of this complication, decreased red blood cell oxygen transport efficiency (i.e., low hematocrit/viscosity ratio) may play a role.

Low‐shear red blood cell oxygen transport effectiveness is adversely affected by transfusion and further worsened by deoxygenation in sickle cell disease patients on chronic transfusion therapy

Simple chronic transfusion therapy (CTT) is a mainstay for stroke prophylaxis in sickle cell anemia, but its effects on hemodynamics are poorly characterized. Transfusion improves oxygen-carrying capacity, reducing demands for high cardiac output. While transfusion decreases factors associated with vasoocclusion, including percent hemoglobin (Hb)S, reticulocyte count, and circulating cell-free Hb, it increases blood viscosity, which reduces microvascular flow. The hematocrit-to-viscosity ratio (HVR) is an index of red blood cell oxygen transport effectiveness that varies with shear stress and balances the benefits of improved oxygen capacity to viscosity-mediated impairment of microvascular flow. We hypothesized that transfusion would improve HVR at high shear despite increased blood viscosity, but would decrease HVR at low shear. To test this hypothesis, we examined oxygenated and deoxygenated blood samples from 15 sickle cell patients on CTT immediately before transfusion and again 12 to 120 hours after transfusion. Comparable changes in Hb, hematocrit (Hct), reticulocyte count, and HbS with transfusion were observed in all subjects. Viscosity, Hct, and high-shear HVR increased with transfusion while low-shear HVR decreased significantly. Decreased low-shear HVR suggests impaired oxygen transport to low-flow regions and may explain why some complications of sickle cell anemia are ameliorated by CTT and others may be made worse.

Effects of hydration and water deprivation on blood viscosity during a soccer game in sickle cell trait carriers

The present study compared the changes in blood viscosity, hydration status, body temperature and heart rate between a group of sickle cell trait (SCT) carriers and a control (Cont) group...

Effect of nitric oxide and nitric oxide donors on red blood cell oxygen transport.

A mechanism has been proposed in which nitric oxide (NO) may bind to cysteine beta93 and be transported by haemoglobin from the lungs to the tissues and modify vascular tone. In addition, it has been reported that treatment of sickle cell anaemia blood with 80 p.p.m. NO gas in air shifts the oxygen affinity, as measured by P50 to the left. We exposed normal and sickle cell anaemia blood to 80 p.p.m. NO in air for 1 h in vitro and found no change in P50 of either normal or sickle cell blood. In addition, we exposed normal and sickle cell blood in buffer to aqueous NO (NO gas dissolved in buffer) at varying concentrations and found that the induced left shift in P50 correlates strongly and linearly with methaemoglobin formation. We also treated normal and sickle cell blood with other nitric oxide donors, such as sodium 2-(N, N-diethylamino)-diazenolate-2-oxide (DEANO), S-nitrosocysteine (CysNO) and sodium trioxodinitrate (OXINO, or Angeli's salt). In all cases, we found a dose-dependent increase in methaemoglobin that was strongly correlated with the dose-dependent P50 reduction. Our data do not support the report that low NO concentrations can selectively increase the oxygen affinity of sickle cell blood without affecting methaemoglobin levels significantly. NO, however, may have benefit in sickle cell disease by other mechanisms.

The relationship of maternal erythrocyte oxygen transport parameters to intrauterine growth retardation

The relation of fetal growth and maternal oxygen transport as assessed by red blood cell 2,3-diphosphoglycerate, hemoglobin oxygen affinity, hemoglobin, pH, and PCO2 was evaluated in 21 pregnant women. The study was performed in the third trimester and each subject evaluated had sonographic evidence of fetal growth retardation without other obvious abnormalities. Decreased maternal 2,3-diphosphoglycerate/hemoglobin molar ratio and hemoglobin oxygen affinity were related linearly to the birth weight normalized for the expected sea level values of gestational age expressed as a birth weight (gestational age-normalized) Z score. The correlation coefficients and p values were r = 0.71, p less than 0.001 and r = 0.67, p less than 0.001, respectively. The ponderal index-normalized Z score correlated with the 2,3-diphosphoglycerate/hemoglobin molar ratio (r = 0.46, p less than 0.04), but the relation was not as strong as the birth weight-normalized Z score. The crown-heel length/head circumference ratio did not correlate with the 2,3-diphosphoglycerate/hemoglobin molar ratio (r = 0.29, NS). The birth weight (gestational age)-normalized Z score did not correlate with hemoglobin, PCO2, or pH. In the regulation of hemoglobin oxygen affinity, calculations indicated that the 2,3-diphosphoglycerate/hemoglobin molar ratio played a highly significant role (p less than 0.001), pH was minimally significant (p less than 0.025), but PCO2 had little or no significant effects in this study. It appears that fetal growth is related to the maternal red blood cell oxygen transport parameters 2,3-diphosphoglycerate/hemoglobin molar ratio and hemoglobin oxygen affinity. Moreover, the 2,3-diphosphoglycerate/hemoglobin molar ratio is the principal regulator of hemoglobin oxygen affinity.

Changes in red blood cell oxygen transport in diabetic pregnancy

Parameters of red cell oxygen transport were studied in 23 nonsmoking, insulin-dependent diabetic women and 20 nonsmoking healthy women late during pregnancy. In the pregnant diabetic women, arterial oxygen saturation (SAT) and arterial oxygen tension were significantly decreased. SAT correlated inversely with hemoglobin AIc (Hb AIc) (diabetic women: r = −0.43, p < 0.05; total material: r = −0.66, p < 0.001). Red blood cell 2,3-diphosphoglycerate (2,3-DPG) was significantly increased in the pregnant diabetic women (p < 0.01), but the 2,3-DPG-induced change in hemoglobin-oxygen affinity was impaired. P50 (oxygen affinity, i.e., Po2 at 50% oxygen saturation) at actual pH correlated inversely with Hb AIc of the diabetic women (r = −0.45, p < 0.05). The suggestion is made that, in diabetic pregnancy particularly in poorly regulated cases, fetal hypoxia may be an important factor for the increased risk of intrauterine fetal death.

Red cell 2,3-diphosphoglycerate and oxygen affinity of hemoglobin in patients with thyroid disorders

We measured red blood cell 2,3-diphosphoglycerate (2,3-DPG), adenosine triphosphate (ATP), and the P50 value in vitro of the oxyhemoglobin dissociation curve, which is the oxygen tension at half saturation of hemoglobin, in order to quantitate red blood cell oxygen transport function in individuals who were diagnosed as hypothyroid, euthyroid, or hyperthyroid based on measurements of thyroxine (T4), triiodothyronine (T3), thyrotropin (TSH), and their clinical status. Hypothyroid (mean T4 2.8 microgram/dl, T3 49 ng/dl, TSH 37 microU/ml) and hyperthyroid (mean T4 14 microgram/dl, T3 271 ng/dl, TSH less than 0.7 microU/ml) patients had normal red cell 2,3-DPG and ATP levels and normal P50 values in vitro. The known changes in oxygen consumption produced by alterations in thyroid hormone levels in patients with hypothyroidism or hyperthyroidism did not affect red blood cell oxygen transport function.

Red Cell 2,3-Diphosphoglycerate and Oxygen Affinity of Hemoglobin in Patients With Thyroid Disorders

Abstract We measured red blood cell 2,3-diphosphoglycerate (2,3-DPG), adenosine triphosphate (ATP), and the P50 value in vitro of the oxyhemoglobin dissociation curve, which is the oxygen tension at half saturation of hemoglobin, in order to quantitate red blood cell oxygen transport function in individuals who were diagnosed as hypothyroid, euthyroid, or hyperthyroid based on measurements of thyroxine (T4), triiodothyronine (T3), thyrotropin (TSH), and their clinical status. Hypothyroid (mean T4 2.8 microgram/dl, T3 49 ng/dl, TSH 37 microU/ml) and hyperthyroid (mean T4 14 microgram/dl, T3 271 ng/dl, TSH less than 0.7 microU/ml) patients had normal red cell 2,3-DPG and ATP levels and normal P50 values in vitro. The known changes in oxygen consumption produced by alterations in thyroid hormone levels in patients with hypothyroidism or hyperthyroidism did not affect red blood cell oxygen transport function.

An oxyhemoglobin dissociation analyzer.

An oxyhemoglobin dissociation analyzer.