scholarly journals Surgical Splenectomy Alters Red Cell Rheology in Patients with Sickle Cell Disease

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1092-1092
Author(s):  
Celeste K Kanne ◽  
Vivien A Sheehan
Keyword(s):  
Blood Viscosity ◽  
Whole Blood ◽  
Pediatric Patients ◽  
Viscosity Ratio ◽  
Blood Rheology ◽  
Red Cell ◽  
Cell Disease ◽  
Whole Blood Viscosity ◽  
Cell Rheology ◽  
The Impact

Abstract Background: Many patients with sickle cell disease (SCD) require a surgical splenectomy for repeat splenic sequestration or hypersplenism, resulting in worsening anemia and/or thrombocytopenia, or abdominal discomfort. Higher rates of thrombosis, pain crises and acute chest syndrome (ACS) have been reported following surgical splenectomy, although the reasons for this are not known. We hypothesize that this clinical worsening post-splenectomy is due to hemorheological changes; studies of the effects of surgical splenectomy on hemorheology in non-SCD animal models found significant reductions in red cell deformability and increase in whole blood viscosity, or blood thickness, following splenectomy. Understanding the impact of surgical splenectomy on blood rheology is especially relevant for patients with SCD, who have many clinical complications as a result of their high whole blood viscosity for their given hemoglobin levels, and low hematocrit-to-viscosity ratio (HVR), a measure of oxygen carrying capacity. Another important measure of SCD rheology is percent dense red blood cells (%DRBC), red cells with a density>1.11 mg/mL; they are typically the result of cellular dehydration, and are less deformable and more likely to sickle. We therefore sought to use our existing longitudinal rheology data, including measures of viscosity and %DRBC, to evaluate the impact of surgical splenectomy on our pediatric patients with SCD. Methods: We identified seven pediatric patients with multiple measurements of whole blood viscosity and %DRBC, collected before and after surgical splenectomy between November 2013 and April 2018 from SCD patients at Texas Children's Hospital on an IRB approved protocol. The cohort included 4 female and 3 male patients, ages 3-12 years old. Whole blood viscosity was measured using a cone and plate viscometer (DV3T Rheometer, AMETEK Brookfield, Middleboro, MA, USA) at 37 degrees Celsius within 4 hours of sample collection in an EDTA vacutainer tube. CBC data including %DRBC was measured on an ADVIA 120 Hematology System (Siemens Medical Solutions USA, Inc., Malvern, PA, USA). Samples collected 1 month before or after an emergency department visit or within 3 months of a packed red blood cell transfusion were omitted from analysis. Results: We found a significant rise in %DRBC following splenectomy (p=0.01). There was a significant increase in whole blood viscosity at 45 s-1 and 225 s-1 (p=0.006 and p=0.004, respectively) and a decline in hematocrit-to-viscosity ratio (HVR) at 45 s-1 and 225 s-1 (p=0.03 and p=0.03, respectively) (Table 1). Hemoglobin and hematocrit did not significantly change after splenectomy (p=0.6 and p=0.5, respectively), suggesting that the rise in viscosity was due to intrinsic changes in red cell rheology. Platelets increased markedly (p<0.00002), a side effect commonly seen following splenectomy, known to contribute to thrombophilia. Conclusion: Overall, the changes in %DRBC, viscosity, and HVR show a worsening of blood rheology following surgical splenectomy with no evidence of a return to baseline 800 days after splenectomy. The increase in viscosity and reduction in HVR in the setting of a rise in %DRBC suggests that the spleen may have played a role in removing these dense or irreversibly sickled cells. Further studies with a larger cohort and long term observation are needed to further elucidate the relationship between worsening rheology and SCD-related complications reported in the literature post-splenectomy. These rheological changes should be considered as part of the decision making for elective splenectomy, monitored post-splenectomy, and addressed therapeutically where possible. Disclosures No relevant conflicts of interest to declare.

Viscosity and Red Cell Deformity in Arterial Disease

1979 ◽  
Author(s):  
G Cella ◽  
H de Haas ◽  
M Rampling ◽  
V Kakkar
Keyword(s):  
Vascular Disease ◽  
Blood Viscosity ◽  
Whole Blood ◽  
Arterial Disease ◽  
Plasma Viscosity ◽  
Control Group ◽  
Fibrinogen Concentration ◽  
Red Cell ◽  
Whole Blood Viscosity ◽  
Significant Difference

Haemorrheological factors have been shown to be affected in many kings of vascular disease. The present study was undertaken to correlate these factors in normal subjects and patients suffering from peripheral arterial disease. Twenty-two patients were investigated; they had moderate or severe intermittent claudication, extent of disease being confirmed by aorto-arteriography and ankle-systolic pressure studies. Twenty-five controls with no symptoms or signs of arterial disease were selected with comparable age and sex distribution. Whole blood viscosity was measured at shear rates of 230 secs-1 and 23 secs-lat 37°c using a Wells Brookfield cone plate microvisco meter. Plasma viscosity was also measured in an identical manner. Erythrocyte flexibility was measured by centrifuge technique and fibrinogen concentration as well as haematocrit by standard techniques. The fibrinogen concentration appeared to be the only significant parameter; the mean concentration in patients with peripheral vascular disease of 463 ± 73mg/l00ml in the control group ( < 0.05). Although whole blood viscosity was high in patients, when corrected to a common haematocrit, there was no significant difference between patients and controls. The same megative correlation was found for plasma viscosity. The red cell flexibility was found to be increased in patients as compared to the control group, but this effect appeared to be simply proportional to the fibrinogen concentration.

scholarly journals Whole blood viscosity and red blood cell adhesion: Potential biomarkers for targeted and curative therapies in sickle cell disease

2020 ◽  
Vol 95 (11) ◽  
pp. 1246-1256 ◽  
Author(s):  
Erdem Kucukal ◽  
Yuncheng Man ◽  
Ailis Hill ◽  
Shichen Liu ◽  
Allison Bode ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Sickle Cell Disease ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Blood Viscosity ◽  
Whole Blood ◽  
Cell Disease ◽  
Whole Blood Viscosity ◽  
Potential Biomarkers

scholarly journals Rheological Effects of L-Glutamine in Patients with Sickle Cell Disease

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3567-3567
Author(s):  
Celeste K. Kanne ◽  
Varun Reddy ◽  
Vivien A. Sheehan
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Blood Viscosity ◽  
Whole Blood ◽  
Blood Cells ◽  
Cell Disease ◽  
Phase 3 ◽  
Whole Blood Viscosity

Background: ENDARITM (oral pharmaceutical L-glutamine powder) received FDA approval in 2017 as a treatment for sickle cell disease (SCD). A pivotal phase 3 clinical study conducted by Emmaus Medical, Inc. showed that L-glutamine resulted in a lower incidence of vaso-occlusive crises (VOC) as well as a lower rate of hospitalizations and shorter hospital stays. No changes in standard clinical laboratory values were noted. The clinical improvements associated with sickle cell complications are believed to be due to an increase in the proportion of the reduced form of nicotinamide adenine dinucleotides in the red blood cells (RBC) of patients with SCD, reducing the oxidative stress. While the endpoints in the phase 3 study are clinically important, it is essential that we identify biomarkers or measurable laboratory changes that can serve as endpoints for future clinical trials assessing dose optimization and the efficacy and safety of L-glutamine in SCD individuals, including those with hepatic and renal dysfunction. RBC rheology is markedly abnormal in SCD; blood is more viscous for a given hematocrit than normal individuals, dense red blood cells (DRBC) are packed with HbS, potentiating sickling, and RBCs are less deformable than those of HbAA or HbAS individuals. High whole blood viscosity, high DRBCs, and poor RBC deformability are associated with higher rates of VOC. Given the demonstrated reduction in pain events, we hypothesized that L-glutamine might improve RBC rheology and sought to test this in vitro and in vivo using a battery of rheological tests. Methods: For the in vitro study, 6 mL of whole blood was drawn into an EDTA vacutainer from ten pediatric patients with sickle cell anemia (HbSS or HbSβ0) during routine clinical checkups under an IRB approved protocol. The cohort included 3 female and 7 male patients, ages 2-19 years old. All patients were on a steady dose of hydroxyurea and did not receive a transfusion within the 3 months prior to sample collection. A 200 mM stock solution of L-glutamine and water was mixed and filtered under light-protected conditions. Aliquots were stored at -20°C to avoid multiple freeze/thaw cycles. L-glutamine was added to 3 mL of whole blood for a final concentration of 1 mM (average in vivo L-glutamine plasma concentration in patients with SCD treated with L-glutamine); 3 mL of the same patient sample with water added served as a control. After a 24-hour incubation period at 4°C, whole blood viscosity was measured using a cone and plate viscometer at 37°C (DV3T Rheometer, AMETEK Brookfield, USA), %DRBCs were measured on an ADVIA 120 Hematology System (Siemens Healthcare Diagnostics, Inc., USA), and deformability measured using a Laser Optical Rotational Red Cell Analyzer (Lorrca®) (RR Mechatronics, the Netherlands) with the Oxygenscan module. The Oxygenscan measures RBC deformability at normoxia (Elmax), deformability upon deoxygenation (EImin), and point of sickling (PoS), the oxygen tension at which deformability begins to decline, reflecting the patient-specific pO2 at which sickling begins. Paired samples (with and without added L-glutamine) were analyzed using Student's t-test. For the in vivo study, rheological tests were performed on peripheral blood from one patient (18-year-old male on hydroxyurea) at baseline and treated with L-glutamine as part of his routine clinical care. Results and conclusions: Addition of L-glutamine in vitro significantly reduced the PoS, meaning RBCs incubated with L-glutamine could tolerate a lower pO2 before sickling compared to the control. RBCs incubated with L-glutamine also had significantly higher EImin, meaning deoxygenated RBCs were more flexible and deformable. Whole blood viscosity at 45s-1 and 225s-1 did not change significantly following incubation with L-glutamine; %DRBCs also did not change significantly (Table 1). The in vivo patient sample tested exhibited a similar improvement in PoS and EImin (Figure 1). We therefore propose to further test the performance of the PoS and EImin as possible biomarkers of response to L-glutamine in vivo. If validated, these biomarkers may also help further elucidate the mechanisms of action of L-glutamine in SCD. Disclosures No relevant conflicts of interest to declare.

Viscosity and Red Cell Deformity in Arterial Disease

1979 ◽  
Author(s):  
G. Cella ◽  
H.A. de Haas ◽  
M. Rampling ◽  
V.V. Kakkar
Keyword(s):  
Vascular Disease ◽  
Blood Viscosity ◽  
Whole Blood ◽  
Arterial Disease ◽  
Plasma Viscosity ◽  
Control Group ◽  
Fibrinogen Concentration ◽  
Red Cell ◽  
Whole Blood Viscosity ◽  
Significant Difference

Haemorrheological factors have been shown to be affected in many kings of vascular disease. The present study was undertaken to correlate these factors in normal subjects and patients suffering from peripheral arterial disease. Twenty-two patients were investigated; they had moderate or severe intermittent claudication, extent of disease being confirmed by aorto-arteriography and ankle-systolic pressure studies. Twenty-five controls with no symptoms or signs of arterial disease were selected withcomparable age and sex distribution. Whole blood viscosity was measured at shear rates of 230 secs-1 and 23 sees-1 at 37°C using a Weils Brookfield cone plate microvisco meter. Plasma viscosity was also measured in an identical manner. Erythrocyte flexibility was measured by centrifuge technique and fibrinogen concentration as well as haematocrit by standard techniques. The fibrinogen concentration appeared to be the only significant parameter; the mean concentration in patients with peripheral vascular disease of 463 ± 73mg/100ml in the control group ( 〈 0.05). Although whole blood viscosity was high in patients, when corrected t. a common haematocrit, there was no significant difference between patients and controls The same megative correlation was found for plasma viscosity. The red cell flexibility was found to be increased in patients as compared to the control group, but this effect appeared to be simply proportional to the fibrinogen concentration.

Abnormal Red Cell Deformability and Aggregation in Sickle Cell Trait

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1001-1001
Author(s):  
Jon Detterich ◽  
Adam M Bush ◽  
Roberta Miyeko Kato ◽  
Rose Wenby ◽  
Thomas D. Coates ◽  
...  
Keyword(s):  
Blood Flow ◽  
Blood Viscosity ◽  
Whole Blood ◽  
Red Cell ◽  
Cell Deformability ◽  
Autologous Plasma ◽  
Red Cell Deformability ◽  
Whole Blood Viscosity ◽  
Rbc Aggregation ◽  
Rbc Deformability

Abstract Abstract 1001 Introduction: SCT occurs in 8% of African Americans and is not commonly associated with clinical disease. Nonetheless, the United States Armed Forces has reported that SCT conveys a 30-fold risk of sudden cardiac arrest and a 200-fold risk from exertional rhabdomyolysis. In fact, rhabdomyolysis in athletes with SCT has been the principal cause of death in NCAA football players in the last decade, leading to recently mandated SCT testing in all Division-1 players. In SCT, RBC sickle only under extreme conditions and with slow kinetics. Therefore, rhabdomyolysis most likely occurs in SCT when a “perfect storm” of factors converges to critically imbalance oxygen supply and demand in muscles. We hypothesize that in SCT subjects, abnormal RBC rheology, particularly aggregation and deformability, play an important role in abnormal muscle blood flow supply and distribution to exercising muscle. To test this hypothesis, we examined whole blood viscosity, RBC aggregation, and RBC deformability in 11 SCT and 10 control subjects prior to and following maximum handgrip exercise. Methods: Maximum voluntary contraction (MVC) was assessed by handgrip dynamometer in the dominant arm. Baseline blood was collected for CBC, whole blood viscosity, RBC aggregation, and RBC deformability. Patients then maintained 60% MVC exercise until exhaustion. Following 8 minutes of recovery, a venous blood gas and blood for repeat viscosity assessments was collected from the antecubital fossa of the exercising limb. Whole blood viscosity over a shear rate range of 1–1, 000 1/s was determined by an automated tube viscometer, RBC deformability from 0.5–50 Pa via laser ektacytometry (LORCA) and RBC aggregation in both autologous plasma and 3% dextran 70 kDa using an automated cone-place aggregometer (Myrenne). Aggregation measurements included extent at stasis (M), strength of aggregation (GT min) and kinetics (T ½). Results: Baseline CBC and aggregation values are summarized in Table 1. Both static RBC aggregation in plasma and RBC aggregation in dextran (aggregability) were significantly increased in SCT (Table 1). The rate of aggregation formation trended higher in SCT but the strength of aggregation was not different between the two groups. In SCT subjects, red cell deformability was impaired at low shear stress but greater than controls at higher shear stress (Figure 1). Red cell deformability was completely independent of oxygenation status states in both SCT and control subjects. Whole blood viscosity did not different between the two groups whether oxygenated or deoxygenated and prior to or following handgrip exercise. Discussion: Three important hemorheological differences were observed for SCT subjects versus controls: a) RBC deformability was below control at low stress levels yet greater than control at higher stress; b) The extent of RBC aggregation in autologous plasma was about 40% greater; c) The extent of RBC aggregation for washed RBC re-suspended in an aggregating medium (i.e., 3% dextran 70 kDa) was about 30% higher. RBC deformability is a major determinant of in vivo blood flow dynamics, especially in the microcirculation; decreased deformability adversely affects tissue perfusion. RBC aggregation is also an important determinant since it affects both resistance to blood flow and RBC distribution in a vascular bed (e.g., plasma skimming). The finding of greater aggregability (i.e., higher aggregation in the defined dextran medium) indicates that RBC in SCT have an altered membrane surface in which the penetration of this polymer into the glycocalyx is abnormal. The combined effects of these three rheological parameters is likely to impair in vivo blood flow in SCT, perhaps to a degree resulting in pathophysiological changes of the cardiovascular system. Disclosures: Coates: Novartis: Speakers Bureau; Apopharma: Consultancy. Wood:Ferrokin Biosciences: Consultancy; Shire: Consultancy; Apotex: Consultancy, Honoraria; Novartis: Honoraria, Research Funding.

scholarly journals Effect of Electroacupuncture Combined with Guizhi Gegen Decoction on Cervical Vertigo and Its Influence on TCD of Vertebrobasilar Artery, Blood Rheology Indexes, and Quality of Life

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Bo Li ◽  
Li Chen ◽  
Dongqiang Wang
Keyword(s):  
Quality Of Life ◽  
Blood Viscosity ◽  
Whole Blood ◽  
Blood Rheology ◽  
Control Group ◽  
Study Group ◽  
Whole Blood Viscosity ◽  
Cervical Vertigo ◽  
Vertebrobasilar Artery

Cervical vertigo is a common clinical disease. In this study, we investigated the clinical efficacy of adding the treatment protocol of Gui Zhi Ge Gen Tang and electroacupuncture to the Western medical treatment in cervical vertigo. The results showed that the total effective rate of the study group was higher than that of the control group P < 0.05 . After treatment, the vertigo, headache, neck and shoulder pain, daily life and work, and psychological and social adjustment scores were higher in the study group than in the control group P < 0.05 . LVA, RVA, and VB were higher in the study group than in the control group after treatment P < 0.05 . The whole blood viscosity high cut, whole blood viscosity low cut, and plasma viscosity levels were lower in the study group than in the control group after treatment P < 0.05 . After treatment, PF, RF, RE, BP, GH, VT, SF, MH, and HT were higher in the study group than those before treatment P < 0.05 . The incidence of adverse reactions was not statistically significant in the study group compared with the control group P > 0.05 . This means that electroacupuncture combined with Gui Zhi Ge Gen Tang can effectively increase the blood flow velocity of the vertebrobasilar artery in patients with cervical vertigo and improve their blood rheology and quality of life with definite efficacy and high safety.

scholarly journals Temperature dependency of whole blood viscosity and red cell properties in desert ungulates: Studies on scimitar-horned oryx and dromedary camel

2018 ◽  
Vol 69 (4) ◽  
pp. 533-543
Author(s):  
Ursula Windberger ◽  
Roland Auer ◽  
Roberto Plasenzotti ◽  
Stephanie Eloff ◽  
Julian A. Skidmore
Keyword(s):  
Blood Viscosity ◽  
Whole Blood ◽  
Dromedary Camel ◽  
Temperature Dependency ◽  
Red Cell ◽  
Whole Blood Viscosity

New Views of Sickle Cell Disease Pathophysiology and Treatment

Hematology ◽  
2000 ◽  
Vol 2000 (1) ◽  
pp. 2-17 ◽  
Author(s):  
Wendell F. Rosse ◽  
Mohandas Narla ◽  
Lawrence D. Petz ◽  
Martin H. Steinberg
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Blood Viscosity ◽  
Whole Blood ◽  
Cell Disease ◽  
Whole Blood Viscosity ◽  
Diagnosis And Management ◽  
Clinical Consequences ◽  
Areas Of Concern

This review addresses several areas of concern in the care of patients with sickle cell disease. In Sections I and II, the fundamental pathogenetic mechanisms of sickle cell disease and their clinical consequences are discussed. Dr. Narla presents the evidence for abnormal cell adhesiveness by SS cells and Dr. Rosse examines the role of the increased whole blood viscosity. In Section III, Dr. Petz reviews common and uncommon alloimmune consequences of transfusion in sickle cell disease and discusses the diagnosis and management of sickle cell patients with hyperhemolysis after transfusion. In Section IV, Dr. Steinberg gives an update on the use of hydroxyurea in the treatment of sickle cell disease, including the SC and S-β thalassemia variants.

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