Blood viscosity is an important determinant of local flow characteristics, which exhibits shear thinning behavior: it decreases exponentially with increasing shear rates. Both hematocrit and plasma ...viscosity influence blood viscosity. The shear thinning property of blood is mainly attributed to red blood cell (RBC) rheological properties. RBC aggregation occurs at low shear rates, and increases blood viscosity and depends on both cellular (RBC aggregability) and plasma factors. Blood flow in the microcirculation is highly dependent on the ability of RBC to deform, but RBC deformability also affects blood flow in the macrocirculation since a loss of deformability causes a rise in blood viscosity. Indeed, any changes in one or several of these parameters may affect blood viscosity differently. Poiseuille's Law predicts that any increase in blood viscosity should cause a rise in vascular resistance. However, blood viscosity, through its effects on wall shear stress, is a key modulator of nitric oxide (NO) production by the endothelial NO-synthase. Indeed, any increase in blood viscosity should promote vasodilation. This is the case in healthy individuals when vascular function is intact and able to adapt to blood rheological strains. However, in sickle cell disease (SCD) vascular function is impaired. In this context, any increase in blood viscosity can promote vaso-occlusive like events. We previously showed that sickle cell patients with high blood viscosity usually have more frequent vaso-occlusive crises than those with low blood viscosity. However, while the deformability of RBC decreases during acute vaso-occlusive events in SCD, patients with the highest RBC deformability at steady-state have a higher risk of developing frequent painful vaso-occlusive crises. This paradox seems to be due to the fact that in SCD RBC with the highest deformability are also the most adherent, which would trigger vaso-occlusion. While acute, intense exercise may increase blood viscosity in
Here we describe the effects of a controlled, 30 min, high-intensity cycling test on blood rheology and the metabolic profiles of red blood cells (RBCs) and plasma from well-trained males. RBCs ...demonstrated decreased deformability and trended toward increased generation of microparticles after the test. Meanwhile, metabolomics and lipidomics highlighted oxidative stress and activation of membrane lipid remodeling mechanisms in order to cope with altered properties of circulation resulting from physical exertion during the cycling test. Of note, intermediates from coenzyme A (CoA) synthesis for conjugation to fatty acyl chains, in parallel with reversible conversion of carnitine and acylcarnitines, emerged as metabolites that significantly correlate with RBC deformability and the generation of microparticles during exercise. Taken together, we propose that RBC membrane remodeling and repair plays an active role in the physiologic response to exercise by altering RBC properties.
The diagnosis of chronic mountain sickness (CMS) is based on a score including 7 clinical features (breathlessness, sleep disturbance, cyanosis, venous dilatation, paresthesia, headache, and ...tinnitus) in the setting of extreme erythrocytosis. Examining individuals in La Rinconada, Peru, the highest city in the world, the authors demonstrated that CMS at extreme altitude is not linked to elevation of hemoglobin, since CMS+ and CMS− individuals had similar levels of erythrocytosis.
Chronic mountain sickness is a maladaptive syndrome that affects individuals living permanently at high altitude and is characterized primarily by excessive erythrocytosis (EE). Recent results ...concerning the impact of EE in Andean highlanders on clotting and the possible promotion of hypercoagulability, which can lead to thrombosis, were contradictory. We assessed the coagulation profiles of Andeans highlanders with and without excessive erythrocytosis (EE+ and EE−). Blood samples were collected from 30 EE+ and 15 EE− in La Rinconada (Peru, 5100–5300 m a.s.l.), with special attention given to the sampling pre‐analytical variables. Rotational thromboelastometry tests were performed at both native and normalized (40%) haematocrit using autologous platelet‐poor plasma. Thrombin generation, dosages of clotting factors and inhibitors were measured in plasma samples. Data were compared between groups and with measurements performed at native haematocrit in 10 lowlanders (LL) at sea level. At native haematocrit, in all rotational thromboelastometry assays, EE+ exhibited hypocoagulable profiles (prolonged clotting time and weaker clot strength) compared with EE− and LL (all P < 0.01). At normalized haematocrit, clotting times were normalized in most individuals. Conversely, maximal clot firmness was normalized only in FIBTEM and not in EXTEM/INTEM assays, suggesting abnormal platelet activity. Thrombin generation, levels of plasma clotting factors and inhibitors, and standard coagulation assays were mostly normal in all groups. No highlanders reported a history of venous thromboembolism based on the dedicated survey. Collectively, these results indicate that EE+ do not present a hypercoagulable profile potentially favouring thrombosis.
What is the central question of this study?
Are Andean highlanders with excessive erythrocytosis (EE+) exhibiting a hypercoagulable profile compared with highlanders without erythrocytosis (EE−) and lowlanders (LL)?
What is the main finding and its importance?
Despite normal plasma coagulation (thrombinography and levels of clotting factors and inhibitors), EE+ exhibited a hypocoagulable rotational thromboelastometry profile (prolonged clotting time and weaker clot strength) compared with EE− and LL. In EE+, haematocrit normalization at 40% corrected maximal clot firmness in rotational thromboelastometry FIBTEM tests, but not in EXTEM and INTEM tests, suggesting that platelets play a role in the native hypocoagulable profile.
Chronic mountain sickness (CMS) is a condition characterized by excessive erythrocytosis in response to chronic hypobaric hypoxia. CMS frequently triggers cardiorespiratory diseases such as pulmonary ...hypertension and right or left heart failure. Ambient hypoxia might be further amplified night-time by intermittent hypoxia related to sleep-disordered breathing (SDB) so that sleep disturbance may be an important feature of CMS. Our aim was to characterize in a cross-sectional study nocturnal hypoxaemia, SDB, blood pressure (BP), arterial stiffness and carotid intima-media thickness (CIMT) in highlanders living at extreme altitude.
Men aged 18 to 55 years were prospectively recruited. Home sleep apnoea test, questionnaires (short-form health survey; Montreal cognitive assessment; Pittsburgh Sleep Questionnaire Index and the Insomnia severity index), 24-h ambulatory BP monitoring, CIMT and arterial stiffness were evaluated in 3 groups: i) Andean lowlanders (sea-level); ii) highlanders living at 3,800 m and iii) highlanders living at 5,100 m. Analyses were conducted in sub-groups according to 1) CMS severity 2) healthy subjects living at the three different altitude.
Ninety-two males were evaluated at their living altitudes. Among the 54 highlanders living at 5,100 m, subjects with CMS showed lower mean nocturnal oxygen saturation (SpO
2
), SpO
2
nadir, lower pulse wave velocity and higher nocturnal BP variability than those with no-CMS. Lower nocturnal SpO
2
nadir was associated with higher CMS severity (ß= −0.14, p=.009). Among the 55 healthy subjects, healthy highlanders at 5,100 m were characterized by lower scores on quality of life and sleep quality scales and lower mean SpO
2
compared to lowlanders.
Lower nocturnal SpO
2
and higher nocturnal BP variability are associated with CMS severity in individuals living permanently at high altitude. The role of lower SpO
2
and higher nocturnal BP variability in the cardiovascular progression of CMS and in the overall prognosis of the disease need to be evaluated in further studies.
Chronic hemolysis, enhanced oxidative stress, and decreased nitric oxide (NO) bioavailability promote vasculopathy in sickle cell anemia (SCA). Oxidative stress and NO are known to modulate eryptosis ...in healthy red blood cells (RBCs); however, their role in SCA eryptosis and their impact on the genesis of RBC-derived microparticles (RBC-MPs) remains poorly described. RBC-MPs could play a role in vascular dysfunction in SCA. The aims of this study were to evaluate the roles of oxidative stress and NO in eryptosis and RBC-MPs release, and to determine whether RBC-MPs could be involved in vascular dysfunction in SCA. Markers of eryptosis and oxidative stress, plasma RBC-MPs concentration and arterial stiffness were compared between SCA and healthy (AA) individuals
experiments were performed to test: 1) the effects of oxidative stress (antioxidant: n-acetylcysteine (NAC); pro-oxidant: cumene hydroperoxide) and NO (NO donor: sodium nitroprusside (SNP); NO-synthase inhibitor (L-NIO)) on eryptosis, RBC deformability and RBC-MP genesis; 2) the effects of SCA/AA-RBC-MPs on human aortic endothelial cell (HAEC) inflammatory phenotype and TLR4 pathway. Eryptosis, RBC-MPs, oxidative stress and arterial stiffness were increased in SCA. NAC increased RBC deformability and decreased eryptosis and RBC-MPs release, while cumene did the opposite. SNP increased RBC deformability and limited eryptosis, but had no effect on RBC-MPs. L-NIO did not affect these parameters. Arterial stiffness was correlated with RBC-MPs concentration in SCA. RBC-MPs isolated directly from SCA blood increased adhesion molecules expression and the production of cytokines by HAEC compared to those isolated from AA blood. TLR4 inhibition alleviated these effects. Our data show that oxidative stress could promote eryptosis and the release of RBC-MPs that are potentially involved in macrovascular dysfunction in SCA.
Purpose
Blood rheology is a key determinant of blood flow and tissue perfusion. There are still large discrepancies regarding the effects of an acute running exercise on blood rheological properties ...and red blood cell (RBC) physiology. We investigated the effect of a 10 km running trial on markers of blood rheology and RBC physiology in endurance trained athletes.
Methods
Blood was sampled before and after the exercise to measure lactate and glucose, hematological and hemorheological parameters (blood viscosity, RBC deformability, and aggregation), eryptosis markers (phosphatidylserine and CD47 exposure, RBC reactive oxygen species), RBC-derived microparticles (RBC-MPs), and RBC electrophysiological activity. Weight was measured before and after exercise. Peripheral oxygen saturation and heart rate were monitored before and during the trial.
Results
Blood lactate and glucose levels increased after exercise and subjects significantly lost weight. All athletes experienced a significant fall in oxygen saturation. Mean corpuscular volume (MCV) was increased from 95.1 ± 3.2 to 96.0 ± 3.3 and mean corpuscular hemoglobin concentration (MCHC) decreased after exercise suggesting a slight RBC rehydration. Exercise increased RBC deformability from 0.344 ± 0.04 to 0.378 ± 0.07, decreased RBC aggregates strength and blood viscosity, while hematocrit (Hct) remained unaffected. While RBC electrophysiological recording suggested a modulation in RBC calcium content and/or chloride conductance, eryptosis markers and RBC-MPs were not modified by the exercise.
Conclusion
A 10 km acute running exercise had no effect on RBC senescence and membrane blebbing. In contrast, this exercise increased RBC deformability, probably through rehydration process which resulted in a decrease in blood viscosity.
Blood rheology is a key determinant of tissue perfusion at rest and during exercise. The present study investigated the effects of race distance on hematological, blood rheological, and red blood ...cell (RBC) senescence parameters. Eleven runners participated in the Martigny-Combes à Chamonix 40 km race (MCC, elevation gain: 2300 m) and 12 others in the Ultra-Trail du Mont Blanc (UTMB, 171 km, elevation gain: 10,000 m). Blood samples were collected before and after the races. After the UTMB, the percentage of RBC phosphatidylserine (PS) exposure was not affected while RBC CD235a levels decreased and RBC-derived microparticles increased. In contrast, after the MCC, RBC PS exposure increased, while RBC CD235a and RBC-derived microparticles levels were not affected. The free hemoglobin and hemolysis rate did not change during the races. RBC aggregation and blood viscosity at moderate shear rates increased after the MCC. RBC deformability, blood viscosity at a high shear rate, and hematocrit decreased after the UTMB but not after the MCC. Our results indicate that blood rheology behavior is different between a 40 km and a 171 km mountain race. The low blood viscosity after the ultra-marathon might facilitate blood flow to the muscles and optimize aerobic performance.
Background:
Although obstructive sleep apnea (OSA) could act as a modulator of clinical severity in sickle cell disease (SCD), few studies focused on the associations between the two diseases.
...Research Question:
The aims of this study were: (1) to explore the associations between OSA, nocturnal oxyhemoglobin saturation (SpO2) and the history of several acute/chronic complications, (2) to investigate the impact of OSA and nocturnal SpO2 on several biomarkers (hematological, blood rheological, and coagulation) in patients with SCD.
Study Design and Methods:
Forty-three homozygous SCD patients underwent a complete polysomnography recording followed by blood sampling.
Results:
The proportion of patients suffering from nocturnal hypoxemia did not differ between those with and those without OSA. No association between OSA and clinical severity was found. Nocturnal hypoxemia was associated with a higher proportion of patients with hemolytic complications (glomerulopathy, leg ulcer, priapism, or pulmonary hypertension). In addition, nocturnal hypoxemia was accompanied by a decrease in RBC deformability, enhanced hemolysis and more severe anemia.
Interpretation:
Nocturnal hypoxemia in SCD patients could be responsible for changes in RBC deformability resulting in enhanced hemolysis leading to the development of complications such as leg ulcers, priapism, pulmonary hypertension or glomerulopathy.
Clinical Trial Registration:
www.ClinicalTrials.gov
, identifier: NCT03753854.
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