Decreased Red Blood Cell Deformability Research Articles

Development of standard tests to examine viscoelastic properties of blood of experimental animals for pediatric mechanical support device evaluation.

We investigated the applicability of measuring the viscoelasticity of bovine, ovine, and porcine whole blood for the evaluation of sublethal damage to red blood cells (RBCs). An increase in blood viscosity and elasticity without changes in hematocrit and plasma viscosity would signify a decrease in RBC deformability. Blood viscoelasticity was assessed using a Vilastic Scientific viscoelastometer. Due to the natural absence of RBC aggregation and small RBC size in normal bovine and ovine blood, viscoelastic properties are less readily detected. However, we found that adjustment of blood hematocrit to a standard level of 40-50% allows for sensitive assessment of viscoelasticity in these blood types demonstrating a marked non-Newtonian behavior mostly related to RBC deformability. Porcine blood showed a pronounced non-Newtonian behavior at all tested hematocrit values, which makes it rheologically comparable to human blood. Both viscosity and elasticity were elevated after blood exposure to a uniform mechanical stress. RBCs rigidified by heat exposure demonstrated a loss of viscoelasticity dependence on shear rate. Measurements of blood viscoelasticity can be meaningful in bovine, ovine, and, especially, porcine blood, and can be used for evaluation of sublethal blood damage during in vitro and animal trials of heart-assist devices.

Blood Viscosity of the Neonate

After completing this article, readers should be able to: 1. List the determinants of blood viscosity in the neonate. 2. List the causes of polycythemia and hyperviscosity in the neonate. 3. List the signs, symptoms, and diagnostic criteria for polycythemia and hyperviscosity. 4. Describe steps for prevention and treatment of polycythemia and hyperviscosity in the neonate. Blood viscosity is defined as resistance to the movement of blood. In a circular vessel or tube, the resistance (R) increases with increasing viscosity (V) of the moving fluid and with the resistance resulting from the vessel geometry (Z): R=Z · V. Thus, blood viscosity describes the contribution of blood rheologic factors to blood flow resistance. However, blood viscosity depends on several factors, and the importance of these factors differs among various vessels. The major determinants of blood viscosity are the hematocrit, plasma viscosity, red blood cell (RBC) aggregation, RBC deformability, leukocyte properties, vessel diameter, and the shear forces acting on the RBC. (1) The hematocrit generally is assumed to be the most important determinant of blood viscosity. Blood viscosity rises exponentially with increasing hematocrit (Fig. 1). A marked rise in blood viscosity is seen when the hematocrit exceeds 0.65 L/L, which typically is defined as the threshold for hyperviscosity of the blood. However, in narrow arteries and arterioles and in capillaries, the plasma viscosity becomes the dominant determinant of blood viscosity. The fetal hematocrit increases from 0.33 L/L in the 12th week of gestation to 0.45 L/L in the 30th week and 0.50 L/L in the 40th week at term. At birth, the hematocrit may rise markedly as a result of “blood transfusion” from the placenta to the neonate. (2) A postnatal hematocrit of 0.45 to 0.65 L/L is considered normal in the healthy term neonate. Figure 1. Blood viscosity in tubes that have a diameter of 50 …

Effect of carbonyl compounds on red blood cells deformability

The effect of Maillard reaction on red blood cells (RBC) deformability was investigated. Exposure of RBC to carbonyl compounds ( dl-glyceraldehyde, glyoxal, glycolaldehyde, 3-deoxyglucosone, and d-glucose) leading to Maillard reaction caused a marked decrease in RBC deformability even at 1 mM level. The decrease rate depended on the kind of carbonyl compounds, in which both dl-glyceraldehyde and glyoxal significantly decreased the RBC deformability ( p < 0.05). In addition, the decrease rate also differed among volunteers tested, indicating that the sensitivity against carbonyl compounds varies among them. In order to elucidate the mechanism of the decrease in RBC deformability, RBC was exposed to carbonyl compounds in the presence of aminoguanidine which is the inhibitor of AGE formation in Maillard reactions. Aminoguanidine inhibited the decrease in RBC deformability by dl-glyceraldehyde and glyoxal. When Hb which has a high reactivity with carbonyl compounds was incubated with those carbonyl compounds, dl-glyceraldehyde and glyoxal showed the high reactivity with Hb compared with other carbonyl compounds. These results indicate that Maillard reaction between RBC proteins and carbonyl compounds leads to the decrease in RBC deformability. On the other hand, O 2 - generated by carbonyl compounds involved in lowering the deformability only to a negligible level.

Effect of Trauma-Hemorrhagic Shock on Red Blood Cell Deformability and Shape

Previous work in our laboratory has demonstrated a decrease in red blood cell (RBC) deformability in sepsis. This has not been studied following hemorrhagic shock. We tested the hypotheses that hemorrhagic shock, associated with soft tissue trauma, leads to decreased RBC deformability and that this is related to alterations in the resting shape of the RBC. Elongation index (EI), a measure of RBC deformability, was determined over a range of shear stresses from 0.3 to 30 Pa in 26 male rats before and at various times after 90 min of hemorrhagic shock. RBC resting shape was determined by scanning electron microscopy. The data demonstrate that EI decreased significantly at the end of shock (before resuscitation), and remained below normal throughout the 6-h postshock period. Eight of the 26 animals decompensated during shock, requiring return of a portion of the shed blood to maintain a mean arterial pressure of 30-40 mmHg. Four of eight decompensated animals died before the end of the study period, compared with none of the compensated rats. The decompensated rats had significantly lower EI at 0.3 Pa by the end of the shock period (0.050 +/- 0.009) than the compensated shock group (0.058 +/- 0.006; P < 0.05). RBC shape alterations were first demonstrated at the end of the shock period and persisted throughout the 6-h postshock resuscitation period. These data indicate that trauma and hemorrhagic shock cause RBC shape alterations and a significant decrease in RBC deformability, which becomes manifested during the shock period and persists for at least 6 h postshock. Additionally, a direct relationship appears to exist between the magnitude of the physiologic insult and the degree of RBC damage.

REDUCED RED BLOOD CELL DEFORMABILITY, AN INDICATOR FOR HIGH FETAL OR MATERNAL RISK, IS FOUND IN PREECLAMPSIA AND IUGR

Objective: Red blood cell (RBC) deformability is one of the factors determining microcirculation. In preeclampsia (PE) and some cases of intrauterine growth restriction (IUGR), microcirculation appears to be reduced. The aim of the study is to examine whether there are differences in RBC deformability in uncomplicated pregnancy when compared to pregnancies complicated by PE and/or IUGR. Material and methods: RBC deformability of 87 pregnant women with initially normal pregnancies was evaluated with the laser diffractoscope. RBC deformability was measured beginning in week 16 of gestation up to 5 days after delivery. Thirty-seven women had an uncomplicated pregnancy. In addition, RBC deformability of 10 nonpregnant women was measured on days 5 and 22 of their menstrual cycle. RBC deformability of women with preeclampsia (PE, N=15), intrauterine growth restriction (IUGR, N=17), or PE plus IUGR (N=17) was measured weekly, beginning with the onset of clinical symptoms, up to 5 days after delivery. Results: In early uncomplicated pregnancies, RBC deformability does not differ from the nonpregnant state. At week 30 of gestation, there is a slight decrease in RBC deformability followed by a return back to the values of nonpregnant women after delivery. Women with PE and/or IUGR show reduced RBC deformability. This is most pronounced in cases with severe fetal or maternal complications. After delivery, RBC deformability also returns to nonpregnancy values within 5 days. Conclusion: Reduced RBC deformability may contribute to a reduced microcirculation in PE and IUGR. Increasing RBC deformability therapeutically in these cases could offer new options for the treatment of decreased uterine and fetal perfusion and their sequelae.

Erythrocyte deformability is a nitric oxide-mediated factor in decreased capillary density during sepsis.

Erythrocyte deformability has been recognized as a determinant of microvascular perfusion. Because nitric oxide (NO) is implicated in the modulation of red blood cell (RBC) deformability and NO levels increase during sepsis, we tested the hypothesis that a NO-mediated decrease in RBC deformability contributes to decreased functional capillary density (CD) in remote organs. With the use of a peritonitis model of sepsis in the rat [cecal ligation and perforation (CLP)] and aminoguanidine (AG) to prevent increases in NO, we measured CD in skeletal muscle (intravital microscopy), mean erythrocyte membrane deformability (; micropipette aspiration), systemic NO production [plasma nitrite/nitrate (NO(x)) chemiluminescence], and NO accumulation in RBC [NO bound to hemoglobin (HbNO) detected by electron paramagnetic resonance spectroscopy]. In untreated CLP animals relative to sham, NO(x) increased 254% (P < 0.05), stopped flow capillaries increased 149% (P < 0.05), and decreased 12.7% (P < 0.05), with a subpopulation (5%) of RBC with deformabilities below the normal range. AG prevented increases in NO(x), accumulation of HbNO, and decreases in both and functional CD. We found no evidence of leukocyte plugging postcapillary venules. Our findings suggest that decreased functional CD during sepsis resulted from a NO-mediated decrease in erythrocyte deformability.

Decrease in red blood cell deformability caused by hypothermia, hemodilution, and mechanical stress: factors related to cardiopulmonary bypass.

During extracorporeal circulation in cardiopulmonary bypass (CPB) surgery, blood is exposed to anomalous mechanical and environmental factors, such as high shear stress, turbulence, decreased oncotic pressure caused by dilution of plasma, and moderate and especially deep hypothermia widely applied during CPB in infants. These factors cause damage to the red blood cells (RBCs), which is manifest by immediate and delayed hemolysis and by changes in the mechanical properties of RBCs. These changes include, in particular, decrease in RBC deformability impeding the passage of RBCs through the microvessels and may contribute to the complications associated with CPB surgery. We investigated in vitro the independent and combined effects of hypothermia, plasma dilution, and mechanical stress on deformability of bovine RBCs. Our studies showed each of these factors to cause a significant decrease in the deformability of RBCs, especially acting synergistically. The impairment of RBC deformability caused by hypothermia was found to be more pronounced for RBCs suspended in phosphate buffered saline (PBS) than for RBCs suspended in plasma. The decrease in RBC deformability caused by mechanical stress was significantly exacerbated by dilution of plasma with PBS. In summary, results of our in vitro study strongly point to a possible detrimental consequence of conventional CPB arising from increased RBC rigidity, which may lead to impaired microcirculation and tissue oxygen supply.

Pathological Flow Properties of Blood in the Fetus and Neonate

Normal Hemorheology: Plasma proteins, plasma viscosity, and red blood cell (RBC) aggregation are very low in the fetus and the preterm infant, but increase with increasing gestational and postnatal age. Moreover, both the viscosity (F~hrffius-Lindqvist effect) and the hematocrit reductions (F~hrffius effect) in narrow tubes are more pronounced in the fetus and neonate than in adults. As a result of these peculiar hemorheological properties, viscosity of blood (measured in 50 ~m diameter tubes) with given hematocrit is markedly lower in the fetus (-50% at 25 wk gestation) and neonate (-25%) than in adults. Blood viscosity in 50-~m tubes is similar in neonates with a hematocrit of 0.70 III as in adults with a hematocrit of 0.50 III. This may explain why polycythemia does not impair systemic, cerebral and intestinal RBC transport in neonates as long as the hematocrit does not exceed 0.70 III and why polycythemic neonates are less susceptible to serious complications than polycythemic children and adults. Pathological Hemorheology: Since high flow conditions in the fetus and neonate are strongly dependent on the favorable rheologic properties of their blood, hemorheolocal abnormalities may contribute to the high risk of the fetus and neonate to ischemic damage of vital organs (e.g. brain) in a variety of disorders: 1) Perinatal asphyxia may be associated with impaired RBC deformability, increased RBC aggregation and leukocyte count, thereby aggravating tissue hypoxia. 2) In growth-retarded fetuses, increased hematocrit, RBC aggregation and leukocyte count may contribute to the high risk of ischemic damage of vital organs (e.g. brain). 3) Fetal and neonatal cells are less protected from radicals than adults, thereby predisposing them to oxidative damage. 4) Neonatal septic shock may be associated with markedly decreased RBC defo rm ability , increase in the count of rigid, immature leukocytes, RBC aggregation and plasma viscosity. 5) Infants of poorly-controlled insulin-dependent diabetic mothers show markedly increased hematocrit and decreased RBC deformability. This may increase their risk of thromboses.

Effects of Acute Exposure to Hyperbaric Oxygen on the Rheology and Morphology of the Red Blood Cells in the Rat

The effects of acute exposure to hyperbaric oxygen (HBO) on the rheology and morphology of red blood cells (RBC) were studied in three groups of Sprague-Dawley rats: a control (CON) group comprised rats not exposed to HBO, a second group was exposed to HBO at 2.8 atm for 6 hr and studied immediately after the exposure (HBO), and a third group was examined after being allowed to recover in room air for 24 hr after exposure to HBO (REC). RBC deformability was assessed by two different techniques, the ektacytometer and the micropore filters. While the ektacytometer did not detect a significant difference among the three groups, the filtration method showed that acute exposure to HBO causes a significant increase in the filtration index (FI), denoting a significant reduction in RBC deformability. However, this reduction returned to the control Level after 24 hr of recovery in air (FI, 7.1 ± 1.2 in CON and 9.5 ± 2.6 in REC compared to 36.2 ± 3.7 in HBO, P < 0.0001). The morphology of RBC was studied by scanning electron microscopy. Immediately after exposure to HBO there was a marked increase in the echinocytes (41.6 ± 5.9%) compared to a control level of 16.7 ± 4.8%, P < 0.05, The increase in the echinocytes became less pronounced after 24 hr of recovery (23.5 < 9.3%). In conclusion, acute exposure to HBO causes significant alterations in RBC rheology and morphology. Due to the sensitivity of the micropore filters, we hypothesize that the decrease in RBC deformability might affect their flow through small-caliber blood vessels. These alterations, however, are reversible after a relatively short period of recovery in air.

In vitro effect of nicotine on red blood cell deformability in untreated and treated essential hypertension.

The in vitro effect of nicotine (10(-7) mol l-1) on red blood cell (RBC) deformability in essential hypertension, efficacy of antihypertensive treatment (with the combination of enalapril, nifedipine and indapamid) on hypertension-induced decrease in RBC deformability and interaction between nicotine and efficacy of antihypertensive treatment were investigated in the blood samples obtained from 16 patients with untreated hypertension (UH) and 18 patients with treated hypertension (TH). Fourteen healthy subjects served as normotensive (NT) group. RBC deformability was assessed by using a gravity-driven microfiltration technique. In the UH group, the RBC deformability was found to be significantly lower than those in NT (0.623 +/- 0.06 versus 0.753 +/- 0.078, p < 0.001) and in TH (0.623 +/- 0.06 versus 0.732 +/- 0.055, p < 0.001) groups. The RBC deformability in the TH group was not significantly different than that in the NT group (0.753 +/- 0.078 versus 0.732 +/- 0.055, p > 0.05). Nicotine, in vitro, decreased deformability in the NT (0.668 +/- 0.067 versus 0.753 +/- 0.078, p > 0.0001), UH (0.509 +/- 0.052 versus 0.623 +/- 0.06, p < 0.0001) and TH (0.651 +/- 0.046 versus 0.732 +/- 0.055, p < 0.001) groups. The effect on the UH group was significantly greater than those in the NT (p < 0.0001) and TH (p < 0.0001) groups. These results suggest that nicotine and hypertension independently and cumulatively decrease the RBC deformability and nicotine inhibits the efficacy of antihypertensive treatment on RBC deformability.

Effect of lipid A on the deformability, membrane rigidity and geometry of human adult red blood cells.

Lipid A is responsible for the activities of endotoxin and may cause circulatory failure and haemolysis. This study evaluated the effects of different lipid A concentrations on red blood cell (RBC) deformation (rheoscope), the aspiration pressure required to aspirate RBC into 3.3 microns pipettes, the membrane shear elastic modulus (i.e. membrane rigidity) and cellular geometry (micropipette system) after 15 min of incubation. Lipid A concentrations of 10 and 100 micrograms ml-1 of RBCs decreased RBC deformability by 26% and 39%, respectively. The aspiration pressure for RBCs into a 3.3 microns micropipette increased by 235% at a lipid A concentration of 10 micrograms ml-1 and by 586% at a concentration of 100 micrograms ml-1. The elastic shear modulus almost doubled at a lipid A concentration of 10 micrograms ml-1 and tripled at 100 micrograms ml-1. At a lipid A concentration of 100 micrograms ml-1, 37% of RBCs showed spicules. These echinocytes were less deformable than discocytes. Mean corpuscular volume, RBC volume and surface area were not affected by lipid A. We conclude that lipid A causes marked reduction of RBC deformability due to increasing membrane rigidity.

Effects of superoxide anions on red cell deformability and membrane proteins.

The effect of superoxide anions (O2-) on red blood cells (RBC) deformability and membrane proteins was investigated using hypoxanthine-xanthine oxidase system. Exposure of RBC to O2- caused a marked decrease in RBC deformability with a concomitant increase in cell volume and shape changes. The RBC exposed to O2- also displayed pronounced degradation of membrane proteins such as band 3 protein and spectrin; new bands of low molecular weight products appeared as the original membrane proteins tended to diminish, without the appearance of high molecular weight products. Since the membrane proteins are involved in processes regulating membrane properties such as permeability and viscoelasticity, the decreased deformability induced by O2- may be attributable to changes in membrane proteins. Interestingly, resealed ghosts exposed to O2- did not show any significant change in membrane proteins, which suggests the existence of further generation of O2- and subsequent production of other active oxygen species mediated by O2(-)-initiated autoxidation of hemoglobin in intact RBC. Furthermore, electrophoretic analysis suggested that active oxygens increased the endogenous proteolytic susceptibility of RBC. In conclusion, a close linkage was suggested between RBC deformability and the membrane proteins.

Red blood cell changes during the evolution of the sickle cell painful crisis

A longitudinal study of the red blood cell (RBC) deformability, percent of dense erythrocytes, and hematologic parameters has been conducted during 117 painful crises affecting 36 patients with sickle cell anemia between January, 1985 and December, 1990. RBC deformability was determined by osmotic gradient ektacytometry and the percentage of dense cells was quantitated by centrifugation on a discontinuous Stractan density gradient. The data indicate that the painful crisis is a process that follows a bimodal form of evolution. The first phase of the painful crisis is characterized by increase in the severity of pain, increase in the number of dense cells, and a decrease in RBC deformability. In some patients the changes in dense cells and RBC deformability are evident 1 to 3 days before the onset of pain. In addition, the hemoglobin level decreases and the reticulocyte count increases during this initial phase. The second phase of the crisis is characterized by reduction in pain intensity, decrease in the number of dense cells, and increase in RBC deformability to values higher than those seen in the steady state. Moreover, the improvement in RBC deformability and the decrease in the number of dense cells at the end of a crisis seem to constitute new risk factors that may incite a recurrence of the crisis within 1 month in about 50% of painful episodes. The pathophysiologic events responsible for this bimodal behavior of RBCs during painful episodes may represent the appearance of factors that induce (1) preferential trapping of deformable cells in the microcirculation during the first phase of the crisis, followed by a decrease of dense cells and the appearance of new deformable RBCs released from the bone marrow during the second phase of the crisis; or (2) variable sickling of all circulating RBCs during the first phase followed by disappearance of dense RBCs and their replenishment by deformable cells during the second phase.

Red Blood Cell Changes During the Evolution of the Sickle Cell Painful Crisis

A longitudinal study of the red blood cell (RBC) deformability, percent of dense erythrocytes, and hematologic parameters has been conducted during 117 painful crises affecting 36 patients with sickle cell anemia between January, 1985 and December, 1990. RBC deformability was determined by osmotic gradient ektacytometry and the percentage of dense cells was quantitated by centrifugation on a discontinuous Stractan density gradient. The data indicate that the painful crisis is a process that follows a bimodal form of evolution. The first phase of the painful crisis is characterized by increase in the severity of pain, increase in the number of dense cells, and a decrease in RBC deformability. In some patients the changes in dense cells and RBC deformability are evident 1 to 3 days before the onset of pain. In addition, the hemoglobin level decreases and the reticulocyte count increases during this initial phase. The second phase of the crisis is characterized by reduction in pain intensity, decrease in the number of dense cells, and increase in RBC deformability to values higher than those seen in the steady state. Moreover, the improvement in RBC deformability and the decrease in the number of dense cells at the end of a crisis seem to constitute new risk factors that may incite a recurrence of the crisis within 1 month in about 50% of painful episodes. The pathophysiologic events responsible for this bimodal behavior of RBCs during painful episodes may represent the appearance of factors that induce (1) preferential trapping of deformable cells in the microcirculation during the first phase of the crisis, followed by a decrease of dense cells and the appearance of new deformable RBCs released from the bone marrow during the second phase of the crisis; or (2) variable sickling of all circulating RBCs during the first phase followed by disappearance of dense RBCs and their replenishment by deformable cells during the second phase.

Effect of Renal Replacement Therapy on Viscosity in End-Stage Renal Disease Patients

Viscosity, an important determinant of microcirculatory hemodynamics, is related to hematocrit (HCT), and may be altered by renal failure or its treatment. To assess these factors, we studied the effect of dialysis on the viscosity of whole blood, plasma, and reconstituted 70% HCT blood of eight continuous ambulatory peritoneal dialysis (CAPD) and nine hemodialysis (HD) patients under steady shear flow conditions at different shear rates, before and after dialysis, compared with nine normal subjects. The density of the red blood cells (RBCs), a marker of cell hydration, was measured in HD patients by a nonaqueous differential floatation technique. Whole blood viscosity was higher in controls than patients, and correlated with HCT before treatment (P less than 0.05) at shear rates of 11.5 to 230 s-1) in HD patients, and 23 to 230 s-1 in all end-stage renal disease (ESRD) patients. In contrast, whole blood viscosity correlated with HCT in CAPD patients only at the lowest shear rates (2.3 and 5.75 s-1, P less than 0.05). Plasma viscosity was higher in CAPD patients than both HD patients before treatment and controls (P less than 0.05, analysis of variance [ANOVA]), despite lower plasma total protein, albumin, and similar fibrinogen concentration compared with HD patients. When all samples were reconstituted to 70% HCT, CAPD patients had higher whole blood viscosity than control subjects'. The high HCT blood viscosity of the ESRD patients was higher than control subjects' at capillary shear rates, suggesting increased RBC aggregation and decreased RBC deformability in patients with renal disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythrocyte deformability in an in vitro model of hypoxia/reoxygenation – protective effects of superoxide dismutase and catalase

An in vitro model was designed to examine the role of ischemialreperfusion and oxygen-derived free radicals on red blood cell (RBC) injury. Normal human RBC suspensions were subjected to various times of hypoxia (1 to 30 min.) followed by various times of reoxygenation (1 to 30 min.). Using a filtration technique, a decrease in RBC deformability was then observed with a maximal effect after 5 min. hypoxial 5 min. reoxygenation. Superoxide anions and hydrogen peroxide could be implicated in this phenomenon, since superoxide dismutase (30 to 300 U/ml) and/or catalase (30 to 300 U/ml) efficiently prevented the membrane rigidity. This study underlines the role of free radicals on RBC functionality and emphasizes the potential use of free radical scavengers in post-ischemic disorders.

Effects of felodipine ER and hydrochlorothiazide on blood rheology in essential hypertension—a randomized, double‐blind, crossover study

The haemorheological effects of felodipine extended release (ER), a new dihydropyridine calcium antagonist, were compared with hydrochlorothiazide (HCTZ) in 28 mild to moderate hypertensives (18 men and 10 women, aged 30-70 years) in a randomized, double-blind, crossover trial. Antihypertensive drugs were gradually discontinued. Felodipine Er, 10 mg, was given once daily for 2 weeks, and after another wash-out period of 1 week, patients were switched to 25 mg HCTZ, once daily, and vice versa. Whole blood viscosity (BV) at three different shear stresses, haematocrit (Hct), plasma viscosity (PV), red blood cell (RBC) aggregation, RBC deformability, and fibrinogen were measured under standardized conditions 2.5 h after medication, and after 2 week of treatment (24 h post-dosing). Felodipine ER improved BV acutely, but not during treatment over a 2-week period. By contrast, HCTZ did not affect BV, but decreased RBC deformability 2.5 h after medication intake. After 2 weeks of treatment, the negative effect on RBC deformability had increased slightly. Furthermore, fibrinogen and PV were significantly elevated at this stage. In summary, felodipine ER did not improve blood rheology over a 2-week treatment period in this study. HCTZ exhibited marginal but significant negative effects on fibrinogen, PV and indices of RBC deformability, but not on RBC aggregation.

Recurrent acute splenic sequestration crisis due to interacting genetic defects: hemoglobin SC disease and hereditary spherocytosis

A 14-year-old boy with hemoglobin SC disease and alpha-thalassemia-2 experienced five episodes of acute splenic sequestration crisis (ASSC), while two of his siblings with identical globin genotypes (SC and - alpha/alpha alpha) had no such experience. To determine if an additional red blood cell (RBC) defect was responsible for the unusual occurrence of frequent ASSCs, we performed detailed rheologic characterization and membrane protein analysis on RBCs from the proband and other members of his family. Reduced surface area, increased mechanical instability, and decreased spectrin content of the membrane, distinguishing features of RBCs in hereditary spherocytosis, were observed in cells from the proband and his mother, but not in cells from other family members. These findings are consistent with the dominant inheritance of spherocytosis by the proband. We suggest that the combined effects of SC disease and spherocytosis in the proband resulted in decreased RBC deformability and led to increased splenic trapping, intrasplenic sickling, and consequently, recurrent sequestration crisis. Marked clinical and hematologic improvement occurred from splenectomy. Thus, inheritance of interacting genetic defects, sickling hemoglobinopathy, and hereditary spherocytosis appear to be responsible for the unusual clinical manifestation of recurrent ASSC in this patient.

Recurrent Acute Splenic Sequestration Crisis Due to Interacting Genetic Defects: Hemoglobin SC Disease and Hereditary Spherocytosis

A 14-year-old boy with hemoglobin SC disease and alpha-thalassemia-2 experienced five episodes of acute splenic sequestration crisis (ASSC), while two of his siblings with identical globin genotypes (SC and -alpha/alpha alpha) had no such experience. To determine if an additional red blood cell (RBC) defect was responsible for the unusual occurrence of frequent ASSCs, we performed detailed rheologic characterization and membrane protein analysis on RBCs from the proband and other members of his family. Reduced surface area, increased mechanical instability, and decreased spectrin content of the membrane, distinguishing features of RBCs in hereditary spherocytosis, were observed in cells from the proband and his mother, but not in cells from other family members. These findings are consistent with the dominant inheritance of spherocytosis by the proband. We suggest that the combined effects of SC disease and spherocytosis in the proband resulted in decreased RBC deformability and led to increased splenic trapping, intrasplenic sickling, and consequently, recurrent sequestration crisis. Marked clinical and hematologic improvement occurred from splenectomy. Thus, inheritance of interacting genetic defects, sickling hemoglobinopathy, and hereditary spherocytosis appear to be responsible for the unusual clinical manifestation of recurrent ASSC in this patient.

The incidence of decreased red blood cell deformability in sepsis and the association with oxygen free radical damage and multiple-system organ failure.

We studied the incidence of decreased red blood cell deformability (RBCD) in sepsis and the association between decreased RBCD and oxygen free radical generation (as measured by malonyldialdehyde) and the occurrence of multiple-system organ failure (MSOF). Patients were divided into three groups: septic (n = 28), nonseptic (n = 15), and control (n = 5). Serial measurements of deformability index, malonyldialdehyde, and MSOF were made. The deformability index for the septic group (0.23 +/- 0.17) was significantly less than that for the nonseptic (1.12 +/- 0.48) and control (1.11 +/- 0.25) groups. The malonyldialdehyde levels for the septic group (4.5 +/- 1.0 nmol/mL) were significantly greater than those for the nonseptic (2.7 +/- 0.9 nmol/mL) and control (2.6 +/- 0.8 nmol/mL) groups. The MSOF index for the septic group (10.1 +/- 2.5) was significantly greater than that for the nonseptic (7.6 +/- 1.7) and control (6.0 +/- 0.0) groups. An inverse correlation existed between malonyldialdehyde and deformability index ( = .501, less than .001, n = 40) and between deformability index and MSOF index (= .350, less than .05, n = 61). We conclude that RBCD is decreased during human sepsis; free radicals generated during sepsis may play a role in the decrease in RBCD. Decreased RBCD may contribute to the MSOF that occurs during sepsis.