scholarly journals Hyperhaemolytic Syndrome in Sickle cell disease: clearing the cobwebs

2020 ◽  
Author(s):  
Anazoeze Jude Madu ◽  
Angela Ogechukwu Ugwu ◽  
Chilota Efobi
Keyword(s):  
Blood Transfusion ◽  
Cell Membrane ◽  
Sickle Cell ◽  
Rare Condition ◽  
Red Cells ◽  
Acute Chest Syndrome ◽  
Membrane Phospholipids ◽  
Dynamic Background ◽  
Red Cell Membrane ◽  
Additional Strain

Sickle cell anaemia presents with a dynamic background haemolysis and deepening anaemia. This increases the demand for transfusion if any additional strain on haemopoiesis is encountered due to any other physiological or pathological. Patients with cerebrovascular accident are placed on chronic blood transfusion; those with acute sequestration and acute chest syndrome are likewise managed with blood transfusion. These patients are prone to develop blood transfusion complications including alloimmunization and hyperhaemolytic syndrome (HHS). This term is used to describe haemolysis of both transfused and ‘own’ red cells occurring during or post-transfusion in sickle cell patients. Hyperhaemolysis results in worsening post-transfusion haemoglobin due attendant haemolysis of both transfused and autologous red cells. The mechanism underlying this rare and usually fatal complication of sickle cell has been thought to be secondary to changes in the red cell membrane with associated immunological reactions against exposed cell membrane phospholipids. The predisposition to HHS in sickle cell is also varied and the search for a prediction pattern or value has been evasive. This review to discusses the pathogenesis, risk factors and treatment of hyperhaemolytic syndrome, elaborating what is known of this rare condition.

scholarly journals Altered plasma membrane phospholipid organization in Plasmodium falciparum-infected human erythrocytes

Blood ◽  
1987 ◽  
Vol 69 (2) ◽  
pp. 401-407
Author(s):  
RS Schwartz ◽  
JA Olson ◽  
C Raventos-Suarez ◽  
M Yee ◽  
RH Heath ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Cell Membrane ◽  
Early Stage ◽  
Red Cells ◽  
Membrane Phospholipid ◽  
Cell Membrane Permeability ◽  
Parasite Development ◽  
Red Cell ◽  
Membrane Phospholipids ◽  
Red Cell Membrane

The intraerythrocytic development of the malaria parasite is accompanied by distinct morphological and biochemical changes in the host cell membrane, yet little is known about development-related alterations in the transbilayer organization of membrane phospholipids in parasitized cells. This question was examined in human red cells infected with Plasmodium falciparum. Normal red cells were infected with strain FCR3 or with clonal derivatives that either produce (K+) or do not produce (K-) knobby protuberances on the infected red cells. Parasitized cells were harvested at various stages of parasite development, and the bilayer orientation of red cell membrane phospholipids was determined chemically using 2,4,6-trinitrobenzene sulphonic acid (TNBS) or enzymatically using bee venom phospholipase A2 (PLA2) and sphingomyelinase C (SMC). We found that parasite development was accompanied by distinct alterations in the red cell membrane transbilayer distribution of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS). Increases in the exoplasmic membrane leaflet exposure of PE and PS were larger in the late-stage parasitized cells than in the early-stage parasitized cells. Similar results were obtained for PE membrane distribution using either chemical (TNBS) or enzymatic (PLA2 plus SMC) methods, although changes in PS distribution were observed only with TNBS. Uninfected cohort cells derived from mixed populations of infected and uninfected cells exhibited normal patterns of membrane phospholipid organization. The observed alterations in P falciparum-infected red cell membrane phospholipid distribution, which is independent of the presence or absence of knobby protuberances, might be associated with the drastic changes in cell membrane permeability and susceptibility to early hemolysis observed in the late stages of parasite development.

scholarly journals Altered plasma membrane phospholipid organization in Plasmodium falciparum-infected human erythrocytes

Blood ◽  
1987 ◽  
Vol 69 (2) ◽  
pp. 401-407 ◽  
Author(s):  
RS Schwartz ◽  
JA Olson ◽  
C Raventos-Suarez ◽  
M Yee ◽  
RH Heath ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Cell Membrane ◽  
Early Stage ◽  
Red Cells ◽  
Membrane Phospholipid ◽  
Cell Membrane Permeability ◽  
Parasite Development ◽  
Red Cell ◽  
Membrane Phospholipids ◽  
Red Cell Membrane

Abstract The intraerythrocytic development of the malaria parasite is accompanied by distinct morphological and biochemical changes in the host cell membrane, yet little is known about development-related alterations in the transbilayer organization of membrane phospholipids in parasitized cells. This question was examined in human red cells infected with Plasmodium falciparum. Normal red cells were infected with strain FCR3 or with clonal derivatives that either produce (K+) or do not produce (K-) knobby protuberances on the infected red cells. Parasitized cells were harvested at various stages of parasite development, and the bilayer orientation of red cell membrane phospholipids was determined chemically using 2,4,6-trinitrobenzene sulphonic acid (TNBS) or enzymatically using bee venom phospholipase A2 (PLA2) and sphingomyelinase C (SMC). We found that parasite development was accompanied by distinct alterations in the red cell membrane transbilayer distribution of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS). Increases in the exoplasmic membrane leaflet exposure of PE and PS were larger in the late-stage parasitized cells than in the early-stage parasitized cells. Similar results were obtained for PE membrane distribution using either chemical (TNBS) or enzymatic (PLA2 plus SMC) methods, although changes in PS distribution were observed only with TNBS. Uninfected cohort cells derived from mixed populations of infected and uninfected cells exhibited normal patterns of membrane phospholipid organization. The observed alterations in P falciparum-infected red cell membrane phospholipid distribution, which is independent of the presence or absence of knobby protuberances, might be associated with the drastic changes in cell membrane permeability and susceptibility to early hemolysis observed in the late stages of parasite development.

Hydroxyurea in the Management of Pediatric Sickle Cell Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4818-4818
Author(s):  
Amal M. El-Beshlawy
Keyword(s):  
Blood Transfusion ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Hospital Admissions ◽  
Ferritin Level ◽  
Laboratory Data ◽  
Red Cells ◽  
Acute Chest Syndrome ◽  
Increased Risk ◽  
The Mean

Abstract Low levels of fetal hemoglobin (HbF) in sickle cell disease (SCD) patients (pts) are associated with a variety of vaso-occlusive complications and an increased risk of early death. Raising HbF levels can reduce the effect of the disease. Hydroxyurea (HU) reduces the production of HbS containing red cells and favors the production of HbF containing red cells. HU has bean used successfully in the management of adults with SCD but still there is a limited data on its efficacy and safety in pediatric age group. This study reviews our clinical experience with HU in the treatment of pediatric pts with SCD attending the Pediatric Hematology Clinic of Cairo University. Sixty SCD pts from 2001 to 2007 who received HU over the period of 6 years (yrs) and who continued therapy for at least 6 months were included. Four pts were excluded because of non compliance to treatment. Response to HU was assessed both clinically and by laboratory findings. Pts were considered responders if they showed ≥50% improvement in clinical and laboratory data. These data included number of blood transfusions/yr, vasoocclusive crisis (VOC)/yr requiring admission to the emergency unit, hospital admissions/yr. Laboratory data included Hb (g/dl), MCV (fl), HbF%, total leucocytic count (TLC), (×103/ml) absolute neutrophil count (ANC), platelets (×103/ml) and reticulocytic count (%) and serum ferritin level (ng/ml). Fifty six pts (44 children and 12 adults [≥ 18 yrs]) were included. Their mean age was 14.05 ± 5.3 yrs (range of 6–28 yrs). Thirty seven were females and 19 males. Twenty four (43%) were sickle-β thalassemia while 32 (57%) were homozygous sickle cell anemia (SS). Splenectomy was done for 26 pts (46.5%), 17 before and 9 after start of HU. Forty four (79%) received blood transfusion > 5 times per yr and 12 had sporadic transfusions. Forty pts (71%) were HCV positive. The main indications for starting HU therapy were frequent VOC, transfusion dependency and acute chest syndrome (91%, 86% and 16% respectively). Other indications included hepatic crisis (5%), bone infarction (7%), sequestration crisis (5%) and pulmonary hypertension in one case. HU was started in a dose of 15mg/kg/day with careful monthly monitoring for side effects. There was no attempt to achieve maximum tolerated dose. Dose increase or decrease was done depending on clinical and laboratory response with a maximum dose of 30mg/kg/day. The mean dose of HU was 15.8mg/kg/day (range 10–30 mg/kg/day) and the mean duration of therapy was 3.25 yrs (range of 0.5–6 yrs). Forty four pts (79%) were found to be responders. There was a significant (p<0.05) improvement in all clinical parameters with VOC/yr reduced from a mean of 6 to 1.98, hospitalization/yr from 3 to 0.32, blood transfusion/yr from 9.25 to 1.45. The mean Hb level of responders increased from 7.58g/dl before HU to 8.01g/dl after HU, although not statistically significant, 28/44 pts (63.64%) showed increase in Hb varies between 2-<1g/dl. Patients who did not show increase in Hb level (16/44) were clinically stable and had decreased number of blood transfusion by >50% or stop blood transfusion. Responders showed a significant decrease in TLC, ANC, Retics and serum ferritin (P values 0.002, 0.019, 0.000, 0.001 respectively). Significant increase in HbF and MCV (p= 0.000, 0.001 respectively) was also observed. HU toxicity was defined by > 3 fold increase in ALT, platelet count < 80,000 μl, ANC <1500 or increase in serum creatinine >50% above baseline. Twenty pts (36%) showed signs of HU toxicity: elevated ALT (n=9), neutropenia (n=7), thrombocytopenia (n=1), unexplained jaundice (n=1) and both neutropenia and jaundice (n=2). Thirteen pts continued therapy with reduction of the dose or temporary stopping of HU while 7 stopped HU. It was noticed that all pts who developed hepatotoxicity were HCV positive (p= 0.036). It was also shown that hepatotoxicity was significantly higher among those receiving Deferiprone with HU (n=20) (p=0.001). There was no relation between response to HU and patients’ age, sex, spleen status or phenotype. HU provides the best available strategy to achieve clinical and hematological improvement in SCD in pediatrics, but requires periodic monitoring of blood count and ALT levels especially for HCV positive pts and those on Deferiprone therapy

scholarly journals Red Cell Membrane Permeability Deduced from Bulk Diffusion Coefficients

1974 ◽  
Vol 64 (6) ◽  
pp. 706-729 ◽  
Author(s):  
W. R. Redwood ◽  
E. Rall ◽  
W. Perl
Keyword(s):  
Cell Membrane ◽  
Membrane Permeability ◽  
Diffusion Coefficients ◽  
Bulk Diffusion ◽  
Red Cells ◽  
Cell Membrane Permeability ◽  
Red Cell ◽  
Cell Column ◽  
Red Cell Membrane ◽  
One Dimensional

The permeability coefficients of dog red cell membrane to tritiated water and to a series of[14C]amides have been deduced from bulk diffusion measurements through a "tissue" composed of packed red cells. Red cells were packed by centrifugation inside polyethylene tubing. The red cell column was pulsed at one end with radiolabeled solute and diffusion was allowed to proceed for several hours. The distribution of radioactivity along the red cell column was measured by sequential slicing and counting, and the diffusion coefficient was determined by a simple plotting technique, assuming a one-dimensional diffusional model. In order to derive the red cell membrane permeability coefficient from the bulk diffusion coefficient, the red cells were assumed to be packed in a regular manner approximating closely spaced parallelopipeds. The local steady-state diffusional flux was idealized as a one-dimensional intracellular pathway in parallel with a one-dimensional extracellular pathway with solute exchange occurring within the series pathway and between the pathways. The diffusion coefficients in the intracellular and extracellular pathways were estimated from bulk diffusion measurements through concentrated hemoglobin solutions and plasma, respectively; while the volume of the extracellular pathway was determined using radiolabeled sucrose. The membrane permeability coefficients were in satisfactory agreement with the data of Sha'afi, R. I., C. M. Gary-Bobo, and A. K. Solomon (1971. J. Gen. Physiol. 58:238) obtained by a rapid-reaction technique. The method is simple and particularly well suited for rapidly permeating solutes.

scholarly journals Microfluidics in Sickle Cell Disease Research: State of the Art and a Perspective Beyond the Flow Problem

2021 ◽  
Vol 7 ◽  
Author(s):  
Anupam Aich ◽  
Yann Lamarre ◽  
Daniel Pereira Sacomani ◽  
Simone Kashima ◽  
Dimas Tadeu Covas ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Flow Problem ◽  
Red Cells ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Intercellular Interaction ◽  
Blood Disorder ◽  
Resource Setting ◽  
Wide Range

Sickle cell disease (SCD) is the monogenic hemoglobinopathy where mutated sickle hemoglobin molecules polymerize to form long fibers under deoxygenated state and deform red blood cells (RBCs) into predominantly sickle form. Sickled RBCs stick to the vascular bed and obstruct blood flow in extreme conditions, leading to acute painful vaso-occlusion crises (VOCs) – the leading cause of mortality in SCD. Being a blood disorder of deformed RBCs, SCD manifests a wide-range of organ-specific clinical complications of life (in addition to chronic pain) such as stroke, acute chest syndrome (ACS) and pulmonary hypertension in the lung, nephropathy, auto-splenectomy, and splenomegaly, hand-foot syndrome, leg ulcer, stress erythropoiesis, osteonecrosis and osteoporosis. The physiological inception for VOC was initially thought to be only a fluid flow problem in microvascular space originated from increased viscosity due to aggregates of sickled RBCs; however, over the last three decades, multiple molecular and cellular mechanisms have been identified that aid the VOC in vivo. Activation of adhesion molecules in vascular endothelium and on RBC membranes, activated neutrophils and platelets, increased viscosity of the blood, and fluid physics driving sickled and deformed RBCs to the vascular wall (known as margination of flow) – all of these come together to orchestrate VOC. Microfluidic technology in sickle research was primarily adopted to benefit from mimicking the microvascular network to observe RBC flow under low oxygen conditions as models of VOC. However, over the last decade, microfluidics has evolved as a valuable tool to extract biophysical characteristics of sickle red cells, measure deformability of sickle red cells under simulated oxygen gradient and shear, drug testing, in vitro models of intercellular interaction on endothelialized or adhesion molecule-functionalized channels to understand adhesion in sickle microenvironment, characterizing biomechanics and microrheology, biomarker identification, and last but not least, for developing point-of-care diagnostic technologies for low resource setting. Several of these platforms have already demonstrated true potential to be translated from bench to bedside. Emerging microfluidics-based technologies for studying heterotypic cell–cell interactions, organ-on-chip application and drug dosage screening can be employed to sickle research field due to their wide-ranging advantages.

Degradation of red cell membrane phospholipids by sea anemone nematocyst venom

Toxicon ◽  
1974 ◽  
Vol 12 (4) ◽  
pp. 379-383 ◽  
Author(s):  
D.A. Hessinger ◽  
H.M. Lenhoff
Keyword(s):  
Cell Membrane ◽  
Sea Anemone ◽  
Red Cell ◽  
Membrane Phospholipids ◽  
Red Cell Membrane

scholarly journals Inhibition of malarial parasite invasion by monoclonal antibodies against glycophorin A correlates with reduction in red cell membrane deformability

Blood ◽  
1989 ◽  
Vol 74 (5) ◽  
pp. 1836-1843 ◽  
Author(s):  
G Pasvol ◽  
JA Chasis ◽  
N Mohandas ◽  
DJ Anstee ◽  
MJ Tanner ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Cell Membrane ◽  
Red Cells ◽  
Malarial Parasite ◽  
Glycophorin A ◽  
Red Cell ◽  
Red Cell Membrane ◽  
Parasite Invasion ◽  
Surface Molecules ◽  
Fab Fragments

Abstract The effect of well-characterized monoclonal antibodies to red cell surface molecules on the invasion of human red cells by the malarial parasites Plasmodium falciparum and Plasmodium knowlesi was examined. Antibodies to glycophorin A (GP alpha) inhibit invasion for both parasite species, and this is highly correlated with the degree to which they decrease red cell membrane deformability as measured by ektacytometry. This effect on rigidity and invasion was also seen with monovalent Fab fragments. The closer the antibody binding site was to the membrane bilayer, the greater was its effect on inducing membrane rigidity and decreasing parasite invasion. Antibodies to the Wright determinant in particular were the most inhibitory. This differential effect of the various antibodies was not correlated with their binding affinities or the number of sites bound per cell. Antibodies to surface molecules other than GP alpha were without effect. A novel mechanism is described whereby monoclonal antibodies and their Fab fragments directed at determinants on the external surface of red cells might act to inhibit invasion by malarial parasites by altering membrane material properties.

Sign in / Sign up

Export Citation Format

Share Document