scholarly journals Thrombotic Thrombocytopenic Purpura and Sickle Cell Crisis

2008 ◽  
Vol 16 (2) ◽  
pp. 224-227 ◽  
Author(s):  
Suresh G. Shelat
Keyword(s):  
Red Blood Cells ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Sickle Cell ◽  
Blood Cells ◽  
Signs And Symptoms ◽  
Activity Level ◽  
Acute Chest Syndrome ◽  
Thrombocytopenic Purpura ◽  
Nucleated Red Blood Cells ◽  
Elevated Lactate

Described is a case of acute chest syndrome in a sickle-cell patient (hemoglobin SS) who also developed signs and symptoms of thrombotic thrombocytopenic purpura, including thrombocytopenia and hemolysis (anemia, elevated lactate dehydrogenase, presence of schistocytes, dark-colored plasma, and elevations in nucleated red blood cells). The ADAMTS13 activity level was normal. Discussed are the diagnosis and therapeutic management issues and the challenges of differentiating the vasoocclusive and hemolytic complications of sickling red blood cells from the thrombotic microangiopathy of thrombotic thrombocytopenic purpura.

scholarly journals Adamts13-Cultured Red Blood Cells to Treat Thrombotic Thrombocytopenic Purpura

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 89-89
Author(s):  
Kai Wang ◽  
Khulan Batbayar ◽  
Karl Roberts ◽  
Emmanuel Olivier ◽  
Eric E. Bouhassira
Keyword(s):  
Red Blood Cells ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Blood Cells ◽  
Vascular System ◽  
Conflicts Of Interest ◽  
Direct Injection ◽  
Culture Method ◽  
Thrombocytopenic Purpura ◽  
Membrane Bound

Red Blood Cells (RBCs) have long been considered a potentially useful means of delivering drugs to the circulation because delivery through therapeutic RBCs as compared to direct injection in the plasma can lengthen the half-life of the therapeutic agent in the circulation, spatially restrict the drugs to the lumen of the cardio-vascular system, and shield the drug from the immune system. Despite some progress, loading the cells with therapeutically useful cargo remains technically challenging. We have recently developed PSC-RED, a chemically-defined scalable method to differentiate induced pluripotent stem cells (iPSCs) into unlimited numbers of enucleated cultured RBCs. This provides an ideal method to produce therapeutic RBCs since iPSCs can be genetically manipulated with powerful CRISPR-based technologies. ADAMTS13, whose deficiency is responsible for congenital and acquire Thrombotic Thrombocytopenic Purpura (TTP) is a good target as a therapeutic that could be delivered through drug-carrying RBCs because large amounts of plasma concentrate, or more recently recombinant proteins, are necessary to treat TTP. We report here we have produced engineered erythroid cells that contains globin-LCR driven ADAMTS13 fusion transgenes inserted at safe harbor AAVS1, and that these cells express a membrane bound version of an inhibitor-resistant version of ADAMTS13. We show using flow cytometry that the fusion protein is express at high levels, and using a FRET assay that detect cleavage of the von Willebrand cognate site, that the membrane bound ADAMTS13 is enzymatically active. Comparison of enzymatic activity with plasma concentrate suggests that about 50 billion engineered ADAMTS13-cRBCs would be sufficient to deliver an amount of ADAMTS13 equivalent to 2 liters of plasma concentrate. This suggests that a transfusion of about 10 mL of ADAMTS13-RBCs could be therapeutic for congenital and acquired TTP. The number of cRBCs necessary to treat even a few patients is very large. This has been considered a major obstacle to the development of treatment based on in vitro produced RBCs because of the volume of culture that is necessary to produce the cells. We also report that we have developed a culture method based on holo-fiber bioreactors that allows the production of cRBCs at a density of 5.108 cell/mL which is sufficient to produce enough cells to performed small clinical trials. Disclosures No relevant conflicts of interest to declare.

scholarly journals Epidemiological and clinical study of sickle cell disease at tertiary care centre in western India

2019 ◽  
Vol 7 (1) ◽  
pp. 97
Author(s):  
Varsha P. Patel ◽  
Archana U. Gandhi ◽  
Chineen Shah
Keyword(s):  
Sickle Cell Disease ◽  
Red Blood Cells ◽  
Sickle Cell ◽  
Blood Cells ◽  
Tertiary Care ◽  
Clinical Profile ◽  
Acute Chest Syndrome ◽  
Care Hospital ◽  
Cell Disease ◽  
Tribal Communities

Background: Sickle cell disorders are structural hemoglobinopathies, rendering red blood cells sickle shaped, less deformable and sticky leading to microvascular vaso-occlusion and premature red blood cells destruction which leads to varied clinical manifestations. It leads to lifelong morbidity thus affecting quality of life and contributes to early mortality thereby reducing the key national resources- the healthy workforce. This study was done to evaluate epidemiological and clinical profile of sickle cell disease attending the centre.Methods: This study was cross-sectional, observational study conducted at tertiary care hospital in Gujarat. After taking ethical clearance patients were enrolled as per inclusion and exclusion criteria and epidemiological and clinical profile of sickle cell disease patients was studied.Results: Mean age of sickle cell disease was 22.58 years. It was found in tribal communities of Gujarat like Rathwa, Baria, Tadvi etc. Commonest symptom was musculoskeletal pain (86.84%), followed by jaundice (71.05%), fever, dyspnoea, abdominal pain and chest pain. Most common systemic manifestation was pain crises (60.66%), followed by hemolytic anemia (31.15%), acute chest syndrome (30%), consolidation (11.67%), hepatopathy (10%) and avascular necrosis of hip. (6.56%).Conclusions: Sickle cell disease is seen in younger patients. In Gujarat mainly tribal communities are affected. Major systemic manifestations of sickle cell disease include pain crisis followed by hemolytic crisis, acute chest syndrome, hepatopathy and AVN of hip.    

scholarly journals Thrombotic Thrombocytopenic Purpura in Childhood

Blood ◽  
1962 ◽  
Vol 19 (2) ◽  
pp. 181-199 ◽  
Author(s):  
JAMES B. MACWHINNEY ◽  
JAMES T. PACKER ◽  
GERALD MILLER ◽  
ROBERT M. GREENDYKE
Keyword(s):  
Red Blood Cells ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Clinical Features ◽  
Blood Cells ◽  
Patient Case ◽  
Thrombocytopenic Purpura ◽  
Renal Vessels ◽  
Kidney Involvement ◽  
Histologic Changes

Abstract (1) Two cases of thrombotic thrombocytopenic purpura (TTP) occurring in childhood are described. Case 1 is unique in that the patient survived for 12 years. (2) The clinical features of 19 reported cases of TTP in children are reviewed. (3) The presence of morphologic abnormalities of red blood cells and the regular occurrence of kidney involvement in this disorder is emphasized. In one patient (Case 2), histologic changes of the disease were limited to the kidney. (4) Certain hematologic and histologic features shared by TTP and eclampsia are described. (5) Unusual histologic lesions of renal vessels are described.

Intravital Imaging of Pulmonary Neutrophils in Sickle Cell Anemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1398-1398
Author(s):  
Natacha Ralainirina ◽  
Grzegorz Chodaczek ◽  
Joel Linden
Keyword(s):  
Red Blood Cells ◽  
Sickle Cell ◽  
Blood Cells ◽  
Neutrophil Infiltration ◽  
Intravital Imaging ◽  
Acute Chest Syndrome ◽  
Inkt Cells ◽  
Cover Glass ◽  
Hypoxia Reoxygenation

Abstract Sickle cell disease (SCD) is a genetic disorder usually caused by a homozygous point mutation in the b subunit of hemoglobin. In sickle patients, hemoglobin polymerizes in low oxygen environments, resulting in red cell shape change, increased adhesiveness and fragility. Individuals with SCD experience periodic bouts of painful vaso-occlusive crises (pVOC), generalized damage to most tissues and sometimes life-threatening acute chest syndrome. Although pVOC is triggered by red blood cell sickling, it is associated with an inflammatory response that further reduces blood flow. pVOC is due in part to adhesion of red blood cells to leukocytes and adhesion of red blood cells and leukocytes to the endothelium. Our team has demonstrated that iNKT cells trigger an innate immune response in sickle cell patients. iNKT cells activation is followed by secondary activation of immune cells such as neutrophils and monocytes. We have developed procedures to image neutrophils in the lung, liver and spleen in living mice. In this study we sought to investigate in vivo neutrophil rolling and adherence to endothelial cells that occurs in multiple tissues including the lung during pVOC. To visualize vascular neutrophils in situ we used a Leica SP5 RS confocal/two-photon microscope. The microscope can be operated to a depth of 50-80 µm with resonant scanning in the confocal mode. Mice are anesthetized by intra-peritoneal injection of a mixture ketamine/xylazine in PBS. Anesthesia is maintained during the experiment by applying half-doses periodically. The depth of the anesthesia is verified by paw pinching before starting the surgical dissection and during imaging. Extra care is taken to minimize inflammation that results from invasiveness of the surgery. Before lung imaging mice are tracheostomized to enable mechanical ventilation and the chest is opened to allow for access to the lung left lobe through a window of few millimeters in diameter. Spleen and liver are accessed by a small incision in the abdomen wall. Organs are kept moist with a drop of PBS. A custom built suction device covered with a No 1.5 cover glass 12 mm in diameter (Electron Microscopy Sciences, Hatfield USA) is placed onto the organ of interest. At the same time, minimal working pressure is exerted to seal the organ and the cover glass together. Throughout the procedure, mice are maintained at 37°C by a heating pad. Once surgery is completed, a mixture of antibodies coupled to fluorophores is given by retro-orbital injection using a U-100 28 1/2 gauge BD insulin syringe. At the end of the experiment, mice are sacrificed by cervical dislocation while still anesthetized. To induce vaso-occlusion we have developped a hypoxia/reoxygenation protocol with 8% O2 for 12h followed by 4h of reoxygenation. We quantify the number of adherent and rolling neutrophils and their velocity in sickle Townes mice subjected to hypoxia/reoxygenation compared to normoxic Townes mice. By intravital confocal microscopy experiments we were able to detect a higher number of infiltrating neutrophils in the lung in sickle mice versus littermate controls in the normoxic state. Moreover, the infiltration of neutrophils was increased in sickle mice subjected to hypoxia/reoxygenation. Interstingly, the infiltration of neutrophils noted in sickle Townes mice subjected to hypoxia/reoxygenation is abrogated by prior NKT-14 antibody-mediated depletion of iNKT cells whereas mice treated with isotype control Abs were not affected. Our results agree with prior results suggesting that iNKT cell activation occurs prior to neutrophil infiltration in the lung. Furthermore, intravital imaging experiments allowed us to demonstrate that neutrophil infiltration and NKT cells are involved in vaso-occlusives crises in vivo. Intravital microscopy may be helpful for the evaluation of novel treatments for reducing vaso-occlusive events in SCD. Disclosures No relevant conflicts of interest to declare.

scholarly journals Crisis in Sickle Cell Disease: Review Article

2021 ◽  
pp. 679-685
Author(s):  
Syed Athhar Saqqaf ◽  
Rajendra Borkar
Keyword(s):  
Sickle Cell Disease ◽  
Red Blood Cells ◽  
Sickle Cell ◽  
Blood Cells ◽  
Well Being ◽  
Review Article ◽  
The Body ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Wide Range

Sickle cell disease is a very common inherited disorder of the hemoglobin. It is inherited in an autosomal recessive manner. Most affected are the people of African, Indian and Arabian origin. It occurs due to change in the single base pair gene wherein thymine replaces adenine in the 6th codon of the beta-globin gene. This result in the sickling shape of the red blood cells. Sickle cell disease includes a variety of phenotypes like the SS, AS, Sickle-thal, SC patterns, etc. Sickle cell- SS pattern also termed as sickle cell anemia is the most common of form of the disorder and is also responsible for the morbidity and mortality caused by the disorder. The sickling pattern of the red blood cells occludes the blood vessels and leads to a wide range of complication in the affected individuals. These complications can be seen in number of different systems of the body and also multiple systems at the same time. These complications are termed as crisis, which then include the vaso-occlusive crisis, acute chest syndrome, splenic sequestration crisis, etc. These crises can negatively affect the quality of life to a large effect, but are also largely controllable or rather delayed and effectively managed as far as possible with reduced effect in the normal well being. Hence the knowledge about these crisis and their treatment is an important aspect of medical practice, especially in the countries where this disorder is commonly seen. Here in this review article we aim to highlight the major crises seen in sickle cell disease and their treatment in brief.

Increased Procoagulant Activity of Red Blood Cells from Patients with Homozygous Sickle Cell Disease and β-Thalassemia

1996 ◽  
Vol 76 (03) ◽  
pp. 322-327 ◽  
Author(s):  
Dominique Helley ◽  
Amiram Eldor ◽  
Robert Girot ◽  
Rolande Ducrocq ◽  
Marie-Claude Guillin ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Red Blood Cells ◽  
Sickle Cell ◽  
Blood Cells ◽  
Annexin V ◽  
Mean Value ◽  
Procoagulant Activity ◽  
Dependent Manner ◽  
Cell Disease ◽  
Homozygous Sickle Cell Disease

SummaryIt has recently been proved that, in vitro, red blood cells (RBCs) from patients with homozygous β-thalassemia behave as procoagulant cells. The procoagulant activity of β-thalassemia RBCs might be the result of an increased exposure of procoagulant phospholipids (i. e. phosphatidylserine) in the outer leaflet of the membrane. In order to test this hypothesis, we compared the catalytic properties of RBCs of patients with β-thalassemia and homozygous sickle cell disease (SS-RBCs) with that of controls. The catalytic parameters (Km, kcat) of prothrombin activation by factor Xa were determined both in the absence and in the presence of RBCs. The turn-over number (kcat) of the reaction was not modified by normal, SS- or (3-thalassemia RBCs. The Km was lower in the presence of normal RBCs (mean value: 9.1 µM) than in the absence of cells (26 µM). The Km measured in the presence of either SS-RBCs (mean value: 1.6 µM) or β-thalassemia RBCs (mean value: 1.5 pM) was significantly lower compared to normal RBCs (p <0.001). No significant difference was observed between SS-RBCs and p-thalassemia RBCs. Annexin V, a protein with high affinity and specificity for anionic phospholipids, inhibited the procoagulant activity of both SS-RBCs and (3-thalassemia RBCs, in a dose-dependent manner. More than 95% inhibition was achieved at nanomolar concentrations of annexin V. These results indicate that the procoagulant activity of both β-thalassemia RBCs and SS-RBCs may be fully ascribed to an abnormal exposure of phosphatidylserine at the outer surface of the red cells.

Nucleated red blood cells and hematological scoring system – Future trends in early onset neonatal sepsis

2019 ◽  
Vol 12 (1) ◽  
pp. 53-58
Author(s):  
Shivendra Vikram Singh ◽  
◽  
Megalamane Supreetha ◽  
Satyavathi R Alva ◽  
◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Neonatal Sepsis ◽  
Blood Cells ◽  
Early Onset ◽  
Scoring System ◽  
Future Trends ◽  
Nucleated Red Blood Cells

Nucleated Red Blood Cells as Markers of Perinatal Adaptation in Preterm Neonates Receiving Minimally Invasive Surfactant Therapy

2021 ◽  
Author(s):  
Itamar Nitzan ◽  
Calum T. Roberts ◽  
Risha Bhatia ◽  
Francis B. Mimouni ◽  
Arvind Sehgal
Keyword(s):  
Minimally Invasive ◽  
Right Ventricular ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Surfactant Therapy ◽  
Preterm Neonates ◽  
Oxygen Requirement ◽  
Nucleated Red Blood Cells ◽  
Intrauterine Hypoxia ◽  
Ventricular Ejection Time

Objective The study aimed to assess the association of nucleated red blood cells (NRBC), a surrogate of intrauterine hypoxia, and elevated pulmonic vascular resistance (E-PVR) and oxygen requirement after minimally invasive surfactant therapy (MIST). Study Design Retrospective study of a cohort of preterm neonates that received MIST in a single unit. Results NRBC were measured in 65 of 75 (87%) neonates administered MIST during the period. In total, 22 of 65 (34%) infants had pre-MIST echocardiography (ECHO).Neonates with elevated NRBC (predefined as >5 × 109/L, n = 16) required higher post-MIST fraction of inspired oxygen (FiO2) than neonates with normal NRBC (<1 × 109/L, n = 17; FiO2 = 0.31 ± 0.10 and 0.24 ± 0.04, respectively, p = 0.02).NRBC correlated positively with % of time in right to left ductal shunt (r = 0.51, p = 0.052) and inversely with right ventricular stroke volume (r = −0.55, p = 0.031) and time to peak velocity to right ventricular ejection time ratio (r = −0.62, p < 0.001). Conclusion Elevated NRBC are associated with elevated FiO2 after MIST and elevated E-PVR. Intrauterine hypoxia may impact postnatal circulatory adaptations and oxygen requirement. Key Points

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