scholarly journals GBT440 inhibits sickling of sickle cell trait blood under in vitro conditions mimicking strenuous exercise

2016 ◽  
Vol 8 (3) ◽  
Author(s):  
Kobina Dufu ◽  
Josh Lehrer-Graiwer ◽  
Eleanor Ramos ◽  
Donna Oksenberg
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Oxygen Demand ◽  
Physical Activities ◽  
Strenuous Exercise ◽  
Cell Disease ◽  
Tissue Oxygen ◽  
Benign Condition ◽  
Life Threatening

In sickle cell trait (SCT), hemoglobin A (HbA) and S (HbS) are co-expressed in each red blood cell (RBC). While homozygous expression of HbS (HbSS) leads to polymerization and sickling of RBCs resulting in sickle cell disease (SCD) characterized by hemolytic anemia, painful vaso-occlusive episodes and shortened life-span, SCT is considered a benign condition usually with minor or no complications related to sickling. However, physical activities that cause increased tissue oxygen demand, dehydration and/or metabolic acidosis leads to increased HbS polymerization and life-threatening complications including death. We report that GBT440, an agent being developed for the treatment of SCD, increases the affinity of oxygen for Hb and inhibits in vitro polymerization of a mixture of HbS and HbA that simulates SCT blood. Moreover, GBT440 prevents sickling of SCT blood under in vitro conditions mimicking strenuous exercise with hypoxia, dehydration and acidosis. Together, our results indicate that GBT440 may have the potential to protect SCT individuals from sickling-related complications during conditions that favor HbS polymerization.

Sickle Cell Trait: A Benign State?

2016 ◽  
Vol 136 (3) ◽  
pp. 147-151 ◽  
Author(s):  
Taiwo R. Kotila
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Dna Analysis ◽  
Sickle Cell Trait ◽  
Beta Thalassemia ◽  
Compound Heterozygous ◽  
Cell Disease ◽  
Benign Condition ◽  
Red Cell Indices ◽  
Heterozygous Form

Background: Sickle cell trait (SCT) is the heterozygous form of sickle cell disease and expectedly should be a benign state with no complications ascribed to it. There are numerous reports challenging its being a benign condition, though this is controversial. Methods and Results: A review of the results of the accompanying investigations done on some of the patients show that beta thalassemia may be responsible for many of the ascribed symptoms and complications. These patients may therefore have sickle cell beta thalassemia, a compound heterozygous form of sickle cell disease. Conclusion: It is important to screen for beta thalassemia using red cell indices and quantitation of the different hemoglobin fractions before attributing any symptoms to SCT. DNA analysis, though useful in ascertaining the presence of the sickle cell gene, is not sufficient. There is the need to exclude the presence of mutations for beta thalassemia, which often is geographical region-specific.

STUDIES IN SICKLE CELL DISEASE

PEDIATRICS ◽  
1958 ◽  
Vol 22 (2) ◽  
pp. 309-318
Author(s):  
George S. Shields ◽  
Herbert C. Lichtman ◽  
Jacqueline Messite ◽  
R. Janet Watson
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Reaction Rate ◽  
Sickle Cell Trait ◽  
Newborn Infants ◽  
Cell Disease ◽  
Specific Reaction Rate ◽  
Specific Reaction

In newborn infants with sickle cell trait, the percentage of erythrocytes capable of being sickled in vitro gradually rose during the first 4 months of life. A concomitant fall in the percentage of Hgb F was demonstrated. The percentage of cells which could be induced to assume the sickled shape was found not to be correlated with the percentage of Hgb S, but instead was correlated with the reciprocal of the concentration of Hgb F. The specific reaction rate of alkali resistant hemoglobin in the infants less than 3 months of age was found to differ from that found in adults and in infants more than 3 months of age.

Selected Testing of Newborns for Sickle Cell Disease

PEDIATRICS ◽  
1989 ◽  
Vol 83 (5) ◽  
pp. 879-880
Author(s):  
Kwaku Ohene-Frempong
Keyword(s):  
Sickle Cell Disease ◽  
Early Detection ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Globin Gene ◽  
Carrier State ◽  
Cell Disease ◽  
Childbearing Age ◽  
Benign Condition ◽  
Cell Testing

There are two main reasons for sickle cell testing: the early detection of those with sickle cell disease and the detection of the carrier state, sickle cell trait. The mortality of the severe forms of sickle cell disease is particularly high during the first 5 years of life. Recent data have shown that early detection of sickle cell disease and institution of expert medical care and follow-up may reduce early mortality and morbidity. The ability to detect most forms of sickle cell disease in the newborn period has made the goal of preventive care theoretically possible. The purpose of the detection of the carrier state, sickle cell trait, is less clear. Sickle cell trait has almost no clinical importance to the individual. Although a few case reports have suggested that sickle cell trait may not be a benign condition, most experts agree that sickle cell trait does not significantly alter health or disease. The main purpose of carrier testing is for genetic counseling. Mass screening of African Americans for sickle cell trait was advocated in the 1960s. However, no data have shown that results of such screening have had any impact on reproductive planning. Ideally, sickle cell testing should provide the following results. All newborns with various forms of sickle cell disease should be diagnosed by 3 months of age, before the onset of clinical problems. All heterozygotes for the βs-globin gene, or the genes for other hemoglobinopathies that may combine with βs gene to produce clinically significant forms of sickle cell disease, should be aware of the relevant genetic information at childbearing age.

scholarly journals Splenic Syndrome in a Young Man at High Altitude with Undetected Sickle Cell Trait

2017 ◽  
Vol 5 (2) ◽  
pp. 153-155 ◽  
Author(s):  
CHKA Fernando ◽  
S Mendis ◽  
AP Upasena ◽  
YJ Costa ◽  
HS Williams ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
High Altitude ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Carrier State ◽  
Splenic Infarction ◽  
Cell Disease ◽  
Rare Presentation ◽  
Abdominal Symptoms ◽  
Life Threatening

Introduction: Splenic syndrome is a rare presentation of sickle cell disease. It is important to rule out this possibility when an ethnically vulnerable patient presents with an acute abdominal symptoms in a background of precipitating events. Case Report: A 26-year-old man who developed a severe abdominal pain at high altitude, found to have a tender splenomegaly. However, further inquiry revealed he is from an area where sickle cell disease is prevalent. Screening for sickle cell disease was positive. Radiological investigations confirmed a massive splenic infarction keeping with a diagnosis of splenic syndrome. Patient was managed conservatively. Conclusion: Sickle cell trait is considered a benign carrier state. However, rarely they can present with life-threatening conditions. Therefore, a high degree of clinical suspicion is required for early diagnosis of these specific entities to avoid increased morbidity and mortality of these patients.

scholarly journals EFFECTS OF THE INTRAMUSCULAR ADMINISTRATION OF BAL (2,3 DIMERCAPTOPROPANOL) IN A SUBJECT WITH THE SICKLE CELL TRAIT: CASE REPORT

Blood ◽  
1949 ◽  
Vol 4 (11) ◽  
pp. 1240-1244
Author(s):  
WILLIAM J. KUHNS
Keyword(s):  
Case Report ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sedimentation Rate ◽  
Sickle Cell Trait ◽  
Intramuscular Administration ◽  
Cell Disease ◽  
Erythrocyte Sedimentation

Abstract The effects of the intramuscular administration of BAL in a Negro harboring the sickle cell trait have been presented. It was observed that the rate of sickling was accelerated and the erythrocyte sedimentation rate was retarded in the presence of BAL both in vitro and apparently in vivo. However, the administration of BAL produced none of the pathologic sequelae characteristic of sickle cell disease.

Microsurgery in the Sickle Cell Trait Population: Is It Actually Safe?

2020 ◽  
pp. 1-2
Author(s):  
Michael Alperovich ◽  
Eric Park ◽  
Michael Alperovich ◽  
Omar Allam ◽  
Paul Abraham
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Free Flap ◽  
Near Infrared ◽  
Sickle Cell Trait ◽  
Cell Disease ◽  
Flap Transfer ◽  
Free Flap Transfer ◽  
Patient Reported ◽  
Deep Inferior Epigastric Perforator

Although sickle cell disease has long been viewed as a contraindication to free flap transfer, little data exist evaluating complications of microsurgical procedures in the sickle cell trait patient. Reported is the case of a 55-year-old woman with sickle cell trait who underwent a deep inferior epigastric perforator (DIEP) microvascular free flap following mastectomy. The flap developed signs of venous congestion on postoperative day two but was found to have patent arterial and venous anastomoses upon exploration in the operating room. On near-infrared indocyanine green angiography, poor vascular flow was noted despite patent anastomoses and strong cutaneous arterial Doppler signals. Intrinsic microvascular compromise or sickling remains a risk in the sickle cell trait population as it does for the sickle cell disease population. Just like in sickle cell disease patients, special care should be taken to optimize anticoagulation and minimize ischemia-induced sickling for patients with sickle cell trait undergoing microsurgery.

Hypoxia-induced acute lung injury in murine models of sickle cell disease

2004 ◽  
Vol 286 (4) ◽  
pp. L705-L714 ◽  
Author(s):  
Kirkwood A. Pritchard ◽  
Jingsong Ou ◽  
Zhijun Ou ◽  
Yang Shi ◽  
James P. Franciosi ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Lung Injury ◽  
Sickle Cell ◽  
Globin Gene ◽  
Heat Shock Protein 90 ◽  
Cell Disease ◽  
Vascular Congestion ◽  
Nitrite Nitrate ◽  
Endothelial Nitric Oxide

Vaso-occlusive events are the major source of morbidity and mortality in sickle cell disease (SCD); however, the pathogenic mechanisms driving these events remain unclear. Using hypoxia to induce pulmonary injury, we investigated mechanisms by which sickle hemoglobin increases susceptibility to lung injury in a murine model of SCD, where mice either exclusively express the human α/sickle β-globin (hαβS) transgene (SCD mice) or are heterozygous for the normal murine β-globin gene and express the hαβStransgene (mβ+/-, hαβS+/-; heterozygote SCD mice). Under normoxia, lungs from the SCD mice contained higher levels of xanthine oxidase (XO), nitrotyrosine, and cGMP than controls (C57BL/6 mice). Hypoxia increased XO and nitrotyrosine and decreased cGMP content in the lungs of all mice. After hypoxia, vascular congestion was increased in lungs with a greater content of XO and nitrotyrosine. Under normoxia, the association of heat shock protein 90 (HSP90) with endothelial nitric oxide synthase (eNOS) in lungs of SCD and heterozygote SCD mice was decreased compared with the levels of association in lungs of controls. Hypoxia further decreased association of HSP90 with eNOS in lungs of SCD and heterozygote SCD mice, but not in the control lungs. Pretreatment of rat pulmonary microvascular endothelial cells in vitro with xanthine/XO decreased A-23187-stimulated nitrite + nitrate production and HSP90 interactions with eNOS. These data support the hypotheses that hypoxia increases XO release from ischemic tissues and that the local increase in XO-induced oxidative stress can then inhibit HSP90 interactions with eNOS, decreasing ·NO generation and predisposing the lung to vaso-occlusion.

In Reply: Sports and Sickle Cell Trait

PEDIATRICS ◽  
1989 ◽  
Vol 83 (4) ◽  
pp. 650-651
Author(s):  
MICHAEL A. NELSON
Keyword(s):  
Sickle Cell Disease ◽  
Sudden Death ◽  
Sickle Cell ◽  
Sports Medicine ◽  
Sickle Cell Trait ◽  
Cell Disease ◽  
Variable Expression ◽  
Military Recruits ◽  
New Information ◽  
Athletic Activities

Sickle cell trait was included because, at that time, a great deal of speculation and new information was forthcoming regarding sudden death in military recruits who had sickle cell trait. The members of the Sports Medicine Committee believed that it was important to indicate that, in spite of these new concerns, there were no data to indicate that anyone with sickle cell trait should not be included in any athletic activities. Sickle cell disease was excluded because it is a disease with variable expression and one which is characterized by numerous exacerbations and periods of quiescence.

PATHOGENESIS OF HYPOSTHENURIA IN PERSONS WITH SICKLE CELL ANEMIA OR THE SICKLE CELL TRAIT

PEDIATRICS ◽  
1960 ◽  
Vol 26 (2) ◽  
pp. 249-254
Author(s):  
L. Schlitt ◽  
H. G. Keitel
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Renal Damage ◽  
Sickle Cell Trait ◽  
Urinary Concentration ◽  
Cell Disease ◽  
Renal Vessels

Hyposthenuria was investigated in subjects with sickle cell trait and in patients with sickle cell anemia. The following were observed: 1) in subjects with sickle cell trait both normal and reduced maxima of urinary concentration are found, whereas all untreated patients with sickle cell anemia over 6 months of age have hyposthenuria; 2) hyposthenuria becomes increasingly more severe with advancing age in both sickle cell anemia and sickle cell trait; 3) in a 6-month-old patient with sickle cell anemia and hyposthenuria, the maxima of urinary concentration returned to normal after two transfusions of normal erythrocytes. Reasons are presented for favoring the hypothesis that hyposthenuria in sickle cell disease is due to renal damage, possibly from intravascular sickling of erythrocytes in renal vessels or from the presence of "free" circulating S-hemoglobin.

Screening for Sickle Cell Disease: A Hospital Based Study in Eastern Odisha, India

2012 ◽  
Vol 2 (2) ◽  
pp. 57-60
Author(s):  
Jayanti Mishra ◽  
Sanghamitra Pati ◽  
Mohammad Akhtar Hussain ◽  
Niraj Srivastava ◽  
Sindhubala Mishra
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Cell Disease ◽  
Medicine Department ◽  
Fetal Haemoglobin ◽  
Medical College ◽  
Rbc Indices ◽  
And Gender ◽  
Cell Gene

The highest frequency of sickle cell gene in India is reported in Odisha. The present study was taken up to assess the presence of sickle cell disease among febrile patients of a medical college of eastern Odisha. Patients referred from both pediatric and medicine department to the Hematology section of the department of Pathology, SCB Medical College, Cuttack were subjected to measurement of RBC indices, Sickling test, Haemoglobin Electrophoresis and Fetal Haemoglobin Estimation. Out of total 1000 referred patients 76(7.6%) were found to be positive for sickling. Two‐third of sicklingpositive patients had sickle cell trait with electrophoretic AS band. There was a significant association between age and positive sickling (χ2 = 24.357; df = 4, P = <0.0001). No significant association was observed between sickling and gender. Sickle cell positive cases are not uncommon in eastern Odisha. Our study demonstrated sickle cell trait to be more common among screened patients than other forms of sickle cell diseases.

Sign in / Sign up

Export Citation Format

Share Document