Alpha thalassemia changes erythrocyte heterogeneity in sickle cell disease.

Noguchi, Constance Tom; Dover, George J.; Rodgers, Griffin P.; Serjeant, G. R.; Antonarakis, SE; Anagnou, Nicholas P.; Higgs, Douglas R.; Weatherall, D. J.; Schechter, Alan N.

doi:10.1172/jci111870

Cited by 54 publications

(26 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, because ofpump stoichiometry (48) and the fact that regulation of pump rate is primarily via intracellular sodium (not potassium) concentration (49) (18) and possibly the content of fetal hemoglobin (52). There is also evidence that for a given patient, heterogeneity exists among various cell populations as to the rate of cellular dehydration (53,54). Maximal sodium pump rates may also vary among certain density fractions of sickle cells (19).…”

Section: Discussionmentioning

confidence: 99%

Cation depletion by the sodium pump in red cells with pathologic cation leaks. Sickle cells and xerocytes.

Joiner¹,

Platt²,

Th³

1986

J. Clin. Invest.

View full text Add to dashboard Cite

The mechanism by which sickle cells and xerocytic red cells become depleted of cations in vivo has not been identified previously. Both types of cells exhibit elevated permeabilities to sodium and potassium, in the case of sickle cells, when deoxygenated. The ouabain-insensitive fluxes of sodium and potassium were equivalent, however, in both cell types under these conditions. When incubated 18 hours in vitro, sickle cells lost cations but only when deoxygenated. This cation depletion was blocked by ouabain, removal of external potassium, or pretreatment with 4,4'-diisothiocyanostilbene-2,2'-disulfonate, which blocks the increase in cation permeability induced by deoxygenation. The loss of cation exhibited by oxygenated xerocytes similarly incubated was also blocked by ouabain. These data support the hypothesis that the elevated "passive" cation fluxes of xerocytes and deoxygenated sickle cells are not directly responsible for cation depletion of these cells; rather, these pathologic leaks interact with the sodium pump to produce a net loss of cellular cation.

show abstract

Section: Discussionmentioning

confidence: 99%

Cation depletion by the sodium pump in red cells with pathologic cation leaks. Sickle cells and xerocytes.

Joiner¹,

Platt²,

Th³

1986

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…The sedimentation rate of red blood cells is related to important red-cell indices 34 and spherocytosis 35 are known to increase the density of some or all of the population of RBCs, while β-thalassemia 33 , α-thalassemia, 36 and malaria 37 decrease RBC density.…”

Section: Experimental Designmentioning

confidence: 99%

Diagnosis of iron deficiency anemia using density-based fractionation of red blood cells

et al. 2016

View full text Add to dashboard Cite

Iron deficiency anemia (IDA) is a nutritional disorder that impacts over one billion people worldwide, it causes permanent cognitive impairment in children, fatigue in adults, and suboptimal outcomes in pregnancy. IDA can be diagnosed by detection of red blood cells (RBCs) that are characteristically small (microcytic) and deficient in hemoglobin (hypochromic), typically by examining the results of a complete blood count performed by a hematology analyzer. These instruments are expensive, not portable, and require trained personnel; they are therefore, unavailable in many low-resource settings. This paper describes a low-cost and rapid method to diagnose IDA using aqueous multiphase systems (AMPS)-thermodynamically stable mixtures of biocompatible polymers and salt that spontaneously form discrete layers having sharp steps in density. AMPS are preloaded into a microhematocrit tube and used with a drop of blood from a fingerstick. After only two minutes in a low-cost centrifuge, the tests (n = 152) were read by eye with a sensitivity of 84% (72-93%) and a specificity of 78% (68-86%), corresponding to an area under the curve (AUC) of 0.89. The AMPS test outperforms diagnosis by hemoglobin alone (AUC = 0.73) and is comparable to methods used in clinics like reticulocyte hemoglobin concentration (AUC = 0.91). Standard machine learning tools were used to analyze images of the resulting tests captured by a standard desktop scanner to 1) slightly improve diagnosis of IDA-sensitivity of 90% (83-96%) and a specificity of 77% (64-87%), and 2) predict several important red blood cell parameters, such as mean corpuscular hemoglobin concentration. These results suggest that the use of AMPS combined with machine learning provides an approach to developing point-of-care hematology.

show abstract

“…Genomic polymorphisms in sickle cell disease [32,33]. The averages of some studies report that, comparing genotypes aa/aa, a-/aa and a-/a-, mean hemoglobin levels are 8.1, 8.6 and 9.2 g/dl, respectively; mean corpuscular volume (MCV) is 92, 83 and 72 fl, respectively, and reticulocyte percentage is 11.4, 9 and 6.7%, respectively [33][34][35][36].…”

Section: Reviewmentioning

confidence: 99%

Genomic polymorphisms in sickle cell disease: implications for clinical diversity and treatment

Fertrin

Costa

2010

Expert Review of Hematology

View full text Add to dashboard Cite

Alpha thalassemia changes erythrocyte heterogeneity in sickle cell disease.

Cited by 54 publications

References 37 publications

Cation depletion by the sodium pump in red cells with pathologic cation leaks. Sickle cells and xerocytes.

Cation depletion by the sodium pump in red cells with pathologic cation leaks. Sickle cells and xerocytes.

Diagnosis of iron deficiency anemia using density-based fractionation of red blood cells

Genomic polymorphisms in sickle cell disease: implications for clinical diversity and treatment

Contact Info

Product

Resources

About