Patient baseline characteristics were obtained including Charlson comorbidity index (CMI), anticoagulation at the time of bleeding, baseline hemoglobin level, hemostatic approaches (hemostatic ...powder/ gel, single/ dual therapy), and frequency of bleeding events. All-comers analysis was conducted to reach statistical power, although individual subgroup analysis was also conducted. Comparison of Bleeding Events Following Use of Topical Hemostatic Agents in Both Therapeutic Intent and Prophylactic Intent Groups Early Bleeding Events(n=15) *P-value Late Bleeding Events(n=8) *P-value Demographics Age, mean (SD) 56.1 (15.3) 0.26 56.3 (16.2) 0.42 Gender Male, n (%) 12 (80) 0.06 8 (100) 0.02 Female, n (%) 3 (20) 0.06 0(0) 0.02 CMI, mean (SD) 6.67( 2.87) 0.14 8.25 (2.05) 0.01 Anticoagulation at time of bleed (%) 6 (40%) 0.55 1 (12.5) 0.43 Baseline Hgb level, mean (SD) 10.62 (2.04) 0.17 11.3 (1.99) 0.97 Hemostasis Hemostatic Powder (%) 10 (66.67) 0.57 7 (87.5) 0.02 Hemostatic Gel (%) 5 (33.33) 0.57 1 (12.5) 0.02 Single Therapy 9 (60) 0.25 5 (62.5) 0.47 Dual Therapy 6 (40) 0.25 3 (37.5) 0.47 Repeat Endoscopy (%) 3 (20) 0.44 7 (87.5) 0.00 *P values rounded to two decimal units SD Standard deviation. (n) count. (%) percentage.
Mechanism of Human Apohemoglobin Unfolding Samuel, Premila P; Ou, William C; Phillips, George N ...
Biochemistry (Easton),
03/2017, Volume:
56, Issue:
10
Journal Article
Peer reviewed
Removal of heme from human hemoglobin (Hb) results in formation of an apoglobin heterodimer. Titration of this apodimer with guanidine hydrochloride (GdnHCl) leads to biphasic unfolding curves ...indicating two distinct steps. Initially, the heme pocket unfolds and generates a dimeric intermediate in which ∼50% of the original helicity is lost, but the α1β1 interface is still intact. At higher GdnHCl concentrations, this intermediate dissociates into unfolded monomers. This structural interpretation was verified by comparing GdnHCl titrations for adult human hemoglobin A (HbA), recombinant fetal human hemoglobin (HbF), recombinant Hb cross-linked with a single glycine linker between the α chains, and recombinant Hbs with apolar heme pocket mutations that markedly stabilize native conformations in both subunits. The first phase of apoHb unfolding is independent of protein concentration, little affected by genetic cross-linking, but significantly shifted toward higher GdnHCl concentrations by the stabilizing distal pocket mutations. The second phase depends on protein concentration and is shifted to higher GdnHCl concentrations by genetic cross-linking. This model for apoHb unfolding allowed us to quantitate subtle differences in stability between apoHbA and apoHbF, which suggest that the β and γ heme pockets have similar stabilities, whereas the α1γ1 interface is more resistant to dissociation than the α1β1 interface.
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Sickle trait, the heterozygous state of normal hemoglobin A (HbA) and sickle hemoglobin S (HbS), confers protection against malaria in Africa. AS children infected with Plasmodium falciparum are less ...likely than AA children to suffer the symptoms or severe manifestations of malaria, and they often carry lower parasite densities than AA children. The mechanisms by which sickle trait might confer such malaria protection remain unclear. We have compared the cytoadherence properties of parasitized AS and AA erythrocytes, because it is by these properties that parasitized erythrocytes can sequester in postcapillary microvessels of critical tissues such as the brain and cause the life-threatening complications of malaria. Our results show that the binding of parasitized AS erythrocytes to microvascular endothelial cells and blood monocytes is significantly reduced relative to the binding of parasitized AA erythrocytes. Reduced binding correlates with the altered display of P. falciparum erythrocyte membrane protein-1 (PfEMP-1), the parasite's major cytoadherence ligand and virulence factor on the erythrocyte surface. These findings identify a mechanism of protection for HbS that has features in common with that of hemoglobin C (HbC). Coinherited hemoglobin polymorphisms and naturally acquired antibodies to PfEMP-1 may influence the degree of malaria protection in AS children by further weakening cytoadherence interactions.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The Sebia Capillarys (capillary zone electrophoresis CE) and the Primus Resolution high-pressure liquid chromatography (HPLC) were used to prospectively evaluate 297 samples for hemoglobinopathies. ...Hemoglobin (Hb) A levels were similar on both techniques (mean, 96.2% and SD, 5.7% by CE; mean, 96.8% and SD, 5.5% by HPLC), but HbA2 levels were higher by CE (mean, 2.8%; SD, 0.8%) than by HPLC (mean, 2.3%; SD, 0.8%). HbS had higher values by CE (mean, 40.6%; SD, 18.9%) than by HPLC (mean, 38.4%; SD, 18.9%). In cases with Hg S, HbA2 levels were greater by HPLC (mean, 4.0%; SD, 1.0%) than by CE (mean, 3.1%; SD, 0.8%). HbA2 was occasionally not separated sufficiently from HbC for measurement by CE, but did separate from HbE by CE. Both methods identified HbS, HbC, HbE, HbS, and HbC together, HbA2&prime, HbD-Los Angeles, HbF variant, HbG-Philadelphia, HbS-G Philadelphia, and Hb Lepore.
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