Point-of-care haemoglobin measurement in pooled capillary blood by a portable autoanalyser: comparison with venous blood haemoglobin measured by reference methods in cross-sectional and longitudinal studies

Population-based surveys commonly use point-of-care (POC) methods with capillary blood samples for estimating haemoglobin (Hb) concentrations; these estimates need to be validated by comparison with reference methods using venous blood. In a cross-sectional study in 748 participants (17-86y, 708 women, Hb: 5.1 to 18.2 g/dL) from Hyderabad, India, we validated Hb measured from a pooled capillary blood sample by a POC autoanalyser (Horiba ABX Micros 60OT, Hb-C-AA) by comparison with venous blood Hb measured by two reference methods: POC autoanalyser (Hb-V-AA) and cyanmethemoglobin method (Hb-V-CM). These comparisons also allowed estimation of blood sample related and equipment related differences in the Hb estimates. We also conducted a longitudinal study in 426 participants (17-21y) to measure differences in the Hb response to iron folate treatment by the capillary blood POC method compared to the reference methods. In the cross-sectional study, Bland Altman analyses showed trivial differences between source of blood (Hb-C-AA and Hb-V-AA; mean difference, limits of agreement: 0.1, -0.8 to 1.0 g/dL) and between analytical methods (Hb-V-AA and Hb-V-CM; mean difference, limits of agreement :< 0.1, −1.8 to 1.8 g/dL). Cross-sectional anaemia prevalence estimated using Hb-C-AA did not differ significantly from Hb-V-CM or Hb-V-AA. In the longitudinal study, the Hb increment in response to IFA intervention was not different when using Hb-C-AA (1.6 ± 1.7 g/dL) compared to Hb-V-AA (1.7± 1.7g/dL) and Hb-V-CM (1.7± 1.7 g/dL). The pooled capillary blood–autoanalyzer method (Hb-C-AA) offers a practical and accurate way forward for POC screening of anaemia.

Multispectral Imaging for MicroChip Electrophoresis Enables Point-of-Care Newborn Hemoglobin Variant Screening

Hemoglobin (Hb) disorders affect nearly 7% of the world's population. Globally, around 400,000 babies are born annually with sickle cell disease (SCD), primarily in sub-Saharan Africa where morbidity and mortality rates are high. Although treatments are available for Hb disorders, screening, early diagnosis, and monitoring are not widely accessible due to technical challenges and cost, especially in low-and-middle-income countries. We hypothesized that multispectral imaging will allow sensitive hemoglobin variant identification in existing affordable paper-based Hb electrophoresis, which is a clinical standard test for Hb variant screening. To test this hypothesis, we developed the first integrated point-of-care multispectral Hb variant test: Gazelle-Multispectral. Here, we evaluated the accuracy of Gazelle-Multispectral for Hb variant newborn screening in 321 completed tests in subjects younger than 6 months with known hemoglobin variants including hemoglobin A (Hb A), hemoglobin F (Hb F), hemoglobin S (Hb S) and hemoglobin C (Hb C). Gazelle-multispectral detected levels of Hb A, Hb F, Hb S, and Hb C, demonstrated high correlations with the results reported by laboratory gold standard high performance liquid chromatography (HPLC) at Pearson Correlation Coefficient = 0.97, 0.97, 0.89, and 0.94. Gazelle-multispectral demonstrated 100% sensitivity and 100% specificity in both disease vs normal and disease vs trait, 98.1% sensitivity and 97.0% specificity in trait vs normal in comparison to HPLC in newborns. The ability to obtain rapid and accurate results on newborn samples suggest that Gazelle-Multispectral is suitable for large-scale newborn screening and potentially for accurate diagnosis of SCD in low resource settings.

Reaction of carbon oxides with an ethylene-bridged PH/B Lewis pair

The ethylene-bridged frustrated Lewis pair, formed by hydroboration of the Mes*P(H)-vinyl phosphane with Piers' borane [HB(C6F5)2], reacted with the CO/ HB(C6F5)2 pair and also with carbon dioxide.

Hemoglobin C/Korle-Bu Identified In A Patient With A Previous Diagnosis Of Hemoglobin S/C Disease

Casestudy Hemoglobin Korle-Bu (Hb-KB) is an uncommon Hb variant that can be mistaken for Hb-S on electrophoretic screening. While Hb-KB alone has no clinical manifestations, there are only limited case studies describing KB in combination with other Hb variants. Here we report a rare case of Hb-C/KB misdiagnosed and managed as Hb-S/C disease for over 20 years. Results A 21-year-old African American woman with presumed Hb-S/C disease presented with generalized abdominal pain, nausea, and vomiting. In 1999, Hb electrophoresis showed 59% of abnormal hemoglobin presumed to be HbS and 41% HbC+A2; agar/acetate gel analysis was not employed and the hemoglobinopathy remained incompletely characterized. She had a history of back, chest, abdomen, and extremity pains requiring multiple hospital admissions, with treatments including dilaudid, oxycontin, oxycodone, and hydroxyurea. Her vital signs were normal and her examination was only significant for abdominal tenderness. Imaging studies did not show any evidence vascular occlusion, avascular necrosis, or end-organ dysfunction. RBC indices were remarkable for mild borderline anemia, microcytosis, decreased MCH/elevated MCHC, and borderline elevated RDW. Peripheral smear showed microcytic red cells with anisocytosis, scattered target cells, and a notable absence of sickled cells and Hb-C-crystals. The diagnosis of Hb-S/C disease was then revisited. HPLC showed abnormal hemoglobins in the Hb-D window at 55.1% and in the Hb-C window at 40.6%, with 3.5% Hb-A2 and no normal Hb-A. Gel electrophoresis with cellulose acetate followed by citrate agar suggested Hb-C in combination with either D, G, or Korle-Bu. Definitive diagnosis was obtained by beta globin gene sequencing that demonstrated one copy Hb-C (19G&gt;A, Glu7Lys) and one copy Hb- Korle-Bu (220G&gt;A, Asp74Asn). Given the absence of Hb-S/C disease, her gastrointestinal distress and pain episodes were re-evaluated. Conclusion Hb-S and Hb-Korle-Bu migrate similarly in cellulose acetate electrophoresis but can be distinguished on citrate agar. Challenging beta chain variants can now be readily differentiated by complete gene sequencing. This case study emphasizes the importance of distinguishing Hb-KB from clinically-significant Hb-S.

Clinical method evaluation of hemoglobin S and C identification by top-down selected reaction monitoring and electron transfer dissociation

Background Biological diagnosis of hemoglobin disorders is a complex process relying on the combination of several analytical techniques to identify Hb variants in a particular sample. Currently, hematology laboratories usually use high-performance liquid chromatography (HPLC), capillary electrophoresis and gel-based methods to characterize Hb variants. Co-elution and co-migration may represent major issues for precise identification of Hb variants, even for the most common ones such as Hb S and C. Methods We adapted a top-down selected reaction monitoring (SRM) electron transfer dissociation (ETD) mass spectrometry (MS) method to fit with a clinical laboratory environment. An automated analytical process with semi-automated data analysis compatible with a clinical practice was developed. A comparative study between a reference HPLC method and the MS assay was performed on 152 patient samples. Results The developed workflow allowed to identify with high specificity and selectivity the most common Hb variants (Hb S and Hb C). Concordance of the MS-based approach with HPLC was 71/71 (100%) for Hb S and 11/11 (100%) for Hb C. Conclusions This top-down SRM ETD method can be used in a clinical environment to detect Hb S and Hb C.

Tandem Deoxygenative Hydrosilation of Carbon Dioxide with a Cationic Scandium Hydridoborate and B(C6F5)3

A scandium hydridoborate complex supported by the dianionic pentadentate ligand B₂Pz₄Py is prepared via hydride abstraction from the previously reported scandium hydride complex with <i>tris</i>-pentafluorophenyl borane. Exposure of [(B₂Pz₄Py)Sc][HB(C₆F₅)₃] to CO₂ immediately forms [(B₂Pz₄Py)Sc][HCOOB(C₆F₅)₃] at room temperature. The formatoborate complex can also be synthesized directly from the starting material (B₂Pz₄Py)ScCl with Et₃SiH and B(C₆F₅)₃ while in the presence of an atmosphere of CO₂ in 81% yield. This compound was evaluated as the transition metal component of a tandem deoxgenative CO₂ hydrosilation catalyst. At 5% loadings, complete consumption of Et₃SiH was observed along with CO₂ reduction products, but conversion to an inactive scandium complex identified as (B₂Pz₄Py)ScOSiEt₃ was observed

Tandem Deoxygenative Hydrosilation of Carbon Dioxide with a Cationic Scandium Hydridoborate and B(C6F5)3

A scandium hydridoborate complex supported by the dianionic pentadentate ligand B₂Pz₄Py is prepared via hydride abstraction from the previously reported scandium hydride complex with <i>tris</i>-pentafluorophenyl borane. Exposure of [(B₂Pz₄Py)Sc][HB(C₆F₅)₃] to CO₂ immediately forms [(B₂Pz₄Py)Sc][HCOOB(C₆F₅)₃] at room temperature. The formatoborate complex can also be synthesized directly from the starting material (B₂Pz₄Py)ScCl with Et₃SiH and B(C₆F₅)₃ while in the presence of an atmosphere of CO₂ in 81% yield. This compound was evaluated as the transition metal component of a tandem deoxgenative CO₂ hydrosilation catalyst. At 5% loadings, complete consumption of Et₃SiH was observed along with CO₂ reduction products, but conversion to an inactive scandium complex identified as (B₂Pz₄Py)ScOSiEt₃ was observed

Controlled living anionic polymerization of cyanoacrylates by frustrated Lewis pair based initiators

Controlled living anionic polymerization of cyanoacrylates promoted by a hydrogenated frustrated Lewis pair ([TMPH+][HB(C6F5)3−]). Preparation of designed block copolymers.