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Red Cells Containing Unstable Hemoglobin Variants
Published in Ronald L. Nagel, Genetically Abnormal Red Cells, 2019
Heinz bodies, the hallmark of the congenital Heinz body hemolytic syndrome that we are discussing, are the product of hemoglobin denaturation. Jacob and Winterhalter27,28 initially suggested that the actual composition of the Heinz bodies was heme-depleted globin chains. The pioneering work of Rachmilewitz in collaboration with Peisach and Blumberg29-32 allowed the identification of the precipitated material as hemichromes. These are derivatives of the low-spin forms of ferric hemoglobin that have the sixth coordination position occupied by a ligand provided by the globin moiety. These ligands can be a hydroxyl group (-OH), protonated histidyl (reversible hemichromes), or unprotonated histidyl (irreversible hemichromes).33 Another type of irreversible hemichromes can be generated by having the fifth coordination position occupied by cysteine and the sixth by an aliphatic amine (Figure 4). All of these compounds can be resolved by EPR but not by absorption spectroscopy as their visible spectra are very similar (Figure 5). In other words, hemichromes are generated when the heme is dissociated from the heme pocket and rebinds elsewhere in the globin after the alpha or the beta chains have suffer some denaturation. Figure 6 explains the difference between high- and low-spin forms of methemoglobin. Irreversible hemichromes seem to be an indispensable stage in the formation of Heinz bodies.
Physiological Implications of Ferrihemoglobinemia
Published in Manfred Kiese, Methemoglobinemia: A Comprehensive Treatise, 2019
Most likely, formation of ferrihemoglobin facilitates the formation of Heinz bodies since ferrihemoglobin or free globin originating from ferrihemoglobin99–101,670,715–717 is more susceptible to the denaturing action of Heinz-body-producing agents than oxyhemoglobin.
Principles of Clinical Pathology
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Niraj K. Tripathi, Jacqueline M. Tarrant
Heinz body formation within red cells is caused by test articles with oxidative properties. Heinz bodies are irreversibly denatured clumps of hemoglobin that attach to the inner surface of the red cell membrane. Macrophages phagocytize affected red cells completely or produce morphologically distinct red cells (e.g., ghost and blister cells) by selective removal of Heinz bodies. If large enough, Heinz bodies can be seen in blood smears using standard Romanowsky-type stains, but even small Heinz bodies stain prominently with supravital stains (e.g., methylene blue, crystal violet, or brilliant cresyl blue). Heinz body size and number are dependent on the causative agent, dose, and time after exposure. A high dose of a potent oxidative agent can cause acute anemia characterized by many red cells with a single large Heinz body (or less frequently multiple small Heinz bodies) and the presence of ghost cells, blister cells, and other morphologic abnormalities. Chronic exposure to a less potent oxidative agent may be associated with notably increased absolute reticulocyte count but only minimally decreased red cell mass because the regenerative process is able to match the increased red cell turnover.
Consideration of Splenectomy in Unstable Hemoglobinopathy: A Case Report of Hb Hammersmith (HBB: c.128T>C)
Published in Hemoglobin, 2022
Michaela M. Pesce, Mandy M. Atkinson, Vaishnavi Sridhar, Erwood G. Edwards
The majority of patients with Hb Hammersmith have been reported to present with severe Heinz body hemolytic anemia, hyperbilirubinemia, splenomegaly and transfusion dependence [6]. In patients with more common forms of hemolytic anemia, such as hereditary spherocytosis and thalassemias, splenectomy is considered an acceptable treatment option when noninvasive therapy has failed. Several studies report the utility of splenectomy in these conditions, with symptomatic improvement as well as a significant increase in Hb levels after either subtotal or total splenectomy [7–9]. However, none of these studies explored the clinical benefit of splenectomy in cases of unstable Hb variants. A review of the literature revealed several case studies that include patients with Hb Hammersmith who have reportedly undergone splenectomy, but only four cases discuss whether there was clinical improvement of patients thereafter.
Identification of a rare compound heterozygous hemoglobin variant β0-thal [β17(A14) Lys>Stop, HBB: c.52A>T] and Hb J-Lome [β59(E3) Lys>Asn, HBB: c.180G>C]
Published in Hematology, 2022
Zixin Chen, Limei Shao, Mingfeng Jiang, Run Ma, Hongfen Ping, Zhuo Wang, Xuejiao Ba, Bingjie Ma, Tao Zhou
In the presented study, the interference produced by both mutants resulted in false low values. As such, patients with abnormally low HbA1c levels can suspect Hb variations, or HbA1c results may differ dramatically from other metabolic control measurements. The IE-HPLC is the most common detection method for HbA1c, and it is also susceptible to interference from Hb variants [9]. From another perspective, IE-HPLC has more advantages than other methods because it is easier to detect abnormal Hb. Therefore, it is particularly important for the laboratory to routinely inspect the chromatogram before issuing the report. In this case, repeat analysis should ideally be performed using methods based on different analytical principles because the effect of a specific Hb variant on HbA1c results is often method dependent. The interference generated from Hb variants depends not only on the analysis method but also on the peculiarity of the variant-such as hemoglobin lifetime. In the follow-up study, the negative results of the Heinz body test both indicated that Hb J-Lome is a stable variant. Negative results of the Heinz body test and hemolysis test suggest that the interference caused by this variant is not related to changes in red blood cell lifespan. For any situation that can cause an abnormal lifespan of red blood cells, the American Diabetes Association (ADA) only recommends the use of glucose criteria for the diagnosis of diabetes [10]. When the interpretation of HbA1c is confused by factors that affect the lifespan of red blood cells, alternative non-Hb-based tests, such as glycosylated serum albumin (GSA), should be performed to assess long-term blood glucose levels.
A Case of Hb Aalborg (HBB: c.223G>C) with Chronic Obstructive Pulmonary Disease: A First Familial Presentation in Japan
Published in Hemoglobin, 2021
Kei Takamura, Taku Komori, Yuiko Hashino, Takatoshi Suzuki, Ai Shiwaku, Hajime Kikuchi, Makoto Yamamoto, Hidetoshi Yamauchi, Yasuhiro Yamashiro
We confirmed that only II-2 was detected with a low SpO2 level, and oxygen therapy was given, so we decided to examine her. After conducting β-globin gene sequencing of this case, similar results were obtained. About II-2, the Heinz body was detected at a rate of 1/700 red blood cells (RBCs), and she had mild anemia (Figure 4). This is the first Japanese familial report of Hb Aalborg. The symptoms of the proband (II-4) were shortness of breath and excessive sputum probably due to COPD. Notably, there was no anemia, so we treated the patient with expectorant and an anticholinergic agent.