Ligand Kinetics in Hemoglobin Hiroshima

Hemoglobin Hiroshima is an electrophoretically fast-moving variant with a fourfold increase in oxygen affinity and a decreased Bohr effect. Based on a decreased rate of dissociation of O(2) in the presence of dithionite and an increased rate of binding of CO by the deoxy form, we have concluded that the kinetic basis of the high affinity exhibited by Hb Hiroshima is the concurrence of a faster combination rate and a slower dissociation rate for ligands.     

Hemoglobin function in stored blood

Serial oxygen dissociation curves were performed on blood units preserved in acid-citrate-dextrose (ACD), ACD-adenine, and ACD-adenine-inosine. Dividing blood from a single donor into two or more bags allowed direct comparison between preservatives. During the 1st wk of storage in ACD, a progressive increase in oxygen affinity was observed. Thereafter, little further change was noted. Oxygen affinity increased even more rapidly during initial storage in ACD-adenine. However, with the inclusion of inosine as a preservative, oxygen affinity remained unaltered during the first 2 wk. Increases in oxygen affinity correlated well with falling levels of red cell 2,3-diphosphoglycerate (2,3-DPG) during storage. No significant changes in glutathione, reduced form (GSH), or A3 (A(I)) hemoglobin levels were noted during the first 3 wk of storage. No significant accumulation of ferrihemoglobin was detected. When blood stored 20 days in ACD or ACD-adenine was incubated with inosine for 60 min at 37 degrees C, 2,3-DPG and adenosine triphosphate (ATP) were resynthesized, and oxygen affinity was decreased. The distribution of 2,3-DPG in fresh and stored red cells appeared to influence experimental values for Hill's n, a measure of heme-heme interaction.     

Hemoglobin solutions as red cell substitutes

Hemoglobin solutions have potential as temporary red cell substitutes. Their efficacy has been demonstrated by their ability to maintain life-supporting levels of O2 consumption and CO2 production in animals virtually free of red cells. They do not exhibit major toxic effects, but transient alterations in renal function remain a concern. Cardiac output does not increase in the face of acute anemia associated with isovolemic exchange transfusion with hemoglobin solution. However, cardiac reserve does not diminish significantly after infusion of hemoglobin solution. Alterations in production techniques may lead to a polymerized hemoglobin solution that has a hemoglobin concentration and P50 close to fresh whole blood. Though this development is encouraging, it is clear that no perfect red cell substitute currently is available.     

Hemoglobin disorders and endothelial cell interactions

Endothelial damage and inflammation make a significant contribution to the pathophysiology of sickle cell disease (SCD) and the β-thalassemia syndromes. Endothelial dysfunction and ensuing vasculopathy are implicated in pulmonary hypertension in the hemoglobinopathies and endothelial activation and endothelial-blood cell adhesion, accompanied by inflammatory processes and oxidative stress, are imperative to the vaso-occlusive process in SCD. Herein, we discuss the role that the endothelium plays in all of these processes and the effect that genetic modifiers and hydroxyurea therapy may have upon endothelial interactions. Therapies targeting the endothelium and endothelial interactions may represent a promising approach for treating these diseases.     

Hemoglobin interference from in vivo hemolysis

Laboratory values for specimens from a case of intravascular hemolysis showed that hemoglobin was significantly increased and thus could interfere with the determination of other analytes. We studied this problem by adding increasing amounts of purified hemoglobin (to a maximum concentration of 19.3 mg/L) to aliquots of pooled serum samples. The hemoglobin significantly interfered with the determination of only five analytes: albumin, aspartate aminotransferase, direct bilirubin, and total protein on the SMAC, and creatinine on the Astra. We propose that for cases of proven intravascular hemolysis, values for only the analytes not affected by hemoglobin should be reported. We find lactate dehydrogenase activity useful in assessing the components of in vivo hemolysis; the differences between serum and plasma values for potassium, lactate dehydrogenase, and hemoglobin are related to in vitro hemolysis. Criteria for specimen collection and assessment of type of hemolysis are proposed.     

血红蛋白A2和F的室间质量评价结果分析

目的 评价中国部分珠蛋白生成障碍性贫血筛查实验室检测血红蛋白A2和F的水平和现状。方法 向50家珠蛋白生成障碍性贫血实验室发放两个批号的质控品,收集实验室回报的HbA2和HbF检测值,对回报的结果按照方法分组进行统计分析,并评价其检测水平。结果 49家实验室回报了检测结果,回报率为98%。HbA2的及格率为42.9%～92.3%,HbF的及格率为27.3%～84.6%。通过稳健Z比分数统计,血红蛋白HbA2项目201311批号样本有3家实验室检测结果为不满意,201312批号样本有4家实验室检测结果为不满意,血红蛋白HbF项目201311批号样本有5家实验室检测结果为不满意,201312批号样本有3家实验室检测结果为不满意。结论 我国珠蛋白生成障碍性贫血筛查实验室检测HbA2和HbF质量有待进一步提高。     

The Determination of Hemoglobin in Blood Banks

The accuracy of the copper sulfate method of determining hemoglobin was investigated under usual blood bank conditions. In our hands this method was found to be grossly inaccurate. Using the cyanmethemoglobin technic, it was demonstrated that 83.9 per cent of females and 80.4 per cent of males rejected as having a low hemoglobin by the copper sulfate method, actually had hemoglobin values above minimum requirements for blood donors. Detailed instruction as to technics and pitfalls of the copper sulfate method was ineffectual in correcting errors as encountered by a large nursing staff carrying out the procedure. Donors found to have acceptable hemoglobin values by the copper sulfate method appeared to be safely accepted as donors; cyanmethemoglobin duplicate checks did not reveal any discrepancies in this group.     

Hemoglobin/hematocrit and other erythrocyte parameters

The authors review erythrocyte physiology, blood collection, and laboratory methodology for enumerating blood cells. The clinical interpretation of abnormal erythrocyte parameters is discussed, and the emergency department approach to anemia and polycythemia is detailed.