Characteristics of marrow production and reticulocyte maturation in normal man in response to anemia

Erythropoiesis in normal man was studied during periods of phlebotomy-induced anemia of varying severity. This study permitted a comparison of marrow production measurements over a wide range of marrow production levels. As long as the serum iron remained above 50 mug/100 ml, measurements of plasma iron turnover provided an excellent index of marrow production at all levels of red cell production. In contrast, the absolute reticulocyte count demonstrated a poor correlation with the other measurements. This was shown to be the result of a prolongation of the time required for circulating reticulocytes to lose their reticulum, which correlated with the severity of the anemia. For the clinical application of the reticulocyte count as a measurement of marrow production, an adjustment must be made for this alteration in the circulating reticulocyte maturation time.     

Reticulocyte count with maturation fractions in pancytopenic evaluation by a fully automated counter

Using a fully automated reticulocyte counter, the roles of the reticulocyte count with maturation in pancytopenia were evaluated. Different groups of pancytopenia including aplastic anemia, infiltrative marrow disorder, hypersplenism, and megaloblastic anemia were recruited. All patients had bone marrow examinations for morphological diagnosis and reticulocyte evaluation using an automated counter. The roles of these parameters were then analyzed statistically in the differential evaluation among these conditions. The following subjects were studied: 292 normal subjects, 67 cases of aplastic anemia, 69 cases of marrow infiltration by different malignancies, 35 cases of hypersplenism, and 13 cases of megaloblastic anemia. The results showed that the absolute retlculocyte counts were lowest in the groups of aplastic anemia and megaloblastic anemia and highest in hypersplenism. Both showed significant differences from the infiltrative groups. The maturation fractions were most immature in the group of marrow infiltration and are significantly different from the other groups. It was concluded that the highest absolute reticulocyte count (>0.09 10¹²/L) obtained in pancytopenic patients suggests it to be a case of hypersplenism. The lowest counts ( < 0.03 10¹²/L) with lowest immature fractions ( < 10%) suggest the groups of aplastic or megaloblastic anemias. The highest immature fractions ( >30%) with a nearly normal reticulocyte count favor the group of marrow infiltration. © 1993 Wiley-Liss, Inc.     

The effect of smoking on the composition of the peripheral blood in normal subjects]

The peripheral blood erythrocytic and leukocytic status was studied in 60 healthy young tobacco-smokers and in 30 non-smokers. The smokers were divided into two subgroups, each with 30 members: those smoking for not more than 5 years and those smoking for 6 to 10 years. A trend to inhibition of erythro- and leukocytopoiesis was detected in Subgroup 1 tobacco smokers: reticulocyte maturation rate was reduced, as was bone marrow production and the level of circulating red cells, macrocyte count was increased and planocytosis was likely to develop, leukocyte counts were decreased at the expense of the neutrophils, eosinophils, and monocytes; basophil count was growing. Subgroup 2 tobacco-smokers presented with normalization of erythro- and leukocytopoiesis: reticulocyte maturation rate was growing, as was bone marrow production and the count of circulating red cells, erythrocytogram normalized, leukocyte count was increasing at the expense of the neutrophils, eosinophils, and lymphocytes; basophil count has decreased. The detected changes in the peripheral blood erythro- and leukocytic composition, related to the duration of tobacco-smoking, appear to reflect different phases of tobacco smoke toxic product effects on the bone marrow and the formation of the defense, adaptive, allergic, and immunologic reactions of the body in conditions of prolonged tobacco antigenemia.     

Use of reticulocyte cellular indices in the diagnosis and treatment of hematological disorders

Automated counting of reticulocytes has markedly increased the precision and accuracy of this assay compared with the traditional manual counts. In addition, several new reticulocyte parameters are now available to clinicians and pathologists. This review examines the potential role of these parameters in the diagnosis and management of anemias. Reticulocyte maturity can now be assessed based on the staining intensity of reticulocytes, which is proportional to their RNA content. However, the clinical value of the numerical estimate of the immature reticulocyte fraction has not been yet demonstrated. In the bone marrow transplant setting, there is no clear evidence that the use of this index results in improved care of these patients, and many studies have failed to show its superiority compared with the traditional white cell count, especially for autologous transplants. Direct measurement of reticulocyte volume, hemoglobin concentration, and hemoglobin content are now available. Studies have shown that these parameters, and hemoglobin content in particular, allow a real-time assessment of the functional state of the erythroid marrow. In the setting of recombinant human erythropoietin therapy, studies of hemoglobin content have shown that this index allows an early detection of functional iron deficiency. Preliminary studies have also shown that this index may be helpful in the diagnosis of iron deficiency and in the monitoring of iron replacement therapy.     

Neutrophil kinetics in man.

A method has been developed for measuring neutrophil cellularity in normal human bone marrow, in which the neutrophil-erythroid ratio was determined from marrow sections and marrow normoblasts were estimated by the erythron iron turnover. Neutrophil maturational categories, defined by morphologic criteria, were supported by autoradiographs of marrow flashed-labeled with 3H-thymidine. Correction for multiple counting error was empirically derived by counting serial sections through cells of each maturational category. The normal neutrophil-erythroid ratio in 13 normal human subjects was 1.5 +/- 0.07. The mean number of normoblasts in the same subjects was estimated to be 5.07 +/- 0.84 X 10(9) cells/kg. Total marrow neutrophils (X 10(9) cells/kg) were 7.70 +/- 1.20, the postmitotic pool (metamyelocytes, bands, and segmented forms) was 5.59 +/- 0.90 and the mitotic pool (promyelocytes + myelocytes) was 2.11 +/- 0.36. Marrow neutrophil ("total") production has been determined from the number of neutrophils comprising the postmitotic marrow pool divided by their transit time Transit time was derived from the appearance in circulating neutrophils of injected 3H-thymidine. The postmitotic pool comprised 5.59 +/- 0.90 X 10(9) neutrophils/kg, and the transit time was 6.60 +/- 0.03 days. From these data marrow neutrophil production was calculated to be 0.85 X 10(9) cells/kg per day. Effective production, measured as the turnover of circulating neutrophils labeled with 3H-thymidine, was 0.87 +/- 0.13 X 10(9) cells/kg per day. This value correlated well with the calculation of marrow neutrophil production. A larger turnover of 1.62 +/- 0.46 X 10(9) cells/kg per day was obtained when diisopropylfluorophosphate-32P was used to label circulating neutrophils. Studies using isologous cells doubly labeled with 3H-thymidine and diisopropylfluorophosphate-32P demonstrated a lower recovery and shorter t1/2 of the 32P label.     

新型网织红细胞参数在缺铁性贫血疗效观察中的应用

目的　观察网织红细胞绝对数 (RET #)、网织红细胞内血红蛋白量 (CHr)、平均网织红细胞体积 (MCVr)及网织红细胞内血红蛋白浓度 (CHCMr)等网红参数在缺铁性贫血 (IDA)患者铁剂治疗中的动态变化 ,确定骨髓对铁剂治疗反应的早期指标。方法　用Advia 12 0血细胞分析仪对 13例缺铁性贫血患者在治疗过程中网红参数的变化进行了动态观察。结果　缺铁性贫血患者在铁剂治疗后 ,网红参数RET #、CHr、MCVr于第 4天明显升高 (P <0 0 1) ,第七天恢复正常 ;血红蛋白于第 14天明显升高 (P <0 0 1) ,第 2 8天恢复正常 ;CH、MCV、CHCM于第 2 8天明显升高 (P <0 0 1) ,第 4 9天后恢复正常 ;RDW于第 7天明显升高 (P <0 0 1) ,14天后又逐渐降低 ,第 12 0天恢复正常。结论　网红参数RET #、CHr、MCVr可作为评价缺铁性贫血患者铁剂治疗后骨髓对治疗反应最敏感的指标     

Iron induced increase in red cell size in haemodialysis patients

In a group of haemodialysis patients who were iron loaded secondary to parenteral iron administration a slight but significant increase in red cell size was noted when compared to a normal population. This macrocytosis was not related to serum B12 or folate levels, or to the reticulocyte count. On stopping iron therapy both mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH) values declined significantly as did serum ferritin and iron levels. Bone marrow smears were of normal or increased cellularity. When iron therapy was discontinued there was a steady fall in serum ferritin levels without a drop in haemoglobin values suggesting that the excess iron was available for haemopoiesis. These findings suggest that the increase in red cell size in this group of patients may have been induced directly by iron overload.     

Erythropoiesis in the anemia of bone marrow failure

The quantitative relationship between red cell volume, erythropoietin level, and erythropoiesis was evaluated in 43 human beings. Results in normal man were compared with studies in patients with anemia from bone marrow failure and with polycythemia vera. The maximum erythropoietin excretion after bleeding normal men was similar to the basal levels found in patients with chronic anemia of similar magnitude. Although erythropoietin values were low in patients with polycythemia vera, bleeding evoked a normal response. In patients anemic from bone marrow failure, basal levels were elevated, and phlebotomy resulted in an increase consistent with the new level of anemia. These observations indicate that erythropoietin level is affected primarily by the degree of anemia and is not influenced by the duration of anemia. In normal subjects, a fivefold increase in urinary erythropoietin was associated with a doubling of erythropoiesis. Despite similar degrees of erythropoietin production, anemic patients with evidence of bone marrow in the lower extremities had greater red cell production. In patients with polycythemia vera, red cell production was inappropriately elevated with regard to the urinary erythropoietin excretion. Bone marrow maturation time was not shortened in patients anemic from bone marrow failure to the same degree as in bled, normal volunteers. In addition to an adequate level of erythropoietin production, normal bone marrow function is necessary for maximal shortening of maturation time.     

Iron Induced Increase in Red Cell Size in Haemodialysis Patients

In a group of haemodialysis patients who were iron loaded secondaryto parenteral iron administration a slight but significant increasein red cell size was noted when compared to a normal population.This macrocytosis was not related to serum B₁₂ or folate levels,or to the reticulocyte count. On stopping iron therapy bothmean corpuscular volume (MCV) and mean corpuscular haemoglobin(MCH) values declined significantly as did serum ferritin andiron levels. Bone marrow smears were of normal or increasedcellularity. When iron therapy was discontinued there was asteady fall in serum ferritin levels without a drop in haemoglobinvalues suggesting that the excess iron was available for haemopolesis.These findings suggest that the increase in red cell size inthis group of patients may have been induced directly by ironoverload.     

Effective Erythropoiesis Induced by 5β-Pregnane-3β-Hydroxy-20-One in Squirrel Monkeys

The erythropoietic effect of 5beta-pregnane-3beta-hydroxy-20-one, a naturally occurring steroid metabolite of progesterone, was evaluated in the squirrel monkey by ferrokinetic studies. red cell survival, and blood volume measurements. The intramuscular administration of this steroid in pharmacologic doses shortened the (59)Fe plasma clearance and increased the plasma iron turnover, thereby indicating an increase in erythropoiesis. A normal (59)Fe red cell uptake was observed, and the bone marrow maturation time was not altered. Red cell survival was the same in the treated and control groups. After five weekly injections of the steroid, the monkeys increased their red cell mass by 57%. A significant increase in white blood cells and a slight elevation of platelet counts in the treated monkeys also suggest a possible direct stimulation of hemopoietic stem cells by the steroid metabolite.These observations indicate that some steroid metabolites can stimulate an early increase in iron turnover (within 48 h) that is not secondary to hemolysis. The increased red cell mass indicates effective erythropoiesis in primates.     

肝硬化患者未成熟网织红细胞指数的观察

目的：观察肝硬化患者未成熟网织红细胞指数（immature reticulocyte fraction，IRF），探讨IRF在肝硬化患者中的变化及临床意义。方法：应用Sysmex XE-2100全自动血细胞分析系统检测97例不同程度的肝硬化患者和50例健康对照者血IRF，并对检测结果进行统计、分析。结果：肝硬化患者的IRF与健康人相比增高有非常显著差异（P〈0．01），并且随着病期的迁延有逐渐升高的趋势。结论：肝硬化患者的IRF增高，检测IRF是反映骨髓造血功能的新型灵敏的指标，利于肝硬化贫血的早期诊断和早期治疗。     

网织红细胞参数在急性白血病化疗中的应用价值

目的研究急性白血病化疗前后网织红细胞参数变化的临床意义。方法 32例急性白血病化疗的患者,化疗后好转。用自动化血液分析仪Sysmex 2000检测患者的网织红细胞比率(RET%)、网织红细胞绝对值((RET#)、低荧光强度的网织红细胞(LFR)、中荧光强度的网织红细胞(MFR)、高荧光强度的网织红细胞(HFR)、白细胞(WBC)、中性粒细胞绝对值(ANC)以及未成熟网织红细胞比率(IRF)。结果急性白血病化疗患者IRF、MFR、HFR化疗后一直减低,化疗第7天降到最低,在化疗第14天开始恢复,化疗第21天恢复至化疗前水平。LFR于化疗第7天开始升高,化疗14d开始降低,WBC和网织红细胞绝对值计数于化疗第7、14天一直降低,化疗21d开始恢复。结论 IRF、MFR、HFR、LFR是反应骨髓恢复的敏感指标,较WBC和网织红细胞的绝对值早7d。     

THE ANEMIA OF SCURVY : EFFECT OF VITAMIN C DIET ON BLOOD FORMATION IN EXPERIMENTAL SCURVY OF GUINEA PIGS

1. Weight loss, progressive anemia, and a moderate increase in reticulated red blood cells occurred in seventeen guinea pigs on a diet deficient in vitamin C. 2. The histological changes of the bone marrow removed from guinea pigs with scurvy showed large numbers of erythrogenic cells, but scant evidence of active maturation to the adult erythrocyte. 3. A reticulocyte response was induced in guinea pigs with scurvy when fed orange juice daily. 4. The histological changes of the bone marrow removed from guinea pigs during the reticulocyte response showed large numbers of mitotic figures and relatively more adult red blood cells than in the bone marrow from guinea pigs with scurvy that had not been treated with orange juice. 5. It is concluded from this study that the anemia of experimentally induced scurvy in the guinea pig is largely dependent upon vitamin C deficiency resulting in retarded maturation of the red blood cell.     

CHr在缺铁性贫血中的诊断意义

目的探讨CHr在缺铁性贫血中的诊断价值。方法选取病例120例,分别建立IDA患者组和非IDA患者组,在体检人群中选出正常对照30例,分别比较正常对照组、IDA贫血组和非IDA贫血组CHr、CH、MCV、SI等参数的均值,并按贫血诊断标准比较这四个参数的灵敏度和特异度。结果IDA贫血组与健康组和非IDA组相比均有统计学意义（P〈0．05）;非IDA组与健康组相比差别无统计学意义（P〉0．5）;四个参数中CHr的灵敏度和特异度均高于其他三个参数。结论CHr能够简便、快速、特异地诊断缺铁性贫血。     

Serum transferrin receptor is a marker of iron deficiency in patients included in programs for preoperative autologous blood donation.

Recently programs for preoperative autologous blood donation (PABD) have expanded to reduce the need for allogenic blood transfusion. Nevertheless, the ability of the patients's bone marrow to replace the red blood cells (RBCs) mass reduced by phlebotomies determines the efficacy of PABD. In mild anemia, known as iron-deficient erythropoiesis (IDE) or iron deficiency without anemia, precipitated by PABD, the marrow response is suboptimal and needs adjuvant therapy. The aim of this study was to evaluate the use of the serum transferrin receptor (sTfR) for the assessment of IDE in patients undergoing PABD. METHODS: Two autologous blood units from 50 consecutive patients scheduled for elective orthopedic surgery were collected preoperatively. Serial measurements of RBCs, haematocrit (Hct), haemoglobin (Hb), serum iron, serum ferritin, reticulocyte count, reticulocyte maturity index (RMI), endogenous erythropoietin (EPO) and sTfR were performed throughout the phlebotomy program. RESULTS: RBC, Hct, Hb and serum iron significantly decreased although within the normal range. There was no change in serum ferritin levels. Reticulocytes, RMI and EPO significantly increased as did sTfR which significantly exceeds the normal range. CONCLUSIONS: These results demonstrate that the sTfR is a reliable laboratory marker for detecting mild anemia or IDE. In patients undergoing PABD increased sTfR levels may suggest a treatment with recombinant human EPO (rh-EPO) or iron to improve the bone marrow performance.     

Coluter-750检测未成熟网织红细胞在急性白血病患者化疗中的意义

目的 寻找敏感的指标来预测骨髓造血功能的恢复,以指导临床治疗白血病(AL)及判断预后.方法 采用Coluter-750全自动血细胞分析仪,对白血病患者外周血进行未成熟网织红细胞指数(IRF)、网织红细胞总数(RET)、白细胞总数(WBC)、中性粒细胞绝对数(NET)及血小板数(PLT)检测.结果 IRF值于化疗后15天开始升高,IRF值开始恢复时间最早比RET和WBC开始升高提前5天,比PLT和NET开始升高提前10天.结论 IRF可作为白血病患者化疗后骨髓红系造血功能恢复的早期指标之一.     

Anemia in the elderly. Symptoms, causes, and therapies

Anemia is common in the elderly, but it is not a normal manifestation of aging and should be evaluated as it would be in a younger person. History taking, physical examination, assessment of red cell morphology, and simple laboratory evaluations (ie, reticulocyte count, iron studies, vitamin levels, sometimes bone marrow examination) usually elucidate the cause. Hypoproliferation of red cells is the most common form of anemia in the elderly, caused more often by chronic disease or iron deficiency and less often by vitamin deficiencies or bone marrow infiltration. Anemia with an elevated reticulocyte count, seen less often in the elderly, suggests acute blood loss or hemolysis. In some patients, the cause is not obvious, and anemia is likely due to increased sensitivity of the hematopoietic system to multiple insults and decreased homeostatic reserve. Transfusions should be used judiciously in patients with symptomatic anemia who are likely to benefit from increased oxygen delivery after transfusion.     

Coulter LH 750仪网织红细胞检测参数的临床价值分析

目的探讨BeckmanCoulterLH750全自动血液分析仪检测网织红细胞及其新型参数的方法及临床应用价值。方法用BeckmanCoulterLH750全自动血液分析仪检测248例住院贫血患者抗凝全血标本的网织红细胞百分比(RET％)、网织红细胞绝对值(RET#)、网织红细胞平均体积(MRV)、未成熟网织红细胞组分(IRF)、高散射光强度网织红细胞百分比(HLR％)等五项网织红细胞参数。结果慢性肾功能不全的贫血患者RET#同对照组比较无显著差异,但HLR％显著高于对照组(P<0.05)。失血性贫血的患者网织红细胞各项指标与对照组相比显著增高;肝硬化与正常对照组RET％、RET#和HLR％有显著差异(P<0.05)。结论测定网织红细胞及其相关参数有助于判断红细胞的活动度,对贫血类型的初筛诊断、治疗监测等有重要的实用价值。     

地中海贫血孕晚期妇女网织红细胞参数及网织血小板的变化分析

目的探讨网织红细胞6项参数及网织血小板在地中海贫血（简称地贫）孕晚期妇女中的变化及意义。方法对经基因确诊的39例地贫孕晚期妇女、30例正常孕晚期妇女和30例正常非孕妇女,应用SysmexXE-5000全自动血细胞分析仪测定网织红细胞绝对值（RET#）、网织红细胞百分率（RET%）、未成熟网织红细胞比率（IRF%）、低荧光强度网织红细胞百分率（LFR%）、中荧光强度网织红细胞百分率（MFR%）、高荧光强度网织红细胞百分率（HFR%）6项网织红细胞参数及网织血小板百分率（IPF%）。结果地贫孕晚期妇女、正常孕晚期妇女、正常非孕妇女的六项网织红细胞参数及网织血小板比较,差异有统计学意义（P〈0.05或P〈0.01）,其中地贫孕晚期妇女RET#、RET%、IRF%、MFR%、HFR%、IPF%明显增高,LFR%明显下降。结论地贫孕晚期妇女在生理和病理的双重刺激下骨髓的造血功能更旺盛,检测妊娠妇女的网织红细胞参数及网织血小板,有助于发现地贫患者,减少及控制危重地贫患儿的出生。