Total Red Cell Mass Research Articles

Karakteristike bolesnika sa sekundarnom eritrocitozom u odnosu na bolesnike sa policitemijom verom

Introduction: Erythrocytosis represents elevated hemoglobin and hematocrit levels above the range of normal values. Primary erythrocytosis - polycythemia vera, is characterized by increased erythrocyte production, due to a disorder at the level of the multipotent stem cell in the bone marrow. On the other hand, secondary erythrocytosis (SE) is the result of bone marrow stimulation by an external factor. Aim: The aim of our study was to determine parameters which are significant in differentiating SE from primary erythrocytosis - polycythemia vera (PV). Materials and methods: This is a retrospective study involving 108 patients with SE and 111 patients with PV, who were diagnosed and treated at the Clinic of Hematology of the Clinical Center of Serbia (CCS), in the period: December 2005 - November 2018.From the patient records, the following data were extracted: demographic characteristics, laboratory parameters, spleen size, total red cell mass, serum erythropoietin (EPO) level, and spontaneous growth of the BFU-E colony. Results: Patients with SE were younger, with a predominance of the male gender and with significantly higher serum EPO values than patients with PV. Patients with PV had significantly higher values of BFU-E, leukocyte and platelet count, spleen size, and LDH level than patients with SE. Total red cell mass analysis did not show a differential diagnostic significance. Conclusion: Findings of normal spleen size, normal leukocyte and platelet count, normal serum LDH level, and elevated EPO, in patients, refer to the diagnosis of secondary erythrocytosis, while the findings of splenomegaly, leukocytosis, thrombocytosis, elevated serum LDH level, decreased EPO, and the presence of spontaneous BFU-E colony speak in favor of the diagnosis of polycythemia vera.

Preoperative anaemia in surgical patients: Intravenous iron and erythropoiesis-stimulating agents (ESAs) to the rescue

Despite the propensity for allogeneic blood transfusion by clinicians, the space for this therapy is steadily being contracted by limited evidence of benefit from its use in most situations, adverse effects of its use, high cost, limited supply and rejection by some religious faithfuls. Available literature concedes to the high prevalence of preoperative anaemia in diverse surgical settings irrespective of geography and reflects the global burden of anaemia. Beyond the poorer surgical outcome directly attributed to preoperative anaemia, it has also been recognized as the major predictor of allogeneic blood transfusion with attendant morbidity and mortality. The concept of Patient Blood Management (PBM) seeks to minimize exposure of patients to allogeneic blood and is based on three pillars of maximizing total red cell mass, minimizing iatrogenic blood loss and harnessing patient’s physiological tolerance of anemia. Consequently, PBM places great premium on correcting preoperative anaemia in surgical patients. With the limited success of leucodepletion and other measures at addressing the complications of allogeneic blood transfusions new interest is expanding in PBM. Several of these have been evaluated and among them the use of newer formulations of intravenous iron with or without erythropoiesis– stimulating agents has been most studied and credited with substantial success and good safety profile. Insight is also offered on the oversubscribed misconception of iron overload in HbSS patients while elucidating on the basis for iron supplementation in proven cases of iron deficiency. Some prevailing barriers, however, threaten the full realization of the potentials of these therapies.

PB2237 THE RED BLOOD CELL COUNT AND THE SEDIMENTATION RATE IN THE DIAGNOSIS OF POLYCYTHAEMIA VERA?

Background:This retrospective cross‐sectional study investigated the effects of microcytosis on the hematocrit (HCT) value in Polycythemia Vera (PV) patients. Since iron deficiency is frequent in PV, and the HCT is a derived value from the Red Blood cell Count x Mean Corpuscular Volume (RBC x MCV), it is reasonable to question if low MCV in PV affects the validity of the HCT value. In addition, we evaluated the Erythrocyte Sedimentation Rate (ESR) as a possible additional diagnostic marker for PV.Aims:To evaluate RBC, hematocrit and the ESR in the diagnosis of PV.Methods:This study included 182 subjects (39 with PV, 27 with Essential Thrombocythemia (ET) and 116 suspected of MPN disease with a secondary cause for either thrombocytosis or erythrocytosis (hereafter named “MPN‐suspects”). The frequencies of microcytosis and low ferritin (<15ug/L) in PV patients were compared to subjects suspected of having a MPN disease. Correlation studies were performed to compare the HCT versus RBC in all subgroups. The ESR was evaluated as a diagnostic marker for PV by a contingency table and a ROC‐curve analysis.Results:In the MPN suspects, 4 of 117 (3 %) had plasma ferritin < 15 ug/L, compared with 6 of 38 (16 %) in the PV‐group (P < 0.05). In the MPN suspects, we found that 3 of 115 (3%) as compared to 6 of 39 (15%) in the PV‐group had MCV < 82 (p < 0.05). Poor linear correlations of RBC versus HCT were found in the PV group compared to the MPN suspects (R2 = 0.62 and R2 = 0.76, respectively). When subjects with microcytosis were excluded, better correlations were observed (R2 = 0.87 in PV and R2 = 0.82 in the MPN suspect group). We found a specificity of 97,7% and a sensitivity of 37,1% for ESR < 2 mm by a ROC‐curve analysis when used for diagnosing PV when PV was suspected. The area under the curve (AUC) was 0,71 (95% CI: 0.60‐0.82), indicating a fair test accuracy for ESR as a diagnostic test.Summary/Conclusion:The HCT is not a valuable parameter in the assessment of expanded RCM in PV, since HCT is falsely lowered due to iron deficiency with microcytosis, which are common findings in patients with PV. The RBC is a simple measurement that may more precisely reflect the total red cell mass which also impacts the ESR as reflected by a low ESR (< 2 mm) in 13 of 35 (37 %) of PV patients at the time of diagnosis. Importantly, the ESR might also be a valuable diagnostic biomarker for PV with a high specificity in patients with elevated HCT, Hb or RBC. A combination of RBC and ESR as simple measures to substitute the Hb‐concentration and the HCT in the diagnosis of PV should be addressed in future well‐designed prospective studies, including the value of the RBC and the ESR in deciding when to phlebotomize patients with PV.

CLINICAL PROFILE OF PATIENTS PRESENTING WITH ANEMIA IN A TERTIARY CARE RURAL HOSPITAL OF WESTERN MAHARASHTRA

Background: Anemia is defined as reduction of the total red cell mass below normal limits. Anemia is usually diagnosed based on a reduction in the haematocrit (the ratio of packed red cells to the blood volume) and the hemoglobin concentration of the blood to levels that are below the normal range. Dermal loss of iron is also suggested as one of the possible contributing factors in the genesis of iron deficiency Anemia in the tropics. In view of the geographical location of western Maharashtra which too has climate similar to tropical parts it was thought prudent to evaluate the clinical profile of anemia in the rural patients presenting with the manifestations of anemia. Objectives: To study Clinical profile, nail changes and type of anemia on Peripheral blood picture of patients presenting with Anemia in a tertiary care rural hospital of Western Maharashtra. Methodology: Total 200 Patients diagnosed to be cases of anemia in a tertiary care rural hospital of Western Maharashtra were enrolled for the study during the study period. All the patients satisfying the above inclusion and exclusion criteria were studied for Clinical profile, nail changes and type of anemia on Peripheral blood picture. Results: In this study out of 200 cases the maximum no of cases seen in >40 yrs were 128(64%). The most frequent symptom was easy fatigability which was present in 190(80%) of patients followed by breathlessness in 132(76%) and the signs noted were Pallor in 188(94%), Venous hum in 88(44%), Pedal edema in 80(40%), signs of Heart failure in 80(40%). The most common type of anemia seen of Peripheral blood smear was Microcytic hypochromic in 84(42%) followed by Dimorphic in 54(27%). The proportion of Platonychia is highly significant than Koilonychias in all types of anemia. Conclusion: The clinical profile of anemia studied in the patients coming to the tertiary care hospital in rural western revealed similar pattern of presentation with other studies with easy fatigability and breathlessness as most common symptoms and pallor as most common sign . The Peripheral blood smears revealed Microcytic hypochromic anemia in 44% patient as most common morphological anemia with Platonychia as most common nail changes in all types of morphological anemia. Keywords: Anemia, Clinical profile, Peripheral Blood Smear , Microcytic Hypochromic, Koilonychias, Platonychia

The three‐pillar matrix of patient blood management

‘Muse before you Transfuse’ For the majority of patients undergoing uncomplicated elective surgery, and in most cases of cancer chemotherapy, it should be possible to minimize or avoid blood transfusion by a standard of care that focuses on the management of a patient's own blood by optimizing and preserving haematopoietic reserves and tolerating deficiencies in reserves. Patient blood management is not an intervention or an alternative to allogeneic blood transfusion; it is sound evidence‐based clinical practice. Patient blood management improves clinical outcomes and as a corollary minimizes or avoids unnecessary allogeneic blood transfusions, reduces risks and helps contain health costs. The use of some autologous transfusion techniques, erythropoiesis‐stimulating agents and antifibrinolytic agents may be regarded as transfusion alternatives, but also bring with them potential hazards and costs that need balancing in the same manner as the decision to transfuse. Managing the triad of haematological risk factors for surgical patients, that is anaemia, haemorrhage and transfusion, is addressed by focusing on the three pillars of patient blood management. Maximizing total red cell mass, minimizing blood loss and tolerating of anaemia are of the essence. Most of the core principles of patient blood management come from a sound understanding of physiological and pathophysiological knowledge of haemopoiesis, haemostasis and oxygen transport and the causative mechanisms of the well‐understood hazards of blood transfusion. The concept of personalized medicine is best epitomized by Sir William Osler in his aphorism: ‘It is much more important to know what sort of a patient has a disease than what sort of a disease a patient has’.

Alpha‐ and beta‐synucleins are new diagnostic tools for acute erythroid leukemia and acute megakaryoblastic leukemia

α-Synuclein is a key component of the Lewy body, a large globular protein complex that forms in the nervous system of patients with Parkinson disease and other dementias [1-3]. Since α-synuclein also occurs in megakaryocytic and erythroid lineages [4-7], we wondered what role synucleins had in the hematopoietic system. Therefore, we studied the expression of α-, β-, and γ-synucleins in a comprehensive panel of patient bone marrows and leukemic cell lines. We observed under expression of α-synuclein in the megakaryocytes of myeloproliferative neoplasm (MPN), but not normal reactive marrow (NRM) or myelodysplastic syndrome (MDS). Conversely, we observed over expression of β-synuclein in the blasts of megakaryoblastic leukemias (MegL), but not acute myeloid leukemia (AML) or erythroleukemia (EryL), suggesting that α- and β-synucleins could be useful adjunct markers for the early detection of MDS and the differential diagnosis of EryL and MegL from other AMLs.

Pre-operative autologous blood donation: clinical parameters and efficacy.

Pre-operative autologous blood donation (PABD) aims to provide a supply of safe blood for patients undergoing surgery who might need a blood transfusion while at the same time increasing the patient's total red blood cell (RBC) mass due to the PABD-induced stimulation of erythropoiesis before scheduled elective surgery. This can, however, only be accomplished if the determinants of RBC regeneration are understood. The improvement of viral safety of allogeneic blood products following the introduction of molecular techniques has led to a decline in the use of autologous blood conservation (ABC) measures, and in particular in the use of PABD. More rational and restrictive indications for allogeneic blood transfusion have evolved and led to a further decrease in the relevance of PABD.

Evidence for Higher Red Blood Cell Mass in Persons With Unconjugated Hyperbilirubinemia and Gilbert’s Syndrome

The genetic polymorphism responsible from Gilbert's syndrome is not sufficient for the clinical phenotype to occur in many persons. Additional factors are believed to contribute in pathogenesis. Red cell mass may be such a factor. We have retrospectively evaluated computer records of all liver function tests assayed between January 2005 and February 2006. The database was screened to find cases with unconjugated hyperbilirubinemia and normal liver enzymes and blood count values on simultaneous assays. The control group for comparison of surrogate markers of total red cell mass comprised of age- and gender-matched persons who had laboratory tests with completely normal results on the same day with the hyperbilirubinemic cases. Gilbert's syndrome cases were found with medical record assessment, and these cases and their control subjects were more strictly assessed. Three different control groups were established for Gilbert's syndrome cases, one of them including healthy blood donors and personnel. In 48,516 otherwise normal laboratory test results, we have found that 491 male subjects and 323 female subjects with unconjugated hyperbilirubinemia had higher hemoglobin, hematocrit, and red blood cell values compared with age- and gender-matched control subjects (P < 0.001 for all comparisons). Twenty-six males who had been followed for Gilbert's syndrome also showed higher hemoglobin, hematocrit and red cell count values in comparison to all control groups. Mean red cell volume value did not differ between the hyperbilirubinemic persons and control groups. Relatively increased red cell mass probably plays a role in the pathogenesis of Gilbert's syndrome.

Effects of forced diving on the spleen and hepatic sinus in northern elephant seal pups.

In phocid seals, an increase in hematocrit (Hct) accompanies diving and periods of apnea. The variability of phocid Hct suggests that the total red cell mass is not always in circulation, leading researchers to speculate on the means of blood volume partitioning. The histology and disproportionate size of the phocid spleen implicates it as the likely site for RBC storage. We used magnetic resonance imaging on Northern elephant seals to demonstrate a rapid contraction of the spleen and a simultaneous filling of the hepatic sinus during forced dives (P < 0.0001, R(2) = 0.97). The resulting images are clear evidence demonstrating a functional relationship between the spleen and hepatic sinus. The transfer of blood from the spleen to the sinus provides an explanation for the disparity between the timing of diving-induced splenic contraction ( approximately 1-3 min) and the occurrence of peak Hct (15-25 min). Facial immersion was accompanied by an immediate and profound splenic contraction, with no further significant decrease in splenic volume after min 2 (Tukey-Kramer HSD, P = 0.05). At the conclusion of the dive, the spleen had contracted to 16% of its predive volume (mean resting splenic volume = 3,141 ml +/- 68.01 ml; 3.54% of body mass). In the postdive period, the spleen required 18-22 min to achieve resting volume, indicating that this species may not have sufficient time to refill the spleen when routinely diving at sea, which is virtually continuous with interdive surface intervals between 1 and 3 min.

Hemodilution accelerates the passage of plasma (not red cells) through cerebral microvessels in rats.

Hemodilution lowers the total circulatory red cell mass and blood viscosity and thereby may alter the time of passage of red cells and plasma through cerebral microvessels. This study was designed to clarify this question. Adult Wistar-Kyoto rats, aged approximately 32 weeks, were divided into hemodilution and control groups. Local cerebral blood flow and microvascular red cell and plasma volumes in 14 brain structures were measured with the use of [14C]iodoantipyrine, 55Fe-labeled red cells, and [14C]inulin, respectively. In the control group, the hematocrit in cerebral microvessels ranged from 0.29 to 0.45 with a mean of 0.36, which was 71% of the systemic hematocrit (0.51). The mean transit times of blood, red cells, and plasma through microvessels were 0.62 to 1.77 seconds (mean, 0.92 second), 0.44 to 1.15 seconds (mean, 0.65 second), and 0.78 to 2.5 seconds (mean, 1.25 seconds), respectively. In the hemodilution group, the mean hematocrit in microvessels was 0.28, which was 89% of the systemic hematocrit (0.32). Local cerebral blood flow was approximately 59% higher (P < .01) than that of the control animals. The rate of oxygen delivered to the brain was slightly increased (9%) after hemodilution. Blood volume in cerebral microvessels was similar to that of the control group. Mean transit time of blood was 0.62 second (68% of the control), transit time of red cells was 0.53 second (85% of the control), and transit time of plasma was 0.67 second (54% of the control). These findings indicate that isovolemic hemodilution accelerates the plasma (not red cell) flow velocity in cerebral microvessels.

Serum immunoreactive erythropoietin and red blood cell mass during pregnancy in conscious rats

Serum erythropoietin concentration increases during human pregnancy and presumably accounts for expansion of red blood cell mass. The mechanism(s) underlying gestational changes of serum erythropoietin are unknown. Moreover, if erythropoietin synthesis increases, then the organ(s) questions about erythropoietin in pregnancy, we first set out to establish an animal model. Chronically instrumented, conscious unrestrained rats were studied. 51Cr-labeled red blood cells and radioimmunoassay were used to assess red blood cell mass and serum erythropoietin, respectively. Except for a lower hematocrit (P < 0.05 vs. virgin rats) and a slightly higher plasma volume (P value not significant) for gravid rats on gestational day 6, all other variables measured in early pregnancy rats were comparable to those measured in virgin control animals. Significant increases in total blood volume, plasma volume, and red blood cell mass were observed by gestational day 13 (midpregnancy) when compared with virgin control rats. These changes were even more pronounced on gestational day 20. Serum immunoreactive erythropoietin was also significantly increased at both of these stages of pregnancy. We conclude that the gravid rat is a reliable animal model of human gestation in which to further investigate erythropoietin in pregnancy.

Blood doping--a literature review.

There is increasing evidence that the technique of reinfusing an athlete's stored blood prior to competition to improve performance has been used on many occasions. Although early experimental results were controversial and the precise mechanism by which the technique improves performance is still debated, there is now strong evidence that if the blood doping produces a sufficient rise in total red cell mass there are significant improvements in physiological variables such as maximum oxygen uptake, lactate buffering and thermoregulation. These physiological changes are matched by improvements in endurance performance. These may persist in diminishing degree for several weeks, but have to be weighed against the detraining effect produced by the repeated venesection required to obtain an adequate amount of stored blood for autologous reinfusion. Experimental evidence suggests that the transient increase in blood volume and cardiac output following reinfusion is too short lived to be of any real importance and the major effect is related to the increase in total red blood cell mass and haemoglobin enabling an increased transport of oxygen and therefore a potentially greater reserve of blood which can be diverted to non-exercising tissues to improve thermoregulation. The increased red cell mass also improves lactate buffering. Although these benefits have been shown in several studies the increases in performance and measured physiological parameters do not bear a direct relationship to the changes in haematological variables. Blood doping is of considerable importance, not only as an abuse of fair competition, but also because of the light it throws on the physiological limits to endurance performance. It has reawakened controversy as to whether oxygen transport is the limiting factor in endurance.

Characterization of the Anaemia of Chronic Renal Failure and the Mode of its Correction by a Preparation of Human Erythropoietin (r-HuEPO). An Investigation of the Pharmacokinetics of Intravenous Erythropoietin and its Effects on Erythrokinetics

Studies were directed to characterization of the anaemia of renal failure of 11 patients on haemodialysis and determination of the way in which it is corrected by human erythropoietin derived from recombinant DNA expressed in Chinese hamster ovary cells (r-HuEPO) administered intravenously. Erythrokinetics before treatment showed that total red cell mass was below normal and that both erythron transferrin uptake and red cell survival were modestly reduced; treatment increased both total red cell mass and erythron transferrin uptake but did not change red cell survival in previously untransfused patients. When BFU-e and CFU-e from patient bone marrow were cultured in autologous serum we found no evidence for inhibitors of erythroid progenitor maturation in patient serum compared with normal. Erythroid expansion in response to r-HuEPO was not limited by the availability of iron, iron requirements for new red cell formation being met from stores (if adequate) or from oral iron supplements. In pharmacokinetic studies the plasma clearance of r-HuEPO could be expressed by a three-parameter exponential curve with T1/2 range of 2.3 to 7.3 h. T1/2 after the first dose of r-HuEPO was not significantly different from that after 14 to 54 weeks treatment when the erythron had expanded to a new steady state. Erythron transferrin uptake before treatment was related to endogenous production of erythropoietin estimated from the plasma clearance of the first dose of r-HuEPO administered intravenously. This finding suggested that the availability of erythropoietin was the main factor limiting expansion of the erythron. This conclusion was supported by the continuity of the relationship during the response to treatment.

Feto-placental blood volume in severely anemic erythroblastotic fetuses.

The feto-placental blood volume was studied using a hemoglobin hemodilution technique in 15 erythroblastotic fetuses at 43 intravascular transfusions. Four severely anemic fetuses (Hb 30 g/l) had significantly larger blood volumes than 11 moderately anemic fetuses (Hb 30-79 g/l), 169 +/- 37 versus 105 +/- 32 ml/kg fetal body weight (p less than 0.001). We speculate that hypovolemia might be an adaptive change to maintain an adequate hemoglobin concentration. An escape of fluid from the intra- to the extra-vascular space will probably compensate for the reduction in total red cell mass and thus slightly increase the hemoglobin concentration. Theoretically, interstitial fluid accumulation will continue until the hydrostatic pressure of the extravascular tissue balances that of the capillary. This compensatory mechanism seems to function until the hemoglobin concentration drops below, 30 g/l, at which point the blood volume will increase, suggesting a change from a hypo- to a hyper-volemic state.

歯肉切開後に異常出血をきたした真性多血症の１例

Polycythemia vera is an insidious disease of unknown cause, characterized by elevation of the total red cell mass. Hemorrhages occur in about one-third of this disease. A case of 54 year old male was reffered to our clinic complaining of abnormal bleeding after gingival incision.In his history, he lacked any apparent bleeding tendency except suspected thrombotic tendency on his left plantar which had occurred two years before. The chief clinical findings of this patient were the abnormal bleeding from gingival wound, reddish blue discoloration of face and arms, body itching and headache. Hematological examination showed remarkably elevated red cell count, hemoglobin levels, white cell count and platelet count. He was admitted to the 1st Department of Internal Medicine, Kyushu University, and is now doing well about two years after the treatment.

Blood Volume Changes in Normal Pregnancy

The plasma volume and total red cell mass are controlled by different mechanisms and pregnancy provides the most dramatic example of the way in which that can happen. A healthy woman bearing a normal sized fetus, with an average birth weight of about 3.3 kg, will increase her plasma volume by an average of about 1250 ml, a little under 50% of the average non-pregnant volume for white European women of about 2600 ml. There is little increase during the first trimester, followed by a progressive rise to a maximum at about 34-36 weeks, after which little or no further increase occurs. It seems certain that the frequently observed fall in plasma volume in the last six weeks of pregnancy is an artefact of measurement due to poor mixing of tracer when the woman lies supine and obstructs the circulation to her lower limbs. The maximum increase depends largely on the size of the conceptus. It is somewhat increased, perhaps to a mean of 1300 ml, in association with the bigger baby of multiparae and increases still more with twins, triplets and quadruplets. Red cell mass increases by relatively much less, a rise of about 250 ml (some 18% of the non-pregnant volume) in women who take no supplemental iron, and between 400 and 450 ml when iron supplements are taken. The rise is probably linear from the end of the first trimester to term, and there is some evidence of a preliminary fall in red cell mass during the first trimester. As a result of the relatively much greater increase in plasma volume, red cells in the blood are 'diluted' and the venous haematocrit drops from a non-pregnant average of about 40 to about 33 during the last trimester. The differential changes are biologically plausible: red cell mass rises proportionately to the need to carry the extra oxygen taken up in pregnancy; the greater plasma volume increment is needed to cope with the very large increases in blood flow to organs which require little extra oxygen, the skin and the kidneys.

Blood Volume Changes in Normal Pregnancy

The plasma volume and total red cell mass are controlled by different mechanisms and pregnancy provides the most dramatic example of the way in which that can happen. A healthy woman bearing a normal sized fetus, with an average birth weight of about 3.3 kg, will increase her plasma volume by an average of about 1250 ml, a little under 50% of the average non-pregnant volume for white European women of about 2600 ml. There is little increase during the first trimester, followed by a progressive rise to a maximum at about 34-36 weeks, after which little or no further increase occurs. It seems certain that the frequently observed fall in plasma volume in the last six weeks of pregnancy is an artefact of measurement due to poor mixing of tracer when the woman lies supine and obstructs the circulation to her lower limbs. The maximum increase depends largely on the size of the conceptus. It is somewhat increased, perhaps to a mean of 1300 ml, in association with the bigger baby of multiparae and increases still more with twins, triplets and quadruplets. Red cell mass increases by relatively much less, a rise of about 250 ml (some 18% of the non-pregnant volume) in women who take no supplemental iron, and between 400 and 450 ml when iron supplements are taken. The rise is probably linear from the end of the first trimester to term, and there is some evidence of a preliminary fall in red cell mass during the first trimester. As a result of the relatively much greater increase in plasma volume, red cells in the blood are 'diluted' and the venous haematocrit drops from a non-pregnant average of about 40 to about 33 during the last trimester. The differential changes are biologically plausible: red cell mass rises proportionately to the need to carry the extra oxygen taken up in pregnancy; the greater plasma volume increment is needed to cope with the very large increases in blood flow to organs which require little extra oxygen, the skin and the kidneys.

Hematopoiesis and aging III: Anemia and a blunted erythropoietic response to hemorrhage in aged mice.

Whether the hematocrit normally declines in the aged or whether such a decline represents inapparent disease in addition to aging is a matter of dispute. Female B6D2f1 mice were studied at ages 3, 13, or 27-28 months, and there was no difference in hematocrit between the younger groups. The hematocrit of 45 aged mice was slightly lower than that of 66 younger mice; mean 43% vs 49% (p less than .001). However, rather unexpectedly, the total red cell mass was not decreased in the aged; rather, the plasma volume was expanded. Survival of mature red blood cells did not differ significantly between young and aged mice. Mice were bled 0.4 ml from the orbital sinus for 4 days, reducing the hematocrit of all groups to a nadir of 20-25%. Recovery of hematocrit began more slowly in aged than in young mice. That this reflected a difference in erythropoiesis rather than a difference in plasma volume equilibration was suggested by studies with 59Fe. 59Fe was given following the second bleed, and 1 day later RBC 59Fe was more than twice as high in young mice than in groups of aged mice. Aged mice that did not appear healthy had been excluded. Aged mice were divided into a group with significant amounts of gray hair and/or patches of hair loss and two groups with normal-appearing hair; the latter was subdivided into those weighing less (25-26 g) or more (30-34 g) than most aged mice. Neither hair condition nor weight influenced hematocrit or response to bleeding. These results suggest, but do not prove, that a mild "dilutional" anemia and a blunted erythropoietic response to hemorrhage may be an expected part of the murine aging process.

Quantification of the distribution of the marginating granulocyte pool in man.

The kinetics of autologous granulocytes, separated from whole blood and labelled with 111In-tropolonate with continuous maintenance in plasma, have been studied in man, using a gamma camera and computer, with the aim of quantifying the distribution of the marginating granulocyte pool (MGP). We have used 3 approaches: dynamic gamma camera imaging immediately following i.v. injection of labelled cells, comparison of the activity signal from 111In-granulocytes with that from previously injected 111In-labelled red cells and absolute quantification of 111In present in liver, spleen and blood. Deconvolution analysis of the hepatic and peripheral blood time activity curves indicated that hepatic granulocyte transit time was 2.5 +/- SE 0.14 min. By comparison with 111In red cells, hepatic transit time was calculated to be 7.4 +/- SE 0.82 that of red cells, which, assuming an hepatic red cell content of 6% that of the total red cell mass, is equivalent to a transit time of 1.8 min. By comparison with 111In red cells, lung granulocyte transit time as a factor of red cel transit time was 5.4 +/- SE 0.7 at 5 min and 2.5 +/- SE 0.13 at 40 min after granulocyte injection. Using these kinetic data, in combination with previously published values for splenic granulocyte transit time, it was calculated that, 5 min after injection, the MGP accounted for 54% of the total blood granulocyte pool (TBGP), was 90% filled, and was distributed between spleen (19%), liver (26%), lung (33%) and the remainder of the body (22%). At 40 min, the MGP accounted for 60% of the TBGP, had equilibrated with the circulating granulocyte pool (CGP), and was distributed between the spleen, liver, lung and remainder of the body according to the following respective percentages: 35, 25, 10 and 30. The total granulocyte contents of the spleen and liver calculated on the basis of the kinetic data were 21% and 22% respectively and in broad agreement with the values, 34 and 23% respectively, calculated from quantitative scanning. It was concluded that about 70% of the body's MGP was present in the spleen, liver and lung. If the MGP is itself 60% of the TBGP then only about 18% of the TBGP marginates in extra-hepatosplenopulmonary sites.

Postnatal regulation of oxygen delivery: hematologic parameters of postnatal dogs

Hematologic parameters influencing tissue oxygen delivery in dogs during the first 4 mo of life have been investigated. The rapid growth and increase in body temperature during this period imply an increased metabolic rate and increased tissue oxygen demand. Hemoglobin concentration and hematocrit decrease during the 1st mo following birth. The total red cell mass does not decrease during this period. The observed hemodilution can be attributed to an increasing plasma volume in the growing animal. The blood oxygen affinity decreases during this same period, resulting in a more effective tissue oxygen delivery. Erythropoiesis, as estimated from the percent circulating reticulocytes, decreases following birth and does not increase until 1 mo of postnatal life. The increase of erythropoietic activity during the 2nd mo of postnatal life coincides with an increase in red cell mass, hematocrit, and hemoglobin concentration.