The effect of haemorrhage on erythropoietin concentration in the mature ovine fetus.

This study examines the response in plasma erythropoietin values to haemorrhage of 20% of the estimated blood volume in chronically cannulated ovine fetuses, of gestational ages 128-144 days. Blood samples were collected at 0, 2, 4, 6 and 24h with respect to the haemorrhage. In 5 control experiments there was no significant change in plasma erythropoietin concentration, across this time period, values being 6.1 +/- 2.3 and 6.4 +/- 2.4 mU/ml at 0 and 24h respectively. Values are mean +/- SEM. Haemorrhage reduced the haematocrit and haemoglobin values, significantly, to 83 +/- 6% and 85 +/- 4% (n = 5) of the initial value, respectively, but did not cause a statistically significant increase in plasma erythropoietin concentrations (7.2 +/- 2.4 and 20.7 +/- 8.2 mU/ml; P = 0.131). A larger degree of haemorrhage, in four fetuses reduced the haematocrit to 64 +/- 2.8% of initial, over 24-54h and increased erythropoietin values very significantly (from 11.9 +/- 3.6 to 91 +/- 8.3 mU/ml; P = 0.001).     

Iron metabolism in pigeons.

Several haematological parameters such as haemoglobin concentration, haematocrit, erythrocyte number, reticulocyte concentration, plasma iron and total iron binding capacity were determined in 118 urban pigeons of both sexes. No statistically significant sex differences among these parameters were found. In 36 specimens (23 males and 13 females), the plasma iron turnover was determined using 59Fe. The results obtained in this species, expressed per 100 ml-1 blood. day-1 and Kg-1 body weight. day-1, were compared with those of turkeys, ducks and chickens calculated from earlier papers. The highest values versus body weight were observed in pigeons. Organ (liver, spleen, tibia, heart, leg muscle, ribs, sternal keel, gonads and blood) distribution of 59Fe intravenous injection was analyzed during a period from 5 min up to 120 days (19 different times) in groups of 4 pigeons. At the 6 h period, the organs retained the highest dose (20% of total Fe injected), but by the 2nd day period, the radioiron in the blood represented about 98% of the total injected. A fast iron uptake by the circulatory blood was checked and compared with that of other species (domestic fowl, ducks and turkeys). The reticulocyte count in pigeons normally ranged from 4 to 12%, which was consistent with these results. A linear decreasing radioactivity in blood, with an inflexion point on the 40th day was observed. An inverse correspondence between blood and liver was found. Content in other organs decreased uniformly with time, except the heart where the iron content was practically constant during the whole time. Ribs and sternal keel are erythropoietic organs in young pigeons.     

Changes in plasma volume and red cell formation after a marathon competition

The purpose of this study was to investigate middle-term influences of a marathon race on plasma volume (PV) and red cell production. We performed the following measurements in the blood of 15 male athletes: haemoglobin ([Hb]), haematocrit (Hct), plasma protein concentration ([Prot]), plasma osmolality, sodium concentration ([Na+]), potassium concentration ([K+]), aldosterone concentration ([Aldo]), haptoglobin concentration ([Hpto]), and the reticulocyte count, as well as the calculation of relative changes in PV, 3 days before and on 3-consecutive days after a marathon race. By the 2nd day of recovery PV had increased by 16%. Plasma osmolality and [K+] remained constant, whereas [Na+] had decreased slightly 2 days after the competition and [Aldo] tended to be elevated 1 day after the competition. [Hpto] was low before and 1 day after the competition and increased on the following days. Reticulocyte count was unaffected 1 day after the race, but increased by 106% on the 2nd day and was still elevated after 3 days. The causes for higher post-marathon plasma volumes and reticulocyte counts could be in the complex variations in hormonal regulation, which have not yet been sufficiently investigated.     

Maximal oxygen uptake and erythropoietic responses after training at moderate altitude

Six well-trained male cross-county skiers trained for 7 days at 2700 m above sea level, their accommodation being at 1695 m. Blood samples for haemoglobin concentration [Hb], erythropoietin concentration [EPO] and reticulocyte count were collected before, during and after altitude exposure. Packed cell volume (PCV), red blood cell count (RBC), transferrin-iron saturation, mean red cell volume (MCV), mean corpuscular haemoglobin concentration (MCHC), maximal oxygen uptake, maximal achieved ventilation and heart rate were determined pre- and postaltitude exposure. The [EPO] increased significantly from pre-altitude (mean 36 mU.ml-1, SD 5) to maximal altitude values (mean 47 mU.ml-1, SD 3). The [Hb] had increased significantly above pre-altitude values (mean 8.8 mmol.l-1, SD 0.5) on day 2 (mean 9.1 mmol.l-1, SD 0.4) and day 7 (mean 9.4 mmol.l-1, SD 0.4) at altitude and on day 4 postaltitutde (mean 9.2 mmol.l-1, SD 0.4). The reticulocyte counts had increased significantly above pre-altitude values (mean 6%, SD 3%) on day 3 at altitude (mean 12%, SD 8%) and day 4 postaltitude (mean 10%, SD 5%). The RBC counts had increased on the 4th postaltitude day. The transferrin-iron saturation had decreased below pre-altitude values (mean 23%, SD 4%) on day 4 postaltitude (mean 14%, SD 5%) and had increased on day 11 postaltitude (mean 22%, SD 7%). There were no significant changes in MCV, MCHC, PCV, maximal oxygen uptake and maximal achieved ventilation, and heart rate pre- to postaltitude. These observations demonstrated an erythropoietic response to the altitude training which was not sufficient to increase the postaltitude maximal oxygen uptake.     

Immunoreactive erythropoietin concentration and haemoglobin type in the perinatal period in sheep of various haemoglobin genotypes

This study examines the hypotheses that (i) erythropoietin (the hormone responsible for red blood cell production) is higher in the fetus (at low PO2) than in the neonate (at high PO2); and (ii) that the level of erythropoietin in the neonate is influenced by the presence of high oxygen affinity haemoglobin. Haematocrit (PCV), PO2 and plasma immunoreactive erythropoietin were measured in 4 chronically cannulated fetal sheep (120 days to birth, n = 22) and in 7 neonatal lambs until 233 days post-conception (75-85 days after birth, n = 83). The percentage of globin chains (alpha, gamma, beta A, beta B, beta C) was quantitated by gel electrophoresis. Plasma erythropoietin values, in 4 fetuses were 9.8 +/- 1.3 mU/ml at 120-132 days of gestation, declined significantly (P less than 0.01) to 5.2 +/- 0.4 at 133 days until birth, then increased significantly (P less than 0.001) to 24.2 +/- 5.5(5), 26.3 +/- 7.3 (6), and 24.8 +/- 8.5 (6), respectively in weeks 1, 2 and 3 of postnatal life. By weeks 5-8 the erythropoietin was 13 +/- 0.6 (4) mU/ml. PO2 was 17.4 +/- 0.9 mmHg before birth and 88.0 +/- 10.7 in the first week after birth. PCV was constant until three weeks after birth and then declined. Fetal haemoglobin had virtually disappeared from the circulation by 166 days (3 weeks after birth); in the 4 heterozygotes (beta A beta B) beta C was expressed transiently, with a maximum value of 4%, whilst in the homozygote lamb (beta A beta A) the maximum beta C was 12%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Histidine for Treatment of Uraemic Anaemia

A group of 28 uraemic patients on dialysis treatment were given daily supplements of histidine by mouth. Plasma amino-acid concentration, plasma iron, serum transferrin, packed cell volume, and reticulocyte count were all measured before and after two months of histidine supplementation. The treatment raised the plasma histidine concentration and at the same time there was a rise in transferrin and iron levels and packed cell volume. Reticulocyte counts fell after two months of histidine supplementation.     

Effect of purified recombinant human erythropoietin on anemia in rats with experimental renal failure induced by five-sixth nephrectomy

Recombinant human erythropoietin (rHuEPO) was purified from the conditioned media of Chinese hamster ovary cells with a transfected human erythropoietin gene. We investigated the effects of the rHuEPO in rats with renal anemia induced by partial nephrectomy. Five-sixth nephrectomy resulted in renal failure with anemia. Twenty-five days after the operation plasma urea nitrogen was increased about 2.5 times, and the red blood cell count, hematocrit, and hemoglobin concentration fell to 85% of normal. The reticulocyte count and plasma erythropoietin level did not change such as they do in patients with anemia due to chronic renal failure. Both total red blood cell volume and the plasma iron turnover rate were depressed in five-sixth nephrectomized rats compared with normal rats.The five-sixth nephrectomized rats were injected with rHuEPO (60 IU/kg) intravenously every second day for a total of six injections. After three injections of rHuEPO, circulation volume of total red blood cells was increased from 9.9 ml to 14.6 ml, and the plasma iron turnover rate was increased from 1.03 mg/kg/day to 2.12 mg/kg/day, and the reticulocyte count was also increased. After six injections, a marked increase of the red blood cell count, hematocrit, and hemoglobin concentration were observed. Plasma urea nitrogen and the creatinine levels as indications for renal function did not change after rHuEPO administration in both normal and five-sixth nephrectomized rats.In conclusion rHuEPO has a potent erythropoietic action and it is possible to cure the anemia caused by renal failure.     

Iron and the liver. Acute and long-term effects of iron-loading on hepatic haem metabolism.

We have determined the dose-response curves (100-900 mg of Fe/kg body wt.) and the time course over 84 days for the effects of a single injection of iron-dextran on rat hepatic 5-aminolaevulinate synthetase, cytochrome P-450, iron content, and GSH (reduced glutathione). Porphyrins in liver and urine have also been measured. (1) At 2 days after treatment, a dose of 500 mg of Fe/kg produced a 20-fold increase in iron concentration, which was maintained for 14 days. Total hepatic iron remained constant over 63 days, falling slightly by 84 days. (2) The activity of 5-aminolaevulinate synthetase was maximally increased (6-fold) 12-24 h after iron treatment. By 48 h the activity fell to less than twice the control value and thereafter remained slightly above the control value (1.1-1.5-fold) until 84 days after iron treatment. Liver GSH concentrations were unaffected by iron. Porphyrins in liver and urine were either unchanged or decreased. (3) Hepatic cytochrome P-450 decreased after iron treatment to a minimum (63% of control) at 48 h after iron administration and gradually returned to the control value by 28 days. (4) Iron-dextran potentiated 2 allyl-2-isopropyl-acetamide-induced synthesis of hepatic 5-aminolaevulinate. Potentiation occurred if the drug was given at the same time or 36 h after iron administration, but did not occur if the drug was given 14 or 64 days after iron administration. (5) The results are discussed in relation to proposed mechanisms for the effects of iron on hepatic haem metabolism.     

Hepatocytes and reticulocytes have different mechanisms for the uptake of iron from transferrin

The uptake of iron from transferrin by isolated rat hepatocytes and rat reticulocytes has been compared. The results show the following. 1) Reticulocytes and hepatocytes express plasma membrane NADH:ferricyanide oxidoreductase activity. The activity, expressed per 10(6) cells, is approximately 60-fold higher in the hepatocyte than in the reticulocyte. 2) Hepatocyte plasma membrane NADH:ferricyanide oxidoreductase activity and uptake of iron from transferrin are stimulated by low oxygen concentration and inhibited by iodoacetate. In reticulocytes, similar changes are seen in NADH:ferricyanide oxidoreductase activity, but not on iron uptake. 3) Ferricyanide inhibits the uptake of iron from transferrin by hepatocytes, but has no effect on iron uptake by reticulocytes. 4) Perturbants of endocytosis and endosomal acidification have no inhibitory effect on hepatocyte iron uptake, but inhibit reticulocyte iron uptake. 5) Hydrophilic iron chelators effectively inhibit hepatocyte iron uptake, but have no effect on reticulocyte iron uptake. Hydrophobic iron chelators generally inhibit both hepatocyte and reticulocyte iron uptake. 6) Divalent metal cations with ionic radii similar to or less than the ferrous iron ion are effective inhibitors of hepatocyte iron uptake with no effect on reticulocyte iron uptake. The results are compatible with hepatocyte uptake of iron from transferrin by a reductive process at the cell surface and reticulocyte iron uptake by receptor-mediated endocytosis.     

Total body haematocrit iron kinetics and erythrocyte life span in pigeons (Columba livia)

1. The mean pigeon erythrocyte life span was found to be 17-25 days by Cr51-labeled erythrocytes and 21 +/- 3.4 days by iron kinetics. 2. Total red blood cell volume has been calculated by Cr51-labeled erythrocytes while total plasma volume was determined both by a dye method and iron kinetic data. From these results total blood volume and total body haematocrit were found to be 0.090 +/- 0.002 ml/g body wt and 36 +/- 4.3%, respectively. 3. Venous haematocrit, haemoglobin concentration, erythrocyte count, mean corpuscular haemoglobin concentration, plasma iron and red blood cell iron have also been measured. 4. A significant difference between total body and venous haematocrit and a short mean red blood cell life span, due to ageing and to random destruction of erythrocytes were shown. 5. The above observations are compared with analogous available data for human beings and their physiological significance is discussed.     

Polymorphism at the porcine Dominant white/KIT locus influence coat colour and peripheral blood cell measures

We have examined the phenotype of different KIT genotypes with regard to coat colour and several blood parameters (erythrocyte numbers and measures, total and differential leucocyte numbers, haematocrit and haemoglobin levels and serum components). The effect of two different iron supplement regimes (one or two iron injections) on the blood parameters was also examined. For a total of 184 cross-bred piglets (different combinations of Hampshire, Landrace and Yorkshire) blood parameters were measured four times during their first month of life, and the KIT genotypes of these and 70 additional cross-bred piglets were determined. Eight different KIT genotypes were identified, which confirms the large allelic diversity at the KIT locus in commercial pig populations. The results showed that pigs with different KIT genotypes differ both in coat colour and in haematological parameters. In general, homozygous Dominant white (I/I) piglets had larger erythrocytes with lower haemoglobin concentration, indicating a mild macrocytic anaemia. The effect of two compared with one iron injection was also most pronounced for the I/I piglets.     

Exercise-Induced Changes in Iron Status and Hepcidin Response in Female Runners

Background and Aims

Exercise-induced iron deficiency is a common finding in endurance athletes. It has been suggested recently that hepcidin may be an important mediator in this process.

Objective

To determine hepcidin levels and markers of iron status during long-term exercise training in female runners with depleted and normal iron stores.

Methods

Fourteen runners were divided into two groups according to iron status. Blood samples were taken during a period of eight weeks at baseline, after training and after ten days’ recovery phase.

Results

Of 14 runners, 7 were iron deficient at baseline and 10 after training. Hepcidin was lower at recovery compared with baseline (p<0.05). The mean cell haemoglobin content, haemoglobin content per reticulocyte and total iron binding capacity all decreased, whereas soluble transferrin receptor and hypochromic red cells increased after training and recovery (p<0.05 for all).

Conclusion

The prevalence of depleted iron stores was 71% at the end of the training phase. Hepcidin and iron stores decreased during long-term running training and did not recover after ten days, regardless of baseline iron status.     

Cost benefits of low dose subcutaneous erythropoietin in patients with anaemia of end stage renal disease.

OBJECTIVE--To assess the cost benefits of low dose subcutaneous recombinant human erythropoietin in correcting the anaemia of end stage renal disease. DESIGN--Three year retrospective study. SETTING--Subregional nephrology service serving a mixed urban and rural population of 800,000. SUBJECTS--60 patients with symptoms of anaemic end stage renal disease treated with erythropoietin (43 receiving haemodialysis; 11 receiving continuous ambulatory peritoneal dialysis; two with predialysis end stage renal disease; four with failing renal transplants). MAIN OUTCOME MEASURES--Costs and savings of achieving and maintaining a haemoglobin concentration of 85-105 g/l with erythropoietin. RESULTS--All patients treated with erythropoietin achieved the target haemoglobin concentration at median induction doses of 97 (95% confidence interval 95 to 108) units/kg/week, and this was maintained with 79 (75 to 95) units/kg/week at an average annual cost per patient of 2260 pounds. Admissions related to anaemia were virtually eliminated (246 v 1 inpatient days for 12 months before and after starting erythropoietin). 54 patients required no blood transfusions after starting erythropoietin, and the total requirements fell from 230 to 21 units in the 12 months before and after starting erythropoietin. Iron stores were maintained with oral or intravenous iron. All patients reported increased wellbeing, appetite, and exercise capacity. Hypertension developed or worsened in 30 patients, resulting in hospital admissions in five patients, one of whom had seizures. CONCLUSION--Low dose subcutaneous erythropoietin restores haemoglobin concentrations sufficiently to abolish blood transfusion requirements and reduce morbidity. The net cost of erythropoietin prescribed in this way (2260 pounds/patient/year) was largely offset by savings in costs of hospital admissions. The true annual cost to the NHS was around 1200 pounds per patient.     

Plasma growth hormone, insulin-like growth factor-I, and milk production responses to exogenous human growth hormone-releasing factor analogs in dairy cows

Responses of plasma growth hormone (GH) and insulin-like growth factor-I (IGF-I), and milk production to subcutaneous (sc) injection(s) of two synthetic human growth hormone-releasing factor (hGRF) analogs were studied in dairy cows. Two mg of each hGRF analog dissolved in 5 ml saline per cow were injected into the shoulder area of each experimental animal, and jugular venous blood samples were collected via an indwelling catheter or by venipuncture. Plasma GH and IGF-I concentrations were measured by radioimmunoassay methods. In dry cows, the mean concentration of plasma GH after a single sc injection of hGRF analogs rose to 22.0-28.3 ng/ml at about 5 h from 1.4-1.7 ng/ml at 0 h (just before injection), and returned to the level before injection after 10-12 h. On the other hand, the plasma IGF-I began to increase after a lag of 4-6 h following a single injection of hGRF analogs, and reached maximum values of 71.1-89.4 ng/ml at 20 h from 43.7-46.4 ng/ml at 0 h. The IGF-I concentration at 24 h after a single injection of hGRF analogs was still higher than the value for the dry cows given saline. In lactating cows, the plasma concentration of GH at 2 h after daily sc injections of hGRF analogs during 14 consecutive days (an injection period) was higher than those for the lactating cows which received saline. Also, during the injection period, the concentration of IGF-I was higher in the lactating cows which received hGRF analog injections than in the cows which received saline injections. During the last 7 days of the injection period, the administration of hGRF analogs increased the mean milk yield by 11-19% in comparison with those for the saline injected cows. A positive correlation was observed between the mean plasma IGF-I concentration and the mean milk yield in the lactating cows treated with hGRF analogs throughout the injection and a postinjection (11 consecutive days after cessation of hGRF analog injection) periods. The results demonstrate that a single sc injection of hGRF analogs stimulates both GH release and the circulating level of IGF-I in dry cows, and that daily sc injections of hGRF analogs over 14 days enhance milk production, and plasma GH and IGF-I levels in lactating cows.     

Prophylactic effects of dexamethasone in lung injury caused by hyperoxia and hyperventilation.

To determine if prophylactic corticosteroids would prevent acute lung injury caused by hyperoxia and barotrauma, 29 piglets (1.2 +/- 0.3 kg, 1-2 days of age) were studied. Ten piglets were hyperventilated [arterial PCO2 (PaCO2) 15-20 Torr] with 100% O2 for 48 h and compared with 10 piglets treated with the identical management but given 0.7 mg/kg of dexamethasone at time 0 and every 12 h for the 48-h study. Six piglets were normally ventilated (PaCO2 40-45 Torr) for 48 h with 21% O2 as an additional control group. Pulmonary function and tracheal aspirates were examined at time 0 and every 24 h. Bronchoalveolar lavage was performed for surfactant analyses at the conclusion of the study. In animals treated with hyperoxia and hyperventilation, lung compliance decreased 32% and tracheal aspirate polymorphonuclear leukocyte (PMN) chemotactic activity increased by 51%, cell counts by 204%, number of PMNs by 277%, elastase activity by 111%, and albumin concentration by 328% over 48 h (P less than 0.05). In contrast, dexamethasone-treated piglets had increases in only tracheal aspirate albumin concentration (206%) over the 48-h study. All cellular and biochemical variables were lower in dexamethasone-treated compared with hyperoxic hyperventilated piglets. Room air normal ventilation controls had only a 108% increase in tracheal aspirate albumin concentration noted. Despite quantitative differences in surfactant among the three groups, activity was unaffected. Results indicate that hyperoxia and hyperventilation for 48 h causes significant inflammatory changes and acute lung injury and that prophylactic high-dose dexamethasone significantly ameliorates this lung damage.     

Haematological effects of stress on a teleost, Esox lucius L.

Stress produces a haemoconcentration, elevated blood lactate, increased glucose concentrations and alters the plasma electrolyte balance in two groups (brackish- and freshwater) of the northern pike, Esox leucius L., after one month's starvation. A method for dorsal aorta catheterization and a receptacle for cannulating fish is described.
The blood glucose level of the freshwater pike was twice that of the brackish-water group, and the plasma sodium and magnesium concentrations in the brackish-water pike were significantly higher. The haematocrit, haemoglobin and blood lactic acid concentrations were higher in freshwater pike. The plasma potassium and calcium concentrations in the two groups did not differ.
Haemoconcentration due to stress by handling for 1.5 min was shown by changes in haematocrit and haemoglobin values. The haemoglobin concentration returned to normal in freshwater pike after 4 h but in brackish-water pike after 12 h.
As a result of handling, the blood lactic acid level rose steeply and required 12 h to return to normal.
The blood glucose concentration rose to its maximum value within 1 h of handling and required two days to return to normal.
The plasma sodium level remained stable after handling, but the potassium level was erratic. In brackish-water, the potassium concentration of the pike remained high for 12 h after stress, but in the freshwater group, after a rise, the concentration fell to below the initial level within 4 h. The changes of the potassium concentrations in relation to sampling time are discussed. The changes in the divalent ion concentrations were marked and similar in the two groups; with an increase lasting 1–4 h and then a fall below the initial level, which was regained after two days.     

Induction of porphobilinogen oxygenase and porphobilinogen deaminase in rat blood under conditions of erythropoietic stress

Porphobilinogen is the substrate of two enzymes: porphobilinogen deaminase and porphobilinogen-oxygenase. The first one transforms it into the metabolic precursors of heme and the second diverts it from this metabolic pathway by oxidizing porphobilinogen to 5-oxopyrrolinones. Rat blood is devoid of porphobilinogen-oxygenase under normal conditions while it carries porphobilinogen-deaminase activity. When the rats were submitted to hypoxia (p_O2 = 0.42 atm) for 18 days, the activity of porphobilinogen-oxygenase appeared at the tenth day of hypoxia and reached the maximum at the 14–16th day. It decreased to a half after 2 days (half-life of the enzyme) and disappeared after 4 days of return to normal oxygen pressure. Porphobilinogen-deaminase activity increased after the first day of hypoxia, reached a maximum at the 14–16th day and did not decrease to normal values until the 15th day after return to normal oxygen pressure. The activities of both prophobilinogen-oxygenase and porphobilinogen-deaminase were induced by administration of erythropoietin. When rats were made anaemic with phenylhydrazine, porphobilinogen-oxygenase activity also appeared in the blood cells. Although the reticulocyte concentration was higher when compared to that obtained under hypoxia, the activities of the oxygenase obtained under both conditions were comparable. Porphobilinogen-deaminase activity was always closely related to the reticulocyte content. The appearance of porphobilinogen-oxygenase under the described erythropoietic conditions was due to a de novo induction of the enzyme, as shown by its inhibition with actinomycin D and cycloheximide. Porphobilinogen-oxygenase as well as porphobilinogen-deaminase were present in the rat bone marrow under normal conditions. Their activities increased in phenylhydrazine treated rats. The properties and kinetics of porphobilinogen-oxygenase from the rat blood and bone marrow were determined and found to differ in several aspects.     

The effect of copper excess on iron metabolism in sheep.

Sheep were treated with large amounts of copper (20 mg of CuSO4,5H2O/kg body wt. per day) for 9 weeks to examine the effect of copper excess on iron metabolism. In addition to confirming that massive haemolysis and accumulation of copper occurs in the liver, kidney and plasma after 7 weeks of exposure to excess copper, it was observed that excess copper produced an increased plasma iron concentration and transferrin saturation within 1 week. Further, iron preferentially accumulated in the spleen between 4 and 6 weeks of copper treatment, producing 3-fold increases in the iron content of both the ferritin and non-ferritin fractions. A 3-4 fold increase was also observed in the amount of ferritin that could be isolated from the spleen. The copper treatment had little or no effect on the concentration of iron in the liver and bone marrow. The following properties of erythrocytes were also unaffected by copper treatment: size, haemoglobin content and pyruvate kinase activity, although the erythrocyte concentration of copper increased after 6 weeks. Copper accumulated in the spleen between 6 and 9 weeks, probably owing to the phagocytosis of erythrocytes containing high concentrations of copper. The data suggest that copper excess influences iron metabolism, initially by causing a compensated haemolytic anaemia, and later by interfering with re-utilization of iron from ferritin in the reticuloendothelial cells of the spleen.     

血红蛋白总量在运动员生物护照兴奋剂检测中的意义

目的：观察注射微量重组人促红细胞生成素（rHuEPO）后,受试者在不同时间段血液某些参数指标的变化,为兴奋剂rHuEPO检测运动员生物护照（ABP）提供实验依据。方法：采用单盲方式对14名健康青年男性受试者进行两个阶段随机安慰剂（n=14）和微量rHuEPO（n=14）皮下注射,每阶段7周,每周2次。EPO注射期间给予每天口服铁剂105 mg;在注射前第7日、第一次注射后第3、10、17、24、31、38和45日、以及第7周最后一次注射后第7、14、21日分别采取静脉血测试血液基础参数（红细胞、血红蛋白浓度[Hb]、红细胞压积、网织红细胞）,改良一氧化碳（CO）吸入法测试血红蛋白总量（tHb）以及全血量（BV）、血浆量（PV）的变化情况;分析这些指标在ABP中的使用,观察总量指标和浓度指标在检测中的有效性和时效性。结果：与安慰剂组相比,14名受试者在微量rHuEPO注射后第2周,即开始出现红细胞数量和[Hb]增加,在注射期间第5~6周达到高峰（分别增加9%和10%左右,P<0.01）,一直持续到最后一次注射后3周左右;tHb在注射后1周即开始增加,5周达到最高峰（增加10%左右,P<0.01）并一直持续到最后一次注射后1周才开始逐级恢复到注射前水平;红细胞总量在实验第5周上升至峰值,幅度为10.89%（P<0.01）,总血量（BV）变化不明显,血浆量（PV）出现下降,血液浓缩。结论：7周微量rHuEPO注射可以显著增加血液总量指标和浓度指标,其中血红蛋白总量更加敏感,可以用ABP血红蛋白总量等监测微量EPO注射;在最后一次注射结束后,血液总量指标如血红蛋白总量恢复正常,而浓度指标仍保持较高水平,可能是血液浓缩的结果。     

Effect of iron therapy on platelet counts in patients with inflammatory bowel disease-associated anemia

Background and Aims

Secondary thrombocytosis is a clinical feature of unknown significance. In inflammatory bowel disease (IBD), thrombocytosis is considered a marker of active disease; however, iron deficiency itself may trigger platelet generation. In this study we tested the effect of iron therapy on platelet counts in patients with IBD-associated anemia.

Methods

Platelet counts were analyzed before and after iron therapy from four prospective clinical trials. Further, changes in hemoglobin, transferrin saturation, ferritin, C-reactive protein, and leukocyte counts, before and after iron therapy were compared. In a subgroup the effect of erythropoietin treatment was tested. The results were confirmed in a large independent cohort (FERGIcor).

Results

A total of 308 patient records were available for the initial analysis. A dose-depended drop in platelet counts (mean 425 G/L to 320 G/L; p<0.001) was found regardless of the type of iron preparation (iron sulphate, iron sucrose, or ferric carboxymaltose). Concomitant erythropoietin therapy as well as parameters of inflammation (leukocyte counts, C-reactive protein) had no effect on the change in platelet counts. This effect of iron therapy on platelets was confirmed in the FERGIcor study cohort (n=448, mean platelet counts before iron therapy: 383 G/L, after: 310 G/L, p<0.001).

Conclusion

Iron therapy normalizes elevated platelet counts in patients with IBD-associated anemia. Thus, iron deficiency is an important pathogenetic mechanism of secondary thrombocytosis in IBD.