Bone Marrow Iron Content Research Articles

Relationship between bone marrow iron load and liver iron concentration in dialysis-associated haemosiderosis

Iron overload due to the excessive use of parenteral iron in haemodialysis is now an increasingly recognised clinical issue. Before erythropoiesis-stimulating agents (ESA) were introduced, a specific feature of patients treated by dialysis and having iron overload was that iron levels in the bone marrow were paradoxically low in most of them, despite severe hepatosplenic siderosis. Whether or not this paradox persists in the actual ESA era was unknown until recently, when an autopsy study in 21 patients treated by haemodialysis revealed similarities between liver and bone marrow iron content. The aim of this study was to further explore these recent findings in a cohort of alive patients on dialysis and to analyse the determinants of iron bone marrow. Liver iron concentration (LIC) and vertebral T2∗ (a surrogate marker of bone marrow iron) were analysed retrospectively in 152 alive patients on dialysis (38.8% female) of whom 47.4% had iron overload by quantitative magnetic resonance imaging (MRI). Vertebral T2∗ differed significantly between patients classified according to liver iron content at MRI: those with mild or moderate and severe liver iron overload had increased vertebral iron content at R2∗ relaxometry MRI (mild: vertebral T2∗=9.9ms (4-24.8); moderate and severe: vertebral T2∗=8.5ms (4.9-22.8)) when compared to patients with normal LIC (vertebral T2∗=13.2ms (6.6-30.5) (p<0.0001 Kruskal-Wallis test)). The paradoxical discrepancy between bone marrow and liver iron-storage compartments observed in the pre-ESA era has disappeared today, as shown by a recent autopsy study and the present study in a cohort of alive patients treated by dialysis. None.

Assessment of bone marrow iron stores using Gale's grading and its correlation with iron deficiency anemia

Background: Iron deficiency anemia (IDA) is a very common condition worldwide, especially in low- and middle-income countries. The most accurate method to evaluate iron status is the measurement of bone marrow iron content by potassium ferrocyanide (Prussian blue)-stained aspirate. Microscopic examination of Prussian blue-stained bone marrow aspirate has been considered the “gold standard” for determining iron-depleted states. Aim: The aim of this study was to assess and classify the iron status in the bone marrow by both Gale's and intensive method, thereby differentiating iron store deficiency from functional deficiency. Methods: The present study was carried out in the Department of Pathology, Government Medical College and Hospital, Jammu, over a period of 1 year. A total of 135 cases of anemia with hemoglobin <10 g/dl were included in the study. Bone marrow aspiration was done; iron assessment was done by both Gale's and intensive method. Iron status assessed by the intensive method was categorized as normal, functional iron deficiency, iron stores deficiency, or combined functional iron and iron stores deficiency. Results: A total of 135 cases were included in the study, out of which 47% (64/135) were male and 53% (71/135) were female. Gale's study revealed hypoferrimic state in only 40 cases out of 135 (29.6%). According to the intensive method, out of these 40 cases, only nine cases were truly deficient cases that too had combined deficiency, two cases had iron store deficiency, 25 cases had functional iron deficiency, and four cases had normal iron stores. In the present study, according to the intensive method, maximum number of cases had functional iron deficiency (54%, 73/135). There were 1.4% (2/135) pure iron-deficient cases and 11.1% (15/135) revealed combined deficiency. Conclusion: Differentiation between IDA and functional iron deficiency is important for accurate diagnosis and treatment of the patient. Although intensive method of grading iron requires more expertise, it has proved to be superior and has more precision in diagnosing iron-deficient cases.

Quantifying Bone Marrow Fat Fraction and Iron by MRI for Distinguishing Aplastic Anemia from Myelodysplastic Syndromes.

BackgroundBone marrow of patients with aplastic anemia (AA) is different from that of patients with myelodysplastic syndrome (MDS) and is difficult to identify by blood examination. IDEAL‐IQ (iterative decomposition of water and fat with echo asymmetry and least‐squares estimation) imaging might be able to quantify fat fraction (FF) and iron content in bone tissues.PurposeTo determine if IDEAL‐IQ measurements of bone marrow FF and iron content can distinguish between patients with AA and MDS.Study TypeRetrospective.PopulationFifty‐seven patients with AA, 21 patients with MDS, and 24 healthy controls.Field Strength/Sequence3.0 T, IDEAL‐IQ sequence.AssessmentThree independent observers evaluated the IDEAL‐IQ images and measured FF and R2* in the left posterior superior iliac spine.Statistical TestsKruskal–Wallis test, linear correlations, and Bland–Altman analysis were used. A P‐value of <0.05 was considered statistically significant.ResultsThe FF in patients with AA (79.46% ± 15.00%) was significantly higher than that in patients with MDS (42.78% ± 30.09%) and control subjects (65.50% ± 14.73%). However, there was no significant difference in FF between control subjects and patients with MDS (P = 0.439). The R2* value of AA, MDS, and controls was 145.38 ± 53.33, (171.13 ± 100.89, and 135.99 ± 32.41/second, respectively, with no significant difference between the three groups (P = 0.553).Data ConclusionQuantitative IDEAL‐IQ magnetic resonance imaging may facilitate the diagnosis of AA and distinguish it from MDS.Level of Evidence3Technical Efficacy Stage2

Serum or plasma ferritin concentration as an index of iron deficiency and overload.

Serum or plasma ferritin concentration as an index of iron deficiency and overload.

Hepcidin-Mediated Ferroportin Control in the Bone Marrow Is Dispensable

25 mg of iron are required every day to sustain hematopoiesis in the bone marrow. Most iron is consumed by erythroid cells that take up transferrin-bound iron to satisfy their demand for hemoglobin biogenesis. Unexpectedly, erythroblasts express high levels of the iron exporter Ferroportin (Fpn). Fpn surface expression and activity is controlled by Hepcidin, a small liver peptide hormone, produced in response to elevated systemic and tissue iron availability. Resistance of ferroportin to hepcidin binding is caused by a gain of function mutation in the FpnC326S residue, which is the reason for iron overload in patients with Hereditary Hemochromatosis type 4. Some years ago we generated the corresponding mouse model hallmarked by this constitutively active iron exporter. We now applied bone marrow transplantation to investigate the role of the hepcidin/ferroportin regulatory system in cell types of the bone marrow (BM-FpnC326S). CD45.1 host mice were irradiated twice with 500 cGy 4h apart and injected with 2 million of BM cells obtained from C57BL/6N mice (control) or from C57BL/6N congenic constitutive FpnC326S animals. Mice were analyzed three months after transplantation, whereby only animals with an engraftment higher than 95% were included for further analyses. Analysis of the erythroid hematological parameters revealed mild macrocytosis in the presence of unaltered red blood cell count (RBC), hematocrit (HCT), hemoglobin (Hb) and mean corpuscular hemoglobin (MCH) values. Serum iron content, transferrin saturation and serum hepcidin levels remained unchanged, despite a strong decrease in splenic iron levels within the red pulp, where reticuloendothelial macrophages are located. The latter phenotype is consistent with high ferroportin surface expression in macrophages derived from FpnC326S monocytes that causes increased iron export and cellular iron deficiency. Cytokine production (IL1β, TNFα and IL6) in the spleen was unchanged suggesting that iron deficiency in splenic macrophages did not cause inflammation. In contrast to the spleen iron content was not changed in other organs analyzed, including the liver, suggesting that de novo monocyte infiltration is not a major feature in these organs. Interestingly, histological analysis of the femurs revealed a marked decrease in bone marrow iron content; we were unable to detect a single iron-stained cell in the bone marrow of BM-FpnC326S mice, contrasting results from control mice. To investigate whether iron deficiency in bone marrow cells alters numbers of immune cells, we performed a detailed characterization by FACS. Unexpectedly, iron deficiency in the bone marrow did not cause changes in total bone marrow cellularity, total numbers of Ter119+ erythroid cells and the percentage of different erythroblast subpopulations, the number of hematopoietic stem cells (HSC) and of common lymphoid (CLP), myeloid (CMP) and megakaryocyte/erythroid (MEP) progenitors. Taken together, our data clearly demonstrate that at steady state, the hepcidin/ferroportin regulatory circuitry in the bone marrow is dispensable and that iron deficiency in bone marrow cells is not altering the normal hematopoietic process. Future studies will have to extend the analysis to stress conditions. Disclosures Muckenthaler: Novartis: Research Funding; Silence Therapeutics: Consultancy.

Disbalanced Erythroid Ferroportin Expression Contributes to Ineffective Erythroid Output in Anemia of Chronic Disease

Iron is essential for proper red blood cell development. During erythroid maturation in the bone marrow iron dependency starts at the basophilic stage, and lasts until the reticulocyte stage. Thereby the majority of iron is delivered in a Tf-TfR dependent manner and is incorporated in hemoglobin of developing red cells. Just recently, it has been discovered that erythroblasts and mature red blood cells not only incorporate iron but also express the sole known iron exporter, ferroportin (Fpn), throughout their development, and thus can also effectively export iron that is not used for heme synthesis. Fpn surface expression is regulated via hepcidin, a hepatocyte-derived peptide, which binds directly to surface-Fpn, inducing its internalization and consequent degradation in lysosomes. Among patients suffering from anemia of chronic disease (ACD), hepcidin is constantly induced due to long-lasting inflammation, leading to impaired iron export capacity. While splenic tissue iron overload, which is associated with the restricted capacity of red pulp macrophages to export recycled iron form degraded erythrocytes is well established, the effect of high hepcidin levels in ACD and its consequences on developing erythroblasts in the bone marrow has not been investigated. First we induced chronic kidney disease (CKD) in C57BL/6 mice via an Adenine - diet. Alongside microcytic anemia, reduced Tf-saturation, increased hepcidin levels and splenic tissue iron overload, we found a ~38% increase in tissue iron content in bone marrows of CKD mice compared to control mice. In parallel, Western blot analysis revealed massively reduced Fpn protein levels in the bone marrow. Moreover, the individual iron-dependent erythroblast precursor populations (i.e. basophilic, polychromatic, orthochromatic erythroblasts and reticulocytes) showed higher levels of intracellular iron as measured by Calcein fluorescence via flow cytometry. We could further corroborate these results by Western blot analysis and flow cytometric work-up of reticulocytes and mature red blood cells in the blood stream, both revealing highly reduced Fpn protein levels on these cells in mice suffering from CKD. Based on these findings we performed additional experiments to investigate the detrimental effect of iron overload on erythroid development and to exclude the possibility of a direct inflammation-regulated process in the CKD model. Therefor we established an iron-overload mouse model via repeated parenteral iron dextran applications. Despite significantly increased Tf-saturation levels as well as hepatic hepcidin levels (&amp;gt;4-fold) and reduced bone marrow Fpn protein levels among iron-treated mice, iron overload led to higher stress levels among erythroid precursor populations. In detail, we could demonstrate via flow cytometry that higher intracellular iron pools (measured by Calcein), correlated with higher levels of mitochondrial stress and higher levels of lipid peroxidation (determined by mean fluorescence intensity of MitoSOX and Bodipy 581/59, respectively). These data indicate that iron is a critical regulator of stress during erythroid development and can be regulated via the hepcidin-Fpn axis. In conclusion, we clearly show that Fpn expression on erythroid precursor cells is inversely regulated to systemic hepcidin levels and affects the erythropoietic bone marrow iron content. Moreover our results reveal a novel model for ineffective erythroid output in patients suffering from ACD due to hepcidin-triggered Fpn internalistation. Based on our data, anti-hepcidin treatment strategies are promising to overcome restricted erythropoiesis, which will be evaluated in future experiments. Disclosures Theurl: Kymab Ltd: Consultancy, Equity Ownership.

Increased Bone Marrow Iron Scores Are Strongly Correlated With Elevated Serum Ferritin Levels and Poorer Survival in Patients With Iron Overload That Underwent Allogeneic Hematopoietic Stem Cell Transplantation: A Single Center Experience.

Iron overload is one of the most significant problems as a leading cause of death in patients with leukemia and those who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). In the current study, we retrospectively evaluated the bone marrow iron scores (BMIS) in patients who underwent alloHSCT (n= 125). The first available bone marrow biopsy specimens prior to the alloHSCT procedure or date of hospitalization (control group) were assessed in a blinded fashion using a standardized scoring system. A total of 125patients were enrolled in the study. Seventy-six (60.8%) of the patients were male, and 49 (39.2%) were female. The median level of pre-transplant serum ferritin was 1023.00 ng/mL (range, 393.80-1627.50 ng/mL). The majority of the patients were diagnosed with acute leukemia (83; 66.4%) and lymphomas (20; 16.0%). The median time for neutrophil engraftment was 14.00 days (range, 13.00-16.00 days) and 11.00 days (range, 10.00-14.00 days) for platelet engraftment. The peri-transplant mortality was similar to international mortality rates (3; 2.4%). The overall survival and disease-free survival were strongly correlated with the degree of BMIS, and both were significantly poorer in patients with high bone marrow iron content (P< .001 and P= .012, respectively). The validation of BMIS for risk stratification in patients who undergo alloHSCT may predict posttransplant outcomes.

Bone Marrow Iron Assessment By MRI-R2* and Its Relation to Deferasirox Treatment in Patients with Iron Overload

Objective: Patients with iron overload suffer from different organ damage due to increased iron concentration. Iron overload in the bone marrow and the influence of iron chelation therapy on bone marrow iron content may play an additional role in these patients and is until now not well examined.Material and Methods: We performed MRI-R2* measurements in the vertebral bone marrow using water-fat chemical shift relaxometry for estimation of iron and fat content in comparison to hepatic and splenic iron concentrations and serum ferritin in patients with iron overload due to hereditary hemochromatosis (HHC) and patients with siderosis due to red blood cell transfusions and /or iron loading anemia.112 patients with iron overload, mean age: 32 y (transfusion dependent thalassemia major (TM) n=65, Diamond-Blackfan anemia (DBA) n=12, HHC n=10, iron loading anemia (EA) n=7, transfusion siderosis n=12 and stem cell transplantation n=6) and 14 control subjects underwent MRI for determination of the transverse relaxation rate R2*assessed from ROI based signal intensities of one transversal slice (10mm) through the liver, spleen, and mid-vertebral bone marrow.Breathhold water-fat relaxometry (12 echo times, TE=1.3-26ms, FA=20°, bandwidth=1955Hz/px) was performed to determine apparent fat contents (aFC) and bone marrow R2*. Additionally, serum ferritin values were assessed.In 67 patients with TM under chelation therapy with Deferasirox (DFX) we compared R2* bone marrow iron content with the ratio of the chelator dose rate (Deferasirox, [mmol/d]) to the total liver iron (LivFe = LIC*volume [g-Fe]).Results: Relative to controls (n=14, R2* = 95s-1) and HHC (n=10, R2* = 95s-1), median bone marrow R2* rates were significantly increased in patients with TM (n=65, R2* = 398s-1, p<10-4) or DBA (n=12, R2* = 252s-1, p = 0.005). R2* of the bone marrow significantly correlated with serum ferritin (rS=0.52, p<10-4), splenic R2* (rS=0.43, p<10-4), cardiac R2* (rS=0.43, p<10-4), and hepatic R2* (rS=0.37, p<10-4). No significant correlation of aFC with marrow R2* could be obtained.The bone marrow iron content was higher in patients with a low Deferasirox (DFX) dose. A DFX dose > 150 (mmol/d)/g-Fe was a negativ predictor for increased bone marrow iron content (R2* > 700 1/s), but a significant correlation couldn't be found (r = 0,077), probably due to the low number of patients. The efficacy dose of DFX for a low bone marrow iron content seems to lay between a dose of 1mmol/d (18mg/d) and 2,5 mmol/d (45mg/d). A DFX dose > 2,5 mmol/d didn't seem to increase the efficacy.Table 1Diagnosis (n)Age Median (IQR)KM R2* [s-1 ] Median (IQR)KM R2* 95 % rangeControl group (14)29.8 (26.0)95 (43)62 - 134TM ( 65)30.6 (16.2)398 (455)73 - 1213HH (10)56.4 (9.3)95 (40)61 - 270EA (7)46.6 (24.8)191 (93)159 - 490DBA (12)27,6 (14.6)252 (250)62 - 652TS(12)32.3 (46.2)322 (304)116 - 607BMT (6)20 (20.8)285 (342)105 - 470Conclusion: Water-fat chemical shift relaxometry allows precise determination of bone marrow R2* rates and estimation of the apparent fat content, which may add additional information to these patients. Patients with transfusion related iron overload have significant higher bone marrow iron content than patients with iron overload due to hereditary hemochromatosis. DFX in an adäquat dose seem to prefent bone marrow iron overload. DisclosuresGrosse:Swedish Orphan Biovitrum: Honoraria; Novartis Oncology: Honoraria, Research Funding.

Magnetic resonance imaging to identify classic and nonclassic forms of ferroportin disease

The ferroportin-related disorder is an increasingly recognized cause of hereditary iron overload. Based on the in vitro behavior of different ferroportin mutant subsets, it was suggested that different forms of the disorder might exist in humans. We used MRI to address this question in vivo in 22 patients from four different pedigrees carrying different ferroportin mutations: A77D, N144H, G80S and Val 162del. We found that, based on the iron status of spleen and bone macrophages, two different forms of the disease can be identified: a classic, common form, characterized by hepatocyte, splenic macrophage and bone marrow macrophage iron retention in patients carrying the A77D, G80S and Val 162del ferroportin variants; a rarer non-classic form, associated with liver iron overload but normal spleen and bone marrow iron content in patients with the N144H mutation. The two forms are likely caused by lack- or gain-of-protein function, respectively. Interestingly, in treated patients with the classic form, the spleen and the spine show appreciable iron accumulation even when serum ferritin is normal and liver iron content low. In conclusion, MRI is a useful non-invasive diagnostic tool to categorize and diagnose the disorder, monitor the status of iron depletion and gain insights on its natural history and management.

Prediction of iron deficiency in chronic inflammatory rheumatic disease anaemia.

We prospectively studied 45 anaemic patients (37 women, 8 men) with chronic inflammatory rheumatic diseases. The combination of serum ferritin and CRP (as well as ESR) in its predictive capacity for bone marrow iron stores was examined. The relationship between other iron-related measurements (transferrin, transferrin saturation, soluble transferrin receptor, erythrocyte porphyrins and percentage of hypochromic/microcytic erythrocytes) and bone marrow iron stores was also investigated. Stainable bone marrow iron was taken as the most suitable standard to separate iron-deficient from iron-replete patients. 14 patients (31%) were lacking bone marrow iron. Regression analysis showed a good correlation between ferritin and bone marrow iron (adjusted R2 = 0.721, P < 0.0001). The combination of ferritin and CRP (ESR) did not improve the predictive power for bone marrow iron (adjusted R2 = 0.715) in this cohort of patients with low systemic inflammatory activity. With respect to the bone marrow iron content the best predictive cut-off value of ferritin was 30 micrograms/l (86% sensitivity, 90% specificity). The other iron-related parameters both individually and when combined were less powerful in predicting bone marrow iron than ferritin alone. Only zinc bound erythrocyte protoporphyrin in combination with ferritin slightly improved prediction (adjusted R2 = 0.731). A cut-off point of 11% hypochromic erythrocytes reached a high specificity (90%), but was less sensitive (77%).

Quantitative Determination of Non-Haem Iron and Ferritin Iron in Bone Marrow Using Flameless Atomic Absorption Spectrophotometry. A Comparative Study on the Cytological and Chemical Determination of the Bone Marrow Iron Content

A method for non-haem iron analysis in bone marrow aspirates using graphite furnace atomic absorption spectrophotometry has been developed. Bone marrow aspirates were obtained from patients with various disorders. A good correlation is observed between chemical and cytological assessment of total non-haem iron in bone marrow. An intra-assay coefficient of variation of 9.0% was observed. The ferritin-iron concentration was also determined and a CVduplo of 11% was found. The ferritin iron concentration increased with an increasing total iron content until saturation of ferritin appeared to be reached at about 3 g ferritin per kg protein. It was concluded that the quantitative determination of bone marrow iron can be of value in the diagnosis and investigation of both hypo- and hyper-ferraemic disorders.

The pathogenesis of anemia in rheumatoid arthritis: A clinical and laboratory analysis

Principal concepts concerning the anemia of RA are summarized in Tables 7 and 8. These concepts have been validated by our analysis of 93 anemic RA patients and by our review of the literature. The fact that anemia in RA may have one or more etiologies, occasionally in the same patient, mandates a reasoned approach to the analysis of anemia in every RA patient in whom it may occur. In particular, iron deficiency is common and determination of bone marrow iron content via an aspirate may be required for a definitive diagnosis. In those RA patients with anemia of chronic disease, the best therapy remains control of the underlying disease, most commonly with second line drugs and/or corticosteroids. The place for recombinant erythropoietin in the therapy of this anemia has not been defined; one specific role for erythropoietin may be in the preparation of RA patients for elective surgery, particularly hip arthroplasty, where correction of the anemia may either obviate the need for transfusion or may allow for donation of blood for purposes of autologous transfusion perioperatively. The pathogenesis of the anemia of chronic disease, as seen in RA anemia, is not completely understood. Inflammatory mediators, particularly the cytokines, appear to be important factors in the impairment of erythropoiesis. The mechanism by which these cytokines impair erythroid progenitor growth and hemoglobin production in developing erythrocytes is an important area for future study.

Anaemia in rheumatoid arthritis: the role of iron, vitamin B12, and folic acid deficiency, and erythropoietin responsiveness.

Thirty six patients with rheumatoid arthritis (RA) (25 with anaemia) were studied to establish the role of iron, vitamin B12, and folic acid deficiency, erythropoietin responsiveness, and iron absorption in the diagnosis and pathogenesis of anaemia in RA. Iron deficiency, assessed by stainable bone marrow iron content, occurred in 13/25 (52%), vitamin B12 deficiency in 7/24 (29%), and folic acid deficiency in 5/24 (21%) of the anaemic patients. Only 8/25 (32%) had just one type of anaemia. The iron deficiency of anaemia of chronic disease (ACD) was distinguished by ferritin concentration, which was higher in that group. Mean cell volume (MCV) and mean cell haemoglobin (MCH) were lower in both anaemic groups, but most pronounced in iron deficient patients. Folic acid, and especially vitamin B12 deficiency, masked iron deficiency by increasing the MCV and MCH. Iron absorption tended to be highest in iron deficiency and lowest in ACD, suggesting that decreased iron absorption is not a cause of ACD in RA. No specific causes were found for vitamin B12 or folic acid deficiency. Haemoglobin concentration was negatively correlated with erythrocyte sedimentation rate in the group with ACD. Erythropoietin response was lower in ACD than in iron deficient patients. It was concluded that generally more than one type of anaemia is present simultaneously in anaemic patients with RA. The diagnosis of each type may be masked by another. Studies on pathogenesis of the anaemia are difficult as deficiencies generally coexist with ACD. Disease activity and, possibly, erythropoietin responsiveness are major factors in ACD pathogenesis.

Antenatal iron supplementation in sickle cell disease

Fourteen pregnant women with sickle cell disease (11 SS and 3 SC) were randomized into two groups to receive routine antenatal supplementation either with ferrous gluconate or with placebo tablets. Their hemoglobin levels and bone marrow iron content were determined prenatally and 6 weeks post partum. The fetal weights and the incidence of pain crisis in both groups were recorded. Using an iron content grading from 0 to 5, no marrow of any subject showed iron depletion. The placebo group showed an aggregate postnatal loss of 4 grades of iron repletion while the iron supplemented group showed an aggregate gain of 2 grades. There were no significant differences between the birth weight or the incidence of pain crises in both groups. We conclude that routine iron supplementation is not justified in pregnant women with sickle cell disease, as it would tend to increase already adequate or excessive iron body stores. We recommend that a clear need for iron should be established before iron supplementation is prescribed to them.

Iron status of 38-year-old women in Gothenburg, Sweden.

ABSTRACTBlood haemoglobin concentration, packed cell volume, blood cell counts, serum iron concentration, total iron binding capacity, bone marrow iron content, sideroblast count, iron absorption and menstrual blood loss were studied in 372 38‐year‐old women who were representative of the general female population of that age resident in Gothenburg, Sweden. The distributions of serum iron concentration, serum total iron binding capacity, and transferrin saturation were slightly skewed, whereas the distributions of iron absorption, reticulocyte count, sideroblast count, and menstrual blood loss were markedly skewed. The other variables studied were mainly normally distributed. One‐third of the women (32 %) had no reticuloendothelial iron and another 14 % only traces of reticuloendothelial iron in smears from sternal bone marrow. Serum iron concentration and total iron binding capacity were rather high and menstrual blood loss low in women taking oral contraceptives, while factors such as country of origin, socio‐economic group, blood donation, previous oral iron therapy or recent infection seemed to have no or only a slight influence on variables reflecting the iron status.

Haematopoiesis and Regeneration: Changes in the Liver, Spleen, Bone Marrow and Hepatic Iron Content during Tail Regeneration in the Scincid Lizard, Mabuya Carinata (Boulenger)

AbstractIn response to the observed changes in blood during tail regeneration, a detailed histophysiological study of the haemopoietic organs such as liver, spleen and bone marrow was undertaken. During regeneration, all three organs were found to undergo histophysiological changes. Increased haemopoietic activity in the marrow and hyperplasia of the white pulp were the important changes shown by the bone marrow and spleen respectively. In the liver, the most marked effect appeared to be the formation of large numbers of lymphocytopoietic nodules. Another interesting observation was the influx and destruction of red blood cells both in the liver and spleen, once during the early regressive phase and once during the late progressive phase of regeneration. An attempt is made to correlate these changes in the three haemopoietic organs with the possible involvement of lymphocytes in the formation of a regeneration blastema and a possible haemoglobin transition during regeneration. The present observations are in concordance with the previous observations on blood.

Iron stores in chronic granulocytic leukaemia at presentation.

In 87 patients with Ph1 positive chronic granulocytic leukaemia (CGL), the bone marrow iron content was studied on smears obtained at diagnosis. A low sideroblast score and a decreased or absent marrow iron on semiquantitative estimation were found in 91% and 85% of cases, respectively. These findings did not correlate with blood parameters reflecting iron status such as Hb concentration, mean corpuscular volume, mean corpuscular haemoglobin, serum iron, total iron-binding capacity and transferrin saturation, which were normal in most cases. In 30 patients, initial serum ferritin was estimated, normal or slightly increased levels being as a rule found. In 24 of such patients, serum ferritin was again measured in remission following busulphan and, although values remained normal, a significant decrease was observed with respect to the initial levels (P less than 0.001). Thus, in spite of the consistent marrow pattern of iron depletion, initial iron stores appear to be normal in CGL. It seems, however, that the disease activity may partially influence the serum ferritin levels.

Serum ferritin as a measure of iron stores during and after normal pregnancy with and without iron supplements.

The iron stores of 32 healthy pregnant women were evaluated longitudinally during pregnancy and 6 months post partum by serum ferritin assay and by bone marrow iron content. Half of the women were receiving oral iron while the others were not given iron supplementation. Women receiving iron could maintain their iron stores throughout the pregnancy. By contrast, women without iron therapy had low serum ferritin values, pointing to the absence of iron stores during the last trimester, and 6 of these 16 women developed anemia. This was confirmed by estimation of the quantity of stainable iron in the bone marrow. In addition serum iron, transferrin and red cell MCV values indicated iron deficient erythropoesis. During a 6-month period after pregnancy the women receiving supplemental iron during pregnancy had a significant increase in their serum ferritin concentrations, indicating restoration of iron stores. Women not receiving iron during pregnancy had exhausted iron stores at term and serum ferritin values stayed low even at 6 months after delivery. If iron therapy was instituted after parturition, serum ferritin assays indicated restoration of iron stores within the ensuing 6 month. To prevent iron deficiency anemia during pregnancy supplemental iron is advisable for all pregnant women in our country.

Serum ferritin in the diagnosis of anemia during pregnancy.

Measurements of serum ferritin were correlated with bone marrow iron content and other laboratory hematological indices in 44 anemic (B-Hb < 110 g/l) pregnant women. Seventy-two % of patients classified as iron deficient by the absence of bone marrow iron had diagnostically low serum ferritin concentrations, which percentage is about double compared with those revealed by measurements of serum transferrin, TIBC, transferrin saturation, serum iron, blood hemoglobin and red cell indices. It is also important that serum ferritin was the only one of these measurements which was able to differentiate between iron deficiency, and anemia due to infection. Seven out of 8 patients with anemia due to infection had elevated serum ferritin levels. In 17% of patients no reason for the fall of blood hemoglobin could be shown. A plausible explanation for the low blood hemoglobin is extensive hemodilution.

Serum Ferritin as an Index of Body Iron Stores in Patients on Chronic Haemodialysis*

Summary: Serum ferritin concentrations have been measured serially over a 12 month period in 35 patients on chronic haemodialysis. All patients on haemodialysis received oral iron and vitamin supplements during the period of study. In 28 of the patients simultaneous bone marrow iron was also estimated. A significant correlation was found between serum ferritin concentration and bone marrow iron content. In all but two patients, oral iron supplements were sufficient to prevent a fall in the serum ferritin concentration during the period of observation. Chronic renal failure per se did not appear to affect the serum ferritin concentration.