Erythrocyte Protoporphyrin in the Detection of Iron Deficiency

1975 ◽  
Vol 21 (8) ◽  
pp. 1121-1127 ◽  
Author(s):  
Gordon D McLaren ◽  
John T Carpenter ◽  
Hipolito V Nino
Keyword(s):  
Bone Marrow ◽  
Iron Deficiency ◽  
Prussian Blue ◽  
Blue Staining ◽  
Comparable Group ◽  
Iron Stores ◽  
Erythrocyte Protoporphyrin ◽  
Bone Marrow Iron ◽  
The Mean ◽  
Mean Concentration

Abstract Any decrease in the availability of iron for incorporation into the heme moieties of hemoglobin results in an increase in the erythrocyte protoporphyrin concentration. Our aim was to compare protoporphyrin concentrations, determined spectrophotometrically, with body iron stores, as assessed from the amount of iron demonstrable by Prussian blue staining of bone marrow aspirates. The mean protoporphyrin concentration (175 µg/dl) in the erythrocytes of a group of patients with markedly decreased stainable marrow iron or no iron Was Significantly Greater (P < .001) than the mean concentration (76 µg/dl) in a comparable group with adequate bone marrow iron stores, except in the presence of certain interfering conditions. These results suggest that the erythrocyte protoporphyrin test may be a useful addition to the methods now available for assessing disorders of heme synthesis, the most common of which is iron deficiency.

Lab Indicators of Iron Level in Bone Marrow Aspirate of Patients Diagnosed with Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5397-5397
Author(s):  
Ankit Mangla ◽  
Sriman Swarup ◽  
Muhammad Umair Mushtaq ◽  
Hussein Hamad ◽  
Sharad Khurana ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Iron Deficiency ◽  
Bone Marrow Aspirate ◽  
Binding Capacity ◽  
Iron Level ◽  
Iron Binding ◽  
Iron Stores ◽  
Bone Marrow Iron ◽  
Iron Binding Capacity

Abstract Introduction Iron plays a critical role in patients with multiple myeloma (MM). The limited availability of iron to the developing erythroid precursors results in the characteristic anemia so frequently seen in these patients. Moreover, iron is also a determinant in growth of the malignant plasma cells that makes it one of the critical factors in progression of the disease. Iron is a key component in success of erythropoietin (EPO) therapy that is often used to maintain hemoglobin (Hb) level of >10g/dL in patients with MM. International Myeloma working group (2011) advised transfusing IV iron to aid in success of EPO therapy. However, apart from determining the iron stores on bone marraow aspirate, there is hardly any reliable clinical or lab indicator of the iron stores in the body. The utility of various iron indices in determining the bone marrow iron stores remains anecdotal. In this study we aim to determine the relation between iron indices and iron level in the bone marrow of patients diagnosed with multiple myeloma. Methods A total of 268 multiple myeloma patients, diagnosed from 2004 to 2015, were identified from tumor registry of John H. Stroger Jr. Hospital of Cook County, Chicago. Accuracy of ferritin, iron level, total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC) and transferrin saturation (TSAT) was evaluated using receiver operating characteristic curves (ROC). Out of sampled patients, 167 patients had a concurrent bone marrow biopsy and aspirate, serum ferritin and iron panel, and were included in ROC analyses. Results The study population consisted of 57% African-Americans, 18% Caucasians and 16% Hispanics. Median age was 61 years and 51% were females. Past history was significant for hypertension (48%), diabetes (31%), co-existing inflammatory conditions (18%), smoking (25%), alcohol abuse (17%) and illicit drug abuse (8%). Median hemoglobin, mean corpuscular volume (MCV), leukocytes and platelets were 10g/dL, 90.3fL, 6,200/mcL and 219,500/mcL respectively. Bone marrow aspirates for iron were rated as absent (37%), mild/moderate (18%) and adequate/normal (45%). Anemia was found in 79% of males (Hb <12.9g/dL) and 76% of females (Hb<11.7 g/dL). Of the patients with anemia, 36% of males and 39% of females had absent iron stores (determined by prussian blue staining method) on bone marrow aspirate. MCV was not significantly related with iron deficiency. Iron level, TIBC, UIBC and TSAT were not significantly associated with bone marrow iron (P>0.05). Only ferritin was significant predictor of iron deficiency and presence of iron in bone marrow (AUC 0.64, 95%CI 0.55-0.74, P=0.002). Ferritin levels of ≤15mcg/L (positive LR 3.77, sensitivity 3.4%, specificity 99.1%), ≤30mcg/L (positive LR 2.59, sensitivity 11.9%, specificity 95.4%) and ≤50mcg/L (positive LR 4.35, sensitivity 32.2%, specificity 92.6%) predicted iron deficiency. Ferritin levels of ≥100mcg/L (positive LR 1.47, sensitivity 76.9%, specificity 47.5%), ≥200mcg/L (positive LR 1.46, sensitivity 54.6%, specificity 62.7%) and ≥500mcg/L (positive LR 1.94, sensitivity 23.1%, specificity 88.1%) ruled out iron deficiency. Conclusion Of all the indices predicting iron deficiency, only ferritin was significantly associated with absent iron in bone marrow aspirates. In MM patients, iron supplementation should be considered with ferritin levels of ≤50mcg/L and can be deferred with ferritin levels of ≥500mcg/L. Further studies are needed to explore the association. Disclosures No relevant conflicts of interest to declare.

Functional Iron Deficiency Effectively Overcome by Adjuvant IV Iron during Epoetin Treatment.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3725-3725
Author(s):  
Gunnar Birgegard ◽  
Anders Osterborg ◽  
Michael Hedenus
Keyword(s):  
Bone Marrow ◽  
Iron Deficiency ◽  
Treated Group ◽  
Iron Availability ◽  
Functional Iron Deficiency ◽  
Iron Restriction ◽  
Iv Iron ◽  
Bone Marrow Iron ◽  
Iron Deposits ◽  
The Mean

Background: 30–40% of anemic cancer patients don’t respond to epoetin treatment. New insights in iron regulation have indicated that one reason for lack of response may be functional iron deficiency (FID), in which an upregulation of hepcidin by imflammatory cytokines impairs the ferroportin-mediated iron export from macrophages. Aims: To assess whether adjuvant IV iron therapy would overcome the iron restriction of FID as well as that of exhaustion of iron stores during epoetin treatment of anemia in patients with lymphoproliferative disorders (LPD) and proven iron presence in the bone marrow. Methods: 67 patients with indolent lymphoid malignancy (19 NHL, 23 CLL and 25 MM), Hb ≥9 to ≤11 g/dl and a positive bone marrow iron staining were randomized to receive epoetin-beta, (NeoRecormon®) 30 000 IU QW or this treatment plus IV iron sucrose, (Venofer®) 100 mg QW, during week 0–6, 100 mg Q2W week 7–16 with dose modifications of epoetin according to the label. 60 patients completed the study. Three patients received transfusion and/or chemotherapy and thus 57 were evaluable. Results: The Hb response rate was superior in the iron-treated group, 91% vs 54%, the time to response (>2 g/dL) half as long, 6 w vs 12 w and the Hb level was 1.2 g/dL higher at the end of study(1). In both groups, the mean transferrin saturation (Tsat) was low at baseline, 22%, and the mean S-ferritin was around 200 ug/L. During treatment, several indicators showed that iron availability was superior in the iron-treated group. In the non-iron group Tsat declined from baseline to <20% in 26 out of 30 patients for the duration of the study, and S-ferritin fell rapidly during the first week and then steadily declined from a baseline value of 191 to 112 ug/L at the end of study. (EOS). The mean soluble transferrin receptor (sTfR) level increased from normal to a maximum of 3.7 mg/L in week 8. In the iron-treated group (n=27) Tsat increased from baseline and stabilized at 30%. S-Ferritin showed no initial fall and continued to increase from 210 at baseline to 398 ug/L at EOS. Discussion. Iron restriction may be present in epoetin treatment of cancer anaemia by two different mechanisms. Iron deposits may be small and become depleted, and secondly iron may be trapped in the macrophages due to FID. In these patients, FID was common, as indicated by the presence of bone marrow iron and the low mean Tsat at baseline. In some patients, small iron deposits were exhausted by the increased erythropoiesis in the non-iron group, as shown by subnormal S-ferritin levels. The fact that the mean Tsat and S-ferritin increased in the iron-treated group indicated that iron availability was constantly better in this group and the reason for the superior Hb response. Conclusions - Functional iron deficiency (low Tsat and iron-restricted erytropoiesis in spite of proven iron stores) is common in patients with anaemia of haematological malignancies. - FID is a common and important reason for lack fo response to epoetin treatment - IV iron treatment improves epoetin response both by overcoming FID and by avoiding iron depletion casued by increased erythropoiesis.

scholarly journals Increased Bone Marrow Iron at Diagnosis Is Associated with Inferior Prognosis in Patients with Myelodysplastic Syndromes

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3700-3700
Author(s):  
Annika Kasprzak ◽  
Sandra Becker ◽  
Martina Rudelius ◽  
Corinna Strupp ◽  
Kathrin Nachtkamp ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Iron Overload ◽  
Median Survival ◽  
Myelodysplastic Syndromes ◽  
Iron Uptake ◽  
Research Funding ◽  
Blue Staining ◽  
Prognostic Impact ◽  
Iron Stores ◽  
Bone Marrow Iron

Abstract Introduction: Iron storage in patients (pts) with myelodysplastic syndromes at the time of diagnosis may vary from normal to iron overload. Even before the first blood transfusion, storage iron can be increased due to down-regulation of hepcidin and subsequent increase in duodenal iron uptake. Iron overload is known to worsen the prognosis of MDS patients, partly due to iron-related organ damage after long-term transfusion therapy, and partly due to an increased risk of infections. However, it is unclear whether increased storage iron at the time of diagnosis already has a prognostic influence. We assessed bone marrow iron stores at the time of MDS diagnosis and correlated them with clinical outcome. Methods: In a retrospective analysis of 3762 adult MDS patients from the Düsseldorf MDS Registry, Prussian blue staining of marrow smears was performed in our cytology lab to assess iron stores according to the following categories: normal or decreased iron stores versus increased iron stores versus iron overload. Patients were followed up for survival and AML evolution until June 2021. Median time of follow-up was 20 months. 67.4% of the patients died during the course of the disease. Results: The study included 3.762 adult patients who received their initial diagnosis of MDS between 1970 and 2021. 58% were diagnosed as non-blastic MDS ( MDS SLD (RS) (n=240), MDS MLD (RS) (n=350), MDSdel(5q) (n=107), and MDS-U (n=25). Iron stores were decreased in 8% of the patients, normal in 44%, increased in 41%, and strongly increased in 7% (massive iron overload). In 282 cases, histologic assessment of storage iron was available. When comparing cytologic and histologic assessment, we found a strong correlation (p&lt;0.0005), since 87% of the patients with increased iron on cytomorphology also showed increased iron as assessed by histopathology. However, 37% of the patients who cytologically showed normal iron stores, were reported to have slightly increased iron as assessed by histopathology. Median and mean serum ferritin values of patients with normal or decreased iron stores were 295 and 629 µg/l, respectively, as compared to 548 and 902 µg/l, respectively, in patients with increased iron stores. The cumulative risk of AML evolution was not associated with the results of iron staining. Regarding survival, we found that patients with decreased or normal storage iron had a median survival of 31 months, whereas those with increased iron had a median survival of 28 months (p=0.007). Focusing on patients with non-blastic MDS, the difference was not significant (46 vs 44 ms). However, patients who presented as EB I (n=435), EBII (n=510), AML MRC (n=264), CMML I (n=254), or CMML II (n=77), showed a prognostic impact of storage iron; patients with increased iron had a median survival of 11 months, as compared to 16 months in patients with normal or decreased iron (p&lt;0.0005). Conclusion: Increased tissue iron in the bone marrow at the time of diagnosis is associated with inferior survival in patients with MDS, primarily in patients with higher risk MDS. At diagnosis, patients are not yet transfusion-dependent. This suggests that increased iron reflects a prolonged period of increased duodenal iron uptake as a consequence of ineffective erythropoiesis. Therefore, increased marrow iron at the time of MDS diagnosis seems to be a surrogate parameter of hematopoietic insufficiency, which is the real cause of inferior prognosis. Disclosures Nachtkamp: Jazz: Honoraria; Bsh medical: Honoraria; Celgene: Other: Travel Support. Gattermann: Novartis: Honoraria; Takeda: Research Funding; Celgene: Honoraria. Germing: Jazz Pharmaceuticals: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria, Other: advisory activity, Research Funding; Janssen: Honoraria; Novartis: Honoraria, Research Funding.

Iron preparations for children

1966 ◽  
Vol 4 (3) ◽  
pp. 9-11
Keyword(s):  
Bone Marrow ◽  
Iron Deficiency ◽  
Blood Smear ◽  
Binding Capacity ◽  
Iron Binding ◽  
Iron Stores ◽  
Plasma Iron ◽  
Hypochromic Anaemia ◽  
Iron Binding Capacity

We have discussed iron preparations for adults in earlier articles;1 much of the information applies equally to children. Iron is not a ‘tonic’ and should be given only to prevent or correct iron deficiency. Estimation of the haemoglobin and inspection of a blood smear are the minimum investigations necessary before iron is prescribed in therapy. When deficiency is suspected in the absence of hypochromic anaemia, plasma iron and iron-binding capacity should be estimated and/or the bone marrow examined for haemosiderin crystals which disappear when iron stores are depleted.

scholarly journals Role of intensive method of bone marrow iron assessment and serum Ferritin in prediction of iron deficiency: a study of 143 patients

2018 ◽  
Vol 5 (4) ◽  
pp. 686-691
Author(s):  
Mayank Singh ◽  
Swati Raj ◽  
Dwijendra Nath ◽  
Pallavi Agrawal ◽  
Sufiya Ahmed
Keyword(s):  
Bone Marrow ◽  
Iron Deficiency ◽  
Serum Ferritin ◽  
Bone Marrow Iron

scholarly journals MRI Tracking of SPIO- and Fth1-Labeled Bone Marrow Mesenchymal Stromal Cell Transplantation for Treatment of Stroke

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Xiaolei Huang ◽  
Yang Xue ◽  
Jinliang Wu ◽  
Qing Zhan ◽  
Jiangmin Zhao
Keyword(s):  
Bone Marrow ◽  
Prussian Blue ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Signal Intensity ◽  
Immunofluorescent Staining ◽  
Blue Staining

We aimed to identify a suitable method for long-term monitoring of the migration and proliferation of mesenchymal stromal cells in stroke models of rats using ferritin transgene expression by magnetic resonance imaging (MRI). Bone marrow mesenchymal stromal cells (BMSCs) were transduced with a lentivirus containing a shuttle plasmid (pCDH-CMV-MCS-EF1-copGFP) carrying the ferritin heavy chain 1 (Fth1) gene. Ferritin expression in stromal cells was evaluated with western blotting and immunofluorescent staining. The iron uptake of Fth1-BMSCs was measured with Prussian blue staining. Following surgical introduction of middle cerebral artery occlusion, Fth1-BMSCs and superparamagnetic iron oxide- (SPIO-) labeled BMSCs were injected through the internal jugular vein. The imaging and signal intensities were monitored by diffusion-weighted imaging (DWI), T2-weighted imaging (T2WI), and susceptibility-weighted imaging (SWI) in vitro and in vivo. Pathology was performed for comparison. We observed that the MRI signal intensity of SPIO-BMSCs gradually reduced over time. Fth1-BMSCs showed the same signal intensity between 10 and 60 days. SWI showed hypointense lesions in the SPIO-BMSC (traceable for 30 d) and Fth1-BMSC groups. T2WI was not sensitive enough to trace Fth1-BMSCs. After transplantation, Prussian blue-stained cells were observed around the infarction area and in the infarction center in both transplantation models. Fth1-BMSCs transplanted for treating focal cerebral infarction were safe, reliable, and traceable by MRI. Fth1 labeling was more stable and suitable than SPIO labeling for long-term tracking. SWI was more sensitive than T2W1 and suitable as the optimal MRI-tracking sequence.

scholarly journals Serum Transferrin Receptor and Its Ratio to Serum Ferritin in the Diagnosis of Iron Deficiency

Blood ◽  
1997 ◽  
Vol 89 (3) ◽  
pp. 1052-1057 ◽  
Author(s):  
Kari Punnonen ◽  
Kerttu Irjala ◽  
Allan Rajamäki
Keyword(s):  
Bone Marrow ◽  
Iron Deficiency ◽  
Transferrin Receptor ◽  
Laboratory Tests ◽  
Bone Marrow Examination ◽  
Deficiency Anemia ◽  
Serum Transferrin ◽  
Iron Stores ◽  
Serum Transferrin Receptor ◽  
Reference Limits

Abstract The objective of the study was to evaluate the diagnostic efficiency of laboratory tests, including serum transferrin receptor (TfR) measurements, in the diagnosis of iron depletion. The patient population consisted of 129 consecutive anemic patients at the University Hospital of Turku who were given a bone marrow examination. Of these patients, 48 had iron deficiency anemia (IDA), 64 anemia of chronic disease (ACD), and 17 patients had depleted iron stores and an infectious or an inflammatory condition (COMBI). Depletion of iron stores was defined as a complete absence of stainable iron in the bone marrow examination. Serum TfR concentrations were elevated in the vast majority of the IDA and COMBI patients, while in the ACD patients, the levels were within the reference limits reported earlier for healthy subjects. TfR measurement thus provided a reliable diagnosis of iron deficiency anemia (AUCROC 0.98). Serum ferritin measurement also distinguished between IDA patients and ACD patients. However, the optimal decision limit for evaluation of ferritin measurements was considerably above the conventional lower reference limits, complicating the interpretation of this parameter. Calculation of the ratio TfR/log ferritin (TfR-F Index) is a way of combining TfR and ferritin results. This ratio provided an outstanding parameter for the identification of patients with depleted iron stores (AUCROC 1.00). In anemic patients, TfR measurement is a valuable noninvasive tool for the diagnosis of iron depletion, and offers an attractive alternative to more conventional laboratory tests in the detection of depleted iron stores.

scholarly journals P0861THE RELATIONSHIP BETWEEN HEPCIDIN-25 AND BONE MARROW IRON IN ANEMIC, NON-DIALYSIS, CHRONIC KIDNEY DISEASE PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Cristina-Stela Capusa ◽  
Ana-Maria Mehedinti ◽  
Gabriela-Adriana Talimba ◽  
Ana Stanciu ◽  
Liliana Viasu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Bone Marrow ◽  
Kidney Disease ◽  
Linear Regression ◽  
Iron Content ◽  
Blood Smear ◽  
Transferrin Saturation ◽  
Peripheral Blood Smear ◽  
Iron Stores ◽  
Bone Marrow Iron

Abstract Background and Aims Hepcidin-25 (Hep25) is a key known regulator of iron metabolism and its interactions with inflammation, iron stores and erythropoietic activity were involved in the pathogenesis of chronic kidney disease (CKD)-associated anemia. Therefore, our aim was to assess the determinants of serum Hep25 level in non-dialysis CKD patients. Method In this cross-sectional, single-center study, 52 subjects (56% men, 65±13 years) with CKD [estimated glomerular filtration rate, eGFR 14.5 (95%CI 16 to 25) mL/min] and anemia [hemoglobin, Hb 9.8 (95%CI 9.2 to 9.9) g/dL], not treated with erythropoiesis-stimulating agents (ESA) or iron in the previous 6 months, were enrolled. Patients with anemia of other causes than CKD, active infectious and inflammatory diseases, malignancy, severe hyperparathyroidism, transfusions during the last 3 months, and immunosuppressive therapy were excluded. The iron status was evaluated using both peripheral and central parameters. The iron stores were assessed by serum ferritin (Fer) and iron content in bone marrow macrophages (iMf, measured quantitively on a scale from 0 to 6). The iron available for erythropoiesis was assessed by transferrin saturation (TSAT) and the percentage of sideroblasts (%Sb). Anemia was further evaluated by a peripheral blood smear, erythrocytes indices and reticulocyte index. Serum Hep25 and erythropoietin (Epo) were assessed by ELISA (Bachem®, and Abcam® 119522, respectively). C-reactive protein (CRP), albumin, and parameters of kidney disease (eGFR, proteinuria) were also measured. Mann-Whitney, Kruskal-Wallis, Chi2 tests, Spearman bivariate correlation and multiple linear regression were used for statistical analysis. Results The median serum Hep25 of the whole cohort was 82.1 (95%CI 68.7 to 92.1) ng/mL. According to median Hep25, subjects were clustered in Group 1 (below median - G1) and Group 2 (above median - G2). %Sb and reticulocyte index had higher levels in G2 than in G1 [9 (95%CI 5 to 14) vs. 5 (95%CI 4 to 7) %, p=0.003 and 0.55 (95%CI 0.39 to 0.77) vs. 0.41 (95%CI 0.32 to 0.58), p=0.05, respectively], while the proportions of subjects with iMf suggestive for iron deficiency or iron overload were similar in G2 and G1 (38% vs. 50%, p=0.40, and 26% vs. 23%, p= 0.75, respectively). Peripheral blood smear, peripheral iron indices and all the other studied parameters were also alike. In bivariate analysis, Hep25 was positively associated both with indices of iron stores, i.e. Fer (rs = 0.30, p=0.03) and iMf (rs = 0.34, p=0.01) and indices of iron available for erythropoiesis, i.e. %Sb (rs = 0.55, p&lt;0.001) and (marginally) with TSAT (rs = 0.26, p=0.06). Meanwhile, Hep25 was not related to serum Epo, CKD parameters or inflammation markers. In a multivariate linear regression model that explained 28% of Hep25 variation, the percentage of bone marrow sideroblasts, i.e. the tissue iron available for erythropoiesis, was the only independent determinant of Hep25: Variables entered in the first step: reticulocyte index, percentage of medullary sideroblasts (%Sb), iron content in the bone marrow macrophages (iMf), serum ferritin, and transferrin saturation Conclusion In stable patients with advanced CKD, not treated with ESA or iron, with low to moderate inflammation, serum hepcidin was related only to bone marrow iron available for erythropoiesis, suggesting that in this clinical setting the need of iron for erythropoiesis prevails over inflammation in regulation of hepcidin synthesis.

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