Iron Deficiency Increases Platelet Counts in Rats

The effect of recombinant human erythropoietin (rHuEpo) on megakaryopoiesis remains controversial. Treatment with rHuEpo in renal failure patients has been associated with a slight elevation of platelet counts. In animal studies, high doses of rHuEpo produced an increase of platelet counts followed by a gradual return to normal after 7 to 15 days or even a substantial degree of thrombocytopenia. However, because iron deficiency is also known to be associated with thrombocytosis, (functional) iron deficiency during rHuEpo could be contributing to these observations. We investigated the impact of iron supply on changes in platelet counts induced by rHuEpo. Rats were either fed normal food (normal rats) or received 1% carbonyl iron for 2 weeks or 3 months, as well as during the experiment, to achieve iron supplementation or overload, respectively. Rats of all three categories then received daily intravenous injections of rHuEpo (10, 50, or 150 U) or normal saline (0 U) for 20 days. With 0 to 10 U rHuEpo, platelets remained stable. In normal rats receiving 50 to 150 U rHuEpo, platelets increased to 120% to 140% of baseline at 4 to 12 days to level off at 120% at 16 to 20 days. This response was less sustained in splenectomized animals. Iron-supplemented rats receiving 50 to 150 U rHuEpo also increased platelets initially, but the peak was at day 4, followed by a gradual return to baseline and even a moderate thrombocytopenia later on. Iron-overloaded rats receiving 50 to 150 U rHuEpo also had increased platelets at day 4, but the duration of platelet increase was shorter, and they experienced a more pronounced degree of thrombocytopenia in proportion to the dose of rHuEpo. Because the early elevation of platelets was of larger magnitude than hematocrit changes, it is unlikely that it could be accounted for by shrinkage of plasma volume. Because it was observed in all three iron conditions, there appears to be some direct positive effect of rHuEpo on platelet production. However, after this transient effect, expanded erythropoiesis appears to exert a negative impact upon platelet production. Secondary thrombocytopenia was not related to splenic pooling, and its very slow correction after cessation of rHuEpo therapy is not compatible with changes in platelet survival. Rather, it is consistent with stem cell competition between erythroid and megakaryocytic development. However, this secondary thrombocytopenia is masked by (functional) iron deficiency in rats not receiving an adequate iron supply from food or stores.

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Thrombocytopenia In Severe Anemia of Iron Deficiency

Blood ◽

10.1182/blood.v116.21.5153.5153 ◽

2010 ◽

Vol 116 (21) ◽

pp. 5153-5153

Author(s):

Getinet D. Ayalew ◽

Juhi Mittal ◽

Ratesh Khillan ◽

Miriam Kim ◽

Albert S. Braverman ◽

...

Keyword(s):

Bone Marrow ◽

Iron Deficiency ◽

African American Women ◽

Conflicts Of Interest ◽

Ferrous Sulphate ◽

Bone Marrow Aspiration ◽

Deficiency Anemia ◽

Platelet Counts ◽

Cell Counts ◽

Erythroid Hyperplasia

Abstract Abstract 5153 Introduction: Iron deficiency suppresses hemoglobin synthesis and erythropoiesis, but the resulting anemia is frequently associated with thrombocytosis. Methods: The clinical and hematologic data of seven women with severe iron deficiency anemia (IDA) and thrombocytopenia were retrospectively analyzed. Results: All patients were African-American women with symptomatic IDA, due to bleeding from uterine fibroids in 6 and from colonic diverticulosis in 1. They were 31–70 years of age, median 38. None had palpable splenomegaly. Hemoglobin ranged from 2.9–5.5, median 4.2 g/dL. MCV ranged from 57–70 fl, median 68. Absolute reticulocyte counts ranged from 19,000 – 23, 000/mm3. The initial serum ferritin ranged from 2 to 42 ng/ml, median 4. Serum iron levels ranged from 10 to 70 mcg/dl with median 30, while iron-binding capacities ranged from 381–426 mcg/dl. Serum erythropoietin (EPO) levels were >2000U/ml in two of the patients. Serum lactic dehydrogenase, bilirubin levels and liver function tests were normal; and Coombs' test negative in all cases. White blood cell counts were normal. The platelet counts ranged from 12 to 103, with a median of 46 × 109/L. Peripheral blood smears showed microcytic hypochromic red blood cells (RBC), with no evidence of platelet clumping. Bone marrow aspiration and biopsy on two patients showed increased numbers of normal megakaryocytes, erythroid hyperplasia and absent iron stores. Six patients were treated with packed RBC transfusions, and ferrous sulphate 325 mg orally was initiated at presentation in 7. Their thrombocytopenia was not treated with steroids or other agents. Three patients' platelet count reached normal or super-normal levels within 72 hours. Six patients were seen at ≥3 months after presentation, and all had achieved normal platelet counts and hemoglobin. Conclusions: These data imply that severe IDA can sometimes cause thrombocytopenia rather than thromobocytosis. We cannot be sure whether these patients' uniform normalization of platelet counts was due to treatment of their anemia by transfusion, or iron therapy. Though bone marrow megakaryocyte numbers were increased in 2 patients, there is no evidence for peripheral platelet destruction. Platelet release from megakaryocytes may have decreased in these patients. Pharmacologic EPO therapy can occasionally cause thrombocytopenia, and high endogenous EPO levels in our patients may have reduce their platelet counts. This conclusion is consistent with their apparent response to transfusion. Though the pathogenesis of IDA-associated thrombocytopenia is not known, our data suggest that the results of anemia and iron deficiency treatment should be evaluated before investigating thrombocytopenia as an independent problem. Disclosures: No relevant conflicts of interest to declare.

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Platelet counts in adults with iron deficiency anemia

Platelets ◽

10.1080/09537100903137306 ◽

2009 ◽

Vol 20 (6) ◽

pp. 401-405 ◽

Cited By ~ 34

Author(s):

Irfan Kuku ◽

Emin Kaya ◽

Saim Yologlu ◽

Remzi Gokdeniz ◽

Ahmet Baydin

Keyword(s):

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Deficiency Anemia ◽

Platelet Counts

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Platelet Counts in Children with Iron Deficiency Anemia

Acta Haematologica ◽

10.1159/000207701 ◽

1978 ◽

Vol 60 (2) ◽

pp. 85-89 ◽

Cited By ~ 9

Author(s):

G. Hiçsönmez ◽

K. Süzer ◽

G. Süloglu ◽

S. Dönmez

Keyword(s):

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Deficiency Anemia ◽

Platelet Counts

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Increased Levels of Thrombopoietin and IPF in Patients with Iron Deficiency Anemia

Blood ◽

10.1182/blood.v124.21.5018.5018 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5018-5018

Author(s):

Kazuo Kawasugi ◽

Tadashi Yamamoto ◽

Naoki Shirafuji ◽

Yoko Oka

Keyword(s):

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Conflicts Of Interest ◽

Inverse Correlation ◽

Deficiency Anemia ◽

Significant Inverse Correlation ◽

Platelet Counts ◽

Immature Platelet Fraction ◽

Healthy Control ◽

Normal Controls

Abstract Background Thrombocytosis has been reported in about 50% of patients with iron deficiency anemia (IDA). However, the mechanism of the increase in the number of platelets is unknown. To investigate the relationship of endogenous thrombopoietin (TPO) and circulating platelet counts, we measured the plasma levels of TPO, immature platelet fraction (IPF) and erythropoietin ( EPO ) in 25 patients with IDA. Patients and methods Patients with IDA (newly diagnosed) were recruited from February 2013 through March 2014 in Teikyo University School of Medicine. TPO (Immuno-Biological Laboratory, Japan), was determined by an EILSA. IPF was measured on the Sysmex XE2100. EPO (Roch Diagnostic Japan) was determined by an EILSA. Results and Conclusions The number of platelets was increasing in the half patients with IDA in this study. Peripheral blood samples for measuring IPF were obtained from 300 healthy adult controls (160 women and 140 men) and 20 patients with IDA, consisting of 19 women and 6 men with age ranging from 16 to 75 years. The etiology of iron deficiency was gastrointestinal (GI) blood loss, menometrorrhagia, previous GI surgery, and low dietary iron intake. The mean absolute-IPF was significantly higher for IDA patients than for healthy control (8193±571 vs. 4254±193 p＜0.05). The endogenous levels of TPO were significantly elevated in patients with IDA (216.4±41 pg/ ml) as compared with normal controls (116.5±23 pg/ml). Also, The endogenous levels of EPO were significantly elevated in patients with IDA as compared with normal controls. There was a significant inverse correlation between serum Fe levels and platelet counts (r=0.551, p＜0.05). Also, a positive correlation (r=0.311, p＜0.05) between platelet counts and endogenous level of TPO was found. Moreover, there was a significant inverse correlation (r=-0.458, p＜0.05) between Hb and TPO. These results suggest that TPO is active regulator, in thrombopoiesis and megakaryocytopoiesis in patients with IDA. Also, it appears there is relationship between erythropoiesis and TPO. Disclosures No relevant conflicts of interest to declare.

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Iron metabolism in patients with rheumatoid arthritis

10.21203/rs.3.rs-29281/v1 ◽

2020 ◽

Author(s):

Wojciech Tański ◽

Mariusz Chabowski ◽

Beata Jankowska-Polańska ◽

Ewa Anita Jankowska

Keyword(s):

Iron Deficiency ◽

Disease Activity ◽

Transferrin Receptor ◽

Transferrin Saturation ◽

Female Gender ◽

Control Group ◽

Soluble Transferrin Receptor ◽

Platelet Counts ◽

Das 28 ◽

Younger Age

Abstract Background. The most common haematological manifestation in RA is anaemia (30-60%). The aim of the study was the assessment of the prevalence of iron deficiency in RA patients using standard parameters and new biomarkers.Material and methods. The study was conducted on 62 RA patients, aged 52±15, treated at the Department of Internal Medicine of the 4th Military Teaching Hospital in Wrocław between 2016 and 2017. The control group comprised 58 healthy individuals, aged 56±9. The following tests were carried out: DAS-28, complete blood count, creatinine, uric acid, AspAT, ALAT, GGT, bilirubin, TSH, lipid profile, iron, TIBC, transferrin saturation, ferritin, soluble transferrin receptor, hepcidin, and IL-6.Results. A higher percentage of RA patients compared with the control group had TSAT values below 20%, ferritin levels below the reference range, soluble transferrin receptor levels above 1.59mg/l and hepcidin levels below 14.5 ng/ml. 60% of RA patients had iron deficiency. The correlations between reduced ferritin levels and younger age, female gender, lower GGT levels and increased platelet counts was shown. The correlations were found between iron deficiency and younger age, female gender, reduced haemoglobin levels, increased platelet counts, increased GFR, reduced GGT levels, lower disease activity and less frequent use of sulfasalazineConclusions. Iron deficiency is common in RA patients with high disease activity. RA patients had lower transferrin saturation, lower ferritin and hepcidin levels and higher serum sTfR levels. The increased DAS-28 scores and reduced haemoglobin levels were the two strongest determinants of iron deficiency in RA patients.

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Platelet Counts Vary by Ethnicity, Sex, and Age: Analysis of NHANES III Data.

Blood ◽

10.1182/blood.v104.11.3937.3937 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3937-3937 ◽

Cited By ~ 1

Author(s):

Jodi B. Segal ◽

Alison R. Molterno

Keyword(s):

Young Adults ◽

Platelet Count ◽

Iron Deficiency ◽

Hormonal Regulation ◽

Mexican Americans ◽

Geometric Mean ◽

The United States ◽

Serum Folate ◽

Nhanes Iii ◽

Platelet Counts

Abstract Background: The possibility of variation in platelet count by age and genetic background has not been examined. Identification of subpopulations with elevated platelet counts, within what is traditionally considered a normal range, may identify a group with excessive morbidity or mortality. Furthermore, platelet count differences may suggest populations in which genetic polymorphisms in regulatory proteins such as the thrombopoietin receptor influence platelet production. We hypothesized that there were differences in platelet count by ethnicity, sex and age not explained by environmental factors. Objective: To demonstrate differences in mean platelet counts by ethnicity, sex, and age while controlling for variables known to influence platelet count. Methods and Design: We used data from the National Health, Nutrition and Examination Survey III (NHANES III), which is a multistage probability sample of the United States population with data collected between 1988 and 1994. Using appropriate weighting for the complex sampling design, the geometric mean platelet count was calculated for the total population and the population stratified by ethnicity, sex, and age, while controlling for C-reactive protein, white blood cell count, iron-deficiency, serum folate, markers of alcohol intake, presence of hepatitis B or C antibodies, and diabetes mellitus. Other potential influences, such as medications, were found not to affect the predicted counts and not included in the models. Results: The lowest mean platelet counts were among whites (259 K/ml [95% C.I. 255–264 K/ml]) and the highest were in non-Hispanic blacks (275 K/ml [95% C.I. 270–280 K/ml]) with Mexican-Americans having intermediate values (266 K/ml [95% C.I. 261–272 K/ml]), when controlled for age and sex. Older men and women of each ethnicity consistently had lower mean platelet counts, with 60–69 years olds having mean counts approximately 7 K/ml lower than young adults (p=0.015) and 70–90 year olds having mean counts 19 K/ml lower than young adults (p<0.001). Even with controlling for iron deficiency, women had significantly higher platelet counts than men (273 K/ml [95% C.I. 269 – 278]) versus 251 K/ml [95% C.I. 245 – 256]) Conclusion: Mean platelet counts differ by ethnicity, sex, and age and these differences are not explained by covariates known to influence platelet count. This suggests that genetic influences on the platelet count are operative. These data also suggest that there may be a hormonal regulation of platelet count. The decline with age may reflect decreased stem cell function with age; alternatively, there may be a survival advantage to having a lower platelet count. Longitudinal studies of platelet count with aging are indicated.

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