History of iron overload Clinically significant anemia due to iron, B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding. If marrow stain for iron is not available, the transferrin saturation (iron/total iron binding capacity Fe/TIBC) must be >20% or serum ferritin must be >100 ng/dL. Iron overload from any cause (not just hemosiderosis or hemochromatosis), even if secondary to frequent blood transfusions, severe chronic hemolysis, excess dietary or parenteral iron, or any other etiology Patients must not have documented iron deficiency; all patients must have documented marrow iron stores; if marrow iron stain is not available, the transferrin saturation must be >= 20% or a serum ferritin >= 100 ng/100 mL or soluble transferring receptor < 5 mg/L. Subjects with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations (Ferumoxytol Investigator’s Drug Brochure, 2009); subjects with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator’s discretion Subjects with known iron overload (genetic hemochromatosis); in subjects with a family history of hemochromatosis, hemochromatosis must be ruled out prior to study entry with normal values of the following blood tests: transferrin saturation (TS) test and serum ferritin (SF) test; all associated costs will be paid by the study Subjects with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations; subjects with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator’s discretion Subjects with known iron overload (genetic hemochromatosis); in subjects with a family history of hemochromatosis, hemochromatosis must be ruled out prior to study entry with normal values of the following blood tests: transferrin saturation (TS) test and serum ferritin (SF) test; all associated costs will be paid by the study Ongoing clinically significant anemia due to factors such as known iron, vitamin B12, or folate deficiencies, auto-immune or hereditary hemolysis, or gastrointestinal (GI) bleeding Clinically significant iron metabolism disorders (eg, sickle cell anemia) Use of iron chelators Have sickle cell disease (confirmed by Hb electrophoresis or more specific tests) or other conditions with iron overload from repeated blood transfusions (see exclusion criteria for exceptions); Clinically significant anemia according to investigator's assessment due to factors such as iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis or gastrointestinal bleeding. IMAGING CORRELATIVE STUDY: Patients will be eligible to participate in the FMX imaging study if the participating study center offers this test and they do not meet any of the following criteria:\r\n* Evidence of iron overload as determined by:\r\n** Fasting transferrin saturation of > 45% and/or\r\n** Serum ferritin levels > 1000 ng/ml\r\n* A history of allergic reactions to any of the following:\r\n** Compounds similar to ferumoxytol or any of its components as described in full prescribing information for ferumoxytol injection\r\n** Any IV iron replacement product (e.g. parenteral iron, dextran, iron-dextran, or parenteral iron polysaccharide preparations)\r\n** Multiple drugs\r\n* Unable to undergo MRI or for whom MRI is otherwise contraindicated (e.g. presence of errant metal, cardiac pacemakers, pain pumps or other MRI incompatible devices; or history claustrophobia or anxiety related to undergoing MRI) Ongoing clinically significant anemia due to factors such as iron, vitamin B12, or folate deficiencies, auto-immune or hereditary hemolysis, or gastrointestinal bleeding. Patients must not have documented iron deficiency; all patients must have documented marrow iron stores; if marrow iron stain is not available, the transferrin saturation must be > 20% or a serum ferritin > 100 ng/mL Patients must not have clinically significant anemia resulting from iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis, or gastrointestinal bleeding Adequate iron stores, defined as transferrin saturation greater than 20 percent (%) and serum ferritin greater than 400 nanogram per Milliliter (ng/mL), measured within the screening period, or adequate iron stores as demonstrated by recent (within 12 weeks prior to first dose) bone marrow examination with iron stain Known allergy to iron dextran or presence of human anti-mouse antibodies Subjects must have liver iron value of < 15 mg/g/dry weight; iron quantitation may be performed by imaging such as T2*magnetic resonance imaging (MRI) or by biopsy PART I: History of iron overload or hemochromatosis PART II: History of iron overload or hemochromatosis Any other evidence of severe iron overload that, in the Investigator's opinion, warrants exclusion. DONOR: Anemia (Hb < 11 gm/dl) or thrombocytopenia (platelets < 100,000 per ul); however, potential donors with Hb levels < 11 gm/dl that is due to iron deficiency will be eligible as long as the donor is initiated on iron replacement therapy and the case is individually approved by National Institutes of Health (NIH) Blood Bank Patients requiring iron supplementation will be excluded Evidence of iron deficiency anemia including, hemoglobin (Hgb) < 11 g/dL, but > 8 g/dL; and transferrin saturation (TSAT) < 20% Any anemia treatment within 4 weeks before inclusion (oral iron, IV iron, or erythropoiesis-stimulating agents), or transfusion of packed red blood cells (PRBCs) in 2 weeks Hemochromatosis or other iron storage disorders Subjects with anemia (defined as a hemoglobin < 12) who have a ferritin < 40 ng/mL and iron percentage of saturation (% sat) < 20% Has history of iron overload Subjects with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations; subjects with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator’s discretion Subjects with known iron overload (genetic hemochromatosis); in subjects with a family history of hemochromatosis, hemochromatosis must be ruled out prior to study entry with normal values of the following blood tests: transferrin saturation (TS) test and serum ferritin (SF) test; all associated costs will be paid by the study Subjects with known hypersensitivity and allergy to iron Subjects with evidence of iron overload with a pre-study ferritin level greater than 370 ng/ml and percent saturation of transferrin level greater than 40%; patients with lab values above these limits may be included in the study if documented hematology consultation rules out hemochromatosis, idiopathic or iatrogenic iron overload Patients with evidence of iron overload, hemosiderosis/hemochromatosis will be excluded for the bone sarcoma study; however, they can undergo MRI exam without ferumoxytol enhancement for the ON study Subjects with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations (Ferumoxytol Investigator’s Drug Brochure, 2009); subjects with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator’s discretion Subjects with known iron overload (genetic hemochromatosis); in subjects with a family history of hemochromatosis, hemochromatosis must be ruled out prior to study entry with normal values of the following blood tests: transferrin saturation (TS) test and serum ferritin (SF) test; all associated costs will be paid by the study Subjects with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations (Ferumoxytol Investigator’s Drug Brochure, 2009); subjects with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator’s discretion Subjects with known iron overload (genetic hemochromatosis); in subjects with a family history of hemochromatosis, hemochromatosis must be ruled out prior to study entry with normal values of the following blood tests: transferrin saturation (TS) test and serum ferritin (SF) test; all associated costs will be paid by the study Participants with concurrent clinical diagnosis, evidence of suspected hemochromatosis, or other diseases of iron metabolism (i.e., iron overload) Subjects with known or suspected iron overload (genetic hemochromatosis or history of multiple transfusions) Subjects with concurrent clinical diagnosis of evidence of active iron overload defined by the following 1) ferritin >= 250 ng/mL in men or >= 200 ng/mL in women AND 2) transferrin saturation, the ratio of plasma iron to transferrin, expressed as percent, >= 45% Subjects with evidence of iron overload Participants with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations, are not eligible; participants with significant drug or other allergies or autoimmune diseases may be enrolled at the Investigator’s discretion Participants that have a known or suspected iron overload (genetic hemochromatosis or history of multiple transfusions) Subjects who have a known allergy to iron Subjects with sickle cell disease, hemoglobinopathy, hemochromatosis or other clinical conditions that may lead to iron overload No other known etiology of the thrombocytopenia (such as infection, medication, etc.) or anemia (such as blood loss, iron deficiency, etc.). Primary or secondary iron overload Clinically documented or risk of primary or secondary iron overloading (e.g. history of thalassemia, sickle cell anemia, hereditary hemochromatosis, multiple transfusions with any reason), anemia not caused by iron deficiency Subjects with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations (Ferumoxytol Investigator’s Drug Brochure, 2012); subjects with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator’s discretion Subjects with known or suspected iron overload (genetic hemochromatosis or history of multiple transfusions) Iron overload from any cause (not just hemosiderosis or hemochromatosis), even if secondary to frequent blood transfusions, severe chronic hemolysis, excess dietary or parenteral iron, or any other etiology Subject has intolerance or hypersensitivity to iron or dextran compounds or to SiennaXP. Subject has an iron overload disease. Serum iron, total iron binding capacity, and serum ferritin within normal institutional limits; patients are eligible even if they are taking an iron supplement Receipt of any other iron-oxide based nanoparticle therapy or IV iron within 4 weeks of scans A known diagnosis of hemochromatosis, mitochondrial disorder, or iron overload