Treatment of HLH often involves administration of cytotoxic chemotherapy, and thus a high diagnostic threshold must be used, given the potential for side effects and complications stemming from treatment. Go to your doctor and tell him you want tests. There were 269 values (0.4%) over 10,000 ng/mL in 86 unique patients ranging from 10,006 ng/mL to 143,931 ng/mL. sHLH is thought to result from a strong activation of the immune system, often caused by infection. HFE -linked hemochromatosis is an unlikely diagnosis in a Filipino, although European colonization could account for HFE C282Y in that geographic region. To further characterize the cases of hyperferritinemia associated with liver disease, patients classified into this category were divided according to whether they had either an acute or a chronic hepatic disease. The conditions associated with more extreme hyperferritinaemia are poorly understood. M Patients who had hyperferritinemia associated with chronic transfusions (30 in total) had serum ferritin values that fell in the lower half of the hyperferritinemic range (<59,000 ng/mL), while the remaining diagnoses displayed a wider range of ferritin values. name the eight diagnostic criteria used to identify hemophagocytic lymphohistiocytosis. Ferritin is a positive acute phase reactant in both adults and children, whereby chronic inflammation results in a disproportionate increase in ferritin in relation to iron reserves. Söder A normal serum transferrin saturation (ideally fasting) usually excludes iron overload (where it is raised) and suggests a reactive cause for raised ferritin. The main problem with a high serum ferritin is that it may reflect high stores of iron in the body. 11 While a high index of suspicion is necessary to avoid missing rare diagnoses, care must be taken to avoid overtesting and overdiagnosis of HLH based on serum ferritin levels alone. Knovich Conclusions: Although this supports the relationship between extreme hyperferritinemia and HLH, it maintains that the positive predictive value of hyperferritinemia for HLH is quite low, and one should consider more common explanations before suspecting HLH. et al.  A ferritin test measures the amount of ferritin in your blood. Our results show that of the 65,536 ferritin levels that were drawn over the course of five years, less than 1% showed extreme hyperferritinemia. Anticoagulation - Rivaroxaban (Xarelto®) or apixaban (Eliquis®), Bone Marrow Biopsy - Post Procedure Instruction, Hereditary Haemorrhagic Telangiectasia (HHT), Peri-operative management of anticoagulation, Fatigue Severity Scale (FSS) - Questionnaire, Idiopathic Thrombocytopenia Purpura (ITP) in Children, Idiopathic Thrombocytopenia Purpura (ITP) in Adults, MGUS (monoclonal gammopathy of undetermined significance), Anticoagulation - Being on long-term anticoagulation medication rivaroxaban (Xarelto®) or apixaban (Eliquis®), Iron Infusion with ferric carboxymaltose (FCM), Anticoagulation (Blood thinning) in Pregnancy, Below Knee DVT - Calf vein thrombosis (Distal deep vein thrombosis (DVT), Peri-operative management of anticoagulation (blood thinning), Increased levels may also be seen in problems with the liver (hepatitis), Excessive alcohol can also increase the levels of serum ferritin, A major cause of raised serum ferritin is when there is too much iron in the body. Liegt dieses über dem alters- und geschlechtsspezifischen Normwert, ist das Ferritin zu hoch. This blood test indirectly provides information about whether there is too much or too little iron available in your body. It has a molecular weight of ≥ 440000 daltons, depending upon the iron content, and consists of a protein shell (apoferritin) of 24 subunits and an iron core containing an average of approx. The population was comprised of 19 pediatric patients (22%), with the remaining 67 patients being adults (78%). A ferritin test measures the amount of a blood protein called ferritin, which stores iron. This is also consistent with other literature that shows the majority of hyperferritinemia cases have values that range in the 10,000 ng/mL to approximately 50,000 ng/mL, with fewer cases reaching serum ferritin values higher than 50,000 ng/mL. Fuchs The clinical significance of extreme hyperferritinaemia has come under scrutiny with the increasing recognition of haemophagocytic lymphohistiocytosis (HLH) in adults. First, this was a retrospective chart review study, and diagnoses were drawn from clinical documentation and may be subject to error. HLH, hemophagocytic lymphohistiocytosis. It should be noted that this sample population is taken from a tertiary care center, so the incidence of less than 1% may be even smaller in other populations. of patients). Ferritin is a type of protein that binds with iron in the blood. Levels may increase in the setting of other illnesses (e.g. Katie Sackett, DO, MS, Maros Cunderlik, Nishant Sahni, MD, MS, Anthony A. Killeen, MD, PhD, Andrew P. J. Olson, MD, Extreme Hyperferritinemia:  Causes and Impact on Diagnostic Reasoning, American Journal of Clinical Pathology, Volume 145, Issue 5, May 2016, Pages 646–650, https://doi.org/10.1093/ajcp/aqw053. Based on the authors’ review, diagnoses were classified into the following categories: “Chronic Transfusion,” “Liver Disease,” “Malignancy—Hematologic,” “Malignancy–Solid,” “Hemoglobinopathy,” “Infection—Bacterial,” “Infection—Fungal,” “Infection–Viral,” “Infection—Other,” “Primary HLH,” “Secondary HLH,” “Macrophage Activation Syndrome,” and “Diagnosis Not Determined.” HLH-2004 criteria as defined by Henter et al 7 were used for the determination of HLH diagnosis. JA Serum ferritin of <1,000 ng/mL at diagnosis remains an important diagnostic test to identify patients with a low risk of advanced hepatic fibrosis and should be used routinely as part of the initial diagnostic evaluation. , Coffman LG Yu MA Erhöhtes Ferritin bedeutet einen Überschuss dieses Proteins, das der Eisenspeicherung dient, im Körper. Measurement of ferritin in blood helps know the iron levels. X Primary HLH affected 11% of the pediatric population and only 1% of the adult population (3% overall). It thus helps store iron in the body. The one patient with hyperferritinemia associated with a hemoglobinopathy had a ferritin value of 14,526 ng/mL. M The University of Minnesota has a robust bone marrow transplantation program, and thus such diagnoses may be overrepresented compared to other populations. All rights reserved. S If the ferritin is low, this often means the body is low in iron. Bacterial, fungal, and viral infections were associated with hyperferritinemia in adults in 3%, 1%, and 0%, respectively; in children, 5% of cases were associated with bacterial infection, 11% with viral infections, and no cases were associated with fungal infection. Ferritin is the major iron storage molecule in glial cells, particularly in oligodendrocytes (Gerber & Connor, 1989). A ferritin test is a blood test that helps your doctor to measure the amount of the protein ferritin present in your blood. One adult patient had hyperferritinemia associated with a Babesia infection, categorized as “Infection–Other,” and comprised 1% of the adult and overall population of this subset. Ferritin is the iron storage protein. These people will generally need some form of treatment for the high levels of ferritin. et al.  What Are Causes of High Ferritin? Overall, bacterial, fungal, and viral infections accounted for 3%, 1% and 2% of overall cases, respectively. The percentage of total patients who had hyperferritinemia associated with viral, bacterial, or fungal infections (2%, 3%, and 1%, respectively) is likely consistent with other populations. 2,3 The magn… KN Da der Serum Ferritin Spiegel aber proportional zu dem Eisenspeicher der Zellen ist, gilt ers als Hauptindikator für einen Eisenmangel oder eine Eisenüberladung des Körpers. Elinder Pietrangelo A. MA JI . G 14. , 4 HLH is an uncommon disorder that affects approximately 1:50,000 patients per year. Bei bestätigter Eisenüberladung mit Ferritin >1000 μg/l oder abnormaler Leberfunktion sollte eine Überweisung zum Hepatologen erfolgen. Ferritin is a molecule that has many roles, ranging from the binding and storage of iron to contributing to inflammation, cell signaling and immune function. A Hereditary hemochromatosis, the most common cause of iron overload, is also called "bronze diabetes" because a patient's skin may be slate-colored, and diabetes occurs in approximately 65 percent of patients. OBJECTIVE —A high prevalence of diabetes has been reported in patients with hepatitis C virus (HCV) infection. The number of iron atoms/ferritin cage is said to average 1000–1500 normally, 73 governed more by iron availability than anything else, with a maximum of 4500 iron atoms normally being quoted (e.g., ref. In patients with … Henter You have to consult your doctor before pinpointing the cause. 8,9 This may be due to incompletely developed illness scripts for both hyperferritinemia and HLH, and clinicians’ utilization of the availability heuristic, in which disorders that are more “available” in a clinician’s mind are more likely to be considered. infections, inflammatory conditions such as arthritis). Instead, common clinical conditions, including liver disease, iron overload and malignancy are much more likely in patients with hyperferritinemia. Ferrlecit is indicated for the treatment of iron deficiency anemia in adult patients and in pediatric patients age 6 years and older with chronic kidney disease receiving hemodialysis who are receiving supplemental epoetin therapy. . Our primary aim was to determine the primary clinical cause of extreme hyperferritinemia in a tertiary care population over a five-year period. Medical Progress: Hereditary Hemochromatosis — A New Look at an Old Disease.  Exam is located at www.ascp.org/ajcpcme . . et al.  Walker 2, There were limitations to our study. Henter Iron Overload. Extreme hyperferritinemia (defined as a ferritin level >10,000 ng/mL) often triggers a thought process that includes many rare and serious differential diagnoses such as HLH, while more common disorders are dismissed. C C For full access to this pdf, sign in to an existing account, or purchase an annual subscription. 2,3 The magnitude of elevation in serum ferritin has been linked with worse prognosis. AC Fine-Needle Aspiration Biopsy of Intraocular Mass-like Lesions: Lymphocytic Esophagitis With Predominance of CD4 T Cells and Expansion of Th1 Cells Is Associated With Achalasia. Number of Patients With Hyperferritinemia Within Each Range of Serum Ferritin a. a The number of patients with ferritin values within each range, with the largest number of patients with hyperferritinemia between 10,000 ng/mL and 19,999 ng/mL. , , B , , Patients should seek further advice and information about Raised Serum Ferritin and or their individual condition from their treating haematologist or doctor. 10 Although the hallmark sign of HLH is hyperferritinemia, our study shows that a very high ferritin level may be sensitive for a diagnosis of HLH, but has a very poor positive predictive value. The distribution of ferritin values across ranges is shown in Table 3 . For a male it is 30 – 300 ug/l. Henter Primary HLH displayed a range from 10,214 ng/mL to 33,000 ng/mL, while sHLH ranged from 10,548 ng/mL to 27,880 ng/mL. Allen Ferritin is a protein that carries iron around in the blood and can be used to measure the amount of iron in the body. et al.  , Serum ferritin evaluations in our institution are performed using a two-site chemiluminescent immunoassay (Vista Centaur; Siemens, Erlangen, Germany). Cytomorphologic Spectrum of SMARCB1-Deficient Soft Tissue Neoplasms: About American Journal of Clinical Pathology, About the American Society for Clinical Pathology, Receive exclusive offers and updates from Oxford Academic, A Descriptive and Quantitative Immunohistochemical Study Demonstrating a Spectrum of Platelet Recruitment Patterns Across Pulmonary Infections Including COVID-19, A Flow Cytometric Study of Reagent Cells to Resolve ABO Typing Discrepancy, Practice of Academic Surgical Pathology During the COVID-19 Pandemic: Perspective on the Situation During the Lockdown From a Leading Center in Pakistan and Reflections on the Future—Fears, Hopes, and Aspirations. Normal serum ferritin levels vary between laboratories but generally concentrations >300 µg/L in men and postmenopausal women and >200 µg/L in premenopausal women are regarded as elevated.1 Low ferritin … Classically, a very limited differential diagnosis has been considered for patients with such extreme hyperferritemia, including sepsis, infection (especially fungal), and iron overload, and rare causes such as hemophagocytic lymphohistocytosis (HLH). Methods: We identified conditions most associated with hyperferritinemia by identifying 65,536 serum ferritin levels at the University of Minnesota Hospital over a five-year period, with 86 values higher than 10,000 ng/mL. 1. 4 Serum ferritin levels can occasionally reach extremes greater than 10,000 ng/mL. 12,13 The approach to a patient with hyperferritinemia should encompass not only the rarer entities described above, but should also include the more common and seemingly mundane differentials of infection and iron overload. Bacterial, viral and fungal infections displayed ranges from 11,300 ng/mL to 25,460 ng/mL, 14,037 ng/mL to 72,710 ng/mL and 18,349 (one patient), respectively. The small amount of ferritin that is released and circulates in the blood is a reflection of the total amount of iron stored in the body. Oxford University Press is a department of the University of Oxford. This is usually related to a condition called. Average serum ferritin by condition. Impact of vaccination by priority group on UK deaths, hospital admissions and intensive care admissions from COVID-19. Ferritin is the storage form of iron in the liver. JI 1 The normal range of serum ferritin is gender and age specific, 7 to 10 ng/mL for infants and 20 to 300 ng/mL for adults. Of the 27% of those patients with liver disease, 16% overall (14 patients) had chronic liver disease; none were pediatric patients. Both diabetes and HCV infection are associated with high serum ferritin levels. et al.  et al.  Allen A number of blood tests and an ultrasound to look at the liver are usually needed in people who have high serum ferritin. For permissions, please e-mail: journals.permissions@oup.com, Mucinous Adenocarcinoma With Intrapulmonary Metastasis Harboring, A Tertiary Academic Medical Center Blood Bank’s Experience With Four-Factor Prothrombin Complex Concentrate. . Storey Do not be persuaded to … RWD This is in agreement with ferritin being the major iron storage molecule. . . Development and dissemination of the national strategic action plan for reducing inappropriate polypharmacy in older Australians. CE The diagnostic criteria for HLH must include five of these eight findings: hyperferritinemia, fever, splenomegaly, bicytopenia, elevated triglycerides and/or decreased fibrinogen, hemophagocytosis identified (usually in a bone marrow, liver or lymph node specimen), decreased or absent NK cell function, and increased soluble IL-2 receptor. For a female the normal level is 15 – 200 ug/l. While there is interest in iron reduction therapy for cancer risk reduction,3 improvement of insulin sensitivity in metabolic syndrome4 and management of fatty liver disease not responding to lifestyle changes,5 the Australian Red Cross Blood Service Therapeutic Venesection program is currently restricted to patients meeting the criteria listed in Table 1, and who also meet the general eligibility criteria for volunteer blood donation. Ferritin is found chiefly in the cytoplasm of cells of the reticuloendothelial system and is a constituent of normal human serum. Most studies of hyperferritinaemia have focused on serum ferritin greater than 1000 μg/L, often in ambulatory patients. If the ferritin level is high, the amount of iron in the blood may also be high. Although iron is important for lots of processes in the body, too much iron over a long period of time can be dangerous and cause a lot of problems with the function of body organs. A Pediatric patients comprised 22% of this population, and adults, 78%. Patients were categorized as adult if their age was greater than 18 years on the date of the ferritin value measurement. , Sahni I started donating blood in January 2013. Increased levels of serum ferritin may occur for a number of reasons. Ferritin is an intracellular iron storage protein and a marker of iron stores. . Clinicians should not be blindly obedient to a lab value; rather one should evaluate the evidence and consider what is common when diagnosing patients with hyperferritinemia. et al.  90–92, and attained for iron overload conditions or when loaded artificially in vitro). The normal level of ferritin varies a bit and can be dependent on age and gender. GidgetD 07/14/2010. In the adult population, sHLH comprised 7% of cases of hyperferritinemia (6% of all subjects), but was not seen in any of the hyperferritinemia cases in children. et al.  Think of your body as a kitchen pantry. Hemophagocytic lymphohistiocytosis can be divided into two types, familial (fHLH) and secondary (sHLH). Low ferritin indicates iron deficiency, while high ferritin indicates excess of iron in the body which can also prove harmful for the body. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. The final two patients, one with a Babesia infection associated with hyperferritinemia (classified as “Infection—Other”) and another with an unknown cause of hyperferritinemia displayed serum ferritin values of 15,219 ng/mL and 16,808 ng/mL, respectively (see Table 2 and Figure 1). . Resources used to produce this information sheet. ; Low levels of ferritin are indicative of iron deficiency, which causes anemia (a reduction in the number of oxygen-carrying red blood cells). I think the number of 1000 before issues occur is a convenient myth perpetuated by doctors who do not know what they are talking about. Elevations in serum ferritin have been observed in common conditions, including sepsis due to bacterial, fungal or viral sources, or iron overload due to hemochromatosis or chronic transfusions, or as a general marker of inflammation. TD Some people have very high levels of serum ferritin – greater than 1000 ug/l. MB Ormseth Here are some causes of iron overload: Objectives: Hyperferritinemia can be a result of inflammation, infection, chronic iron overload, or other uncommon pathologies including hemophagocytic lymphohistiocytosis (HLH). The mean age of patients in this subgroup was 46.6 years. G Rosrio Ferritin helps distribute iron to body cells. Bennett H. Jordan I would also be concerned about damage with ferritin over 1,000 but we are all so differant in the ways our body handles the iron but one thing is for sure and thats fatigue .The percentage of people having damage with ferritin over 1,000 is low so dont panic . The protein is produced by almost all living organisms, including archaea, bacteria, algae, higher plants, and animals. Crook Some pathology companies use different ways to measure ferritin and so the “normal levels” may change a little. Unfortunately, high levels of ferritin in the blood do not always mean the amount of iron in the body is high since there are other factors that can increase the level of ferritin. Percentage of Conditions Associated With Hyperferritinemia a. HLH, hemophagocytic lymphohistiocytosis. Also known simply as a "ferritin test" or a "serum ferritin level," the test has been available since the 1970s. et al.  Today, June 1, 2015 ferritin count is 246, BP is 115/75, HDL/LDL all within range; heaven knows who my blood helped, but they are out there. Summary of notifiable diseases—United States 2012, © American Society for Clinical Pathology, 2016. If the levels are low, it indicates iron deficiency or other diseases. The patients with any single measurement greater than 10,000 ng/mL were identified and selected for the study. Data are given as percent (No. Horne The average ferritin value for each diagnosis is displayed in the descending order along with the error bars indicating 95% confidence interval computed using normal distribution. CA The primary diagnosis in the majority of cases in both the pediatric and adult populations with hyperferritinemia was iron overload from chronic transfusions (35% total, 37% pediatric, 34% adult). Er gibt Auskunft über das im Körper vorhandene Eisen. Hyperferritinemia associated with solid malignancy displayed a range from 13,613 ng/mL to 14,754 ng/mL. This test measures the amount of ferritin in the blood. F Ferritin isn’t the same thing as iron. A large proportion of hyperferritinemic states were due to chronic transfusion and malignancies. Serum ferritin greater than 1,000 mcg/L indicates the …