Hemosiderosis is a form of

iron overload disorder Iron overload or hemochromatosis (also spelled ''haemochromatosis'' in British English) indicates increased total accumulation of iron in the body from any cause and resulting organ damage. The most important causes are hereditary haemochromatosi ...

resulting in the accumulation of

hemosiderin Hemosiderin image of a kidney viewed under a microscope. The brown areas represent hemosiderin Hemosiderin or haemosiderin is an iron-storage complex that is composed of partially digested ferritin and lysosomes. The breakdown of heme gives rise ...

. Types include: *

Transfusion hemosiderosis Transfusional hemosiderosis is the accumulation of iron in the body due to frequent blood transfusions. Iron accumulates in the liver and heart, but also endocrine organs. Frequent blood transfusions may be given to many patients, such as those ...

* Idiopathic pulmonary hemosiderosis * Transfusional diabetes Organs affected: * Hemosiderin deposition in the lungs is often seen after

diffuse alveolar hemorrhage Pulmonary hemorrhage (or pulmonary haemorrhage) is an acute bleeding from the lung, from the upper respiratory tract and the trachea, and the pulmonary alveoli. When evident clinically, the condition is usually massive.Goodpasture's syndrome Goodpasture syndrome (GPS), also known as anti–glomerular basement membrane disease, is a rare autoimmune disease in which antibodies attack the basement membrane in lungs and kidneys, leading to bleeding from the lungs, glomerulonephritis ...

granulomatosis with polyangiitis Granulomatosis with polyangiitis (GPA), previously known as Wegener's granulomatosis (WG), is a rare long-term systemic disorder that involves the formation of granulomas and inflammation of blood vessels (vasculitis). It is a form of vasculitis ...

, and idiopathic pulmonary hemosiderosis.

Mitral stenosis Mitral stenosis is a valvular heart disease characterized by the narrowing of the opening of the mitral valve of the heart. It is almost always caused by rheumatic valvular heart disease. Normally, the mitral valve is about 5 cm2 during d ...

can also lead to pulmonary

hemosiderosis Hemosiderosis is a form of iron overload disorder resulting in the accumulation of hemosiderin. Types include: * Transfusion hemosiderosis * Idiopathic pulmonary hemosiderosis * Transfusional diabetes Organs affected: * Hemosiderin deposit ...

. * Hemosiderin collects throughout the body in

hemochromatosis Iron overload or hemochromatosis (also spelled ''haemochromatosis'' in British English) indicates increased total accumulation of iron in the body from any cause and resulting organ damage. The most important causes are hereditary haemochromatos ...

. * Hemosiderin deposition in the

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

is a common feature of

and is the cause of liver failure in the disease. * Selective iron deposition in the beta cells of pancreatic islets leads to

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...

due to distribution of transferrin receptor on the beta cells of islets and in the skin leads to hyperpigmentation. * Hemosiderin deposition in the brain is seen after bleeds from any source, including chronic subdural hemorrhage,

cerebral arteriovenous malformation A cerebral arteriovenous malformation (cerebral AVM, CAVM, cAVM) is an abnormal connection between the arteries and veins in the brain—specifically, an arteriovenous malformation in the cerebrum. Signs and symptoms The most frequently observed ...

cavernous hemangioma Cavernous hemangioma, also called cavernous angioma, venous malformation, or cavernoma, is a type of venous malformation due to endothelial dysmorphogenesis from a lesion which is present at birth. A cavernoma in the brain is called a cerebral ca ...

ta. * Hemosiderin collects in the skin and is slowly removed after bruising; hemosiderin may remain in some conditions such as stasis dermatitis. * Hemosiderin in the kidneys has been associated with marked hemolysis and a rare blood disorder called

paroxysmal nocturnal hemoglobinuria Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease of the blood characterized by destruction of red blood cells by the complement system, a part of the body's innate immune system. This destructive process occu ...

. Hemosiderin may deposit in diseases associated with iron overload. These diseases are typically diseases in which chronic blood loss requires frequent

blood transfusion Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mo ...

s, such as

sickle cell anemia Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red bl ...

and thalassemia, though beta thalassemia minor has been associated with hemosiderin deposits in the liver in those with

non-alcoholic fatty liver disease Non-alcoholic fatty liver disease (NAFLD), also known as metabolic (dysfunction) associated fatty liver disease (MAFLD), is excessive fat build-up in the liver without another clear cause such as alcohol use. There are two types; non-alcoholic ...

independent of any transfusions. Iron overload occurs when iron intake is increased over a sustained period of time due to regular transfusion of

whole blood Whole blood (WB) is human blood from a standard blood donation. It is used in the treatment of massive bleeding, in exchange transfusion, and when people donate blood to themselves. One unit of whole blood (~517 mls) brings up hemoglobin level ...

and

red cells Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...

or because of increased absorption of iron through the gastrointestinal tract (GI). Both these phenomena occur in thalassaemias, with

therapy being the major cause of

iron overload Iron overload or hemochromatosis (also spelled ''haemochromatosis'' in British English) indicates increased total accumulation of iron in the body from any cause and resulting organ damage. The most important causes are hereditary haemochromatos ...

in thalassaemia major and increased GI absorption being more important in patients with intermedia thalassaemia who are not frequently transfused. Each unit of blood contains about 200 mg iron. After 50 units have been transfused, or earlier in children, siderosis develops, with increased pigmentation of skin exposed to light and susceptibility to infection, reduced growth and delayed sexual development and puberty⁽²⁴⁾. The recommended red cell transfusion scheme for patients with β-thalassaemia amounts to 116–232 mg iron per Kg weight on an annual basis (0.32-0.64 mg/Kg/day). The human body lacks a mechanism to excrete excess iron. Iron accumulation is toxic to many tissues, causing heart failure,

cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue rep ...

, liver cancer,

growth retardation Delayed milestone, also called developmental delays, is used to describe the condition where a child does not reach one of these stages at the expected age. However, in most cases, a wide variety of ages can be considered normal, and not a cause fo ...

and endocrine abnormalities. In the absence of regular iron chelation therapy, the iron loading rates vary. Monitoring of transfusion iron overload is essential for effective and safe iron chelation tailored to the individual's specific needs. Serum ferritin (SF) measured at least every 3 months (the currently accepted target value is between 500 and 1000 mg/L) should also be evaluated along with the liver iron concentration (LIC) assessed using a validated and standardized MRI technique and myocardial iron as measured by MRI-based methods with specific software T2*. For monitoring of transfusion iron overload, other organ function and iron-mediated damage, surveillance of the patient for

, hypothyroidism,

hypoparathyroidism Hypoparathyroidism is decreased function of the parathyroid glands with underproduction of parathyroid hormone (PTH). This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany (involuntary m ...

and

hypogonadotropic hypogonadism Hypogonadotropic hypogonadism (HH), is due to problems with either the hypothalamus or pituitary gland affecting the hypothalamic-pituitary-gonadal axis (HPG axis). Hypothalamic disorders result from a deficiency in the release of gonadotropic r ...

is recommended.

Diagnosis

Kupffer cell with hemosiderin and hepatocyte with lipofuscin

There are several methods available for diagnosing and monitoring hemosiderosis including: * Serum ferritin *

Liver biopsy Liver biopsy is the biopsy (removal of a small sample of tissue) from the liver. It is a medical test that is done to aid diagnosis of liver disease, to assess the severity of known liver disease, and to monitor the progress of treatment. Medica ...

MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...

Serum ferritin is a low cost, readily available, and minimally invasive method for assessing body iron stores. However, the major problem with using it as an indicator of hemosiderosis is that it can be elevated in a range of other medical conditions unrelated to iron levels including infection, inflammation, fever, liver disease, renal disease and cancer. While liver

biopsies A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a dise ...

provide a direct measure of liver iron concentration, the small

sample size Sample size determination is the act of choosing the number of observations or replicates to include in a statistical sample. The sample size is an important feature of any empirical study in which the goal is to make inferences about a populatio ...

relative to the size of the liver can lead to sampling errors given the heterogeneity of iron concentration within the liver. Furthermore, the invasive nature of liver biopsy and the associated risks of complications (which can range from pain, haemorrhage,

gallbladder In vertebrates, the gallbladder, also known as the cholecyst, is a small hollow organ where bile is stored and concentrated before it is released into the small intestine. In humans, the pear-shaped gallbladder lies beneath the liver, although ...

perforation and other morbidities through to death in approximately 1 in 10,000 cases) prevent it being used as a regular monitoring tool. Magnetic resonance imaging (MRI) is emerging as an alternative method for measuring liver iron loading because it is non- invasive, safer and generally cheaper to perform than liver biopsy; does not suffer from problems with sampling variability; and can be used more frequently than performing liver biopsies.

Treatment

Treatment for hemosiderin focuses on limiting the effects of the underlying disease leading to continued deposition. In hemochromatosis, this entails frequent

phlebotomy Phlebotomy is the process of making a puncture in a vein, usually in the arm, with a cannula for the purpose of drawing blood. The procedure itself is known as a venipuncture, which is also used for intravenous therapy. A person who performs a p ...

granulomatosis, immune suppression is required. Limiting blood transfusions and institution of iron

chelation therapy Chelation therapy is a medical procedure that involves the administration of chelating agents to remove heavy metals from the body. Chelation therapy has a long history of use in clinical toxicology and remains in use for some very specific me ...

when iron overload is detected are important when managing sickle-cell anemia and other chronic

hemolytic anemia Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular). This most commonly ...

s. The aims of iron chelation therapy include (a) prevention therapy in order to minimize the risk of onset of iron-mediated complications, (b) rescue therapy for the removal of storage iron and (c) emergency therapy if heart failure develops or if there is a downward trend of left ventricular (LV) function that requires hospitalisation using continuous intravenous desferrioxamine (DFO), possibly combined with

deferiprone Deferiprone, sold under the brand name Ferriprox among others, is a medication that chelates iron and is used to treat iron overload in thalassaemia major. It was first approved and indicated for use in treating thalassaemia major in 1994 and h ...

(DFP). It aims to balance the rate of iron accumulation from

by increasing iron excretion in urine and in faeces with chelators. There are currently three licensed iron chelators, DFO, DFP and

Deferasirox Deferasirox, sold under the brand name Exjade & Asunra (in injectable form) & Oleptiss (Tablet formulation) both by Novartis among others, is an oral iron chelator. Its main use is to reduce chronic iron overload in patients who are receiving l ...

(DFX). The Guide for the Management of Transfusion Dependent Thalassaemia (TDT) issued by th
Thalassaemia International Federation
(TIF Publication No23, 2017) contains details of dose and regimen adjustment of iron chelation therapy, adherence to therapy and use of combination therapies as well as monitoring of chelation therapy in special circumstances such as pregnancy, renal impairment and summary recommendations.

References

8. The Guide for the Management of Transfusion Dependent Thalassaemia (TDT) 3rd edition, editors Cappellini MD, Cohen A, Porter J, Taher A, Viprakasit V, published and issued by the Thalassaemia International Federation (TIF Publication No23, 2017)

External links

FerriScan
- MRI-based test to measure iron overload {{Inborn errors of metal metabolism Iron metabolism

Diagnosis

Treatment

See also

References

External links