Materiały źródłowe

• #1 Anemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK499994/

  Anemia is described as a reduction in the proportion of the red blood cells. Anemia is not a diagnosis, but a presentation of an underlying condition. Whether or not a patient becomes symptomatic depends on the etiology of anemia, the acuity of onset, and the presence of other comorbidities, especially the presence of cardiovascular disease. Most patients experience some symptoms related to anemia when the hemoglobin drops below 7.0 g/dL. […] The pathophysiology of anemia varies greatly depending on the primary cause. For instance, in acute hemorrhagic anemia, it is the restoration of blood volume with intracellular and extracellular fluid that dilutes the remaining red blood cells (RBCs), which results in anemia. A proportionate reduction in both plasma and red cells results in falsely normal hemoglobin and hematocrit.

• #2 Anemia epidemiology, pathophysiology, and etiology in low- and middle-income countries

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6697587/

  Anemia affects a third of the worlds population and contributes to increased morbidity and mortality, decreased work productivity, and impaired neurological development. […] Understanding anemias varied and complex etiology is crucial for developing effective interventions that address the context-specific causes of anemia and for monitoring anemia control programs. […] We outline definitions and classifications of anemia, describe the biological mechanisms through which anemia develops, and review the variety of conditions that contribute to anemia development. […] We emphasize the risk factors most prevalent in low- and middle-income countries, including nutritional deficiencies, infection/inflammation, and genetic hemoglobin disorders. […] Recent work has furthered our understanding of anemias complex etiology, including the proportion of anemia caused by iron deficiency (ID) and the role of inflammation and infection.

• #3 Anemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK499994/

  RBC are produced in the bone marrow and released into circulation. Approximately 1% of RBC are removed from circulation per day. Imbalance in production to removal or destruction of RBC leads to anemia. […] The main mechanisms involved in anemia are listed below: 1. Increased RBC destruction […] 2. Deficient/defective erythropoiesis.

• #4 Etiology of Anemia – Hematology and Oncology – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hematology-and-oncology/approach-to-the-patient-with-anemia/etiology-of-anemia

  Anemia is a decrease in the number of red blood cells (RBCs), which leads to a decrease in the hematocrit and the red cell hemoglobin content. […] Thus, anemia can result from one or more of 3 basic mechanisms: Blood loss, Deficient or ineffective erythropoiesis, Excessive hemolysis (RBC destruction). […] Anemia may not develop until several hours after acute blood loss when interstitial fluid diffuses into the intravascular space and dilutes the remaining RBC mass. […] Deficient or inefficient erythropoiesis has myriad causes. Complete cessation of erythropoiesis results in a decline in RBCs of about 7 to 10%/week (1%/day). Impaired erythropoiesis, even if not sufficient to decrease the numbers of RBCs, often causes abnormal RBC size and shape. […] Excessive hemolysis can be caused by intrinsic abnormalities of RBCs or by extrinsic factors, such as the presence of antibodies or complement on their surface, that lead to their early destruction. An enlarged spleen sequesters and destroys RBCs more rapidly than normal. Some causes of hemolysis deform as well as destroy RBCs. Hemolysis normally causes increased reticulocyte production unless iron or other essential nutrients are depleted or there is erythropoietin deficiency.

• #5 Anemia: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/198475-overview

  Anemia is strictly defined as a decrease in red blood cell (RBC) mass. The decrease may result from blood loss, increased destruction of RBCs (hemolysis), or decreased production of RBCs. […] The physiologic response to anemia varies according to acuity and the type of insult. Gradual onset may allow for compensatory mechanisms to take place. With anemia due to acute blood loss, a reduction in oxygen-carrying capacity occurs along with a decrease in intravascular volume, with resultant hypoxia and hypovolemia. […] Basically, only three causes of anemia exist: blood loss, increased destruction of RBCs (hemolysis), and decreased production of RBCs. Each of these causes includes a number of disorders that require specific and appropriate therapy. […] Current evidence suggests that susceptibility to idiosyncratic reactions involves certain genetic polymorphisms involving cellular detoxifying enzymes. As a result, exogenous toxins that would normally be converted to nontoxic compounds are instead metabolized into reactive compounds that modify cellular proteins, which can be recognized by the immune system and trigger autoimmunity. […] Rare causes of anemia due to a hypoplastic bone marrow include familial disorders and the acquired pure red cell aplasias. The latter are characterized by a virtual absence of erythroid precursors in the bone marrow, with normal numbers of granulocytic precursors and megakaryocytes.

• #6

  https://healthmatch.io/anemia/pathophysiology-of-anemia

  Anemia is the decrease in the blood’s total amount of red blood cells (RBCs), where hemoglobin or hematocrit is below normal. It is a common condition where the body cannot deliver enough oxygen to the body tissues. […] Generally, anemia results from decreased RBC production, issues with RBC production, blood loss, increased RBC destruction, or poor RBC maturation. The pathophysiology of anemia is key to understanding when the condition starts developing, early diagnosis, and prevention. […] At a biological level, anemia results from an imbalance between erythrocyte loss subject to production or issues with hemoglobin. This occurs due to the following: […] The pathophysiology of anemia differs significantly depending on the underlying etiology. For example, restoring blood volume with intracellular and extracellular fluid in acute hemorrhagic anemia dilutes the remaining RBCs and can cause anemia.

• #7 Mechanisms | eClinpath

  https://eclinpath.com/hematology/anemia/mechanisms-of-anemia/

  Decreased or ineffective bone marrow production of erythroid cells will result in a non-regenerative anemia. […] Insufficient production or activity of erythropoietic cytokines, e.g. chronic kidney disease (erythropoietin is produced in the kidney). […] Suppression of erythropoiesis: This can be mediated by drugs, cytokines (TNF, interleukin-1, IFN), tumor cells or immune cells. […] Deficiency of minerals/vitamins/nutrients: The bone marrow needs fuel to do its work. Iron and copper essential for hemoglobin synthesis, whereas DNA synthesis requires folate and vitamin B12. […] Defective hemoglobin synthesis: This is usually secondary to iron deficiency and results in a microcytic hypochromic anemia. […] Defective DNA synthesis or nuclear maturation: Impairment of DNA synthesis characteristically results in macrocytic anemias. […] Destruction of bone marrow hematopoietic cells: This can affect RBC only or multiple hematopoietic lineages. […] Replacement of hematopoiesis: This is due to neoplasia (e.g. acute leukemia), which can efface the marrow or crowd out normal hematopoietic cells.

• #8 Anemia – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/anemia/symptoms-causes/syc-20351360

  Anemia occurs when the blood doesn’t have enough hemoglobin or red blood cells. […] This can happen if: The body doesn’t make enough hemoglobin or red blood cells. […] Bleeding causes loss of red blood cells and hemoglobin faster than they can be replaced. […] The body destroys red blood cells and the hemoglobin that’s in them. […] Different types of anemia have different causes. […] Too little iron in the body causes this most common type of anemia. Bone marrow needs iron to make hemoglobin. Without enough iron, the body can’t make enough hemoglobin for red blood cells. […] Besides iron, the body needs folate and vitamin B-12 to make enough healthy red blood cells. […] Diseases that cause ongoing inflammation can keep the body from making enough red blood cells. […] This rare, life-threatening anemia occurs when the body doesn’t make enough new blood cells.

• #9 Chemotherapy-induced anemia: etiology, pathophysiology, and implicatio | IJCTM

  https://www.dovepress.com/chemotherapy-induced-anemia-etiology-pathophysiology-and-implications–peer-reviewed-fulltext-article-IJCTM

  Anemia, derived from the Greek word anaimia meaning lack of blood, refers to a decreased oxygen-carrying capacity in the blood and is commonly associated with cancer. Anemia is the most common and persistent hematological abnormality in oncology patients. Chemotherapy-induced anemia (CIA) is a consequence of malignant invasion of normal tissue leading to blood loss, bone marrow infiltration with disruption of erythropoiesis, and functional iron deficiency as a consequence of inflammation. CIA is a significant consequence of chemotherapy and may delay or limit therapy as well as contribute to both fatigue and diminished quality of life. […] In advanced hematologic malignancies, cytokine release from tumor cells is a main mechanism by which erythropoiesis is disrupted. These cytokines, including interferon-gamma, IL-1, and tumor necrosis factor, disrupt endogenous erythropoietin synthesis in the kidney and suppress differentiation of erythroid progenitor cells in the bone marrow.

• #10 Overview of Hemolytic Anemia – Hematology and Oncology – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/hematology-and-oncology/anemias-caused-by-hemolysis/overview-of-hemolytic-anemia

  Hemolysis is defined as premature destruction and hence a shortened RBC life span (120 days). Anemia results when bone marrow production can no longer compensate for the shortened RBC survival; this condition is termed uncompensated hemolytic anemia. If the marrow can compensate, the condition is termed compensated hemolytic anemia. […] Hemolysis may also be extravascular, intravascular, or both. […] Most pathologic hemolysis is extravascular and occurs when damaged or abnormal RBCs are cleared from the circulation by the spleen and liver. […] Intravascular hemolysis is an important reason for premature RBC destruction and occurs when the cell membrane has been severely damaged by any of a number of different mechanisms, including immune phenomena, direct trauma, shear stress, disseminated intravascular coagulation (DIC), and toxins.

• #11 Mechanisms | eClinpath

  https://eclinpath.com/hematology/anemia/mechanisms-of-anemia/

  There are three main mechanisms for anemia: […] Hemolysis: This is due to destruction of RBCs within the body before they have finished their normal lifespan. […] Decreased bone marrow production: These anemias are usually non-regenerative. Decreased production can be due to: […] A regenerative anemia typically results from loss of RBC (hemorrhage) or premature destruction of RBC (hemolysis). […] Hemolysis indicates reduced RBC lifespan due to destruction of RBC. […] Extravascular hemolysis occurs when RBCs are phagocytized by macrophages in the spleen, liver and bone marrow. […] Intravascular hemolysis results from the rupture or lysis of RBC within the circulation, i.e. the RBC are lysing in vivo. […] Intravascular hemolysis is not good for the patient. It results in tissue injury (through initiating oxidant injury and scavenging the important protective vasodilator and platelet inhibitor, nitric oxide), inciting inflammation and triggering thrombosis.

• #12 Hemolytic Anemia: Evaluation and Differential Diagnosis | AAFP

  https://www.aafp.org/pubs/afp/issues/2018/0915/p354.html

  Hemolytic anemia is defined by the premature destruction of red blood cells, and can be chronic or life-threatening. […] Mechanisms include poor deformability leading to trapping and phagocytosis, antibody-mediated destruction through phagocytosis or direct complement activation, fragmentation due to microthrombi or direct mechanical trauma, oxidation, or direct cellular destruction. […] The primary extravascular mechanism is sequestration and phagocytosis due to poor RBC deformability (i.e., the inability to change shape enough to pass through the spleen). Antibody-mediated hemolysis results in phagocytosis or complement-mediated destruction, and can occur intravascularly or extravascularly. The intravascular mechanisms include direct cellular destruction, fragmentation, and oxidation. Direct cellular destruction is caused by toxins, trauma, or lysis. Fragmentation hemolysis occurs when extrinsic factors produce shearing and rupture of RBCs. Oxidative hemolysis occurs when the protective mechanisms of the cells are overwhelmed.

• #13 Anemia: Symptoms, types, treatment, causes, diet, and more

  https://www.medicalnewstoday.com/articles/158800

  Anemia occurs when there is a decrease in circulating red blood cells. When this happens, the blood cannot provide enough oxygen to the body. A person with anemia may feel tired or weak. […] Other health conditions, such as those that interfere with the body’s production of healthy red blood cells (RBCs) or increase the rate of the breakdown or loss of these cells, can cause anemia. Anemia can lead to symptoms including fatigue, shortness of breath, and lightheadedness. […] The body needs RBCs to survive. They transport hemoglobin, a complex protein that attaches to iron molecules. These molecules carry oxygen from the lungs to the rest of the body. […] Various health conditions can result in low levels of RBCs and cause anemia. […] The three main causes of anemia are: […] Blood loss can lead to low levels of iron in the blood, causing anemia.

• #14 Iron Deficiency Anemia – Hematology and Oncology – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hematology-and-oncology/anemias-caused-by-deficient-erythropoiesis/iron-deficiency-anemia

  Severe and prolonged iron deficiency also may cause dysfunction of iron-containing cellular enzymes. […] Blood loss is the major cause of iron deficiency. In men and postmenopausal women, the most frequent cause of blood loss is chronic occult bleeding, usually from the gastrointestinal tract (eg, due to peptic ulcer disease, malignancy, hemorrhoids, or vascular ectasias). […] Increased iron requirements may contribute to iron deficiency. From birth to age 2 and during adolescence, when rapid growth requires a large iron intake, dietary iron often is inadequate. […] Decreased iron absorption can result from gastrectomy or malabsorption syndromes such as celiac disease, atrophic gastritis, Helicobacter pylori infection, achlorhydria, short bowel syndrome, and rarely IRIDA (iron-refractory iron deficiency anemia).

• #15 Iron deficiency anaemia: pathophysiology, assessment, practical management | BMJ Open Gastroenterology

  https://bmjopengastro.bmj.com/content/9/1/e000759

  The WHO has recognised iron deficiency anaemia (IDA) as the most common nutritional deficiency in the world, with 30% of the population being affected with this condition. […] Although the most common causes of IDA are gastrointestinal bleeding and menstruation in women, decreased dietary iron and decreased iron absorption are also culpable causes. […] Iron is required for various cellular functions, including but not limited to enzymatic processes, DNA synthesis, oxygen transport and mitochondrial energy generation. […] This resultant hypoxemia can subsequently cause a compensatory decrease in intestinal blood flow, leading to motility disorder, malabsorption, nausea, weight loss and abdominal pain. […] Iron is an essential element and is controlled primarily by dietary intake, intestinal absorption and iron recycling.

• #16 Iron Deficiency Anemia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/202333-overview

  Iron deficiency anemia develops when body stores of iron drop too low to support normal red blood cell (RBC) production. Inadequate dietary iron, impaired iron absorption, bleeding, or loss of body iron in the urine may be the cause. […] Iron equilibrium in the body normally is regulated carefully to ensure that sufficient iron is absorbed in order to compensate for body losses of iron. […] Iron is vital for all living organisms because it is essential for multiple metabolic processes, including oxygen transport, DNA synthesis, and electron transport. Iron equilibrium in the body is regulated carefully to ensure that sufficient iron is absorbed in order to compensate for body losses of iron. […] Either diminished absorbable dietary iron or excessive loss of body iron can cause iron deficiency. Diminished absorption usually is due to an insufficient intake of dietary iron in an absorbable form. Hemorrhage is the most common cause of excessive loss of body iron, but it can occur with hemoglobinuria from intravascular hemolysis.

• #17 Iron Deficiency Anemia – Hematology and Oncology – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hematology-and-oncology/anemias-caused-by-deficient-erythropoiesis/iron-deficiency-anemia

  Iron deficiency is the most common cause of anemia and usually results from blood loss; malabsorption, such as occurs in celiac disease, is a much less common cause. […] Iron is distributed in active metabolic and storage pools. Total body iron is approximately 3.5 to 4.5 mg/kg of body weight in healthy men (~4 g of iron), but is lower in premenopausal women; the difference in the total body iron relates to women’s smaller body size and dearth of stored iron because of iron loss due to menses. […] Iron deficiency develops in stages. In the first stage, iron requirement exceeds intake, causing progressive depletion of bone marrow iron stores. As stores decrease, absorption of dietary iron increases in compensation. During later stages, deficiency impairs RBC synthesis, ultimately causing anemia.

• #18 Pathophysiology | Iron Deficiency Anemia

  https://u.osu.edu/irondeficiencyanemia/pathophysiology/

  IDA is a hypochromic-microcytic anemia red blood cells (RBCs) are abnormally small with low levels of hemoglobin (hgb) […] Despite the cause, IDA occurs when the body’s iron demand exceeds that of its supply […] Mechanism low iron stores leads to demand supply […] Mechanism depleting iron stores faster than replacing combined while increasing body’s demand for iron […] Mechanism delivery to bone marrow to be utilized in the production of RBCs is impaired […] Mechanism even when delivered, there is impaired use of iron in the bone marrow to produce RBCs […] Iron regulates immune effector mechanisms cytokine activity, nitric oxide formation, and T-cell proliferation […] Acquired IDA may be body’s response to a pathogen many pathogens require iron to survive […] Reduction in iron transport to bone marrow, causing iron-deficient RBC production (hemoglobin content of RBC is reduced) […] Small, hemoglobin-deficient cells enter circulation, replacing normal RBC.

• #19 Iron Deficiency Anemia: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/202333-overview

  Iron uptake in the proximal small bowel occurs by 3 separate pathways. These are the heme pathway and 2 distinct pathways for ferric and ferrous iron. […] Ferric iron utilizes a different pathway to enter cells than ferrous iron. […] Most iron delivered to nonintestinal cells is bound to transferrin. Transferrin iron is delivered into nonintestinal cells via 2 pathways: the classical transferrin receptor pathway and the pathway independent of the transferrin receptor. […] In contrast to findings in iron deficiency, enhanced erythropoiesis, or hypoxia, endotoxin rapidly diminishes iron absorption without altering enterocyte iron concentration. This suggests that endotoxin and, perhaps, cytokines alter iron absorption by a different mechanism. This is the effect of hepcidin and the balance of hepcidin versus erythropoietin.

• #20 Iron deficiency anaemia: pathophysiology, assessment, practical management | BMJ Open Gastroenterology

  https://bmjopengastro.bmj.com/content/9/1/e000759

  Dietary iron can be found in two forms: haem and non-haem iron. […] Compounds such as phytate, oxalate, polyphenols and tannin, which are found in plants, diminish the uptake of non-haem iron, as do some drugs, such as proton pump inhibitors. […] Hepcidin, a hepatic peptide hormone, controls ferroportin, the sole iron exporter, by promoting its endocytosis. […] Hepcidin is increased in the presence of inflammation, which then promotes the degradation of ferroportin and subsequently impairs the exportation of cellular iron into plasma. […] The WHO defines anaemia as blood Hb level below 130g/L in men and 120g/L in women. […] In isolated iron deficiency, serum ferritin (the storage molecule for iron) should be less than 30ug/L. […] Thus, if there is evidence of concomitant inflammation, such as elevated C reactive protein, ferritin less than 100ug/L is indicative of IDA.

• #21 Physiology and Inflammation Driven Pathophysiology of Iron Homeostasis—Mechanistic Insights into Anemia of Inflammation and Its Treatment

  https://www.mdpi.com/2072-6643/13/11/3732

  Immune activation in response to microbes, auto-antigens or tumor antigens stimulates release of several pro-inflammatory cytokines by immune cells, which then cause disturbances in iron homeostasis. Interferon gamma (IFN-γ), lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNF-α) upregulate the expression of DMT1 and downregulate the expression of FPN1 with subsequent increased iron uptake and reduced iron release from pro-inflammatory macrophages of the reticuloendothelial system. […] Inflammation also upregulates the expression of the iron-regulatory protein hepcidin. IL-6, and to a lesser extent IL-22, stimulate HAMP expression in hepatocytes via the JAK/STAT3 signaling pathway. […] Inflammation-related EPO reduction thus aggravates hepcidin-mediated iron limitation to erythroid progenitor cells.

• #22 Anemia epidemiology, pathophysiology, and etiology in low- and middle-income countries

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6697587/

  For example, in iron deficiency anemia (IDA), decreased iron availability has well-established negative effects on brain development and functioning even prior to anemia development. […] Anemia of chronic disease or AI is generally normocytic with a low reticulocyte count and characterized to be mild-to-moderate (Hb concentrations 810 g/L). […] In AI, proinflammatory cytokines released in the host defense response to infection (IL-6 in particular, but other cytokines are also involved) alter iron metabolism so that iron is sequestered within cells of the reticuloendothelial system (liver and spleen) and intestinal enterocytes, and RBC production and life span are reduced. […] AI has been called the second most common cause of anemia after IDA, and while disease/infections are the top causes of anemia, the proportion of global anemia due to inflammation is not known, and likely varies by setting and disease burden.

• #23 Anemia – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/anemia/

  Anemia of chronic disease: inflammation increase in cytokines (esp. IL-6) and hepcidin results in the outcomes listed below: Reduced iron release from macrophages in the reticuloendothelial system and reduced intestinal iron absorption reduced iron available systemically. […] Reduced response (of production) to erythropoietin (EPO) and relative reduction of EPO levels reduced RBC synthesis. […] Reduced erythrocyte survival and lifespan. […] Sideroblastic anemia: anemia caused by defective heme metabolism, which leads to iron trapping inside the mitochondria. […] Pathophysiology: thought to be related to abnormal T-cell function and IgG antibodies that target erythroblasts and erythropoietin.

• #24

  https://haematologica.org/article/view/5484

  Anemia in inflammatory bowel disease (IBD) is a prototype of a combination of iron deficiency and anemia of inflammation (i.e. anemia of chronic disease; ACD) which is caused by negative effects of an activated immune system at different levels of erythropoiesis. […] Inflammation affects three major steps essential for normal erythropoiesis and can, therefore, lead to the development of anemia of inflammation. These effects are: (i) an immunity-driven diversion of iron traffic leading to retention of the metal in macrophages and thus to iron-deficient erythropoiesis; (ii) blunting of the biological activity of erythropoietin, the major erythropoiesis-stimulating hormone; and (iii) inhibition of the differentiation and proliferation of erythroid progenitor cells. […] The changes in body iron distribution are caused by cytokines and acute phase proteins. Among these, the master regulator of iron homeostasis, hepcidin, appears to play a pivotal role. Hepcidin is an anti-microbial peptide formed of 25 amino acids, which is produced mainly in the liver in response to iron overload or upon induction by pro-inflammatory stimuli, such as lipopolysaccharide or interleukin-6.

• #25 Physiology and Inflammation Driven Pathophysiology of Iron Homeostasis—Mechanistic Insights into Anemia of Inflammation and Its Treatment

  https://www.mdpi.com/2072-6643/13/11/3732

  Anemia is very common in patients with inflammatory disorders. Its prevalence is associated with severity of the underlying disease, and it negatively affects quality of life and cardio-vascular performance of patients. Anemia of inflammation (AI) is caused by disturbances of iron metabolism resulting in iron retention within macrophages, a reduced erythrocyte half-life, and cytokine mediated inhibition of erythropoietin function and erythroid progenitor cell differentiation. AI is mostly mild to moderate, normochromic and normocytic, and characterized by low circulating iron, but normal and increased levels of the storage protein ferritin and the iron hormone hepcidin. […] The pathophysiology of anemia of inflammation (AI) is characterized by increased iron acquisition and retention within macrophages of the reticuloendothelial system. Concurrent intestinal iron absorption is suppressed, with consequently reduced serum iron concentrations thus limiting iron availability for erythropoiesis. Erythropoiesis is also directly inhibited by cytokines. They damage senescent erythrocytes together with inflammation driven radicals and reduce erythrocyte half-life which is further reduced by stimulation of erythrophagocytosis.

• #26 Anemia of the Critically Ill Patient: Pathophysiology, Lessons from Animal Models | SpringerLink

  https://link.springer.com/10.1007/978-1-4614-8503-2_133-1

  Critically ill patients have a high prevalence of anemia. The mechanisms underlying this anemia are multiple and often entangled. Two main mechanisms are involved: inflammation and blood losses. Inflammation is a major contributor to this anemia, with similarities with anemia of inflammation or anemia of chronic disease, by impairing bone marrow erythropoiesis, repressing erythropoietin synthesis, and decreasing red blood cell life span. Blood losses are important during ICU hospitalization, due to invasive procedures (drainage, catheterizations, dialysis), occult bleedings (gastrointestinal), and repeated blood samplings. These blood losses are directly responsible for hemoglobin loss but also for iron losses. The resulting iron deficiency slows erythropoiesis and contributes to worsen the anemia. Interestingly, inflammation interacts with iron metabolism too. Indeed, proinflammatory cytokines (notably IL-6) induce hepcidin synthesis, the master regulator of iron metabolism, which prevents the release of iron from store cells (macrophages and duodenal cells). The resulting hypoferremia due to the repressed iron mobilization from stores is called functional iron deficiency. Different animal models have been used to explore all these mechanisms. These models involve mainly rodents (mice and rats) and helped to better describe the link between inflammation and erythropoiesis, and the interaction between inflammation, iron deficiency, and iron metabolism. However, new animal or human studies are needed to improve our knowledge on the pathophysiology of this anemia and to evaluate therapeutic targets such as hepcidin modifications or iron treatment.

• #27

  https://haematologica.org/article/view/5484

  All these events lead to retention of iron within phagocytes and to the development of functional iron deficiency, meaning that although iron is abundant in the body the metal is not available for erythropoiesis. […] In IBD, this scenario is typically associated with iron deficiency which is a consequence of recurrent bleeding episodes from ulcerated intestinal mucosa. The combination of functional iron deficiency due to ACD and chronic blood loss is the most common finding in IBD. […] Erythropoietin levels in ACD have been found to be inadequate for the degree of anemia in many but not all conditions including IBD which may be partly due to interleukin-1- and TNF–mediated inhibition of erythropoietin promoter activity and a cytokine-driven formation of toxic radicals, thereby damaging erythropoietin-producing cells and inhibiting erythropoietin formation in the kidney.

• #28

  https://haematologica.org/article/view/5484

  Pro-inflammatory cytokines, such as interferon-, interferon-, TNF- and interleukin-1, inhibit erythopoiesis by exerting pro-apoptotic effects towards erythroid burst-forming units (BFU-E) and CFU-E. […] Finally, anemia in IBD can also be induced by deficiency of vitamins, such as cobalamin and folic acid, a condition which further impairs the proliferation of hematopoietic progenitor cells, or by certain medications, such as thiopurine analogs (6-mercaptopurine, azathioprine), sulfasalazine and methotrexate, most of which can inhibit erythropoiesis directly. […] The persistence of anemia is associated with impaired cardiac and renal function, reduced systemic oxygen delivery, decreased physical activity, fatigue, and impaired quality of life. […] Iron supplementation has been shown to be an effective therapy in IBD patients with anemia. Administration of iron is most effective, and mandatory, in subjects with ACD/IDA since these individuals are completely depleted of iron.

• #29 Acquired aplastic anemia: Pathogenesis, clinical manifestations, and diagnosis – UpToDate

  https://www.uptodate.com/contents/acquired-aplastic-anemia-pathogenesis-clinical-manifestations-and-diagnosis

  Aplastic anemia (AA) refers to pancytopenia in association with bone marrow hypoplasia. The term „aplastic anemia” is a misnomer because this disorder manifests pancytopenia rather than anemia alone. AA is a life-threatening condition that, if untreated, is associated with very high mortality. […] Most cases of AA are associated with an autoimmune attack on hematopoietic stem cells, but the trigger is often unidentified. These cases are described as immune AA or idiopathic AA, to distinguish them from other causes of bone marrow hypoplasia. […] AA is a clinicopathologic diagnosis based on the presence of ≥2 cytopenias and bone marrow hypoplasia. AA is graded according to the severity of the cytopenias and the degree of bone marrow hypoplasia. […] The diagnostic evaluation must distinguish AA from transient cytopenias (eg, from infections or drugs) and other causes of persistent pancytopenia, including megaloblastic anemia, various malignancies, bone marrow infiltrative disorders, and inherited bone marrow failure syndromes (IBMFS).

• #30 Aplastic anemia – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/aplastic-anemia/symptoms-causes/syc-20355015

  Aplastic anemia is a condition that happens when your bone marrow stops making enough new blood cells. […] In aplastic anemia, stem cells are damaged. As a result, the bone marrow makes fewer new blood cells. […] The most common cause of aplastic anemia is from your immune system attacking the stem cells in your bone marrow. […] Aplastic anemia can be a temporary side effect of these treatments. […] Toxic chemicals, such as some used in pesticides and insecticides, and benzene, an ingredient in gasoline, have been linked to aplastic anemia. […] Some medicines, such as those used to treat rheumatoid arthritis and some antibiotics, can cause aplastic anemia. […] An autoimmune disorder, in which your immune system attacks healthy cells, might involve stem cells in your bone marrow.

• #31 Current Concepts of the Pathogenesis of Aplastic Anemia

  https://www.eurekaselect.com/article/97280

  Abnormal activation of the immune system plays an important role in the pathogenesis of aplastic anemia (AA). Various immune cells and cytokines constitute a complex immune network, leading to bone marrow failure. The known pathogenesis is an increase of the myeloid dendritic cell (mDC)/ plasmacytoid dendritic cell (pDC) ratio, which causes the ratio of T helper (Th)1/Th2 to be skewed in favor of Th1 and eventually leads to an abnormal activation of cytotoxic T lymphocyte (CTL). […] In this process, regulatory T (Treg), Th17, natural killer (NK) cell, memory T cell and negative hematopoietic regulatory factors are also involved. In addition, genetic background (e.g., chromosomal abnormalities, telomere attrition, somatic cell mutations), abnormal bone marrow hematopoietic microenvironment and viral infection may also contribute to the pathogenesis of AA.

• #32 Current concepts in the pathophysiology and treatment of aplastic anemia. | Read by QxMD

  https://read.qxmd.com/read/16778145/current-concepts-in-the-pathophysiology-and-treatment-of-aplastic-anemia

  Aplastic anemia, an unusual hematologic disease, is the paradigm of the human bone marrow failure syndromes. The pathophysiology is immune mediated in most cases, with activated type 1 cytotoxic T cells implicated. The molecular basis of the aberrant immune response and deficiencies in hematopoietic cells is now being defined genetically; examples are telomere repair gene mutations in the target cells and dysregulated T-cell activation pathways. Immunosuppression with antithymocyte globulins and cyclosporine is effective at restoring blood-cell production in the majority of patients, but relapse and especially evolution of clonal hematologic diseases remain problematic. Allogeneic stem-cell transplant from histocompatible sibling donors is curative in the great majority of young patients with severe aplastic anemia; the major challenges are extending the benefits of transplantation to patients who are older or who lack family donors. Recent results with alternative sources of stem cells and a variety of conditioning regimens to achieve their engraftment have been promising, with survival in small pediatric case series rivaling conventional transplantation results.

• #33 Aplastic anemia – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/aplastic-anemia/symptoms-causes/syc-20355015

  Viral infections that affect bone marrow can play a role in the development of aplastic anemia. […] Your immune system might attack your bone marrow during pregnancy. […] In many cases, doctors aren’t able to identify the cause of aplastic anemia. This is called idiopathic aplastic anemia. […] Some people with aplastic anemia also have a rare disorder known as paroxysmal nocturnal hemoglobinuria, which causes red blood cells to break down too soon. […] Fanconi’s anemia is a rare, inherited disease that leads to aplastic anemia.

• #34 Anemia – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/anemia/symptoms-causes/syc-20351360

  Diseases such as leukemia and myelofibrosis can affect how the bone marrow makes blood. […] This group of anemias is from red blood cells being destroyed faster than bone marrow can replace them. […] This inherited and sometimes serious condition is a type of hemolytic anemia. An unusual hemoglobin forces red blood cells into an unusual crescent shape, called a sickle.

• #35 Anemia – Hematology.org

  https://www.hematology.org/education/patients/anemia

  Anemia occurs when you do not have enough red blood cells or when your red blood cells do not function properly. […] Iron-deficiency anemia is the most common type of anemia. It happens when you do not have enough iron in your body. Iron deficiency is usually due to blood loss but may occasionally be due to poor absorption of iron. […] Aplastic anemia is a rare bone marrow failure disorder in which the bone marrow stops making enough blood cells (red blood cells, white blood cells, and platelets). This occurs as a result of destruction or deficiency of blood-forming stem cells in your bone marrow, in particular when the body’s own immune system attacks the stem cells. […] Hemolytic anemia occurs when red blood cells are broken up in the bloodstream or in the spleen. Hemolytic anemia may be due to mechanical causes (leaky heart valves or aneurysms), infections, autoimmune disorders, or congenital abnormalities in the red blood cell.

• #36 Normocytic Anemia | AAFP

  https://www.aafp.org/pubs/afp/issues/2000/1115/p2255.html

  Hemolytic anemias other than the alloimmune hemolytic anemias of newborns can be categorized as congenital or acquired. […] Congenital hemolytic anemias include the hemoglobinopathies, red blood cell membrane disorders and red blood cell enzyme deficiencies. […] Acquired hemolytic anemias include autoimmune hemolytic anemias, mechanical hemolysis and paroxysmal nocturnal hemoglobinuria. […] Hypersplenism leads to anemia only after the spleen reaches three to four times its normal size, as may occur in cirrhosis, chronic infections and myeloproliferative diseases. The anemia is primarily caused by the removal of red blood cells from the circulation, but increased destruction of red blood cells is usually a contributing factor. […] The treatment of a normocytic anemia begins with timely identification of its cause. In most patients, therapy is individualized to the underlying disorder. Treatments may include avoidance of trigger exposure in patients with hemolytic anemia, correction of iron, folate or vitamin B12 deficiency in patients with mixed disorders, or splenectomy in patients with hypersplenism.

• #37 Autoimmune hemolytic anemia: current knowledge and perspectives | Immunity & Ageing | Full Text

  https://immunityageing.biomedcentral.com/articles/10.1186/s12979-020-00208-7

  Autoimmune hemolytic anemia (AIHA) is mediated by autoantibodies directed against red blood cells (RBCs) causing premature erythrocyte destruction. The pathogenesis of AIHA is complex and still not fully understood. Recent studies indicate the involvement of T and B cell dysregulation, reduced CD4+ and CD25+ Tregs, increased clonal expansions of CD8+T cells, imbalance of Th17/Tregs and Tfh/Tfr, and impaired lymphocyte apoptosis. […] It is generally thought that autoimmunity is a result of the interaction of genetic predisposition and environmental factors. All components of the immune system, i.e. autoantibodies, cytokines, the complement system, phagocytes, B and T lymphocytes including cytotoxic CD8+T cells and CD4+T regulatory cells (Tregs), and NK cells are important players in the pathogenesis of AIHA, and all change with age.

• #38 Biophysical chemistry behind sickle cell anemia and the mechanism of voxelotor action | Scientific Reports

  https://www.nature.com/articles/s41598-024-52476-8

  Sickle cell anemia disease has been a great challenge to the world in the present situation. It occurs only due to the polymerization of sickle hemoglobin (HbS) having ProValGlu typed mutation, while the polymerization does not occur in normal hemoglobin (HbA) having ProGluGlu peptides. […] The low oxygen affinity of a mutant hemoglobin is a characteristic of SCAD. It has already been confirmed that one of the glutamic acid residues of ProGluGlu (PGG) present in normal hemoglobin (HbA) is replaced by valine residue i.e. ProValGlu (PVG) in sickle cells, also called E6V mutation. […] The production of abnormal Red Blood Cells (RBCs) under hypoxic conditions and low HbS solubility are just because of the polymerization of the same. […] The deoxygenated form of HbS (dHbS) takes part in the polymerization reaction rapidly while its oxygenated form (OHbS) does not.

• #39 Biophysical chemistry behind sickle cell anemia and the mechanism of voxelotor action | Scientific Reports

  https://www.nature.com/articles/s41598-024-52476-8

  The polymerization of a biomolecule involves two steps. The first is the conformational change of the native monomer; the second is the binding of the open, flipped, monomer to the growing interdigitating polymer. […] The steric and electrostatic effects of the residue hosted through the mutation have also been found as a reason for the low oxygen affinity of a mutant hemoglobin. […] This electrostatic equilibrium perturbation is of functional significance for the overall structural stability of Hb. […] The presence and strength of the salt bridge make the Hb molecule stable which was proved when a different form of HbS was observed after the substitution of Lys132 with Asn132. […] The same thing was also supported by the earlier study of molecular dynamics simulation confirming the inter-facial electrostatic collaborations accountable for HbS polymerization.

• #40 Biophysical chemistry behind sickle cell anemia and the mechanism of voxelotor action | Scientific Reports

  https://www.nature.com/articles/s41598-024-52476-8

  The mechanism of Voxelotor (GBT-440) action to stop the HbS polymerization was also explained with the help of computationally collected data. […] The main findings regarding the pH effect showed that the lowered pH over the physiological range promotes not only HbS polymerization but also RBC sickling. […] The exact mechanism by which protons (H+) facilitate the HbS polymerization to cause a lowering in oxygen affinity at low pH is not known. […] The most important thing noted in the literature data was the lower oxygen affinity of hemoglobin caused by the accumulation of 2,3-DPG at higher pH, while at lower pH, the RBC sickling was found promoted. […] Voxelotor (GBT440), the first hemoglobin oxygen-affinity modulator, when bound to HbS, inhibits polymerization and red blood cell sickling.

• #41

  https://healthmatch.io/anemia/pathophysiology-of-anemia

  The bone marrow produces RBC and releases it into circulation. An imbalance in production to destruction or removal of RBC can result in anemia. […] Anemia is classified as either chronic or acute. Chronic anemia is a decline in RBCs or hemoglobin due to chronic diseases, iron, or other nutritional deficiencies. Acute anemia occurs when RBCs/Hb drop abruptly, usually by acute hemorrhage or hemolysis. […] Hemolytic anemia occurs when there is an excessive increase in the hemolytic process. This overshoots the capability of the bone marrow to produce RBC. […] Inefficient/defective erythropoiesis leads to a series of circumstances. This can cause anemia, bone marrow expansion, hemolysis, or iron deficiency. […] Megaloblastic anemias are defined by inefficient erythropoiesis, meaning there is reduced efficiency of cell division and nuclear-cytoplasmic dyssynchrony. Ineffective erythropoiesis is the production of defective erythroid precursor cells.

• #42 Pernicious anemia – Wikipedia

  https://en.wikipedia.org/wiki/Pernicious_anemia

  Pernicious anemia is a disease where not enough red blood cells are produced due to a deficiency of vitamin B12. […] Pernicious anemia refers to a type of vitamin B12 deficiency anemia that results from lack of intrinsic factor. Lack of intrinsic factor is most commonly due to an autoimmune attack on the cells that create it in the stomach. […] Because pernicious anemia is due to a lack of intrinsic factor, it is not preventable. […] Pernicious anemia is the most common cause of clinically evident vitamin B12 deficiency worldwide. […] Although the healthy body stores three to five years’ worth of B12 in the liver, the usually undetected autoimmune activity in one’s gut over a prolonged period of time leads to B12 depletion and the resulting anemia; pernicious anemia refers to one of the hematologic manifestations of chronic auto-immune gastritis, in which the immune system targets the parietal cells of the stomach or intrinsic factor itself, leading to decreased absorption of vitamin B12.

• #43 Pernicious anemia | Pathophysiology, Symptoms, & Treatment | Britannica

  https://www.britannica.com/science/pernicious-anemia

  Pernicious anemia is a disease in which the production of red blood cells (erythrocytes) is impaired as a result of the body’s inability to absorb vitamin B12, which is obtained in the diet and is necessary for red blood cells to mature properly in the bone marrow. […] In pernicious anemia vitamin B12 is unavailable owing to a lack of intrinsic factor, a substance responsible for intestinal absorption of the vitamin. […] When intrinsic factor is prevented from binding with vitamin B12 or when the parietal cells are unable to produce intrinsic factor, the vitamin is not absorbed and pernicious anemia results. This effect is thought to stem from an autoimmune reaction in which the malfunctioning immune system produces antibodies against intrinsic factor and against the parietal cells. […] Without an adequate amount of vitamin B12, the body is unable to synthesize DNA properly. This in turn affects red blood cell production: the cells divide, but their nuclei remain immature. These cells, called megaloblasts, are for the most part destroyed in the bone marrow and are not released to the circulation. Some megaloblasts mature to become large red blood cells called macrocytes; they reach the circulation but function abnormally.

• #44 Pernicious Anaemia: Mechanisms, Diagnosis, and Management | EMJ

  https://www.emjreviews.com/hematology/article/pernicious-anaemia-mechanisms-diagnosis-and-management/

  Pernicious anaemia (PA) is an autoimmune disease of multifactorial aetiology involving environmental and immunological factors. […] The disease is a macrocytic anaemia caused by a vitamin B12 deficiency, which, in turn, is the result of intrinsic factor deficiency, a protein that binds avidly to dietary vitamin B12 and promotes its transport to the terminal ileum for absorption. […] The deficiency of IF is a consequence of the presence of atrophic gastritis, which results in the destruction of the oxyntic mucosa and thus the loss of parietal cells, which normally produce hydrochloric acid as well as IF. […] PA is a complex, autoimmune, multifactorial disease. […] The environment appears to play a crucial, independent role in the pathogenesis of PA. […] Even though PA associated with gastric atrophy is now considered an outcome of chronic H. pylori infection, the relationships between PA and H. pylori is still not clear with conflicting views.

• #45 Pernicious Anaemia: Mechanisms, Diagnosis, and Management | EMJ

  https://www.emjreviews.com/hematology/article/pernicious-anaemia-mechanisms-diagnosis-and-management/

  The immune response is directed against the gastric H+/K+-ATPase, which accounts for the associated achlorhydria. […] The atrophic gastritis is caused by the action of autoreactive CD4+ T cells that recognise H+/K+-ATP ase, which leads to their immune destruction. […] Patients with PA have been shown to have two types of antibodies: one to parietal cells and the other to IF (IFA) or its binding site in the small bowel. […] These antibodies lead to cobalamin malabsorption in the terminal ileum that leads to cobalamin deficient megaloblastic PA. […] The clinical management of patients with PA has two different aspects: the treatment of cobalamin deficiency and the monitoring of iron deficiency onset. […] PA is caused by inadequate secretion of gastric IF, which is necessary for vitamin B12 absorption and thus cannot be treated with oral vitamin B12 supplements.

• #46 Pernicious anemia – Wikipedia

  https://en.wikipedia.org/wiki/Pernicious_anemia

  B12 is required by enzymes for two reactions: the conversion of methylmalonyl-CoA to succinyl-CoA, and the conversion of homocysteine to methionine. […] The neurological aspects of the disease are thought to arise from the accumulation of methylmalonyl-CoA due to the requirement of B12 as a cofactor to the enzyme methylmalonyl-CoA mutase.

• #47

  https://haematologica.org/article/view/5094

  The most obvious cause of anemia in celiac disease is impaired absorption of iron and other nutrients including folate and cobalamin. Villous atrophy of the intestinal mucosa is an important cause of abnormal iron absorption and this is reflected in the clearcut laboratory evidence of iron deficiency anemia in most anemic patients with celiac disease. Abnormal iron absorption is also supported by the failure to increase serum iron following oral iron loading, and refractoriness to oral iron treatment. […] […] As discussed above, pro-inflammatory cytokines play an essential role in the inflammatory and cytotoxic mechanisms involved in the pathogenesis of celiac disease. Such cytokines, in particular interferon- (IFN-), and IL6, are powerful mediators of hypoferremia in inflammation inducing the synthesis of the iron regulatory hormone hepcidin. Increased hepcidin synthesis in turn is responsible for increased ferroportin degradation and the inhibition of iron release from macrophages and enterocytes leading to the well known abnormalities in iron homeostasis associated with the anemia of chronic disease. […]

• #48

  https://haematologica.org/article/view/5094

  In a study focusing on the clinical features of anemia in celiac disease, Harper et al. noted that although serum ferritin was indicative of iron deficiency in the majority of anemic subjects, unexpectedly, in 13% of patients it was increased. Because a gluten-free diet resulted in increased serum ferritin in iron-deficient patients, but decreased ferritin levels in those with previously high ferritins, they concluded that nutritional deficiencies alone do not explain anemia in all cases, and that inflammation appears to contribute in some individuals, as evidenced by the presence of anemia of chronic disease. […] […] An encouraging aspect of the Bergamaschi study was that after one year on a gluten-free diet, the response was equally favorable in the IDA and ACD subjects indicating that the suppression of inflammatory intestinal changes by a gluten-free diet improves anemia both by correcting iron and vitamin malabsorption as well as by abolishing the mechanisms responsible for the anemia of inflammation.

• #49 Helicobacter pylori-Associated Iron Deficiency Anemia in Childhood and Adolescence-Pathogenesis and Clinical Management Strategy

  https://www.mdpi.com/2077-0383/11/24/7351

  Many epidemiological studies and meta-analyses show that persistent Helicobacter pylori infection in the gastric mucosa can lead to iron deficiency or iron deficiency anemia (IDA), particularly in certain populations of children and adolescents. […] However, the pathogenesis and specific risk factors leading to this clinical outcome in H. pylori-infected children remain poorly understood. […] It is known that H. pylori is closely associated with the development of IDA in children. […] Improvement of the associated IDA by eradication of H. pylori appears to be dependent primarily upon pediatric age groups, which might not be generalizable to adult populations. […] These facts lead to a hypothesis that the pathogenesis of the IDA differs from that of gastric ulcer or cancer caused by long-term infection of H. pylori.

• #50 Helicobacter pylori-Associated Iron Deficiency Anemia in Childhood and Adolescence-Pathogenesis and Clinical Management Strategy

  https://www.mdpi.com/2077-0383/11/24/7351

  It is thought that the pathogenesis and clinical outcome of H. pylori-associated diseases, including IDA, depend upon multiple factors, including but not limited to bacterial virulence and environmental factors, as well as host genetic and acquired factors. […] However, the specific mechanisms underlying H. pylori-associated IDA remain poorly understood. […] IDA can be directly caused by blood loss from H. pylori-induced mucosal injury and gastroduodenal lesions such as erosions and ulcerations. […] Impaired iron absorption due to reduced gastric acidity and ascorbic acid concentration, both of which are related to H. pylori gastritis and, in particular, atrophic gastritis, are suggested as important pathogenetic factors of H. pylori-associated IDA in adults. […] Hepcidin plays a key mediator of hypoferremia observed and associated with inflammation.

• #51 Helicobacter pylori-Associated Iron Deficiency Anemia in Childhood and Adolescence-Pathogenesis and Clinical Management Strategy

  https://www.mdpi.com/2077-0383/11/24/7351

  It has been recently hypothesized that competition between H. pylori and humans for iron availability could lead to IDA. […] It has been reported that H. pylori strains from IDA patients show more rapid growth and enhanced uptake of both ferrous and ferric ions compared to those from non-IDA patients. […] Studies on an association between H. pylori-specific genes and IDA are limited. […] A higher salt concentration induces a higher SabA transcription level. […] These facts lead to the recognition that sabA gene is an important virulence factor in the development of childhood H. pylori-associated diseases, including H. pylori-associated IDA.

• #52 Anemia in Heart Failure: Pathophysiology, Pathogenesis, Treatment, and Incognitae – Revista Española de Cardiología (English Edition)

  https://www.revespcardiol.org/en-anemia-in-heart-failure-pathophysiology–articulo-13109937

  In patients with HF, anemia is a risk factor for mortality, hospital admission, and severity, and doubles the risk associated with other factors, such as diabetes mellitus, age, smoking, and a low ejection fraction. […] Anemia can favor the progression of CRD in patients with HF and be, in itself, a risk factor and a predictor for the development of HF in patients with end-stage CRD. […] The production and action of EPO are the critical points of erythropoiesis. […] The activation state of HIF in HF is unknown, and there are no data published concerning its measurement. […] The regulation of EPO production is controlled by an enhancer that binds HIF-1 and, thus, is referred to as HRE (hypoxia responsive element). […] In studies that relate an increase in EPO to a poorer prognosis in HF, the patients with elevated erythropoietin levels are usually more anemic. […] The existing preparations can be administered either subcutaneously or intravenously, although for practical reasons, the former is preferred. […] The critical points of the treatment of anemia in HF are the pharmacological tools and the therapeutic target, that is, the point of optimal yield.

• #53 Anemia in Heart Failure: Pathophysiology, Pathogenesis, Treatment, and Incognitae – Revista Española de Cardiología (English Edition)

  https://www.revespcardiol.org/en-anemia-in-heart-failure-pathophysiology–articulo-13109937

  Of the few attempts to establish the pathogenic classification of anemia in HF, most have corresponded to the pattern described for anemia associated with chronic diseases and, less frequently, to iron deficiency, nutritional deficiencies, and other causes. […] The cardiorenal anemia syndrome is based on the theoretical assumption that chronic HF and renal failure have a reciprocal negative influence, and that anemia is an aggravating factor. […] Heart failure frequently coexists with a chronic inflammatory component, with the production of a repertoire of cytokines (TNF-, interleukins [IL] 1, 6, and 10, interferon) that contribute to the pathogenesis of anemia through different mechanisms. […] Hepcidin probably plays a relevant role in a high percentage of the anemia of HF. […] The pathogenesis of anemia in HF also involves different groups of drugs.

• #54 The Pathogenesis of Anemia in Patients with Hodgkin Lymphomalogo-32logo-40logo-60NEJM Journal WatchnejmJW_1L_RGB-b

  https://www.jwatch.org/oh201006150000006/2010/06/15/pathogenesis-anemia-patients-with-hodgkin

  Hepcidin and interleukin-6 play interrelated roles in the process. […] When the iron-regulatory hormone hepcidin degrades ferroportin’s capacity to export iron from cells, iron absorption decreases and iron-poor erythropoiesis ensues. Interleukin (IL)-6, a cytokine associated with anemia and malignancies such as Hodgkin lymphoma (HL), stimulates expression of hepcidin. […] Hepcidin levels, measured in 59 HL patients, were significantly higher, on average, than in a comparison group of 24 nonanemic controls without HL (7.90 nmol/L vs. 2.77 nmol/L; P=0.001), even after adjustment for age, sex, and ferritin levels (P=0.002). […] Elevated IL-6 was significantly associated with older age, stage IV disease, B symptoms, and a high-risk IPS; elevated IL-6 inversely correlated with hemoglobin levels. Hepcidin levels correlated positively and strongly with levels of both IL-6 and fibrinogen, an acute-phase reactant. […] However, these data suggest that patients with active disease (B symptoms, stage IV disease, or a high-risk IPS) also have elevated levels of IL-6 and hepcidin, the latter of which is associated with iron-poor erythropoiesis and the anemia of chronic inflammation.

• #55 Chemotherapy-induced anemia: etiology, pathophysiology, and implicatio | IJCTM

  https://www.dovepress.com/chemotherapy-induced-anemia-etiology-pathophysiology-and-implications–peer-reviewed-fulltext-article-IJCTM

  CIA is often precipitated by platinum-based therapies. Factors that are associated with the development of platinum-induced anemia include early decrease in hemoglobin following treatment, cumulative platinum dose, advanced age, failure to respond to chemotherapy, and high concentration of residual platinum in the bloodstream following administration. Mechanisms of CIA by platinum-based regimens involve direct suppression of erythroid progenitor cells within the bone marrow as well as nephrotoxic effects on erythropoietin-producing cells within the kidney. […] Malignancy and toxicity-induced inflammatory cytokine cascades reduce erythropoietic function and affect iron homeostasis. Blood transfusions increase prostaglandin E as well as both local and circulating proinflammatory cytokines, some of which include angiogenin, tumor necrosis factor-alpha, EGF, and platelet-derived growth factor BB.

• #56 Anemia epidemiology, pathophysiology, and etiology in low- and middle-income countries

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6697587/

  Accumulating evidence indicates that the proportion of anemia due to ID differs by population group, geographical setting, infectious disease burden, and the prevalence of other anemia causes. […] At a biological level, anemia develops because of an imbalance in erythrocyte loss relative to production; this can be due to ineffective or deficient erythropoiesis (e.g., from nutritional deficiencies, inflammation, or genetic Hb disorders) and/or excessive loss of erythrocytes (due to hemolysis, blood loss, or both). […] Anemia is frequently classified based on the biological mechanism of causation (e.g., IDA, hemolytic anemia, and anemia of inflammation (AI)) and/or the RBC morphology. […] The negative effects on health and development outcomes from anemia arise from the impacts of decreased oxygen delivery to tissues (in which multiple organ systems may be affected), as well as effects related to the underlying causes of anemia, which are difficult to disentangle.

• #57 Iron deficiency anaemia: pathophysiology, assessment, practical management | BMJ Open Gastroenterology

  https://bmjopengastro.bmj.com/content/9/1/e000759

  Patients with IDA should be treated with the aim of replenishing iron stores and returning the Hb to a normal level. […] Iron replenishment can occur via three routes: oral iron, parenteral oral and transfusion of packed red cells. […] The British Society of Gastroenterology recommends ferrous preparations, specifically ferrous sulphate, as first-line therapy for iron replenishment as they are cheap, have good bioavailability, available in multiple preparations and have been shown to replenish iron stores and correct anaemia effectively. […] A systematic review demonstrated that GI side effects were the most problematic with constipation being the most frequent complaint, followed by nausea and diarrhoea. […] Sodium feredetate is a water-soluble EDTA compound with higher bioavailability than the ferrous iron salt preparations.

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