scholarly journals Physiology and Inflammation Driven Pathophysiology of Iron Homeostasis—Mechanistic Insights into Anemia of Inflammation and Its Treatment

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3732
Author(s):  
Lukas Lanser ◽  
Dietmar Fuchs ◽  
Katharina Kurz ◽  
Günter Weiss
Keyword(s):  
Iron Homeostasis ◽  
Underlying Disease ◽  
Erythroid Progenitor ◽  
Vitamin Deficiencies ◽  
Life Threatening ◽  
Iron Retention ◽  
Bleeding Episodes ◽  
Cardio Vascular ◽  
New Treatments ◽  
Anemia Of Inflammation

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 primary therapeutic approach for AI is treatment of the underlying inflammatory disease which mostly results in normalization of hemoglobin levels over time unless other pathologies such as vitamin deficiencies, true iron deficiency on the basis of bleeding episodes, or renal insufficiency are present. If the underlying disease and/or anemia are not resolved, iron supplementation therapy and/or treatment with erythropoietin stimulating agents may be considered whereas blood transfusions are an emergency treatment for life-threatening anemia. New treatments with hepcidin-modifying strategies and stabilizers of hypoxia inducible factors emerge but their therapeutic efficacy for treatment of AI in ill patients needs to be evaluated in clinical trials.

scholarly journals Established and Emerging Concepts to Treat Imbalances of Iron Homeostasis in Inflammatory Diseases

2018 ◽  
Vol 11 (4) ◽  
pp. 135 ◽  
Author(s):  
Verena Petzer ◽  
Igor Theurl ◽  
Günter Weiss
Keyword(s):  
Iron Deficiency ◽  
Iron Supplementation ◽  
Iron Homeostasis ◽  
Inflammatory Diseases ◽  
Clinical Investigation ◽  
Underlying Disease ◽  
Mononuclear Phagocyte ◽  
Diagnostic Approaches ◽  
Iron Retention ◽  
Parenteral Iron

Inflammation, being a hallmark of many chronic diseases, including cancer, inflammatory bowel disease, rheumatoid arthritis, and chronic kidney disease, negatively affects iron homeostasis, leading to iron retention in macrophages of the mononuclear phagocyte system. Functional iron deficiency is the consequence, leading to anemia of inflammation (AI). Iron deficiency, regardless of anemia, has a detrimental impact on quality of life so that treatment is warranted. Therapeutic strategies include (1) resolution of the underlying disease, (2) iron supplementation, and (3) iron redistribution strategies. Deeper insights into the pathophysiology of AI has led to the development of new therapeutics targeting inflammatory cytokines and the introduction of new iron formulations. Moreover, the discovery that the hormone, hepcidin, plays a key regulatory role in AI has stimulated the development of several therapeutic approaches targeting the function of this peptide. Hence, inflammation-driven hepcidin elevation causes iron retention in cells and tissues. Besides pathophysiological concepts and diagnostic approaches for AI, this review discusses current guidelines for iron replacement therapies with special emphasis on benefits, limitations, and unresolved questions concerning oral versus parenteral iron supplementation in chronic inflammatory diseases. Furthermore, the review explores how therapies aiming at curing the disease underlying AI can also affect anemia and discusses emerging hepcidin antagonizing drugs, which are currently under preclinical or clinical investigation.

Anemia of Inflammation

Hematology ◽  
2010 ◽  
Vol 2010 (1) ◽  
pp. 276-280 ◽  
Author(s):  
Cindy N. Roy
Keyword(s):  
Inflammatory Diseases ◽  
Underlying Disease ◽  
Comorbid Condition ◽  
Regulatory Pathways ◽  
Hepcidin Expression ◽  
Disease States ◽  
Poor Outcomes ◽  
The Impact ◽  
Inflammatory Insult ◽  
Anemia Of Inflammation

Abstract Inflammation arising from various etiologies, including infection, autoimmune disorders, chronic diseases, and aging, can promote anemia. The anemia of inflammation (AI) is most often normocytic and normochromic and is usually mild. Characteristic changes in systemic iron handling, erythrocyte production, and erythrocyte life span all contribute to AI. The preferred treatment is directed at the underlying disease. However, when the inflammatory insult is intractable, or the cause has not been diagnosed, there are limited options for treatment of AI. Because anemia is a comorbid condition that is associated with poor outcomes in various chronic disease states, understanding its pathogenesis and developing new tools for its treatment should remain a priority. Hepcidin antimicrobial peptide has taken center stage in recent years as a potent modulator of iron availability. As the technology for quantitative hepcidin analysis improves, hepcidin's role in various disease states is also being revealed. Recent insights concerning the regulatory pathways that modify hepcidin expression have identified novel targets for drug development. As the field advances with such therapeutics, the analysis of the impact of normalized hemoglobin on disease outcomes will confirm whether anemia is a reversible independent contributor to the morbidity and mortality associated with inflammatory diseases.

Severe pulmonary complications in Japanese patients after bortezomib treatment for refractory multiple myeloma

Blood ◽  
2006 ◽  
Vol 107 (9) ◽  
pp. 3492-3494 ◽  
Author(s):  
Shigesaburo Miyakoshi ◽  
Masahiro Kami ◽  
Koichiro Yuji ◽  
Tomoko Matsumura ◽  
Masaaki Takatoku ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Effects ◽  
Gastrointestinal Symptoms ◽  
Japanese Patients ◽  
The United States ◽  
Underlying Disease ◽  
Pulmonary Complications ◽  
Bortezomib Treatment ◽  
Toranomon Hospital ◽  
Life Threatening

Bortezomib is a novel proteasome inhibitor with significant antimyeloma activity. Its frequent adverse effects are manageable, including gastrointestinal symptoms, peripheral neuropathy, and thrombocytopenia. Severe lung toxicity has not previously been reported. Between June 2004 and September 2005, 13 Japanese patients with multiple myeloma were treated with bortezomib in Toranomon Hospital, Juntendo University School of Medicine, and Jichi Medical School. Four of them developed severe pulmonary complications, and 2 died of respiratory failure without progression of underlying disease. To our knowledge, this is the first report on life-threatening pulmonary adverse effects after bortezomib therapy. Previous clinical studies on bortezomib, mostly in the United States and Europe, have shown low incidences of pulmonary adverse effects. Our study suggests that bortezomib can cause serious lung injury, and that its incidence might vary among different ethnicities. Clinicians need to be alert to the possibility.

scholarly journals Recombinant factor XIII: a safe and novel treatment for congenital factor XIII deficiency

Blood ◽  
2012 ◽  
Vol 119 (22) ◽  
pp. 5111-5117 ◽  
Author(s):  
Aida Inbal ◽  
Johannes Oldenburg ◽  
Manuel Carcao ◽  
Anders Rosholm ◽  
Ramin Tehranchi ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Autosomal Recessive Disorder ◽  
Allergic Reactions ◽  
Open Label ◽  
Impaired Wound Healing ◽  
Bleeding Rate ◽  
Life Threatening ◽  
A Subunit ◽  
Bleeding Episodes ◽  
Congenital Factor

Congenital factor XIII (FXIII) deficiency is a rare, autosomal-recessive disorder, with most patients having an A-subunit (FXIII-A) deficiency. Patients experience life-threatening bleeds, impaired wound healing, and spontaneous abortions. In many countries, only plasma or cryoprecipitate treatments are available, but these carry a risk for allergic reactions and infection with blood-borne pathogens. The present study was a multinational, open-label, single-arm, phase 3 prophylaxis trial evaluating the efficacy and safety of a novel recombinant FXIII (rFXIII) in congenital FXIII-A subunit deficiency. Forty-one patients ≥ 6 years of age (mean, 26.4; range, 7-60) with congenital FXIII-A subunit deficiency were enrolled. Throughout the rFXIII prophylaxis, only 5 bleeding episodes (all trauma induced) in 4 patients were treated with FXIII-containing products. The crude mean bleeding rate was significantly lower than the historic bleeding rate (0.138 vs 2.91 bleeds/patient/year, respectively) for on-demand treatment. Transient, non-neutralizing, low-titer anti-rFXIII Abs developed in 4 patients, none of whom experienced allergic reactions, any bleeds requiring treatment, or changes in FXIII pharmacokinetics during the trial or follow-up. These non-neutralizing Abs declined below detection limits in all 4 patients despite further exposure to rFXIII or other FXIII-containing products. We conclude that rFXIII is safe and effective in preventing bleeding episodes in patients with congenital FXIII-A subunit deficiency. This study is registered at http://www..clinicaltrials.gov as number NCT00713648.

scholarly journals Cardioprotective Therapy in the Practice of an Anaesthesiologist

2020 ◽  
Author(s):  
Arina Viacheslavovna Balan
Keyword(s):  
Neurological Status ◽  
Underlying Disease ◽  
Research Papers ◽  
Vital Functions ◽  
Level Of Consciousness ◽  
Life Threatening ◽  
Published Research ◽  
The Brain ◽  
Careful Assessment

All components of anaesthesia have a direct or indirect depressing effect on the myocardium and functional activity of the brain. Given the initial failure of the coronary blood flow, life-threatening disorders of the heart are possible. The higher the severity of the underlying disease, the greater the risk of transient neurological deficit, stroke. Extended continuous monitoring of vital functions, careful assessment of the neurological status of the patient with special attention to the level of consciousness, the presence or absence of symptoms of increased ICP is necessary. The purpose of this study is to evaluate the beneficial effect of cardioprotectors Mexicor, Meldonium in the fight against ischemia in patients with CHD, GB in the department of surgical profile. The following methods have been used: review of literature, previously published research papers. Results: this article discusses the main drugs with cardioprotective properties, describes the positive experience of using them by specialists, and proves the effectiveness of using drugs in the long term.

Life-threatening conditions in pericarditis of different etiologies: diagnosis and treatment

2019 ◽  
pp. 40-45
Author(s):  
A. Ya. Kosonogov ◽  
S. V. Nemirova ◽  
V. I. Pozdishev ◽  
A. B. Nikolskiy ◽  
K. A. Kosonogov ◽  
...  
Keyword(s):  
Cardiac Tamponade ◽  
Postoperative Period ◽  
Underlying Disease ◽  
Electrolyte Balance ◽  
Symptomatic Therapy ◽  
Electrolyte Disorders ◽  
Results Of Treatment ◽  
Cardiac Compression ◽  
Pericardial Diseases ◽  
Life Threatening

Purpose of the study: to analyze the etiology, diagnostic criteria and results of treatment of life-threatening conditions in pericarditis of different etiologies (based on our clinic materials).Materials and methods. The study included cases of hospitalization of patients with a diagnosis of «Pericarditis» and ICD-10 codes for pericardial diseases for the period from 2009 to 2018. In the course of the work, the history and clinical picture of the disease, laboratory and radiation research methods were analyzed. All patients started treatment of the underlying disease and performed symptomatic therapy, including those aimed at restoring hemodynamics and normalizing water and electrolyte disorders, stopping inflammation and auto-aggression of the immune system. When signs of compression/cardiac tamponade were detected, pericardiocentesis was performed, according to indications, drainage/fenestration of the cardiac sac, pericardiotomy were performed. In the postoperative period was carried out antibacterial and symptomatic therapy.Results. Life-threatening diseases of the pericardium accounted for 32,03% of all patients treated in the hospital for pericarditis. The most frequently detected signs of a hemodynamically significant compression and cardiac tamponade, less often purulent and constrictive P. Isolated 25 patients underwent closed drainage with pericardiocentesis, in 1 case the drainage was supplemented with f ibrinolytic therapy. Sanitation of the cavity and fenestration of the pericardium were carried out in 11 patients, pericardiotomy with notched drainage in 2 patients, thoracotomy with pericardiectomy – 4. In the postoperative period, the symptoms of inflammation were reduced, the level of cardiac enzymes decreased, the electrolyte balance stabilized. Most patients noted a distinct regression of the symptoms of pericarditis and cardiac compression. Recurrent P was noted in 5 cases, deaths occurred in 4 cases (8,16%).Conclusion. Early verification of the diagnosis and timely decompression of the heart with fractional evacuation of the exudate or pericardectomy with respect to the sequence of release of the heart chambers from adhesions and adhesions against the background of complex therapy allows to achieve positive dynamics, and fenestration of the cardiac bag with the formation of a sufficiently sized opening during recurrent fluid accumulation or intrapericardial fibrin. development of severe complications of pericarditis even in patients with multiple concomitant diseases evanii and oncopathology.

scholarly journals Inhibition of bone morphogenetic protein signaling attenuates anemia associated with inflammation

Blood ◽  
2011 ◽  
Vol 117 (18) ◽  
pp. 4915-4923 ◽  
Author(s):  
Andrea U. Steinbicker ◽  
Chetana Sachidanandan ◽  
Ashley J. Vonner ◽  
Rushdia Z. Yusuf ◽  
Donna Y. Deng ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Iron Homeostasis ◽  
Iron Bioavailability ◽  
Bmp Signaling ◽  
Neoplastic Disease ◽  
Type I ◽  
Hepcidin Expression ◽  
Hepatic Expression ◽  
Morphogenetic Protein ◽  
Anemia Of Inflammation

Abstract Anemia of inflammation develops in settings of chronic inflammatory, infectious, or neoplastic disease. In this highly prevalent form of anemia, inflammatory cytokines, including IL-6, stimulate hepatic expression of hepcidin, which negatively regulates iron bioavailability by inactivating ferroportin. Hepcidin is transcriptionally regulated by IL-6 and bone morphogenetic protein (BMP) signaling. We hypothesized that inhibiting BMP signaling can reduce hepcidin expression and ameliorate hypoferremia and anemia associated with inflammation. In human hepatoma cells, IL-6–induced hepcidin expression, an effect that was inhibited by treatment with a BMP type I receptor inhibitor, LDN-193189, or BMP ligand antagonists noggin and ALK3-Fc. In zebrafish, the induction of hepcidin expression by transgenic expression of IL-6 was also reduced by LDN-193189. In mice, treatment with IL-6 or turpentine increased hepcidin expression and reduced serum iron, effects that were inhibited by LDN-193189 or ALK3-Fc. Chronic turpentine treatment led to microcytic anemia, which was prevented by concurrent administration of LDN-193189 or attenuated when LDN-193189 was administered after anemia was established. Our studies support the concept that BMP and IL-6 act together to regulate iron homeostasis and suggest that inhibition of BMP signaling may be an effective strategy for the treatment of anemia of inflammation.

The role of the physiotherapist in the management of people with haemophilia: defining the new normal

2020 ◽  
Vol 81 (8) ◽  
pp. 1-8
Author(s):  
AJ Wells ◽  
D Stephensen
Keyword(s):  
Physical Activity ◽  
Recurrent Bleeding ◽  
Significant Shift ◽  
New Era ◽  
Assessment And Treatment ◽  
Bleeding Episodes ◽  
New Treatments ◽  
Improve Health

Physiotherapists aim to maximise quality of life and movement potential within the spheres of promotion, prevention, treatment/intervention and rehabilitation. Haemophilia care is witnessing a significant shift towards a new era of potentially life-changing treatments which offer a future of minimal or no bleeds for people with haemophilia. As such, physiotherapy intervention should be more proactive rather than reactive to treat and rehabilitate recurrent bleeding episodes. The role of the physiotherapist within the multidisciplinary team includes the differential diagnosis of musculoskeletal bleeding, supporting and encouraging higher levels of physical activity, rehabilitation to maximise physical potential and capabilities, assessment and treatment of non-bleed-related musculoskeletal issues, managing comorbidities and falls risk, and improving the longitudinal surveillance of musculoskeletal health. Encouraging and supporting people with haemophilia to become more active will improve wellbeing and improve health and health outcomes, and physical activity is becoming one of the most important outcomes for people with haemophilia. Recommendations on the best way to accurately capture these data are vital to ensure the full health benefits of new treatments for people with haemophilia are clear.

Systemic lupus erythematosus presenting as thrombotic thrombocytopaenic purpura in a child: a diagnostic challenge

2020 ◽  
Vol 13 (9) ◽  
pp. e232002
Author(s):  
Irene Alejandra Orbe Jaramillo ◽  
Carmen De Lucas Collantes ◽  
Amelia Martínez de Azagra ◽  
Elena Sebastián
Keyword(s):  
Lupus Erythematosus ◽  
Thrombotic Microangiopathy ◽  
Underlying Disease ◽  
Adamts13 Activity ◽  
Diagnostic Challenge ◽  
Class V ◽  
Capillary Membrane ◽  
Life Threatening ◽  
Functional Deficiency

Thrombotic thrombocytopaenic purpura (TTP) is a life-threatening thrombotic microangiopathy characterised by microangiopathic haemolytic anaemia, thrombocytopaenia and organ ischaemia. TTP is caused by a severe functional deficiency of ADAMTS13 activity. We describe a 10-year-old girl presenting anaemia and thrombocytopaenia with schistocytes. Urine protein to creatinine ratio was within nephrotic range. ADAMTS13 activity was 0%, and no anti-ADAMTS13 antibodies were found. A renal biopsy showed deposits of IgG, C3 and C1q in the capillary membrane, compatible with class V lupus nephritis. Therapeutic plasma exchange (TPE) was performed in conjunction with therapy consisting of steroids and mycophenolate mofetil. After 11 months of follow-up, the patient remains in remission with normal ADAMTS13 activity. Although acquired TTP is a rare finding in children, differential diagnosis of thrombotic microangiopathy should include ADAMTS13 and the assay should be performed early. TTP treatment is based on TPE, although the underlying disease must be ruled out to optimise treatment and prevent relapse.

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