Medicine – Anemia of Chronic Disease (ACD)
Basic Description Also known as anaemia of chronic inflammation The production of proinflammatory mediators results in the suppression of erythropoiesis as well as an imbalance in iron homeostasis after chronic systemic infection, inflammation, or cancer. ACD is defined as a normocytic, normochromic, hypoproliferative anaemia and is characterised by low serum iron levels, increased ferritin levels, and elevated total iron-binding capacity (TIBC). Haemoglobin (Hgb), which is normally mild to moderate anaemia, is infrequently below 8 g/dL. EPIDEMIOLOGY Incidence Data on the prevalence of ACD are few. Prevalence Due to the ageing population, the high incidence of chronic infections, and the prevalence of inflammatory illnesses in the United States, ACD is the second most frequent anaemia after iron deficiency anaemia (IDA). Undifferentiated anaemia is thought to be present in 24.8% of people globally. PATHOPHYSIOLOGY AND AETIOLOGY Functional iron shortage causes a reduction in the production of red blood cells. ● The severity of the underlying illness will typically match the degree of the anaemia. Iron homeostasis is altered in a number of ways by proinflammatory cytokines such interleukins (IL), tumour necrosis factor (TNF), bone morphogenic proteins (BMP), and interferons (IFN): - Impaired red blood cell progenitor cell growth and differentiation - Dysregulated iron homeostasis - Diminishing the erythropoietic response - Increasing phagocytosis and death of erythrocytes Hepcidin, a hormone that regulates iron absorption, is produced more in hepatocytes, macrophages, and enterocytes as a result of iron overload and the proinflammatory cytokines IL-1, IL-6, and BMP6. Hepcidin binds to ferroportin, causing internalisation and degradation, inhibiting iron efflux from stores in macrophages and hepatocytes, and stopping iron absorption by duodenal enterocyte RBC survival may be decreased by erythrophagocytosis and oxidative damage brought on by inflammatory cytokines. RISK FACTORS Hepatic disease, renal disease, and other autoimmune or infectious causes of the disorders listed below are risk factors for anaemia caused by chronic illness. GENERAL PREVENTION Treating the problems listed below promptly is important for preventing anaemia, a chronic disease. CONDITIONS OFTEN Associated with Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), sarcoidosis, temporal arteritis, inflammatory bowel disease (IBD), and systemic inflammatory response syndrome (SIRS) are examples of chronic systemic disorders. Hepatic dysfunction or illness Coronary artery disease or congestive heart failure Acute or chronic infections - viral - HIV, HCV - bacterial - Abscess, subacute bacterial endocarditis, TB, osteomyelitis - Fungal - Parasitic - Chronic kidney disease (CKD) A malignancy Hypometabolic conditions include protein deficiency, thyroid disorders, panhypopituitarism, diabetes mellitus, and Addison disease. Cytokine dysregulation (aging-related anaemia) DISEASE HISTORY ACD is frequently found by chance after a routine CBC with differential. ACD manifests with the underlying infectious, inflammatory, or neoplastic condition without any evidence of occult bleeding; frequently, patients will experience moderate and ambiguous anaemia symptoms, including fatigue, dizziness, and palpitations. Even a relatively low Hgb level (10 to 11 g/dL) might cause angina symptoms, shortness of breath, and decreased exercise tolerance in people with cardiovascular conditions. MEDICAL ANALYSIS The results of the physical examination are related to the underlying ailment. DIFFERENTIAL DIAGNOSIS: Thalassemia; Sideroblastic anaemia; Dilutional anaemia; Drug-induced marrow suppression or hemolysis; IDA; Anaemia of Chronic Kidney Disease; Initial tests (lab, imaging) Diagnostic tests and interpretation Hgb/Hct, mean corpuscular volume (MCV), ferritin, folate and B12, reticulocyte count, serum iron, and TIBC Hgb levels are typically between 12 and 13 g/dL in women and 13 g/dL in men. Anaemia may have a secondary aetiology that is contemporaneous with a Hgb of less than 8 g/dL. MCV is typically normal (80 to 100 fL), but in around 25% of instances, microcytosis may also be present in addition to concurrent iron shortage or chronic illness. RBC morphology: normocytic and normochromic; raised protoporphyrin levels; serum ferritin: normal or slightly elevated (30 to 200 g/L); in CKD, ferritin can exceed 800 g/L; serum ferritin is a nonspecific acute phase reactant. - A concurrent iron deficit is suggested by serum ferritin levels below 30 g/L. Serum iron levels are low (50), TIBC is extremely low (300), and the absolute reticulocyte count is abnormally low (reticulocyte index, 20,000 to 25,000/mL), which is caused by impaired erythropoiesis. Serum B12 and folate levels have dropped as a result of poor absorption or food deficiencies. Other/Diagnostic Procedures Bone marrow biopsy with Prussian blue stainable iron along with anaemia, hypoferremia, and low TSAT is the conventional gold standard. The quality of staining makes it potentially inaccurate. 28 pg of Reticulocyte Hgb concentration Hepcidin levels can be measured using an enzyme-linked immunosorbent assay to help distinguish between iron deficiency anaemia and chronic disease-related anaemia. Soluble transferrin receptor (sTfR) and the sTfR/log ferritin index (Ratio) reflect erythropoiesis within bone marrow and distinguish between ACD, IDA, and ACD + IDA; however, sTfR alone may have greater clinical value than the sTfR index since transferrin is unaffected by chronic disease/inflammation, in contrast to ferritin. ACD is more consistent with normal results than with elevated sTfR, which implies IDA. Functional test: iron supplementation raises H/H in IDA but has minimal impact on ACD Despite the possibility of a recognised cause of anaemia, iron, B12, and folate deficiency should be ruled out. GENERAL TREATMENT MEASURES The root of ACD should be the primary management goal. - Restoring Hgb to baseline is usually accomplished by treating the underlying illness. When primary treatment is not an option (such as with terminal cancer or end-stage renal illness), other treatment options may be taken into account. Erythropoietin-stimulating agents (ESAs) and transfusions are the two main therapy options. - Pharmacologic doses of ESAs (epoetin-, darbepoetin) are frequently effective in treating ACD (5). - Increase iron levels to improve ESA performance. – Only in the case of acute symptoms or severe anaemia should transfusion be started. There is currently no target Hgb, however treatment to Hgb >13 g/dL is linked to unfavourable results. In severe cases of anaemia, a coexisting B12 or folate deficit should be taken into account and treated. - Patients with chronic illnesses frequently have lower nutritional intake from their diets. Patients who frequently have hemodialysis frequently lose them during therapy. ESAs are specifically approved for the treatment of kidney disease (CKD), but there is evidence that they may also be useful for the treatment of RA, IBD, HIV, and cancer. Hgb levels below 10 g/dL are a requirement for ESA therapy (5)[C]. ESAs had little effect on the outcomes or symptoms of moderate CHF anaemia. Breast, cervical, head and neck, lymphoid, and non-small cell lung malignancies should not be used. Patients with active cancer who are not undergoing curative therapy shouldn't receive medication. Epoetin - Significance 10 g/dL Hgb Exertional intolerance or fatigue CKD (eGFR 60 mL/min) IBD, RA, and hepatitis C-related anaemia; chemotherapy for individuals with particular cancers (palliative therapy)—dosing and schedule Lowest effective dose to keep Hgb levels between 10 and 12 g/dL usually (1),(5),(6) CKD related: Start three times per week with 50 to 100 U/kg SC/IV. - Cancer patients getting chemotherapy: 40,000 U once a week or 150 U/kg SC three times weekly - Negative effects: Enhanced danger of cardiovascular issues, death, and thromboembolism Pure red cell aplasia (low reticulocyte count, normal WBC, and platelets, as well as a drop in Hgb) Risk of tumour growth in some cancer patients Darbepoetin is a long-acting, molecularly modified EPO preparation that has a half-life that is three to four times longer than recombinant human EPO. The dosage and schedule for this medication are as follows. In patients on hemodialysis, the IV route is recommended; provide SC/IV every 1-2 weeks; hold if Hgb >12 g/dL. - Negative results Similar to EPO, adjust epoetin or darbepoetin dosage according to the labelling approved by the FDA. – Treatment that lasts longer than 6 to 8 weeks without a proper rise in Hgb (>1 to 2 g/dL) is not advised. Initial Line First-line therapy options include darbepoetin or epoetin. These ought to be initiated concurrently with the management of the underlying chronic illness. IRON (5) - INDICATIONS FOR ADDITIONAL THERAPIES Coexisting iron insufficiency Forms of resistance to EPO Ferrous sulphate used orally. GI side effects and poor tolerance; insufficient absorption because of hepcidin Negative consequences of intravenous administration of ferric gluconate, ferric sucrose, ferric dextran, and ferrumoxytol Benefits: May increase hepcidin production and make iron restriction worse. Cheap and relatively safe May result in a reduction in ESA needs (DRIVE research) 1 to 2 U packed red blood cells are given during transfusions. Severe or life-threatening anaemia: To direct transfusion in asymptomatic patients, a "restrictive threshold" of Hgb 7 to 8 g/dL should be utilised (7)[A]. Patients with active ACS, underlying cardiac or pulmonary disease, advanced age, severe bleeding, or hemorrhagic shock may need transfusions at higher Hgb thresholds (>10 g/dL). Symptoms of anaemia, such as chest discomfort, SOB, and/or alterations in the electrocardiogram (ECG) Lack of reaction to medical treatment - Potential side effects Volume overload; infection (HIV, hepatitis); transfusion response; specific advantages Rapid correction of anaemia - It is preferable to stop taking EPO and rely on transfusion therapy until the infection is properly cured when it happens while taking the medication. Future directions include ferroportin stabilisers, anti-BMP antibodies, and inhibitors of hepcidin synthesis. vitamin D (which reduces hepcidin) - Heparin (hinders the transcription of hepcidin) CONTINUING CARE AFTERCARE RECOMMENDATIONS Referral to a haematologist should be taken into consideration in cases when anaemia is resistant to treatment of the underlying illness and the aforementioned drugs. patient observation Hgb shouldn't be raised above 11 to 12 g/dL because doing so has been linked to higher mortality. Every three months, baseline and ongoing monitoring of ferritin and transferrin saturation levels may be beneficial. DIET Diet has a significant impact on a number of the chronic illnesses linked to ACD. An iron-rich diet that is well-balanced and full of fruits and vegetables may help with treatment. EDUCATION OF PATIENTS The following potential risks should be disclosed to patients receiving medical treatment: mortality, cardiovascular complications, thrombosis, and cancer progression PROGNOSIS ACD generally does not advance. COMPLICATIONS ACD side effects include: - Mortality - Cardiovascular issues - Symptoms that interfere with daily life - Negative effects of ESAs: - Increased mortality risk and/or cardiovascular issues in CKD patients - Increased mortality risk and/or tumour growth risk in cancer patients - Increased thromboembolism risk
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