Lesson 24 - Treatment of Anemia PDF

Lesson 24 Treatment of anaemia 3° Medicine Professor: Vittoria Carrabs PhD Academic year: 2024/25  What is anaemia? Anaemia is a clinical condition defined by a decrease in the number of red blood cells (RBCs), hemoglobin concentration, or hematoc...

Lesson 24 Treatment of anaemia 3° Medicine Professor: Vittoria Carrabs PhD Academic year: 2024/25  What is anaemia? Anaemia is a clinical condition defined by a decrease in the number of red blood cells (RBCs), hemoglobin concentration, or hematocrit, resulting in impaired oxygen transport to peripheral tissues. Anaemia is diagnosed when hemoglobin levels fall below 13 g/dL in men and 12 g/dL in women, though these values can vary based on the population and laboratory reference ranges.  1. Anaemia PATHOPHISIOLOGY: TYPES Hypochromic, microcytic anaemia Macrocytic anaemia Normochromic normocytic anaemia (fewer normal-sized red cells, each with a normal hemoglobin content)  1. Anaemia SYMPTOMS: Patients with anemia often presents nonspecific symptoms due to reduced oxygen delivery to tissues: ✓ General Symptoms: Fatigue, weakness, dizziness, pallor, and shortness of breath on exertion. ✓ Cardiac Symptoms: Tachycardia, palpitations, and angina (in severe cases). ✓ Neurological Symptoms: Headache, difficulty concentrating. In B12 deficiency, neurological findings like paresthesias and ataxia can occur.  TREATMENT OF ANAEMIA The treatment of anemia depends on the underlying cause and the severity of the condition. 1. Haematinic agents 2. Haemopoietic growth factors 3. Treatment of hemolytic anemia 1. Haematinic agents ✓ A hematinic agent is a substance or drug that promotes the formation of blood, particularly by stimulating the production of red blood cells (erythropoiesis) or hemoglobin. ✓ They are commonly used to treat various forms of anemia, as they provide essential nutrients or enhance the processes necessary for red blood cell production. The use of haematinic agents is often only an adjunct to treatment of the underlying cause of the anaemia. TYPES: -Iron -Folic acid -Vitamin B12 (cobalamin) 1. Haematinic agents IRON iron enter ike ferric iron in diet then plasma ferrous iron METABOLISM PATHWAY 1. Haematinic agents IRON Usually administered orally (if administered with vit C, absorption is increased) FERROUS SULFATE FERROUS SUCCINATE An adequate renal function is FERROUS GLUCONATE necessary to absorb iron properly FERROUS FUMARATE. In renal chronic disease eritropoyetin Parenterally is not produced properly, so the signal IRON-DEXTRAN (IM,IV) to create new red cells is not adequate: iron is not absorbed IRON-SUCROSE (IV) In case of: Not able to absorb oral iron (malabsorption syndromes) Do not tolerate oral preparations Chronic renal failure Chemotherapy-induced anaemia 1. Haematinic agents IRON ADRs: Oral iron:Nausea, abdominal cramps and diarrhoea. Parenteral iron: Anaphylactic reactions,Infections ACUTE IRON TOXICITY Severe necrotising gastritis with vomiting, haemorrhage and diarrhoea, followed by circulatory collapse.  IRON Acute toxicity: clinical case We report a 42 years old woman, admitted due to the intentional ingestion of iron pills with suicidal purposes. A plain abdominal X ray showed at least 20 pills in the gastric fundus and antrum. THE INGESTION OF IRON-CONTAINING PRODUCTS IS A POTENTIAL TOXICOLOGICAL EMERGENCY She was successfully treated with intravenous DESFERROXAMINE (Fe) chelators are substances designed to bind iron in the gastrointestinal tract (gut), preventing its absorption into the bloodstream. 1. Haematinic agents TO TREAT ACUTE IRON OVERLOAD: DESFERRIOXAMINE (IV, IM and intragastrically) It forms complexes with ferric iron which are excreted in the urine and avoids the absorption of Fe in the gut CHRONIC IRON TOXICITY: Occurs in chronic haemolytic anaemias: THALASSAEMIAS HAEMOCHROMATOSIS: abnormal accumulation of iron in the organism DESFERRIOXAMINE (s.c) DEFERIPRONE (ORAL) In patients with thalassaemia and people that are unable to tolerate desferrioxamine 1. Haematinic agents FOLIC ACID Liver and green vegetables are rich sources of folate. In healthy non-pregnant adults, the daily requirement is about 0.2 mg daily, but this is increased during pregnancy. 10 1. Haematinic agents FOLIC ACID Reduction of FOLIC ACID, give rise to dihydrofolate (FH2) and tetrahydrofolate (FH4) FH4 is essential for DNA synthesis and for reactions involved in amino acid metabolism Administered orally and absorbed in the ileum. 11 1. Haematinic agents FOLIC ACID CLINICAL USES OF FOLIC ACID – Malabsorption syndromes – Drugs Treatment or prevention of toxicity from METHOTREXATE Prophylactically in individuals at hazard from developing folate deficiency, –PREGNANT WOMEN AND BEFORE CONCEPTION – PREMATURE INFANTS – PATIENTS WITH SEVERE CHRONIC HAEMOLYTIC ANAEMIAS Treatment of MEGALOBLASTIC ANAEMIA* can be caused by: – Poor diet 1. Haematinic agents VITAMIN B12 The vitamin B12 preparation used therapeutically is HYDROXOCOBALAMIN. The principal dietary sources are meat eggs and dairy products. Daily requirement: 2–3 µg. Absorption requires intrinsic factor (a glycoprotein secreted by gastric parietal cells). It is stored in the liver MAIN FUNCTIONS: DNA synthesis The conversion of methyl-FH 4 to FH 4. Glucogenogenesis Isomerisation of methylmalonyl–coenzyme A (CoA) to succinyl-CoA 1. Haematinic agents VITAMIN B12 Usually given by injection Patients with PERNICIOUS ANAEMIA Life-long therapy, with maintenance injections every 3 months following a loading dose. PROPHYLACTICALLY After SURGICAL OPERATIONS that remove the site of Production of intrinsic factor (the stomach) Vitamin B12 absorption (the terminal ileum).  2. Haemopoietic growth factors ERYTHROPOIETIN GRANULOCYTE COLONY STIMULATING FACTORS FILGRASTIM (sc/iv) LENOGRASTIM (sc/iv) PEGFILGRASTIM(sc) THROMBOPOIETIN and oral agonists  2. Haemopoietic growth factors Erythropoietin is a glycoprotein that stimulates erythroid progenitor cells to proliferate and generate erythrocytes. Indications: Used to treat anaemia caused by erythropoietin deficiency. For example in patients with chronic kidney disease, AIDS , cancer Recombinant human erythropoietins: EPOETIN DARBEPOETIN A hyperglycosylated form, longer half-life and can be administered less frequently METHOXY POLYETHYLENE GLYCOL-EPOETIN: Long half-life. ADRs: Influenza-like symptoms are common. Hypertension can cause encephalopathy with headache, disorientation and convulsions. 2. Haemopoietic growth factors CLINICAL USES OF ERYTROPOETIN. Anaemia of chronic renal failure. Anaemia during chemotherapy for cancer. Prevention of the anaemia that occurs in premature infants To increase the yield of autologous blood before blood donation. Anaemia of AIDS (exacerbated by zidovudine which is used as an anti-viral).  2. Haemopoietic growth factors Before starting treatment with erytropoetin Iron or folate deficiency must be corrected before starting treatment. Haemoglobin must be monitored and maintained within the range 10–12 g/dl to avoid the unwanted effects. ADRs: HYPERTENSION IRON DEFICIENCY THROMBOSIS 2. Haemopoietic growth factors ERYTHROPOIETIN GRANULOCYTE COLONY STIMULATING FACTORS FILGRASTIM (sc/iv) LENOGRASTIM (sc/iv) PEGFILGRASTIM(sc) THROMBOPOIETIN and oral agonists 2. Haemopoietic growth factors CLINICAL USES OF THE COLONY-STIMULATING FACTORS Used in specialist centres: To reduce the severity/duration of neutropenia induced by cytotoxic drugs during: – intensive chemotherapy necessitating autologous bone marrow rescue – following bone marrow transplant. For persistent neutropenia in advanced HIV infection. In aplastic anaemia.  2. Haemopoietic growth factors THROMBOPOIETIN and oral agonists Made in liver and kidney, stimulates proliferation and maturation of megakaryocytes to form platelets. Thrombocytopenia is a predictable and limiting toxicity of many chemotherapeutic regimens in oncology. ELTROMBOPAG (ORAL) ITP unresponsive to other treatments. ROMIPLOSTIM (INJECTABLE) Aplastic anaemia  3. Treatment of Haemolytic anaemia Anaemia associated with increased red cell destruction GENETIC CAUSES: Sickle cell - mutations in the HBB gene that affects hemoglobin resulting in production of abnormal hemoglobin known as hemoglobin S (HbS) Thalassemia Paroxysmal nocturnal hemoglobinuria (PNH) –hemolysis and thrombosis NON-GENETIC CAUSES Autoimmunity Infections Adverse drug reactions. 3. Treatment of Haemolytic anaemia DRUGS USED TO TREAT HAEMOLYTIC ANAEMIAS HYDROXYCARBAMIDE: Cytotoxic drug. Orally/daily Inhibits DNA synthesis by inhibiting ribonucleotide reductase Used to lower the red cell and platelet counts in: Polycythaemia rubra vera- the bone marrow produces too many red blood cells Chronic myeloid leukaemia sickle cell disease Reduced doses are used in patients with impaired renal function. The blood count and haemoglobin are monitored and the dose adjusted accordingly. ADRs: Myelosuppression, nausea and rashes. 3. Treatment of Haemolytic anaemia DRUGS USED TO TREAT HAEMOLYTIC ANAEMIAS ECULIZUMAB Is a humanised monoclonal antibody used to treat PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA: IV infusion weekly for 4 weeks and then approximately every 2 weeks. 3. Treatment of Haemolytic anaemia TREATMENT IS SYMPTOMATIC Analgesics for painful vaso-occlusive crisis in patients with sickle cell disease. AND SUPPORTIVE Attention to fluid balance Oxygen therapy Blood transfusion ANTIBIOTICS AND IMMUNISATION to reduce the risk of infections GLUCOCORTICOIDS*(decreasing the immune system, avoids red cell destruction)