- Author: Joseph E Maakaron, MD; Chief Editor: Emmanuel C Besa, MD more...
Therapeutic approaches to anemia include the use of blood and blood products, immunotherapies, hormonal/nutritional therapies, and adjunctive therapies. The goal of therapy in acute anemia is to restore the hemodynamics of the vascular systems and to replace lost red blood cells. To achieve this, the practitioner may use mineral and vitamin supplements, blood transfusions, vasopressors, histamine (H2) antagonists, and glucocorticosteroids.
Documentation of the etiology of anemia is essential in the selection of therapy. Not all microcytic anemias are caused by iron deficiency; some are iron-overloading disorders. Similarly, not all megaloblastic anemias are associated with either vitamin B-12 deficiency or folic acid deficiency. Hereditary hemolytic disorders do not improve with corticosteroid therapy.
Blood and Blood Products
Correction of acute anemia often requires blood and/or blood products. With significant ongoing hemorrhage or hemolysis, transfusion of blood alone is insufficient. Nonetheless, providing timely transfusion to restore hemoglobin to safe levels can prevent major complications of acute anemia.
Packed red blood cells
Packed red blood cells (PRBCs) are used preferentially to whole blood, since they limit volume, immune, and storage complications. PRBCs have 80% less plasma, are less immunogenic, and can be stored about 40 days (versus 35 d for whole blood). PRBCs are obtained after centrifugation of whole blood. Leukocyte-poor PRBCs are used in patients who are transplant candidates/recipients and in those with prior febrile transfusion reactions. Washed or frozen PRBCs are used in individuals with hypersensitivity transfusion reactions.
Fresh frozen plasma (FFP) contains coagulation factors, as well as protein C and protein S. Its uses include the treatment of coagulopathies and thrombotic thrombocytopenic purpura (TTP) and the reversal of warfarin. FFP does not transmit infections.
This agent is used for the treatment of Von Willebrand disease. It contains fibrinogen, factor VIII, and von Willebrand factor and can be used in lieu of factor VIII concentrate if the latter is unavailable.
Patients who are thrombocytopenic and have clinical evidence of bleeding should receive a platelet transfusion. Patients with platelet counts of less than 10,000/mcL are at risk for spontaneous cerebral hemorrhage and require a prophylactic transfusion.
The preferred treatment for TTP and hemolytic-uremic syndrome is large-volume plasmapheresis with FFP replacement. Immune thrombocytopenic purpura (ITP) is rarely treated with transfusion, as the transfused platelets are destroyed rapidly. In stable patients, initial treatment is with prednisone. High-dose immunoglobulin and splenectomy are very effective treatments.
Hemophilia B is treated with factor IX concentrate. Recombinant factor IX currently is undergoing clinical trials (the current treatment is FFP or prothrombin-rich plasma concentrate).
This is used to treat hemophilia A.
Iron salts are used to provide adequate iron for hemoglobin synthesis and to replenish body stores of iron. Iron is administered prophylactically during pregnancy because of the anticipated requirements of the fetus and the losses that occur during delivery.
Mineral supplements are used to provide adequate iron for hemoglobin synthesis and to replenish body stores of iron. Iron is administered prophylactically during pregnancy because of the anticipated requirements of the fetus and the losses that occur during delivery.
Carbonyl iron is used as a substitute for ferrous sulfate. It has a slower release of iron and is more expensive than ferrous sulfate. The slower release affords the agent greater safety if ingested by children. On a milligram-for-milligram basis, it is 70% as efficacious as ferrous sulfate. Claims are made that there is less gastrointestinal (GI) toxicity, prompting use when ferrous salts are producing intestinal symptoms and in patients with peptic ulcers and gastritis. Tablets are available containing 45 mg and 60 mg of iron.
Iron dextran complex replenishes depleted iron stores in the bone marrow, where it is incorporated into hemoglobin. Parenteral use of iron-carbohydrate complexes has caused anaphylactic reactions, and its use should be restricted to patients with an established diagnosis of iron deficiency anemia whose anemia is not corrected with oral therapy.
The required dose can be calculated (3.5 mg iron/g of hemoglobin) or obtained from tables in the prescribing information. For IV use, this agent may be diluted in sterile 0.9% NaCl. Do not add to solutions containing medications or parenteral nutrition solutions.
Ferric carboxymaltose is a nondextran IV colloidal iron hydroxide in complex with carboxymaltose, a carbohydrate polymer that releases iron. It is indicated for iron deficiency anemia (IDA) in adults who have intolerance or an unsatisfactory response to oral iron. It is also indicated for IDA in adults with non-dialysis-dependent chronic kidney disease.
Vitamins are used to meet necessary dietary requirements and are used in metabolic pathways, as well as DNA and protein synthesis.
Cyanocobalamin (vitamin B12) and folic acid are used to treat megaloblastic and macrocytic anemias secondary to deficiency. Both vitamin B12 and folic acid are required for synthesis of purine nucleotides and metabolism of some amino acids. Each is essential for normal growth and replication. Deficiency of either cyanocobalamin or folic acid results in defective DNA synthesis and cellular maturation abnormalities. Consequences of deficiency are most evident in tissues with high cell turnover rates (eg, hematopoietic system).
Vitamin K deficiency causes elevation of prothrombin time and is commonly seen in patients with liver disease.
Deoxyadenosylcobalamin and hydroxocobalamin are active forms of vitamin B12 in humans. Microbes synthesize vitamin B12, but humans and plants do not. Vitamin B12 deficiency may result from intrinsic factor (IF) deficiency (pernicious anemia), partial or total gastrectomy, or diseases of the distal ileum.
Folic acid is an essential cofactor for enzymes used in the production of red blood cells (RBCs).
A decrease in levels of vitamin K–dependent factors (II, VII, IX, X, protein C, protein S) can lead to bleeding. Vitamin K is also used to treat hemorrhagic disease of the newborn, warfarin-induced bleeding, and hypothrombinemia from other causes (eg, antibiotic, aspirin).
Serum potassium levels can fall during therapy for severe cobalamin or folate deficiency and can lead to sudden death. Therefore, potassium supplements may be indicated.
Essential for transmission of nerve impulses, contraction of cardiac muscle, maintenance of intracellular tonicity, skeletal and smooth muscles, and maintenance of normal renal function. Gradual potassium depletion occurs via renal excretion, through GI loss or because of low intake.
Depletion usually results from diuretic therapy, primary or secondary hyperaldosteronism, diabetic ketoacidosis, severe diarrhea, if associated with vomiting, or inadequate replacement during prolonged parenteral nutrition.
Potassium depletion sufficient to cause 1 mEq/L drop in serum potassium requires a loss of about 100 to 200 mEq of potassium from the total body store.
These drugs decrease portal circulation pressure by diminishing blood flow due to vasoconstriction. The major indication is variceal bleeding.
Vasopressin causes vasoconstriction of vascular smooth muscles and increases water permeability and reabsorption in the collecting tubules. It decreases portal pressure in patients with portal hypertension.
Somatostatin diminishes blood flow to the portal system due to vasoconstriction, thus decreasing variceal bleeding. It has similar effects to vasopressin but does not cause coronary vasoconstriction. No longer marketed in the United States.
Histamine (H2) Antagonists
These agents produce a blockade of H2 receptors.
The primary indication is to reduce symptoms and accelerate healing of gastric ulcers. In the acutely bleeding patient, it has limited benefit.
Ranitidine inhibits histamine stimulation of the H2 receptor in gastric parietal cells, which, in turn, reduces gastric acid secretion, gastric volume, and hydrogen ion concentrations.
Famotidine competitively inhibits histamine at H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen ion concentrations.
Nizatidine competitively inhibits histamine at the H2 receptor of the gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and reduced hydrogen concentrations.
These agents are used to treat idiopathic and acquired autoimmune hemolytic anemias.
Glucocorticoids inhibit phagocytosis of antibody-covered platelets. Treatment of ITP during pregnancy is conservative unless the condition is severe. For severe cases, use the lowest dose of glucocorticoids. In neonates, if the platelet count drops below 50,000-75,000 platelets/µL, consider prednisone and exchange transfusions and immunoglobulin.
Veng-Pedersen P, Chapel S, Schmidt RL, Al-Huniti NH, Cook RT, Widness JA. An integrated pharmacodynamic analysis of erythropoietin, reticulocyte, and hemoglobin responses in acute anemia. Pharm Res. 2002 Nov. 19(11):1630-5. [Medline].
Liang R, Ghaffari S. Advances in understanding the mechanisms of erythropoiesis in homeostasis and disease. Br J Haematol. 2016 Jul 21. [Medline].
Adamson JW, Longo DL. Anemia and polycythemia. Harrison's Principles of Internal Medicine. 15th ed. New York, New York: McGraw-Hill; 2001. Vol 1.: 348-354.
Babushok DV, Li Y, Roth JJ, Perdigones N, Cockroft JD, Biegel JA, et al. Common polymorphic deletion of glutathione S-transferase theta predisposes to acquired aplastic anemia: Independent cohort and meta-analysis of 609 patients. Am J Hematol. 2013 Oct. 88 (10):862-7. [Medline]. [Full Text].
Hung M, Besser M, Sharples LD, Nair SK, Klein AA. The prevalence and association with transfusion, intensive care unit stay and mortality of pre-operative anaemia in a cohort of cardiac surgery patients. Anaesthesia. 2011 Sep. 66(9):812-8. [Medline].
Servilla KS, Singh AK, Hunt WC, et al. Anemia management and association of race with mortality and hospitalization in a large not-for-profit dialysis organization. Am J Kidney Dis. 2009 Sep. 54(3):498-510. [Medline].
Adebisi OY, Strayhorn G. Anemia in pregnancy and race in the United States: blacks at risk. Fam Med. 2005 Oct. 37(9):655-62. [Medline].
Silva DG, Priore SE, Franceschini Sdo C. Risk factors for anemia in infants assisted by public health services: the importance of feeding practices and iron supplementation. J Pediatr (Rio J). 2007 Mar-Apr. 83(2):149-56. [Medline].
Oliveira MA, Osorio MM, Raposo MC. Socioeconomic and dietary risk factors for anemia in children aged 6 to 59 months. J Pediatr (Rio J). 2007 Jan-Feb Epub 2007 Jan 12. 83(1):39-46. [Medline].
Borgna-Pignatti C, Rugolotto S, De Stefano P, et al. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica. 2004 Oct. 89(10):1187-93. [Medline].
Kuku I, Kaya E, Yologlu S, Gokdeniz R, Baydin A. Platelet counts in adults with iron deficiency anemia. Platelets. 2009 Aug 3. 1-5. [Medline].
Stamatoyannopoulos G, Majerus PW, Perimutter RM. The Molecular Basis of Blood Diseases. Philadelphia, Pa: WB Saunders Co; 2000.
Dhar R, Zazulia AR, Videen TO, et al. Red blood cell transfusion increases cerebral oxygen delivery in anemic patients with subarachnoid hemorrhage. Stroke. 2009 Sep. 40(9):3039-44. [Medline]. [Full Text].
DeLoughery TG. Microcytic anemia. N Engl J Med. 2014 Oct 2. 371(14):1324-31. [Medline].
Mozaffari-Khosravi H, Noori-Shadkam M, Fatehi F, Naghiaee Y. Once weekly low-dose iron supplementation effectively improved iron status in adolescent girls. Biol Trace Elem Res. 2009 Aug 4. epub ahead of print. [Medline].
[Guideline] Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, et al. Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol. 2016 Jan. 172 (2):187-207. [Medline]. [Full Text].
[Guideline] Barone A, Lucarelli A, Onofrillo D, Verzegnassi F, Bonanomi S, et al. Diagnosis and management of acquired aplastic anemia in childhood. Guidelines from the Marrow Failure Study Group of the Pediatric Haemato-Oncology Italian Association (AIEOP). Blood Cells Mol Dis. 2015 Jun. 55 (1):40-7. [Medline].
|Condition||Serum Iron||Total Iron-Binding Capacity (TIBC)||Bone Marrow Iron||Comment|
|Iron deficiency||↓||↑||0||Responsive to iron therapy|
|Chronic inflammation||↓||↓||++||Unresponsive to iron therapy|
|Thalassemia major||↑||N||++++||Reticulocytosis and indirect bilirubinemia|
|Thalassemia minor||N||N - ↓||++||Elevation of fetal hemoglobin and Hb A2, target cells, and poikilocytosis|
|Lead poisoning||N||N||++||Basophilic stippling of RBCs|
|Sideroblastic||↑||N||++++||Ring sideroblasts in marrow|
|↓ = decreased; ↑ = increased; 0 = absent; +'s indicate the amount of stainable iron in bone marrow specimens, on a scale of 0-4; N = normal.|
|Megaloblastic bone marrow||Deficiency of vitamin B-12|
|Deficiency of folic acid|
|Drugs affecting deoxyribonucleic acid (DNA) synthesis|
|Inherited disorders of DNA synthesis|
|Nonmegaloblastic bone marrow||Liver disease|
|Hypothyroidism and hypopituitarism|
|Accelerated erythropoiesis (reticulocytes)|
|Hypoplastic and aplastic anemia|
|Infiltrated bone marrow|
|Macrocyte||Larger than normal (>8.5 µm diameter). See Table 2.|
|Microcyte||Smaller than normal (< 7 µm diameter). See Table 1.|
|Hypochromic||Less hemoglobin in cell. Enlarged area of central pallor. See Table 1.|
|Spherocyte||Loss of central pallor, stains more densely, often microcytic. Hereditary spherocytosis and certain acquired hemolytic anemias|
|Target cell||Hypochromic with central "target" of hemoglobin. Liver disease, thalassemia, hemoglobin D, and postsplenectomy|
|Leptocyte||Hypochromic cell with a normal diameter and decreased MCV. Thalassemia|
|Elliptocyte||Oval to cigar shaped. Hereditary elliptocytosis, certain anemias (particularly vitamin B-12 and folate deficiency)|
|Schistocyte||Fragmented helmet- or triangular-shaped RBCs. Microangiopathic anemia, artificial heart valves, uremia, and malignant hypertension|
|Stomatocyte||Slitlike area of central pallor in erythrocyte. Liver disease, acute alcoholism, malignancies, hereditary stomatocytosis, and artifact|
|Tear-shaped RBCs||Drop-shaped erythrocyte, often microcytic. Myelofibrosis and infiltration of marrow with tumor. Thalassemia|
|Acanthocyte||Five to 10 spicules of various lengths and at irregular intervals on surface of RBCs|
|Echinocyte||Evenly distributed spicules on surface of RBCs, usually 10-30. Uremia, peptic ulcer, gastric carcinoma, pyruvic kinase deficiency, and preparative artifact|
|Sickle cell||Elongated cell with pointed ends. Hemoglobin S and certain types of hemoglobin C and l|
|Intracorpuscular defect||Hereditary spherocytosis
Congenital dyserythropoietic anemias
Hereditary RBC enzymatic deficiencies
Rarer hereditary abnormalities
|Vitamin B-12 and folic acid deficiency
Paroxysmal nocturnal hemoglobinuria
Severe iron deficiency
|Extracorpuscular defect||Physical agents: Burns, cold exposure
Traumatic: Prosthetic heart valves, march hemoglobinuria, disseminated intravascular coagulation (DIC), graft rejection
Chemicals: Drugs and venoms
Infectious agents: Malaria, toxoplasmosis, mononucleosis, hepatitis, primary atypical pneumonia, clostridial infections, bartonellosis, leishmaniasis
Hepatic and renal disease
Collagen vascular disease
Malignancies: Particularly hematologic neoplasia
Transfusion of incompatible blood
Hemolytic disease of the newborn
Autoimmune hemolytic anemia Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS)