anemia
Side Effects of Oral Iron Therapy
50% or more of those taking oral iron complain of nausea, constipation, diarrhea, epigastric distress and/or vomiting Management: patient may take an iron preparation with a smaller dose of elemental iron (i.e. switch from ferrous sulfate to ferrous gluconate) or switch from tablet to liquid preparation. Patient may slowly increase the dose from 1 tablet per day to the recommended 3 tablets per day Pt. may try taking it with meals but that will decrease absorption by about 40%
erythropoietin
A hormone produced and released by the kidney that stimulates the production of red blood cells by the bone marrow in response to falling levels of oxygen/ hypoxia in the tissues. It binds to receptors on proerythroblasts, resulting in increased red cell production and maturation and expansion of the erythron
Microcytic-hypochromic anemias
Abnormally small RBCs with less amounts of hemoglobin due to lack of material to make hemoglobin. Examples include iron deficiency, and thalassemia. Causes: Disorders of iron metabolism Disorders of heme synthesis Disorders of globin synthesis
How to Evaluate/Compare Current Status of Anemia
Always look at previous CBC results to see if the anemia is new, old, or progressive. In addition to looking at RBC indices, look for other clues in the CBC: Anisocytosis (Size variation) Pokilocytosis (Shape variation) WBC abnormalities
what causes vitamin B deficiency
Antibiotic use or excessive ingestion of raw egg whites, Exposure to isoniazid (INH), hydralazine, and penicillamine. Vitamin B6 deficiency can result in distal sensorimotor peripheral neuropathy.
What should be suspected in a pt that presents with pancytopenia following drug intake, exposure to toxins or viral infections?
Aplastic anemia
name 4 types of Normcytic-normochromic anemia
Aplastic anemia Post hemorrhagic anemia Hemolytic anemia Anemia of chronic diseases
What is the condition with a reduction in red blood cells, white blood cells, and platelets?
Aplastic anemia occurs with pancytopenia, which is a decrease in all three cell types.
Macrocytic-Normochromic anemias
B12 and folic acid deficiencies cause this. Characterized by unusually large stem cells (megaloblasts) in marrow that have normal color that mature into erythrocytes that are unusually large in size, thickness, and volume. Hemoglobin content is normal. also termed megaloblastic anemia (MB). sometimes oval in shape. defective DNA synthesis due to deficiencies of vitamin B12 or folate. DNA synthesis is slowed, RNA proceeds so erythrocytes grow as an abnormal large cell with small nucleus. these defective cells die early. overproduction of hemoglobin during prolonged cellular division, creating a larger-than-normal erythrocyte
Failure to Respond to Oral Iron Therapy
Coexisting diseases interfering with marrow response (infection, inflammatory disorder, malignancy, uncorrected hypothyroidism, coexisting folic acid or vitamin B12 deficiency) Diagnosis of IDA is incorrect (Look for Thalassemia, lead poisoning, Anemia of chronic disease/chronic inflammation, copper deficiency (zinc toxicity), Myelodysplastic syndrome/refractory sideroblastic anemia Patient is not taking the medication Medication is being taken but not absorbed (Rapid intestinal transit bypasses area of maximum absorption, patient taking enteric coated product and coating is not dissolving, patient has malapsorbtion for iron (sprue, atrophic gastritis), medication is being taken with an agent that interferes with absorption (antacids, tetracycline, tea) Continued blood loss or need in excess of iron dose being ingested (Treat if possible i.e bleeding peptic ulcer). If cause is not treatable or cannot be met by oral iron (e.g. renal failure) then refer to hematologist for possible parenteral iron therapy
differential dx of microcytic anemia
Colitis, malignancy, or malabsorption from inflammatory disease should be considered in the differential diagnosis. Tailor your work-up to the patient's symptoms. If he has symptoms referable to the upper GI tract (e.g., dyspepsia), consider an upper GI endoscopy in addition to colonoscopy.
Possible clinical findings in Iron Deficiency Anemia
Conjunctival Palor Angular Cheilitis Koilonychia pallor of palms and hands decreased tongue papillae
Vitamin B12 is important for :
DNA synthesis, Formation and maintenance of myelin sheaths, Synthesis of neurotransmitters, Erythropoiesis
Risk Factors for Vitamin B12 Deficiency
Decreased ileal absorption, Crohn's disease , Ileal resection, Tapeworm infestation, H. Pylori infection, Decreased intrinsic factor, Atrophic gastritis, Pernicious anemia, Postgastrectomy syndrome Genetic (Transcobalamin II deficiency) Inadequate intake, Alcohol abuse, Older persons, Vegetarians (includes exclusively breastfed children of vegetarian mothers) Prolonged medication use Histamine H2 blockers, Metformin (Glucophage), Proton pump inhibitors, Food/Vitamin B12 malabsorption
Anemia of Chronic Disease/Inflammation/CKD Anemia of CKD is a multifactorial process related to:
EPO deficiency Uremic-induced inhibitors of erythropoiesis Disordered iron homeostasis Shortened erythrocyte survival New recognition of the role of hepcidin in CKD anemia
Clinical Presentation of anemia in elderly
Fatigue, weakness, and dyspnea are symptoms that are commonly reported by elderly persons with anemia. Conjunctival pallor is recommended as a reliable sign of anemia in the elderly and commonly noted in patients with hemoglobin less than 9 g/dL.
Oral Iron Therapy: Dosing in Older Adults
Ferrous sulfate elixir contains 44mg of elemental iron per 5ml. One preparation is: 10 ml of ferrous sulfate elixir (88 mg of elemental iron) mixed in 1/5th glass of orange juice taken 30 minutes before breakfast. The dose can be reduced to 5ml if 10ml causes irritation. Also, a 50 or 100mg ascorbic acid tablet can be substituted for the orange juice.
common cause of microcytic anemia in adults is
GI blood loss
clinical signs associated with types of anemia
Glossitis, decreased vibratory and positional senses, ataxia, paresthesia, confusion, dementia, and pearly gray hair at an early age are signs suggestive of vitamin B12-deficiency anemia. Folate deficiency can cause similar signs, except for the neurologic deficits. Profound iron deficiency may produce koilonychias (spoon nails), glossitis, or dysphagia. Other clinical manifestations of anemia include jaundice and splenomegaly. Jaundice can be a clue that hemolysis is a contributing factor to the anemia, whereas splenomegaly can indicate that a thalassemia or neoplasm may be present.
WHO criteria for definition of anemia in adults > age 18:
HGB < 13 g/dL for males HGB < 12 g/dL for non pregnant females HGB < 11 g/dL for pregnant females
Some Causes of Hemolytic Anemias
Hereditary Spherocytosis Glucose-6-phosphate dehydrogenase (G6PD) Deficiency, Thrombotic Thrombocytopenic Purpura (TTP), Hemolytic Uremic Syndrome, Autoimmune Hemolytic Anemia, Infections (Malaria, Babesiosis, Sepsis) Toxins from some snake bites, insect bites
H. Pylori and Iron Deficiency Anemia (IDA)
How H. pylori causes IDA: Increased iron loss due to active hemorrhage secondary to gastritis, peptic ulcer, or gastric cancer. Achlorhydria induced by chronic pangastritis resulting in reduced iron absorption. Reduced secretion of ascorbic acid to the gastric mucosa. Iron utilization by the bacterium.
labs tests to determine Iron Deficiency Anemia vs Anemia of Chronic Inflammation
IDA vs Anemia Chr. Dz Serum iron: Low vs Low or normal TIBC: High vs Low Transferrin saturatxn: Low vs Low or normal Serum ferritin: Low vs Normal or high
Folate Deficiency
If the serum folate concentration is >4ng/ml (9.1nanomol/L)folate deficiency is effectively ruled out. In the absence of recent anorexia or fasting, a serum concentration <2ng/ml (4.5nanomol/L) is diagnostic of folate deficiency.
Expected Response to Oral Iron Therapy
Immediate disappearance of pica or RLS Improved feeling of well being within first few days of treatment In patients with moderate to severe anemia, a modest reticulocytosis will be seen in 7-10 days. Those with mild anemia may have no reticulcytosis. Hemoglobin will rise slowly after approximately 1-2 weeks and will rise 2g/dL over approximately 3 weeks. The hemoglobin deficit should be halved by approximately 1 month and the hemoglobin level should return to normal by 6-8 weeks.
Common Causes of Normocytic/Normochromic Anemia
Increased red blood cell loss or destruction: Acute bleed, Hemolysis [Sickle cell anemia is normochromic but not normocytic] Decreased production/release of normal sized RBCs: Aplastic anemia [decrease in all cell lines: HCT, HGB, WBC, Platelets], Anemia of chronic disease/inflammation, Endocrine disorders causing secondary bone marrow failure r/t decreased stimulation of erythropoietin secretion Overexpansion of plasma volume: Pregnancy, Fluid overload
name a Microcytic-hypochromic anemias
Iron deficiency aniema
Initial approach/ questions to ask about the anemia
Is the patient bleeding now or in the past Is there evidence for increased RBC destruction? Is the bone marrow suppressed? Is the patient iron deficient? If yes, why? Is the patient deficient in folic acid, or vitamin B12? If yes, why?
CAUSES OF ANEMIA BY RED CELL VOLUME
Low MCV (usually <80 fL) Anemia of chronic disease Copper deficiency Iron deficiency anemia Lead poisoning Sideroblastic anemias Thalassemias Normal MCV (usually 80-100 fL): Acute blood loss Anemia of chronic disease Chronic renal insufficiency Early iron deficiency Endocrine (e.g., hypothyroidism) Primary bone marrow disorders High MCV (usually >100 fL): Alcohol effects B12 deficiency Drug effect (e.g., Hydroxyurea, AZT) Folate deficiency Hemolytic anemia Hypothyroidism (less commonly macrocytic, usually normocytic) Liver disease Primary bone marrow disease Reticulocytosis (hemolytic anemia, response to blood loss)
Anemia of Chronic Disease/Inflammation
Many infections, chronic inflammatory disorders and cancers are associated with anemia of chronic disease/inflammation. Macrophages are stimulated during the inflammatory process and activated macrophages release cytokines (e.g. IL-6). IL-6 induces hepcidin which inhibits iron release from macrophages as well as intestinal iron absorption.
Management of Anemia of Chronic Disease/Inflammation
May order ESR/C-reactive protein to look for chronic inflammatory states. Look for other specific disorders such as liver disease, thyroid disease, renal disease, autoimmune disorders, inflammatory bowel disorders, rheumatoid arthritis, SLE Management is focused on treating the underlying condition.
Differential Diagnosis of Anemia by MCV classifications
Microcytic anemia MCV <80: iron deficiency Thalassemia Anemia of chronic dz/chronic inflammation Sideroblastic anemia lead poisoning Normocytic anemia MCV 80-99: Sickle cell Aplastic anemia hemolytic anemia Anemia of chronic dz/chronic inflammation Macrocytic anemia>100: b12 deficiency folate deficiency
distinguish 3 types of anemia
Most common approach to classification is based on Mean Corpuscular Volume (MCV) level: Microcytic anemia: MCV < 80 fL Normocytic anemia: MCV 80 - 99 fL Macrocytic anemia: MCV > 100 fL
Iron Deficiency Anemia
Most common type of anemia in the world. Earliest indicator is low ferritin level. S/S: Often asymptomatic but may c/o fatigue, decreased exercise tolerance, weakness, palpitations, irritability, headaches. Possible Causes: inadequate intake, malabsorption, increased requirements, blood loss, malignancies.
Summary: A 65-year-old woman with worsening dyspnea on exertion, fatigue, dizziness, and palpitations. She is found to have conjunctival pallor and guaiac-positive stool. Most likely diagnosis: Next diagnostic step: Next step in therapy: Assuming that the initial workup for cardiac and pulmonary causes is negative and that the hemoglobin and hematocrit levels are low, next goal is .....
Most likely diagnosis: Anemia secondary to gastrointestinal bleeding; other considerations should include new-onset angina, congestive heart failure, and atrial fibrillation. Next diagnostic step: A complete blood count (CBC) to evaluate for the anemia. To evaluate for the other conditions on your differential diagnosis list, you should perform an electrocardiogram (ECG) and cardiac enzymes. A prothrombin time (PT) and partial thromboplastin time (PTT) to look for coagulation abnormalities would be helpful as well. Next step in therapy: Further workup, including blood transfusion (if needed), completion of two more sets of cardiac enzymes, and ECGs. A gastroenterology consult for esophagogastroduodenoscopy (EGD) and colonoscopy is appropriate because of the positive guaiac findings. Assuming that the initial workup for cardiac and pulmonary causes is negative and that the hemoglobin and hematocrit levels are low, a thorough evaluation for the cause of the anemia is necessary. A CBC with peripheral smear, reticulocyte count, iron studies, vitamin B12, and folic acid levels would provide clues to the type of anemia that this patient has. A gastroenterology consult for possible EGD and colonoscopy to further investigate the source of gastrointestinal bleeding should be considered. The presence of epigastric and LUQ pain, along with long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs), should also raise a flag for testing to rule out a bleeding ulcer. The presence of other findings may direct your workup toward other diagnoses. If this patient was from a developing country, the possibility of intestinal parasites would need to be considered. If the PT and PTT were abnormal, gastrointestinal (GI) bleeding from a coagulopathy or liver disease would be possibilities. Weight loss, lymphadenopathy, and coagulopathy may warrant evaluation for nongastrointestinal malignancies, such as leukemias or lymphomas. In younger patients, sickle cell disease, thalassemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and other inherited causes of anemia would be on the differential diagnosis list. These are unlikely to manifest as an initial diagnosis at the age of 65.
Iron deficiency anemia
Name the hypochromic microcytic anemia due to lack of an element in the diet or to element loss as a result of chronic bleeding
Thalassemia
Not a single disorder but a group of inherited blood disorders caused by variant or missing genes that affect how the body makes hemoglobin. Alpha thalassemia minor [most common in those with ancestry from Southeast Asia, India, China, Philippines] or beta thalassemia minor [most common in those with ancestry from Mediterranean, Middle Eastern, African, Asian ancestry] most often heterozygous for the alpha or beta forms of this syndrome and may not be anemic: May have splenomegaly, peripheral smear shows target cells, tear drop forms and basophilic stippling. The RBC count may be increased and uncomplicated patients have normal or increased iron stores. Thalasssemia intermedia and major are usually diagnosed within the first few years of life & should be followed by a hematologist.
History and PE Findings in Vitamin B12 Deficiency
Numbness and paresthesias, May have cognitive impairment and depression, Symmetrically decreased vibration and proprioception in feet, Absent or diminished DTRs in Lower Extremities
what is the most common type of megaloblastic anemia caused by vitamin B12 deficiency, which is often associated with the end-stage type A chronic atrophic (congenital or autoimmune) gastritis. It generally occurs in older adults with a mean age of onset of 60 years.
Pernicious anemia
name types of Macrocytic-Normochromic anemias
Pernicious anemia (B12 deficiency) Folate deficiency anemia
RDW
RBC size variation; ↑ iron deficiency; normal in other microcytic anemias
Pancytopenia
Reduction or absence of all three types of blood cells
Vitamin B12 (Cobalamin) Deficiency
Serum Vitamin B12 level is a late biomarker and has low sensitivity and specificity for Vitamin B12 deficiency when used alone. (Reference ranges vary among labs) Holotranscobalamin (holoTC), also known as active B12, is the earliest laboratory parameter for B12 deficiency. (Abnormal level is < 35 pmol/L). Both elevated homocysteine (> 13 umol/L) and elevated methylmalonic acid (MMA) are seen in vitamin B12 deficiency but MMA (> 0.4 umol/L) is more specific for vitamin B12 deficiency. If Pernicious Anemia is suspected, anti-intrinsic factor antibody testing should be done.
Oral Iron Therapy
Should not be given with food because phosphates, phyates, and tannates in food bind the iron and impair its absorption. Other factors that can impair absorption of iron: Antacids, H2 receptor blockers, proton pump inhibitors, calcium-containing foods and beverages, calcium supplements, certain antibiotics (quinolones; tetracycline) and the ingestion of iron along with cereals, dietary fiber, tea, coffee, eggs, or milk Iron should be given 2 hours before or 4 hours after ingestion of antacids Iron is best absorbed as the ferrous (Fe++) salt in a mildly acidic medium so add a 250 mg ascorbic acid tablet or a half-glass of orange juice at the time of iron administration to enhance absorption. The least expensive preparation is ferrous sulfate that contains 65 mg of elemental iron in a 325 mg tablet. The recommended oral daily dose for the treatment of iron deficiency in adults is in the range of 150-200 mg/day of elemental iron. So a single 325 mg ferrous sulfate tablet taken orally tid between meals provides 195 mg of elemental iron per day.
Duration of Oral Iron Therapy
Some disagreement about how long to treat: Some providers stop iron treatment when the hemoglobin level becomes normal so that further blood loss will alert them to the return of the problem that causes the iron deficiency. Others treat for at least 6 months following normalization of the hemoglobin in order to replenish iron stores.
Treatment with folic acid
Special requirements for folic acid intake prior to conception and during pregnancy to prevent neural tube deficits. Folic acid 1mg orally per day for documented folate deficiency in adults. Cobalamin deficiency should be ruled out before treatment with folic acid begins because folic acid replacement can mask neurological symptoms of cobalamin deficiency.
A 47-year-old woman presents to your office complaining of tongue soreness, fatigue, and dyspnea with exertion. She denies unusual bleeding, weight loss, fevers, and night sweats. Her past medical history includes hypothyroidism, for which she takes levothyroxine. She does not drink alcohol or smoke. Physical examination reveals a tired-appearing woman with lemon-yellow colored skin, temperature 37°C, pulse 110 bpm, BP 120/74 mm Hg, and respirations 12 bpm. The examination is otherwise unremarkable. A CBC demonstrates a WBC count 4000/mm3, Hgb 9 g/dL, platelet count 140,000/mm3, and an MCV of 105 fL. Her B12 level is 100 pg/mL (normal >300 pg/mL) and folate 40 ng/mL. Which of the following historical elements is LEAST likely to contribute to her condition? A History of working as a park ranger in Canada. B History of Zollinger-Ellison syndrome. C History of hypothyroidism. D History of new vegetarian diet started last month. E History of GI surgery.
The correct answer is "D." Most likely, this woman has pernicious anemia caused by B12 deficiency. Pernicious anemia is caused by immune destruction of parietal cells in the stomach, resulting in decreased absorption of B12. It typically develops in people over the age of 40 and is more common in people of northern European descent or in African Americans, as well as people with type A blood. Laboratory findings include antiparietal cell antibodies in 90% of affected patients (5% of normal individuals also have the antibody) and antibodies to intrinsic factor in 70% of patients. Individuals commonly have other autoimmune diseases such as thyroid disease, diabetes, and vitiligo. Individuals may complain of paresthesias, GI symptoms, sore tongue, or weight loss. The lemon-yellow appearance of the skin is due to anemia and mild jaundice. Other causes of cobalamin (B12) deficiency include gastrectomy, Zollinger-Ellison syndrome (inability to alkalinize the small intestine), blind loop syndrome, bacterial overgrowth from previous surgery, and ingestion of undercooked fish infested with the tapeworm Diphyllobothrium latum (found in Canada, Alaska, and the Baltics—hence, the history of working as a park ranger). Although a strict vegetarian diet can cause B12 deficiency, there are sufficient stores to last 3 to 5 years (in other words, more than 1 month).
A 68-year-old man is found to have an incidental finding of anemia while in the hospital for alcohol abuse. expected labs results: A Normal MMA; decreased serum folate level B Elevated MMA; decreased serum B12 level C Elevated ferritin; normal MCV; decreased serum iron level D Decreased ferritin; decreased MCV; decreased serum iron level
The correct answer is A. Explanation: Alcohol abuse is a common cause of folate deficiency. A normal MMA level essentially rules out a concomitant vitamin B12 deficiency.
A 68-year-old man is found to have an incidental finding of anemia while hospitalized with pneumonia. His physical examination is normal except for crackles in the left lower lobe. Serum laboratory examinations reveal a normal MMA and a decreased serum folate level. Which of the following is the best next step? A Administer CAGE questionnaire B Esophagogastroduodenoscopy C Serum iron assay D Neurology consultation
The correct answer is A. Explanation: Alcohol abuse, which may be assessed by the CAGE questionnaire, is a common cause of folate deficiency. CAGE is an acronym which stands for Cut back, Annoyed, Guilty, and Eye-opener. A normal MMA level essentially rules out a concomitant vitamin B12 deficiency. Gastric endoscopy—to look for atrophic gastritis—would be indicated for pernicious anemia. A serum iron assay would likely be high because of increased turnover of iron in patients with megaloblastic anemia due to either B12 or folate deficiency. A neurology consultation would be needed if the patient had neurologic signs or symptoms of B12 deficiency.
A 58-year-old woman comes to your office complaining of fatigue. She has also noticed a burning sensation in her feet over the past 6 months. A CBC shows anemia with an increased MCV. Which of the following is the most likely cause of her anemia? A Lack of intrinsic factor B Inadequate dietary folate C Strict vegetarian diet D Chronic GI blood loss
The correct answer is A. Explanation: The clinical presentation and CBC findings are consistent with macrocytic anemia due to B12 deficiency. Pernicious anemia (lack of intrinsic factor) is the most common cause. B12 deficiency can also be seen in patients who follow a strict vegetarian diet; however, the body's B12 stores can last several years before they are depleted.
A 52-year-old woman with a history of rheumatoid arthritis is in your clinic for a 1-month follow-up after having a knee prosthesis removed secondary to a joint infection and osteomyelitis (Staphylococcal aureus). You obtain a CBC, revealing a WBC 8,000/mm3, Hgb 9.5 g/dL, hematocrit 28%, platelet count 450,000/mm3, and MCV 83 fL (normal). Serum iron levels are low with a normal serum transferrin receptor and increased ferritin. What is the most likely diagnosis? A Iron deficiency anemia due to rheumatoid arthritis. B Anemia of chronic disease due to rheumatoid arthritis and osteomyelitis. C Hemolytic anemia induced by antibiotics. D Acute blood loss during surgery. E Myelodysplastic syndrome (MDS) associated with rheumatoid arthritis.
The correct answer is B. Explanation: Anemia of chronic disease is a hypoproliferative anemia that occurs in the setting of chronic infection, inflammation, malignancy, heart failure, diabetes, and other serious health conditions. The anemia is usually mild and characterized by low serum iron, increased ferritin (remember that ferritin is an acute-phase reactant and these patients often have inflammation), decreased serum transferrin, normal (or low) serum soluble transferrin receptor level, and decreased transferrin saturation. In addition, the reticulocyte count is typically low, the erythropoietin may be mildly elevated, and the peripheral smear may show hypochromic, microcytic RBCs or normochromic, normocytic RBCs. If differentiation between iron deficiency anemia and anemia of chronic disease is not apparent, a bone marrow biopsy can be obtained to assess iron stores.
A 65-year-old man with a history of rheumatoid arthritis is found to have a microcytic anemia. He had a colonoscopy 1 year ago which was normal and stool guaiac is negative. Which of the following is the most likely cause of his anemia? A Iron deficiency B Chronic disease C Pernicious anemia D Folate deficiency
The correct answer is B. Explanation: Anemia of chronic disease can cause normocytic or microcytic anemia, and may be secondary to rheumatoid arthritis in the patient. Iron-deficiency anemia is less likely with a normal colonoscopy and negative stool guaiac, and serum iron studies could be used to help differentiate the two.
A 67-year-old man with dizziness and a positive stool guaiac test. Expected lab results: A Normal MMA; decreased serum folate level B Elevated MMA; decreased serum B12 level C Elevated ferritin; normal MCV; decreased serum iron level D Decreased ferritin; decreased MCV; decreased serum iron level
The correct answer is D. Explanation: Low serum iron, low MCV, and low ferritin levels, along with a finding of blood in the stool, are consistent with iron-deficiency anemia. A workup for the source of the GI blood loss should ensue.
Question 1 of 4 A 72-year-old gentleman is brought to your office because a home health nurse noted he was becoming progressively weaker and more fatigued. He has a history of celiac disease for which he follows a strict gluten-free diet, but he has not been eating well. He also has a history of a seizure disorder and takes phenytoin. His review of systems is positive for dyspnea on exertion and mild anorexia. He has no other symptoms. Physical examination reveals a thin, pale-appearing man with normal vital signs. His conjunctivae are pale and his tongue is smooth, with moist mucosa and no oropharyngeal lesions. The remainder of the examination is unremarkable. A CBC reveals a WBC 4,500/mm3, Hgb 9 g/dL, hematocrit 28%, platelet count 140,000/mm3, MCV 102 fL, RDW 14, and B12 level 900 ng/L (normal). Which of the following statements is most likely FALSE? A The patient may have a high homocysteine level. B The patient's condition could be made better with a trial of folate replacement. C The patient may have a low RBC folate level. D The patient's condition will likely require chronic blood transfusions. E The patient may have a normal serum folate level.
The correct answer is D. Explanation: This patient likely has folate deficiency, given a normal B12, macrocytic anemia, and risk factors for folate deficiency—old age, poor diet, avoidance of gluten (flour is normally fortified with folate), use of phenytoin, and possible malabsorption due to GI disease (celiac disease in this case, but also any other infiltrating or inflammatory process of the bowel). Dietary deficiency is uncommon in the United States due to supplementation of grain products with folate. Foods naturally high in folate include melons, bananas, leaf vegetables, asparagus, and broccoli. The recommended intake is 400 μg/day, and the body stores approximately a 4-month supply. If he has had recent adequate folate intake, the serum folate level may be normal, but the RBC folate will still be low, reflecting the deficiency (think of it as the HbA1C of folate). To differentiate folate from B12 deficiency, check serum homocysteine and methylmalonate levels. Both will be elevated with B12 deficiency, while only homocysteine will be elevated in folate deficiency. Remember, you must exclude B12 deficiency before replacing folate because folate replacement can reverse the anemia but will permit progression of neurologic effects of B12 deficiency, so "B" is true.
A 15-year-old female presents to your office complaining of fatigue. She reports menarche at age 13 and complains of heavy menses. Her physical examination reveals a well-developed, well-nourished, pale female. You find no hepatosplenomegaly. Her laboratory results reveal a WBC 6,000/mm3, Hgb 8.9 g/dL, hematocrit 27%, platelet count 400,000/mm3, MCV 72 fL, red blood cell distribution width (RDW) 16. You order more laboratory tests. What are the expected findings in this patient? A Increased iron, decreased ferritin, increased total iron binding capacity. B Decreased iron, decreased ferritin, decreased total iron binding capacity. C Increased iron, increased ferritin, increased total iron binding capacity. D Decreased iron, increased ferritin, decreased total iron binding capacity. E Decreased iron, decreased ferritin, increased total iron binding capacity.
The correct answer is E. Explanation: This patient likely has iron deficiency anemia related to her heavy menses. Iron deficiency anemia is characterized by anemia along with a decreased serum iron, decreased ferritin, increased total iron binding capacity (TIBC), and decreased transferrin saturation. The decrease in serum ferritin is proportional to the decrease in total body iron stores. Hypochromic microcytic RBCs are found on peripheral smear. See Table 6-3 for a general guide to the causes of anemia based on red cell indices.
What is that transferrin receptor?
The transferrin receptor can help to differentiate between iron deficiency anemia and anemia of chronic disease. The serum transferrin receptor level is inversely correlated to iron storage levels. When the iron is low, the soluble transferrin receptor level is high. Thus, high serum transferrin receptor levels are associated with iron deficiency but not with anemia of chronic disease in which iron stores are adequate. One caveat, the serum transferrin receptor level will also be elevated in states in which there is rapid cell turnover (hemolytic anemia, for example). However, it should not be checked in this situation so you shouldn't get confused.
B12 and folic acid (folate)
They are co-enzymes for nuclear maturation and the DNA synthesis pathway Vitamin requirements for Erythropoiesis Folate is an essential vitamin for RNA and DNA synthesis within the maturing erythrocyte.
erythrocytes
They are responsible for tissue oxygenation. Are the most abundant cells of the blood (48% in men; 42% in women). Have a 120-day life cycle. Erythrocytes carry hemoglobin, are responsible for tissue oxygenation, and do not have a nucleus or mitochondria; therefore they cannot divide or synthesize proteins. These cells make up 42% to 48% of blood volume
Prevention and Treatment of Vitamin B12 Deficiency
Those at high risk for Vitamin B12 deficiency (older adults, vegetarians, vegans etc) need oral supplementation and should be encouraged to eat fortified breakfast cereals. Underlying conditions r/t absorption (H. pylori) should be treated. Treatment of deficiency [One of the following regimens]: 1000 ug (1 mg) daily X 1 week then weekly X 1 month then monthly for life (unless cause of underlying etiology is removed). 1000- 2000 mcg of crystalline cobalamin orally qd.
enhances iron absorption
Vitamin C (supplements or orange juice) enhances iron absorption and should be considered if a patient is not responding to iron therapy. Meat can also increase iron absorption
Pernicious anemia
What is the name for B12 deficiency macrocytic (megaloblastic) normochromic anemia when caused by a lack of protein intrinsic factor that helps the body absorb vitamin B-12 from the gastrointestinal tract?
Reticulocyte Count in Iron Deficiency Anemia
When bone marrow is stimulated, reticulocytes are released prematurely. Reticulocyte count is the best test to distinguish RBC underproduction from hemolysis. High reticulocyte counts occur when the bone marrow is responding normally to blood loss, hemolysis, or replacement of iron. Normal reticulocyte count is 0.5 - 1.5% Reticulocyte count should increase in 7-10 days with iron therapy and MCV should normalize.
Initial workup of anemia should include these labs
a CBC with measurement of red blood cell (RBC) indices, a peripheral blood smear, and a reticulocyte count.
Paroxysmal nocturnal hemoglobinuria
a hemolytic anemia. Deficiency in CD55 and CD59: Cause complement-mediated intravascular lysis and release of hemoglobin. Results in Anemia, severe fatigue, abdominal pain, and thrombosis.
Iron deficiency could be confirmed by subsequent testing that shows
a low serum iron, low ferritin, and high total iron-binding capacity (TIBC).
anemia
a reduction in the total number of erythrocytes in the circulating blood or a decrease in the quality or quantity of hemoglobin. A decrease in the number of erythrocytes, hemoglobin or both.
the most common cause of a normocytic anemia in elderly is
anemia of chronic inflammation (formerly known as anemia of chronic disease)
Anemia of chronic inflammation is
anemia that is secondary to some other underlying condition that leads to increased inflammation and bone marrow suppression. Along with causing a normocytic anemia, anemia of chronic inflammation can also present as a microcytic anemia. This type of anemia can easily be confused with iron-deficiency anemia because of its similar initial laboratory picture.
*Aplastic anemia caused by
characterized by an absence or reduction of all formed blood elements, red cells, white cells, and platelets (pancytopenia) caused by the failure of blood cell production in the bone marrow due to stem cell dysfunction . causes: most are autoimmune disorders; some are due to chemical exposure (benzene, arsenic, chemotherapy drugs). diagnosed by bone marrow biopsy. Hypocellular bone marrow that has been replaced with fat.
macrocytic anemias
characterized by unusually large stem cells (megaloblasts) in the marrow that mature into unusually large cells (macrocytes) in the circulation. These cells have increased size, thickness, and volume. These anemias are the result of defective erythrocyte deoxyribonucleic acid (DNA) synthesis, which is commonly caused by deficiencies of vitamin B12 (cobalamin) or folate (folic acid) or defective coenzymes that are required for nuclear maturation and DNA synthesis.
In the elderly, iron deficiency is frequently caused by
chronic gastrointestinal blood loss, poor nutritional intake, or a bleeding disorder. A thorough evaluation of the gastrointestinal tract for a source of blood loss, usually requiring a gastroenterology consultation for upper and lower GI endoscopy, should be undertaken, as iron-deficiency anemia may be the initial presentation of a GI malignancy.
Normcytic-normochromic anemia
erthrocytes are normal in size and hemoglobin content but insufficient in number. Are less frequent than macrocytic-normochromic and microcytic-hypochromic anemias.
Anemia with an elevated MCV, macrocytic anemia, is most often a manifestation of
folate or vitamin B12 deficiency; other causes include drug effects, liver disease, and hypothyroidism. The presence of macrocytic anemia, with or without the symptoms previously mentioned, should lead to further testing to determine B12 and folate levels. An elevated methylmalonic acid (MMA) level can be used to confirm a vitamin B12 deficiency; an elevated homocysteine level can be used to confirm folate deficiency. Folate deficiency anemia is usually seen in alcoholics, whereas B12-deficiency anemia mostly occurs in people with pernicious anemia, a history of gastrectomy, and diseases associated with malabsorption (eg, bacterial infection, Crohn disease, celiac disease). Under normal conditions, the body stores 50% of its B12 (2-5 mg total in adults) in the liver for 3 to 5 years. A minimal amount of B12 is lost daily through gastrointestinal secretions. B12 deficiency anemia is rare but possible in long-term vegans and vegetarians. B12 deficiency can be distinguished clinically from folic acid deficiency by the presence of neurologic symptoms.
Iron-deficiency anemia is treated first by
identification and correction of any source of blood loss. Most iron deficiency can be corrected by oral iron replacement. Oral iron is given as ferrous sulfate 325 mg (contains 65 mg of elemental iron) three times a day. In uncomplicated anemia, it is considered first-line therapy given its low cost and easy accessibility. Adherence to oral iron may be poor due to gastrointestinal side effects (dark stools, nausea, vomiting, and constipation) and the required 6 to 8 weeks of treatment needed to correct the anemia. Individuals with malabsorptive conditions, malignancy, chronic kidney disease, heart failure, or significant blood loss may not benefit from oral iron replacement and therefore require parenteral iron preparations. It is recommended that patients requiring parenteral administration be given iron intravenously and not intramuscular (IM). Given the high risk of side effects, only trained clinicians should administer intravenous iron.
Alcohol related to what vitamin deficiency
interferes with folate metabolism in the liver, causing a profound depletion of folate stores.
Vitamin B12 deficiency traditionally has been treated by
intramuscular B12 therapy with a regimen of 1000 μg IM daily for 7 days, then weekly for 4 weeks, then monthly for the rest of the patient's life. Newer research shows that many patients can be successfully treated with oral B12 therapy using 1000 to 2000 μg PO in a similar regimen. Folate deficiency can be treated with oral therapy of 1 mg daily until the deficiency is corrected.
anemia caused by vitamin b12 deficiency due to?
intrinsic factors Pernicious anemia caused by a lack of the protein intrinsic factor that helps the body absorb vitamin B-12 from the gastrointestinal tract What disorder is characterized by autoantibodies to IF?
The most common cause of anemia with a low mean corpuscular volume (MCV), microcytic anemia is
iron deficiency
A widened RDW and an elevated platelet count are typical of
iron deficiency anemia. Conversely, the RDW will be normal in thalassemias.
Which is true concerning drug-induced anemia?
is a form of immune hemolytic anemia from an allergic reaction against foreign antigens (antibiotics). Usually the drug is small molecular weight and functions as a hapten that binds to proteins on the surface of an erythrocyte. Cessation of administration of the drug results in rapid resolution of the anemia. This form of drug-induced anemia occurs 1 to 2 weeks after exposure to the antibiotic.
Post hemorrhagic anemia
is a normocytic-normochromic anemia caused by acute blood loss. Initial manifestations of this event depend on the severity of the blood loss. When blood loss exceeds 1500 ml, symptoms are apparent, even in a recumbent position. Volume loss reduces mean systemic filling pressure, resulting in decreased venous return and hypotension
Ferritin
is not a useful test for iron deficiency in hospitalized patients or in those who are chronically ill. Ferritin is an acute-phase reactant and thus may be elevated in these patients even when the patient has iron deficiency anemia (where the ferritin should be low). However, you can check a soluble transferrin receptor.
Folate deficiency anemia
lacking this essential vitamin required for RNA and DNA synthesis in RBC. More common than Pernicious. A normochromic (normal amnt of Hg), macrocytic (big) anemia. Dietary deficiency common in alcoholics or patients who are malnourished . Consists of neurological manifestations (ataxia). Treatment involves oral ingestion of missing vitamin.
sources of iron from food
meat veggy bread
Anemia of chronic diseases
most common anemia in the hospitalized patient. Decreased erythropoiesis, decreased erythrocyte life span, suppressed production of erythropoietin, ineffective bone marrow erythroid progenitor response to erythropoietin, altered iron metabolism and iron sequestion in macrophages.
In anemia of chronic inflammation, the body's iron stores (measured by serum ferritin) are
normal, but the capability of using the stored iron in the reticuloendothelial system becomes decreased. A lack of improvement in symptoms and hemoglobin level with iron supplementation are important clues indicating that the cause is chronic disease and not iron depletion, regardless of the laboratory picture. Another cause of normocytic anemia is renal insufficiency due to decreased erythropoietin production. Although bone marrow iron store remains the gold standard to differentiate between iron-deficiency anemia and anemia of chronic disease, simple serum testing is still used to diagnose and differentiate these two types of anemia
Even if it looks like iron deficiency anemia, always consider
other causes of anemia such as B12 deficiency, folate deficiency, and thalassemia. Often patients will have more than one cause for their anemia. Mixed vitamin B12 and iron deficiencies may present with normocytic anemia with an elevated RDW.
Hemolytic anemia
reduction in red cells due to excessive destruction characterized by an inadequate number of circulating red blood cells due to premature destruction of the RBCs by the spleen or immunologic by antibody and complement or phagocytosis. Congenital versus acquired. Intravascular versus extravascular hemolysis. if due to Autoimmune, Autoantibodies against antigens normally on the surface of erythrocytes.
Other causes of iron overload include
thalassemia, sideroblastic anemia, and frequent blood transfusions.
Other causes of microcytic anemia include
thalassemias and anemia of chronic disease.
There may be no reticulocytosis with treatment of iron deficiency if
the patient is simply iron deficient without anemia.
Anemia of chronic inflammation is managed primarily by treatment of
the underlying condition in order to decrease inflammation and bone marrow suppression. When anemia of chronic inflammation is severe (hemoglobin <10 g/dL), the risks and benefits of two modalities of treatment, blood transfusion and erythropoiesis-stimulating agents, may be considered. To note, the goals of treatment of anemia of chronic inflammation in patients with chronic kidney disease undergoing dialysis are to maintain a hemoglobin level between 10 and 12 g/dL; higher hemoglobin levels in this patient population are associated with increased rates of death and cardiovascular events.
