Anemia: Diagnosis and Management

Educational Objectives

The goal of this program is to improve the management of hematuria and anemia. After hearing and assimilating this program, the clinician will be better able to:

1. Differentiate between iron deficiency anemia and anemia of chronic disease or inflammation.

2. Diagnose and treat vitamin B12 anemia.

Summary

Initial laboratory evaluation: complete blood count (CBC) — hemoglobin (Hb); hematocrit; mean corpuscular volume (MCV; indicates size of RBCs), RBC distribution width (RDW; indicates variation in size of RBCs); peripheral blood smear — used to study RBC, white blood cell, and platelet morphology; reticulocyte count — measurement of newly produced RBCs; marker of responsiveness of bone marrow

Morphologic classification: normocytic (MCV 80-100 µ3); microcytic (<80 µm3); macrocytic (>100 µm3); microcytic anemia — seen in iron deficiency anemia (IDA), thalassemia, anemia of chronic disease or inflammation (ACI), sideroblastic anemia, and lead poisoning; normocytic anemia — seen in acute blood loss before development of compensatory reticulocytosis; also seen in ACI, hypersplenism, malfunction of bone marrow, and hemolysis; macrocytic anemia — seen with vitamin B12 or folate deficiency, hemolysis with reticulocytosis, some types of chemotherapy, hypothyroidism, and myelodysplastic syndrome

Presentation: often discovered on routine CBC; patients may also present with symptoms of tissue hypoxia (eg, fatigue, lightheadedness, weakness, dyspnea) or compensation (eg, palpitations, tachycardia); ferritin excellent indicator of iron stores; iron profile useful for differentiating IDA from ACI; total iron-binding capacity (TIBC) measures amount of iron in blood when all transferrin saturated with iron

Iron deficiency anemia: clues to diagnosis — microcytic anemia; level of serum iron low to normal (varies diurnally); RDW and TIBC high; percent saturation of transferrin (iron/TIBC ratio) low, usually <10%; ferritin — storage form of iron; low in IDA; acute-phase reactant, so variations possible; ferritin <15 ng/L diagnostic; may be normal in acute or chronic infection, active inflammatory diseases, cancer, or CKD; peripheral smear — sizes and shapes of RBCs vary; reactive thrombocytosis — common; etiology — IDA not diagnosis in and of itself; in women of reproductive age, menstrual bleeding most common cause; in men and postmenopausal women, gastrointestinal (GI) bleeding most common cause; however, even in individuals who undergo GI evaluation with endoscopy and colonoscopy, causative lesions found in only ≈60% of cases; celiac sprue, gastric bypass, and use of proton pump inhibitors can influence absorption

Treatment: unless IDA severe or absorption issues suspected, oral iron first option at dose of 325 mg 3 times daily; ferrous sulfate has greatest amount of elemental iron; ferrous gluconate less constipating but has only 30 mg of elemental iron; absorption of oral iron inhibited by antacids, certain antibiotics, tannins, and dietary fiber; best absorbed on empty stomach, but best tolerated with food; side effects include nausea, abdominal pain, constipation, and black stools; vitamin C aids in absorption; response to therapy — reticulocytosis seen within 1 wk; Hb responds in 1 to 2 wk; anemia usually resolves within 4 to 6 wk; continue oral supplementation for 3 to 6 mo to replenish stores

Erythropoietin (EPO): cytokine produced by kidneys in response to hypoxia; in bone marrow, signals differentiation into RBCs

Anemia of chronic disease or inflammation: mild to moderate anemia persistent for >2 mo in patients with infectious, inflammatory, or neoplastic disease; other causes must be excluded; typically hypoproliferative (expect low reticulocyte count); normocytic, but may be microcytic in later stages; serum iron low, percent saturation low, and ferritin normal to elevated (reticuloendothelial iron stores adequate); pathophysiology — overall suppression of EPO production and alterations in iron metabolism (increased levels of inflammatory cytokines [particularly interleukin-6] associated with increase in hepcidin levels, which in turn signals intestines to decrease absorption of iron and macrophages in liver to retain iron); survival of RBC moderately decreases; differentiating between IDA and ACI — percent saturation and serum ferritin lower in IDA (ferritin normal to high in ACI); in significant renal failure, ferritin <100 ng/mL consistent with IDA; MCV lower in IDA; RDW higher in IDA; TIBC high normal and greater in IDA (low to low-normal in ACI); treatment — not usually required; iron replacement typically not necessary; erythrocyte-stimulating agent can be given in setting of renal disease (however, excessive Hb levels correlated with increased risk for HTN and thrombosis); treat underlying cause

Vitamin B12 deficiency: common in patients >50 yr of age and in patients with history of gastric bypass surgery; vitamin B12 found primarily in animal-derived foods; deficiency due to decreased intake may take many years to develop because hepatic reservoir large and renal reabsorption usually efficient; deficiency almost always due to malabsorption; in pernicious anemia, atrophy of stomach mucosa results in decreased production of intrinsic factor (essential for absorption of vitamin B12); in achlorhydria, decreased production of gastric acid results in poor absorption of vitamin B12; vitamin B12 deficiency also seen in inflammatory bowel disease, celiac disease, pancreatic insufficiency, bacterial overgrowth, and alcoholism; clinical presentation — onset insidious; patients present with glossitis, weight loss, and pale yellow skin; neurologic manifestations — loss of position or vibratory sense, which can progress to spastic ataxia; may occur with mild anemia; possibly irreversible; psychiatric disorders (hallucinations, dementia, and psychosis or megaloblastic mania) — can occur without evidence of hematologic abnormalities; may be irreversible; laboratory findings — cobalamin typically <200 ng/L; if in low to normal range (ie, 200-350 ng/L), check methylmalonic acid (MMA) and homocysteine (each elevated in patients with vitamin B12 deficiency); MMA more sensitive than low-normal cobalamin alone; if pernicious anemia suspected (especially in individuals >50 yr of age), test for parietal cell or IF autoantibodies

Treatment: typical parenteral dose 1000 µg intramuscularly for 5 days, followed by once-weekly dose for 4 to 5 wk (once monthly afterward); oral dose 1000 to 2000 µg/day; reticulocytosis seen in 3 to 5 days, and blood counts normalize by 2 to 3 mo; folate supplementation — check vitamin B12 level before initiating; may lead to slight improvement in anemia but mask vitamin B12 deficiency (and therefore fail to correct neuropsychiatric manifestations)

Readings

Suggested Reading

Abe M et al: International normalized ratio decreases after hemodialysis treatment in patients treated with warfarin. J Cardiovasc Pharmacol, 2012 Dec;60(6):502-7; Barbour SJ et al: Individuals of Pacific Asian origin with IgA nephropathy have an increased risk of progression to end-stage renal disease. Kidney Int, 2013 Nov;84(5):1017-24; Divate PG, Patanwala R: Neurological manifestations of B(12) deficiency with emphasis on its aetiology. J Assoc Physicians India, 2014 May;62(5):400-5; Gross O et al: Early angiotensin-converting enzyme inhibition in Alport syndrome delays renal failure and improves life expectancy. Kidney Int, 2012 Mar;81(5):494-501; Miller J: Iron deficiency anemia: a common and curable disease. Cold Spring Harb Perspect Med, 2013 Jul 1;3(7) pii: a011866; Pichler R et al: The need for repeated urological evaluation in low-risk patients with microscopic hematuria after negative diagnostic work-up. Anticancer Res, 2013 Dec;33(12):5525-30; Pramono LA et al: IgA nephropathy. Acta Med Indones, 2013 Apr;45(2):148-9; Sharp V et al: Assessment of asymptomatic microscopic hematuria in adults. Am Fam Physician, 2013 Dec 1;88(11):747-54; Shimizu A et al: Clinical and pathological studies of IgA nephropathy presenting as a rapidly progressive form of glomerulonephritis. Intern Med, 2013;52(22):2489-94; Sihler KC et al: Hepcidin in trauma: linking injury, inflammation, and anemia. J Trauma, 2010 Oct;69(4):831-7; Stabler SP: Clinical practice. Vitamin B12 deficiency. N Engl J Med, 2013 Jan 10;368(2):149-60; Sultana GS et al: Value of red cell distribution width (RDW) and RBC indices in the detection of iron deficiency anemia. Mymensingh Med J, 2013 Apr;22(2):370-6; Wu YC et al: Oral manifestations and blood profile in patients with iron deficiency anemia. J Formos Med Assoc, 2014 Feb;113(2):83-7; Yeoh M et al: Macroscopic haematuria — a urological approach. Aust Fam Physician, 2013 Mar;42(3):123-6.

Disclosures

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, members of the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Mandernach was recorded at the 45th Annual Topics in Internal Medicine, held September 18-20, 2014, in Lake Buena Vista, FL, and sponsored by the University of Florida College of Medicine. For information about upcoming CME activities from the University of Florida College of Medicine, please visit www.topics.cme.ufl.edu. The Audio Digest Foundation thanks the speaker and the sponsor for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

IM621802

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.