Page 2625 - Hematology_ Basic Principles and Practice ( PDFDrive )

e6 Part XIII Consultative Hematology

Erythropoietin
Summary points • Glycoprotein hormone secreted mostly by kidney but also liver
• Level varies inversely with hematocrit, stimulated by hypoxia
• May be secreted by certain tumors, leading to polycythemia
• Results obtained with one method may differ significantly from those obtained with another—any serial testing over
time should be performed using the same test method
Methodology Immunoassay
Specimen requirements Lithium heparin, EDTA, or plain tube
Indications Can differentiate primary (decreased concentration) from secondary erythrocytosis (elevated), but testing may be
problematic given the broad overlap between the two groups. Levels are usually increased in anemia except in chronic
renal failure patients, in whom levels may be used to monitor erythropoietin therapy
Reference range Adult values approximately 3–16 milli–International Unit/mL; Table 162.13
Interpretation Normal or low levels with primary polycythemia; elevated levels with most forms of secondary polycythemia
Interfering substances Lipemia
Reference Cotes PM, Doré CJ, Yin JA, et al: Determination of serum immunoreactive erythropoietin in the investigation of
erythrocytosis. N Engl J Med 315:283, 1986.

EDTA, Ethylenediaminetetraacetic acid.

Folate (RBC or Serum/Plasma)
Summary points • Folate—commonly assessed in setting of macrocytic anemia along with vitamin B 12 (should be done concurrently)
• RBC folate less sensitive to short-term dietary changes than serum folate; more reflective of tissue folate stores, more
specific for folate deficiency
• Folate deficiency usually nutritional in origin or due to inadequate intake in the setting of increased demand
(pregnancy, hemolytic anemias, liver disease)
Methodology Immunoassay
Specimen requirements RBC: whole blood: EDTA; protect from light for RBC
Serum: plain or serum separator tube (fasting state preferred)
Indications Macrocytic or megaloblastic anemia, workup of possible nutritional deficiencies or myelodysplastic syndrome, unexplained
neurologic symptoms or dementia
Reference range Table 162.14
Interpretation • Decreased in nutritional deficiencies (pregnancy, alcoholism, older adults), antimetabolite therapy (methotrexate, for
example), rarely due to inherited metabolic disorders
• May be decreased in vitamin B 12 (cobalamin) deficiency
• Additional testing for pathway intermediates homocysteine and MMA can help distinguish between folate and vitamin
B 12 deficiency in patients who have borderline levels of either
• Homocysteine—elevated in both folate and vitamin B 12 deficiency
• MMA—elevated in vitamin B 12 but not folate deficiency
Related tests Vitamin B 12 , homocysteine, MMA, complete blood count
Interfering substances Excessive light exposure before testing, hemolysis, lipemia
Reference Kaferle J, Strzoda CE: Evaluation of macrocytosis. Am Fam Physician 79:203, 2009.
EDTA, Ethylenediaminetetraacetic acid; MMA, methylmalonic acid; RBC, red blood cell.

Vitamin B 12 (Cobalamin)

Summary points • Commonly assessed in setting of macrocytic anemia along with folate (should be done concurrently to avoid
undiagnosed vitamin B 12 deficiency)
• Deficiency often due to inadequate gastric absorption (pernicious anemia, gastric bypass) or lack of small bowel
reabsorption (malabsorption, Crohn disease, small intestinal surgery)
• Nutritional deficiency uncommon but strict vegans are at risk (vitamin B 12 available only from animal sources); also
seen in alcoholics, older adults, malnutrition
• Elevated vitamin B 12 may accompany severe disease states and warrants consideration of additional evaluation
Methodology Immunoassay
Specimen requirements Plain or serum separator tube
Indications Macrocytic or megaloblastic anemia, pancytopenia, workup of possible nutritional deficiencies or myelodysplastic
syndrome, unexplained neurologic symptoms or dementia, hypersegmented neutrophils on peripheral smear
Reference range Table 162.15
Interpretation • Low levels diagnostic of deficiency; pregnancy lowers vitamin B 12 level
• Follow-up testing for low levels to diagnose pernicious anemia: parietal cell antibodies, antiintrinsic factor antibodies
• Additional testing for pathway intermediates homocysteine and MMA can help distinguish between folate and vitamin
B 12 deficiency in patients with borderline levels of either
• Homocysteine—elevated in both folate and vitamin B 12 deficiency
• MMA—elevated in vitamin B 12 but not folate deficiency
• High vitamin B 12 may accompany solid neoplasms, hematologic malignancy, liver or kidney disease, functional B 12
deficiency, and autoimmune lymphoproliferative syndrome
Related tests Folate, homocysteine, MMA, complete blood count, parietal cell antibodies, antiintrinsic factor antibodies, serum gastrin
Interfering substances Excessive light exposure before testing, hemolyzed sample
References Andres E, Serraj K, Zhu J, et al: The pathophysiology of elevated vitamin B 12 in clinical practice. Q J Med 106:505, 2013.
Kaferle J, Strzoda CE: Evaluation of macrocytosis. Am Fam Physician 79:203, 2009.

MMA, Methylmalonic acid.