Table 2.

Criteria for common anemia etiologies

Conditions	Criteria
Vitamin B12 deficiency	Vitamin B12 < 200 pg/mL Further diagnostic studies (e.g., methylmalonic acid) or a treatment trial may be considered for a B12 level of 200–300 pg/dL. Oral or parental B12 treatment recommended. Oral therapy should entail 1000 mcg or more daily. A 3-month trial of B12 therapy with normalization of B12 level and ongoing anemia will exclude B12 deficiency anemia and allow enrollment.
Folate deficiency	Folate level < lower limit of normal A 3-month trial of adequate folate correction and ongoing anemia will exclude folate deficiency and allow enrollment.
Renal insufficiency	Creatinine clearance by 4-variable MDRD of < 30 mL/min
Thyroid dysfunction	Thyrotropin < 0.1 mcU/mL or > 10 mcU/mL 3 months of thyroid therapy with a normal free T4 and ongoing anemia will exclude thyroid dysfunction and allow enrollment.
Myelodysplastic syndrome	Myelodysplastic syndrome by bone marrow evaluation using the WHO criteria A bone marrow examination should be performed if clinically indicated. Indications include an MCV ≥ 100 fL, a platelet count < 120 K/uL, or a neutrophil count < 1200 K/uL not attributable to another cause. A bone marrow evaluation should be considered if prior chemotherapy, radiation therapy, an abnormal peripheral blood smear, or if over time the MCV has been rising, platelets falling, or leukocyte count falling.
Anemia of chronic inflammation/disease	Anemia in association with any inflammatory condition, including: Auto-immune diseases (systemic lupus erythematosis, rheumatoid arthritis, mixed connective tissue disease, sarcoidoisis, bronchiolitis obliterans, vasculitis, polymyalgia rheumatica, temporal arteritis, inflammatory bowel disease or related diseases) that are active or requiring systemic treatment in the past 3 months. However, non-steroidal anti-inflammatory agents (e.g. ibuprofen), acetaminophen, or aspirin as the sole systemic treatment will not be considered active treatment and will allow enrollment. Chronic infection (HIV, viral hepatitis, tuberculosis, osteomyelitis) or acute infection (pneumonia, sepsis, bacteremia, prostatitis, urosepsis, pyelonephritis, cholecystitis). Cancer. Any cancer (aside from non-melanoma skin cancer) in the past 2 years or on therapy for cancer. In addition, prostate cancer will be excluded if subjects have metastatic disease, have had prostatectomy within the prior 6 months, have ever received external beam radiation therapy or brachytherapy, or have received androgen deprivation therapy in the prior 24 months. Subjects with a history of any other form of cancer will likewise be excluded if they have received any radiation or chemotherapy in the prior 24 months Treatment with immunosuppression may also be used as criteria as per the judgment of the study investigator.
Plasma cell dyscrasia	Multiple myeloma or plasma cell dyscrasia that may be causing anemia Monoclonal gammopathy ≥ 1 g/dL. A monoclonal paraprotein of < 1 g/dL without bone lesions on skeletal survey, hypercalcemia, < 5% light chain restricted plasma cells, and no other evidence of progressive disease or multiple myeloma will exclude a plasma cell dyscrasia and be allowable.
Thalassemia trait	An MCV < 80 fL and red blood cell count within the normal reference range without iron deficiency in the appropriate ethnic group. An elevated hemoglobin A2 (> 3.5%) without iron deficiency on hemoglobin electrophoresis or demonstrated two deletions for alpha thalassemia confirms thalassemia trait. A single alpha thalassemia deletion will not be excluded on this protocol. A documented decline of hemoglobin of 1.5 g/dL over time without another cause except for baseline thalassemia will be acceptable to the protocol.
Alcohol	Evidence of alcohol overuse Overuse of alcohol will be determined by the clinician. Consider alcohol overuse if more than 3–4 drinks per occasion for woman and more than 4–5 drinks per occasion for men. A trial of 3 months of using < 3 drinks per week and ongoing anemia will exclude alcohol overuse.
Other	Physical exam showing lymphadenopathy ≥ 2 cm or splenomegaly without another cause. Any condition that can reasonably be assumed to be causing or a major contributor to the anemia and has not been corrected for 3 months. Any prior history of a hematologic malignancy.

Abbreviations: MDRD, Modification of Diet in Renal Disease equation (186.3 × serum creatinine^−1.154 × age^−0.203 × [0.742 if female] × [1.212 if black]); WHO, World Health Organization; MCV, mean cell volume.