Differentials
Radiation injury
SIGNS / SYMPTOMS
History of radiation exposure to marrow-bearing areas.
INVESTIGATIONS
Clinical diagnosis.
Chemotherapy
SIGNS / SYMPTOMS
History of chemotherapy.
INVESTIGATIONS
Clinical diagnosis.
HIV infection
SIGNS / SYMPTOMS
History of HIV risk factors or opportunistic infections.
INVESTIGATIONS
HIV testing positive.
Vitamin B12 deficiency
SIGNS / SYMPTOMS
Dietary history of deficiency.
Intestinal disease or resection.
Neurologic abnormalities.
INVESTIGATIONS
Serum B12 levels below the lower limit of normal; macrocytic anemia; megaloblastic changes in bone marrow cells.
Folate deficiency
SIGNS / SYMPTOMS
Dietary history of deficiency.
Intestinal disease or resection.
INVESTIGATIONS
Folate levels below the lower limit of normal; macrocytic anemia; megaloblastic changes in bone marrow cells.
Hypothyroidism
SIGNS / SYMPTOMS
May be asymptomatic, or may present with low energy, weight gain despite poor appetite, and changes in hair and skin texture.
INVESTIGATIONS
Thyroid-stimulating hormone elevated, and free thyroxine low.
Systemic lupus erythematosus (SLE)
SIGNS / SYMPTOMS
Classically, butterfly rash, joint pains.
INVESTIGATIONS
SLE and some other connective tissue disorders can cause pancytopenia through an autoimmune mechanism.
Positive antinuclear antibody and anti-double-stranded DNA can help diagnose SLE.
Marrow is usually cellular or fibrotic, although rarely may also be hypocellular.
Tuberculosis and atypical mycobacterial infections
SIGNS / SYMPTOMS
May include cough, lymphadenopathy, and weight loss.
INVESTIGATIONS
Acid-fast bacilli stain or mycobacterial culture from an involved site can diagnose these infections.
Bone marrow is not hypocellular (and may show granulomata in tuberculosis).
Ehrlichiosis
SIGNS / SYMPTOMS
Severe headache, myalgias, fever, chills.
INVESTIGATIONS
Bone marrow not hypocellular.
Ehrlichiosis IgG titer elevated.
Overwhelming sepsis
SIGNS / SYMPTOMS
Fever or hypothermia. Hypotension. Poor peripheral perfusion. Multiorgan failure.
INVESTIGATIONS
Blood cultures positive.
Bone marrow not hypocellular.
Hypocellular myelodysplastic syndrome (MDS)
SIGNS / SYMPTOMS
May have no differentiating clinical features.
Might have history of exposure to leukemogenic agents (e.g., alkylating agents, topoisomerase II inhibitors, and radiation).
Can be complication of AA.
INVESTIGATIONS
The following features of the bone marrow exam may suggest MDS:[31][33]
1) prominent dysplasia on marrow or peripheral blood exam (particularly in the myeloid and megakaryocyte lineages; AA can often show some erythroid dysplasia)
2) circulating blasts or an increased number of marrow blasts (or CD34+ cells on immunohistochemical staining)
3) presence of an increased proportion of ringed sideroblasts in the marrow
4) marrow fibrosis
5) cytogenetic abnormalities (especially abnormalities of chromosome 5 or 7, trisomy 8, 20q-, trisomy 21, or complex karyotypes), but AA can also be associated with cytogenetic abnormalities.
Hypocellular acute myelogenous leukemia (AML)
SIGNS / SYMPTOMS
Constitutional and often related to cytopenias: weakness, low energy, pallor, easy bruising, easy bleeding.
INVESTIGATIONS
Peripheral blood smear may show blasts.
Bone marrow exam reveals abnormal cell population.
Multiple myeloma
SIGNS / SYMPTOMS
Often asymptomatic. May have symptoms related to cytopenias: weakness, low energy, pallor, easy bruising, easy bleeding.
INVESTIGATIONS
Monoclonal urine Ig spike.
Careful bone marrow exam reveals abnormal cell population.
Non-Hodgkin lymphoma
SIGNS / SYMPTOMS
May have lymphadenopathy, night sweats, weight loss, or anorexia.
May have symptoms related to cytopenias: weakness, low energy, pallor, easy bruising, easy bleeding.
INVESTIGATIONS
Bone marrow exam reveals abnormal cell population.
Hodgkin lymphoma
SIGNS / SYMPTOMS
May have lymphadenopathy.
May have night sweats, weight loss, anorexia.
May have symptoms related to cytopenias: weakness, low energy, pallor, easy bruising, easy bleeding.
INVESTIGATIONS
Bone marrow exam reveals abnormal cell population, usually clonal.
Characteristic Reed-Sternberg cells may be seen on bone marrow biopsy.
Carcinoma metastatic to marrow
SIGNS / SYMPTOMS
Primary tumor is usually apparent by the time metastasis causes pancytopenia.
INVESTIGATIONS
Metastatic cells in bone marrow.
Hypocellular acute lymphoblastic leukemia (ALL)
SIGNS / SYMPTOMS
May present with features of pancytopenia; hypocellular ALL occurs in 2% to 3% of childhood ALL.[34]
INVESTIGATIONS
Complete blood count shows pancytopenia with neutropenia more pronounced than thrombocytopenia.
Peripheral blood smear may show blasts.
Bone marrow exam reveals abnormal cell population and may show increased reticulin.
Hairy cell leukemia
SIGNS / SYMPTOMS
Symptoms of pancytopenia, often with splenomegaly.
INVESTIGATIONS
Complete blood count shows pancytopenia but with accompanying monocytopenia.
Anorexia nervosa or prolonged starvation
SIGNS / SYMPTOMS
Low body mass index and body fat.
INVESTIGATIONS
Bone marrow may show hypocellularity with gelatinous transformation, loss of fat cells, and presence of increased ground substance on hematoxylin and eosin staining.
Use of this content is subject to our disclaimer