eMedicine Specialties > Hematology > Red Blood Cells and Disorders

Aplastic Anemia: Differential Diagnoses & Workup

Author: Sameer Bakhshi, MD, Associate Professor of Pediatric Oncology, Department of Medical Oncology, Dr BRA Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, India
Coauthor(s): Esteban Abella, MD, Consulting Staff, Arizona Pediatric Hematology/Oncology, PLLC
Contributor Information and Disclosures

Updated: Oct 4, 2009

Differential Diagnoses

Acute Lymphoblastic Leukemia
Myelodysplastic Syndrome
Acute Myelogenous Leukemia
Myelophthisic Anemia
Agnogenic Myeloid Metaplasia With Myelofibrosis
Osteopetrosis
Human Herpesvirus Type 6
Systemic Lupus Erythematosus
Lymphoma, Non-Hodgkin
Megaloblastic Anemia
Multiple Myeloma

Other Problems to Be Considered

Workup

Laboratory Studies

  • Determination of complete blood cell (CBC) count and peripheral smears
    • A paucity of platelets, red blood cells (RBCs), granulocytes, monocytes, and reticulocytes is found in patients with aplastic anemia. Mild macrocytosis is occasionally observed. The degree of cytopenia is useful in assessing the severity of aplastic anemia. The corrected reticulocyte count is uniformly low in aplastic anemia.
    • The peripheral blood smear is often helpful in distinguishing aplasia from infiltrative and dysplastic causes. Teardrop poikilocytes and leukoerythroblastic changes suggest an infiltrative process.
    • Patients with MDS often have certain characteristic abnormalities such as dyserythropoietic RBCs and neutrophils with hypogranulation, hypolobulation, or apoptotic nuclei reaching to the edges of the cytoplasm. Monocytes are similarly hypogranular, and their nuclei may contain nucleoli.
    • A leukemic process may result in evidence of blasts (myeloblasts) on the peripheral smear.
  • Peripheral blood testing
    • Hemoglobin electrophoresis and blood-group testing may show elevated levels fetal hemoglobin and red cell I antigen, suggesting stress erythropoiesis. These findings are observed in both aplastic anemia and MDS and are often proportional to the macrocytosis.
    • Ordering a biochemical profile is useful in evaluating the etiology and in the differential diagnosis. The profile includes a Coombs test; an analysis of kidney function; and measurement of transaminase, bilirubin, and lactic dehydrogenase (LDH) levels.
    • Serologic testing for hepatitis and other viral entities, such as EBV, CMV, and HIV, may be useful.
    • An autoimmune-disease evaluation for evidence of collagen-vascular disease may be performed.
    • The Ham test, or the sucrose hemolysis test, is frequently performed to diagnose PNH. However, at present, the fluorescence-activated cell sorter (FACS) profile of PIGA anchor proteins, such as CD55 and CD59, may be more accurate than the Ham test for excluding PNH.
    • Diepoxybutane incubation is performed to assess chromosomal breakage for Fanconi anemia. This test is required even in the absence of phenotypic features of Fanconi anemia, because 30% of patients may not have any clinical stigmata.
    • Histocompatibility testing should be conducted early to identify potential related donors, especially those for young patients. Because the extent of previous transfusion significantly affects the outcomes of patients undergoing BMT for aplastic anemia, the rapidity with which these data are obtained is crucial.

Imaging Studies

  • Radiologic studies are generally not needed to establish a diagnosis of aplastic anemia.
  • A skeletal survey is especially useful for the inherited marrow-failure syndromes, many of which cause skeletal abnormalities.

Procedures

  • Review of peripheral smears
  • Bone marrow aspiration and biopsy
    • Bone marrow biopsy is performed in addition to aspiration to assess cellularity both qualitatively and quantitatively. In aplastic anemia, the specimens are hypocellular. Aspiration samples alone may appear hypocellular because of technical reasons (eg, dilution with peripheral blood), or they may appear hypercellular because of areas of focal residual hematopoiesis.By comparison, core biopsy better reveals cellularity: The specimen is considered hypocellular if it is <30% cellular in individuals aged <60 years or if it is <20% in those aged >60 years. A relative or absolute increase in mast cells may be observed around the hypoplastic spicules. A proportion of marrow lymphocytes >70% is correlated with poor prognosis in aplastic anemia. Some dyserythropoiesis with megaloblastosis may be observed in aplastic anemia.
    • In MDS, the cellularity may be increased or decreased. Myelodysplastic features are usually observed in hematopoietic precursors and progeny. Islands of immature cells or abnormal localization of immature progenitors (ALIP) indicate MDS. These patients may have megakaryocytic abnormalities (micromegakaryocytes, megakaryocytes with dyskaryorrhexis), >5% ring sideroblasts (observed only on iron stains), and granulocytic abnormalities (pseudo – Pelger-Huët cells, hypogranulation, excess of blasts) On occasion, marrow fibrosis may be observed.
    • Leukemia and metastatic cancers may be diagnosed with bone marrow examination.
    • Chromosomal rearrangements are considered diagnostic of MDS, with trisomies of 8 and 21 and deletions of 5, 7, and 20 being the most common. However, the conventional karyotype technique reveals abnormalities in only about 50% of patients with MDS. In hypoplastic marrows, obtaining sufficient sample for karyotyping is often difficult.
    • The issue of malignant versus nonmalignant clonality in aplastic anemia can sometimes be resolved by using fluorescent in situ hybridization (FISH) to visualize chromosomal abnormalities in interphase cells.
    • Bone marrow culture is useful in diagnosing mycobacterial and viral infections. However, the yield is generally low.

Histologic Findings

Histologic findings of aplastic anemia include hypocellular bone marrow with fatty replacement and relatively increased nonhematopoietic elements, such as plasma cells and mast cells. Perform careful examination to exclude metastatic tumor foci on biopsy.

Staging

Staging of aplastic anemia is based on the criteria of the International Aplastic Anemia Study Group, as follows23 :

  • Blood
    • Neutrophils – Less than 0.5 X 109/L
    • Platelets – Less than 20 X 109/L
    • Reticulocytes – Less than 1% corrected (percentage of actual hematocrit [Hct] to normal Hct)
  • Marrow
    • Severe hypocellularity
    • Moderate hypocellularity, with hematopoietic cells representing less than 30% of residual cells
  • Severe aplasia is defined as including any 2 or 3 peripheral blood criteria and either marrow criterion.
  • A further subclassification developed after the recognition that individuals with neutrophil counts lower than 0.2 X 109/L had very SAA (VSAA). This group is less likely than others to respond to immunosuppressive therapy.

More on Aplastic Anemia

Overview: Aplastic Anemia
Differential Diagnoses & Workup: Aplastic Anemia
Treatment & Medication: Aplastic Anemia
Follow-up: Aplastic Anemia
Multimedia: Aplastic Anemia
References
Further Reading
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Keywords

aplastic anemia; anemia; anemia, aplastic; hypoplastic anemia; bone marrow disease; bone marrow failure; bone marrow failure syndrome; severe aplastic anemia; SAA; progressive hypocythemia; aregeneratory anemia; aleukia hemorrhagica; panmyelophthisis; toxic paralytic anemia; peripheral pancytopenia; myelodysplastic syndrome; MDS

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Contributor Information and Disclosures

Author

Sameer Bakhshi, MD, Associate Professor of Pediatric Oncology, Department of Medical Oncology, Dr BRA Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, India
Disclosure: Nothing to disclose.

Coauthor(s)

Esteban Abella, MD, Consulting Staff, Arizona Pediatric Hematology/Oncology, PLLC
Esteban Abella, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and West Virginia State Medical Association
Disclosure: Nothing to disclose.

Medical Editor

David Aboulafia, MD, Medical Director, Bailey-Boushay House; Clinical Professor, Department of Medicine, Division of Hematology, University of Washington
David Aboulafia, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Medical Directors Association, American Society of Hematology, Infectious Diseases Society of America, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Troy H Guthrie, Jr, MD, Director of Cancer Institute, Baptist Medical Center
Troy H Guthrie, Jr, MD is a member of the following medical societies: American Federation for Medical Research, American Medical Association, American Society of Hematology, Florida Medical Association, Medical Association of Georgia, and Southern Medical Association
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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