Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (293 page)

   Severe malnutrition: kwashiorkor, anorexia nervosa.

   Leukemia may be the underlying disease in 1−5% of patients who present with AA.

   PNH (see p. 378) develops in 5−10% of patients with AA; conversely, AA develops in 25% of patients with PNH.

   Who Should Be Suspected?

An individual who presents with a clinical picture of increasing symptoms of anemia, mucosal bleeding, or fever, mucosal ulcerations, and bacterial infections due to neutropenia, in whom an initial CBC demonstrates pancytopenia. Pancytopenia from other causes, such as chemotherapy, should be ruled out (see below). The disease is frequent in East Asia.

   Laboratory Findings

   RBC: anemia is normocytic, normochromic. Hg may be <7 g/L. RDW is normal. MCV is frequently elevated at presentation.

   Reticulocytes are invariably decreased to absent.

   WBC: neutropenia (absolute neutrophil count <1,500/μL) is always present, often accompanied by monocytosis. Abnormal WBCs are not seen. Lymphocyte count is normal (false lymphocytosis if one observes the percent of WBC rather than the absolute count).

   Platelets are decreased, but severity varies.

   Bone marrow (BM) is hypocellular, with an “empty” marrow in severe cases. Less than 30% of residual cells are hematopoietic. Hematopoiesis is not megaloblastic. The appearance of the BM in inherited or acquired AA is identical. Aspiration and biopsy are both necessary to rule out MDS, leukemias, granulomatous disease, or tumors. The BM examination must also exclude the viral hemophagocytic syndrome.

   
Cytogenetics
: normal karyotype.

   
Flow cytometry
phenotyping shows virtual absence of CD34 hematopoietic stem cells in blood and marrow. AA and PNH overlap in approximately 40−50% of cases.

   Serum iron studies are normal.