Ann IM 2002;136:534; Nejm 1997;336:1365

Cause:

A stem cell disease. Autoimmune via anti-erythropoietin antibodies (Nejm 2009;361:1848, 1901), drugs, infectious agent, or chronic immune disease, eg, quinidine (Nejm 1979;301:621), phenylbutazone, chloramphenicol, gold salts; viral hepatitis

EB virus (Ann IM 1988;109:695), parvovirus B19 (Ann IM 1990;113:926; Nejm 1989;321:484, 519, 536); thymomas, rheumatoid arthritis (Ann IM 1984;100:202), SLE, myasthenia gravis, myxedema, viral hepatitis (Nejm 1997;336:1059)

Pathophys:Sudden insult to stem cell from lymphocytic immune response; rarely folate-responsive in adult type (Nejm 1978;298:469); perhaps antibody to erythropoietin in some cases

Pregnancy may induce relapse, but still possible

Sx:Recent PNH (15%); petechiae, infection, anemia

Hematologic and solid tumors after marrow transplant or immunization (Nejm 1993;329:1152); PNH (Paroxysmal Nocturnal Hemoglobinuria) (Ann IM 1999;131:401, 467) in 25% of immunologically mediated aplastic anemias

Lab:

Hem:Pancytopenia, NCNC anemia, retics <2%, nucleated rbc's, normal Fe and TIBC

Path:Marrow shows marked decrease in rbc precursors, E/M ratio <<1:3

Serol:Parvovirus B19 IgM and IgG titers (Erythema Infectiosum (Fifth Disease)); or by DNA hybridization studies of serum if immunosuppressed (Ann IM 1990;113:926)

Rx:

(Nejm 1991;324:1297)

• Erythropoietin or eptn receptor agonists (Nejm 2009;361:1848, 1901)
• Marrow transplant if young and compatible donor, 69% 15-yr survival (Ann IM 1997;126:107)
• High-dose cyclophosphamide 50 mg/kg iv qd × 4 d; 65% complete remission (Ann IM 2001;135:477)
• Antilymphocyte globulin + prednisone + cyclosporine (Jama 2003;289:1130; Nejm 1991;324:1297), 68% response, 55% 7-yr and 38% 15-yr survival (Ann IM 1997;126:107); same response in older pts, though mortality higher (Ann IM 1999;130:193)
• Transfusions; use irradiated blood to prevent graft-vs-host disease from transfused lymphocytes
• Androgens, probably only help when hypoplasia not aplasia, eg, stanozolol 2 mg qd; try others if 1st doesn't work