Sickle cell anemia (SCA) is an inherited disorder of hemoglobin synthesis that is characterized by life-long severe hemolytic anemia, attacks of pain crisis, and chronic organ system damage. A third of the hemolysis in SCA is intravascular and the resulting urinary losses of iron may lead to iron deficiency. There is no evidence of iron overload in SCA and iron deficiency may be more common than suspected, especially in men. Absence of bone marrow iron remains a gold standard for the diagnosis of iron deficiency in these patients. Although low serum ferritin is highly specific for the diagnosis of iron deficiency, its sensitivity is quite low in SCA because of non-specific elevation due to increased red cell turnover. The kinetics of sickling is strongly concentration dependent such that small decreases in the mean corpuscular deoxyhemoglobin-S concentration (MCHC-S) cause a substantial delay in sickle hemoglobin polymerization. Prolongation of the 'delay time of gelation' in excess of the capillary transit time may allow the erythrocyte to traverse the capillary bed to escape to the arterial side before there is rheologic impairment of the erythrocyte from polymerization of sickle hemoglobin. Overt iron deficiency lowers the MCHC-S and thereby decreases the sickling tendency and the severity of hemolysis. The clinical improvement in SCA following the induction of iron deficient erythropoiesis by repeated phlebotomies or by erythrocytapheresis has been reported. Prospective controlled studies are needed to evaluate further, the therapeutic strategy of inducing controlled iron-deficient erythropoiesis in selected patients witb SCA. Am.

We report the cases of six patients with AIDS in whom reactive hemophagocytic syndrome (RHPS) secondary to disseminated histoplasmosis was diagnosed. RHPS was diagnosed by established criteria, including fever (duration of > or = 7 days, with peak temperatures of > 38.5 degrees C), unexplained thrombocytopenia with anemia and/or neutropenia, and bone marrow biopsy findings of hemophagocytic histiocytosis. Disseminated Histoplasma capsulatum infection was diagnosed on the basis of the results of cultures of the bone marrow sample. The serum lactate dehydrogenase (LDH) level was elevated (> 1,000 IU/L) in all patients, and five of six patients had hyperferritinemia (range of ferritin level, 15,848-425,984 ng/mL). Five patients had features resembling severe sepsis with multiorgan dysfunction. Three patients recovered, and the findings of RHPS resolved following therapy with amphotericin B. In patients with AIDS, the combination of fever, cytopenia, elevated serum LDH level (> 1,000 IU/L), and/or hyperferritinemia (ferritin level of > 10,000 ng/mL) is a clue to the diagnosis of RHPS and disseminated histoplasmosis; bone marrow biopsy is valuable in establishing the diagnosis.

The optimal management of chronic pure red cell aplasia caused by parvovirus B19 (B19-PRCA) in patients with AIDS is unclear. Our purpose was to determine the effects of intravenous immunoglobulin (IVIg) in the treatment of B19-PRCA in patients with AIDS. The patients were eight adults with AIDS admitted during the period 1993-1997. A diagnosis of B19-PRCA was made if all the following criteria were met: 1. Bone marrow biopsy finding of pure red cell aplasia; 2. Detection of parvovirus B19 DNA in serum; and 3. No alternative explanation for PRCA. Initial (induction) therapy was with IVIg 1 g/kg daily for 1-2 days. Relapses were treated with IVIg 1 g/kg for 2 days. Maintenance therapy with IVIg 0.4-1.0 g/kg q 4 weeks was given to those patients who developed a second or subsequent relapse. The patients were followed for a mean of 27 months (range 8-38 months). All patients responded to initial therapy with IVIg. Six patients with CD4 counts < 80 cells/mm3 relapsed. The response was short lived in two patients with a CD4 count < 80 cells/mm3 who were given a single infusion of IVIg 1 g/kg as initial therapy. Four patients were given regular maintenance IVIg therapy following a second or subsequent relapse and remain in remission. Two patients whose CD4 counts were > 300 cells/mm3 remain in continuous unmaintained remission from B19-PRCA for over 8 and 11 months, respectively, following induction therapy with IVIg. AIDS patients with B19-PRCA respond well to therapy with IVIg 2 g/kg given over 2 days. Most patients with CD4 counts of < or = 80 cells/mm3 suffer relapse within six months necessitating retreatment with IVIg; maintenance therapy with IVIg 0.4 g/kg q 4 weeks is effective in preventing relapse of B19-PRCA, and may be cost effective. Routine maintenance therapy is probably not indicated in patients with CD4 counts over 300 cells/mm3. Prospective studies are needed to confirm these findings.

Persistent infection with parvovirus B19 (B19) is an important treatable cause of anemia in HIV-infected patients. B19 has a tropism for erythroid progenitors and causes pure red cell aplasia (PRCA). The failure to produce neutralizing antibodies to the virus following B19 infection in immunodeficient persons may result in persistent viremia and chronic PRCA (B19-PRCA). The seroprevalence rates for B19 in unselected persons with HIV infection are high, similar to those seen in the general population. Reports of B19-related anemia in HIV infected patients, however, are infrequent. A partial explanation may be that B19-PRCA is predominantly a complication associated with advanced immunodeficiency. The condition is probably underdiagnosed as well. The finding of an unexplained normocytic anemia with absent reticulocytes, in an afebrile HIV-infected patient without renal dysfunction suggests a diagnosis of B19-PRCA. The diagnosis is established when the following criteria are met: (1) bone marrow biopsy showing PRCA, (2) serum or bone marrow positivity for B19 DNA by PCR or dot-blot hybridization, and (C) no alternate explanation for the PRCA. Serological methods are unreliable for the diagnosis because these patients often lack IgM and IgG antibodies to B19. Nearly all patients with B19-PRCA respond to treatment with intravenous immunoglobulin (IVIg) with a rise in the hemoglobin to levels appropriate for the clinical condition of the patient. An alternative explanation for the anemia must be sought in patients not responding to IVIg. Most patients with CD4+ T-lymphocyte counts of < or = 100 cells/mm3 relapse to anemia, usually within 6 months of IVIg therapy. Such patients must be retreated with IVIg 2 g/kg given over 2 to 5 days. The routine use of maintenance IVIg 0.4 g/kg q 4wk may be considered in these patients to prevent relapse.