While the workup and treatment plan are being established, attention should be directed at supportive care for prevention of complications. The most common complications leading to death in patients with significant pancytopenia and neutropenia are opportunistic infections and hemorrhagic complications.2
Transfusion support is critical to avoid symptomatic anemia and hemorrhagic complications related to thrombocytopenia, which typically occur with platelet counts lower than 10,000 cells/µL. However, transfusion carries the risk of alloimmunization (which may persist for years following transfusion) and transfusion-related graft versus host disease (trGVHD), and thus use of transfusion should be minimized when possible.56,57 All blood products given to patients with aplastic anemia should be irradiated and leukoreduced to reduce the risk of both alloimmunization and trGVHD. Guidelines from the British Society for Haematology recommend routine screening for Rh and Kell antibodies to reduce the risk of alloimmunization.58 Infectious complications remain a common cause of morbidity and mortality in patients with aplastic anemia who have prolonged neutropenia (defined as an ANC < 500 cells/µL).59-62 Therefore, patients should receive broad-spectrum antibiotics with antipseudomonal coverage. In a study evaluating the role of granulocyte-colony stimulating factor (G-CSF) in patients with SAA receiving immunosuppressive therapy, 55% of all patient deaths were secondary to infection.63 There was no OS benefit seen in patients who received G-CSF, though a significantly lower rate of infection was observed in the G-CSF arm compared to those not receiving G-CSF (56% versus 81%, P = 0.006). This difference was largely driven by a decrease in infectious episodes in patients with VSAA treated with G-CSF as compared to those who did not receive this therapy (22% versus 48%, P = 0.014).63
Angio-invasive pulmonary aspergillosis and Zygomycetes (eg, Rhizopus, Mucor species) remain major causes of mortality related to opportunistic mycotic infections in patients with aplastic anemia.18 The infectious risk is directly related to the duration and severity of neutropenia, with one study demonstrating a significant increase in risk in AML patients with neutropenia lasting longer than 3 weeks.64 Invasive fungal infections carry a high mortality in patients with severe neutropenia, though due to earlier recognition and empiric antifungal therapy with extended-spectrum azoles, overall mortality secondary to invasive fungal infections is declining.62,65
While neutropenia related to cytotoxic chemotherapy is commonly associated with gram-negative bacteria due to disruption of mucosal barriers, patients with aplastic anemia have an increased incidence of gram-positive bacteremia with staphylococcal species compared to other neutropenic populations.61,62 This appears to be changing with time. Valdez et al demonstrated a decrease in prevalence of coagulase-negative staphylococcal infections, increased prevalence of gram-positive bacilli bacteremia, and no change in prevalence of gram-negative bacteremia in patients with aplastic anemia treated between 1989 and 2008.65 Gram-negative bacteremia caused by Stenotrophomonas maltophila, Escherichia coli, Klebsiella pneumoniae, Citrobacter, and Proteus has also been reported.62 Despite a lack of clinical trials investigating the role of antifungal and antibacterial prophylaxis for patients with aplastic anemia, most centers initiate antifungal prophylaxis in patients with SAA or VSAA with an anti-mold agent such as voriconazole or posaconazole (which has the additional benefit compared to voriconazole of covering Mucor species).60,66 This is especially true for patients who have received ATG or undergone HSCT. For antimicrobial prophylaxis, a fluoroquinolone antibiotic with a spectrum of activity against Pseudomonas should be considered for patients with an ANC < 500 cells/µL.60 Acyclovir or valacyclovir prophylaxis is recommended for varicella-zoster virus and herpes simplex virus. Cytomegalovirus reactivation is minimal in patients with aplastic anemia, unless multiple courses of ATG are used.
Iron overload is another complication the provider must be aware of in the setting of increased transfusions in aplastic anemia patients. Lee and colleagues showed that iron chelation therapy using deferasirox is effective at reducing serum ferritin levels in patients with aplastic anemia (median ferritin level of 3254 ng/mL prior to therapy, 1854 ng/mL following), and is associated with no serious adverse events (most common adverse events included nausea, diarrhea, vomiting, and rash).67 Approximately 25% of patients in this trial had an increase in creatinine, with patients taking concomitant cyclosporine affected to a greater degree than those on chelation therapy alone. For patients following HSCT or with improved hematopoiesis following immunosuppressive therapy, phlebotomy can be used to treat iron overload in lieu of chelation therapy.58
