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COVID-19 and Aplastic Anemia: Frequently Asked Questions

(Version 2.0; last updated November 30, 2020)

Input from Drs. Neal Young, with input from Robert Brodsky, Cynthia Dunbar, Judith Marsh, and Regis Peffault de la Tour

Note: Please review ASH's disclaimer regarding the use of the following information.

How do patients with aplastic anemia (AA) fare if they get COVID-19?

To date, there is too little known about the course of people with aplastic anemia who get COVID-19, with only scattered case reports thus far in the literature. For those who are receiving active treatment for AA, immunosuppression may place them at a higher risk for infection and complications but may be beneficial if immunosuppression decreases late hyperinflammatory tissue destruction.

For the new patient with severe AA (SAA), what are realistic treatment options now?

The definitive therapies for SAA remain transplant or immunosuppression with horse anti-thymocyte globulin, cyclosporine, and eltrombopag (IST). In patients with an ANC<200/uL (super severe AA), delaying transplant or IST therapy has known risks which likely outweigh the unknown risks of exposure to the coronavirus during hospitalization or the impact of immunosuppression on the course of COVID-19. However, optimal management may not be practical. Transplant as an option may be restricted in the coming weeks to months. However, centers are still taking patients to transplant who are at high risk of death without transplant intervention. Moving to transplant in patients with SSAA (ANC<200/uL) and an available healthy matched donor may be indicated.

ATG and cyclosporine are not a profoundly immunosuppressive regimen. ATG affects mainly T cells and declines in circulating lymphocytes are relatively brief. While increased viral load for herpesviruses after ATG are frequent, clinical viral disease is not, in contrast to following allogeneic transplantation, with caution needed for extrapolation from herpesviruses to a novel coronavirus. More frequent and more severe viral infections are not expected with cyclosporine alone.

Hospitalization of patients for ATG administration may be problematic given lack of bed availability and risk of exposure to COVID-19 patients. Expectant care, with oral cyclosporine and eltrombopag alone is a possibility, particularly in patients with an ANC>200/uL. NHLBI has such a protocol for patients unable to receive ATG immediately that is approved; starting low dose cyclosporine and full dose eltrombopag as an outpatient supervised by the local physician, with drugs supplied by the NIH, and telemedicine utilized to enroll on protocol and to monitor for toxicity.

Should I modify blood count monitoring and transfusion? Can I treat febrile neutropenia at home? What about drug availability?

Schedules can be modified depending on the stability of levels and established patterns in an individual patient with the goal to keep them out of clinics and hospitals as much as possible. Testing every two weeks may be sufficient, with efforts to combine laboratory testing and red cell transfusion. Platelets are conventionally administered prophylactically to maintain levels >10,000/uL, but in a marrow failure patient without bleeding, expectant transfusion could be acceptable, with platelet transfusions only as needed. G-CSF has not been shown to improve outcomes in SAA, and should not be instituted, nor should corticosteroids other than as required with hATG to prevent serum sickness.

We are still hospitalizing SAA patients with febrile neutropenia for initial management. Earlier discharge to home with continued oral antibiotics may be possible in clinically stable patients.

If ATG treatment is elected, determine first that the hospital pharmacy has an adequate supply. Cyclosporine and eltrombopag should be readily available. Cyclosporine blood concentrations in a patient who has demonstrated stability of levels may be determined less frequently than weekly to avoid laboratory visits.

Patients with PNH, frequent in the setting of AA, who require anti-complement therapy should not have it interrupted because of the risk of serious and irreversible thrombosis. Ravulizumab, requiring administration only every 8 weeks, would be preferable eculizumab to minimize visits to a physician’s office or infusion center.

What is the role of monitoring for COVID-19 in patients who are neutropenic and/or immunosuppressed?

Patients being considered for rapid definitive treatment with transplant or IST should be screened and if positive, therapy delayed until the virus has cleared. While early treatment is preferred, hematologic improvement after immunosuppressive therapy is not immediate, usually only occurring after several weeks to months, so delaying IST for a week or two for viral clearance would not greatly impact on time to improvement in blood counts.

Should AA patients receive a SARS-C0V-2 vaccine when available?

There are case reports of AA developing post-vaccination, and of recovered AA patients relapsing following vaccine administration. In the setting of the COVID-19 pandemic, risk versus benefit would favor vaccine administration, particularly in any patient with additional risks for severe COVID-19 disease (ie age, obesity, other comorbidities associated with increased risk). Those patients within 6 months of ATG/cyclosporine initiation are unlikely to mount an appropriate immune response to a vaccine, and instead could be considered for passive antibody therapies or convalescent plasma if available. Those AA patients remaining on cyclosporine more than 6-12 months post-ATG treatment may respond to a SARS-CoV-2 vaccine, but no data on efficacy in immunosuppressed patients has been made available to date for any of the SARS-CoV-2 vaccines in development. AA patients within 6 months of allogeneic transplantation or at later time points in the setting of active GVHD are unlikely to respond to a SARS-CoV-2 vaccine. Post-transplantation AA patients should follow standard post-transplantation guidelines for vaccine administration. These will be updated regarding SARS-CoV-2 vaccines when they become available, extrapolating from recommendations for other vaccines. More information on considerations surrounding SARS-CoV-2 vaccine administration in immunocompromised hematology patients can be found in this FAQ.

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