From the Guidelines
Viral infections such as parvovirus B19, cytomegalovirus (CMV), and Epstein-Barr virus (EBV) are known to cause nucleated red blood cells (RBCs) in peripheral blood, and their diagnosis should be considered when nucleated RBCs are detected 1.
Causes of Nucleated RBCs
The presence of nucleated RBCs in peripheral blood can be caused by various viral infections, including:
- Parvovirus B19, which directly infects erythroid progenitor cells, causing temporary arrest of red blood cell production and resulting in reticulocytopenia with nucleated RBCs appearing during recovery 1
- CMV and EBV, which can cause hemolytic anemia with compensatory erythropoiesis, leading to the release of immature red blood cells into circulation 1
- Other viruses, such as HIV and hepatitis viruses, which may lead to bone marrow dysregulation and the release of nucleated RBCs into peripheral blood
Diagnostic Approach
When nucleated RBCs are detected, a diagnostic work-up should be performed to identify the underlying cause, including:
- Viral studies, such as CMV, HHV6, EBV, and parvovirus 1
- CBC, smear, and reticulocyte count to evaluate the severity of anemia and reticulocytopenia
- Bone marrow biopsy and aspirate analysis to identify marrow hypo/aplasia or other abnormalities
- Peripheral blood analysis, including neutrophil count and proportion of GPI-negative cells by flow for PNH
Clinical Implications
The presence of nucleated RBCs in peripheral blood represents a stress response as the bone marrow attempts to compensate for anemia by accelerating red blood cell production, releasing immature forms before complete maturation and nuclear extrusion. Early diagnosis and treatment of the underlying viral infection are crucial to prevent complications and improve patient outcomes 1.
From the Research
Viral Infections Causing Nucleated RBC
- Parvovirus B19 is a viral infection that can cause nucleated red blood cells (RBC) in immunocompromised hosts 2.
- The infection can lead to pure red-cell aplasia, resulting in chronic or recurrent anemia with reticulocytopenia 2.
- Diagnosis of parvovirus B19 infection is established by detection of B19 DNA in serum in the absence of IgG antibody to B19 2.
- Treatment options for parvovirus B19 infection include red-cell transfusion, adjustment in medications to restore or improve the patient's immune system, and administration of intravenous immunoglobulin (IVIG) 2, 3, 4.
Effects of Parvovirus B19 Infection
- Parvovirus B19 infection can cause severe anemia in fetuses and neonates, particularly in cases of hydrops fetalis 3.
- The infection can also lead to pancytopenia and pure red blood cell aplasia in patients with underlying hematologic malignancy or hemolytic diseases 5.
- Patients with sickle-cell disease and thalassemia are at high risk of developing life-threatening anemia due to parvovirus B19 infection 6.
Treatment with Intravenous Immunoglobulin (IVIG)
- IVIG therapy has been shown to be effective in treating parvovirus B19 infection and restoring erythropoiesis in immunocompromised patients 3, 4.
- IVIG treatment can correct hemoglobin levels and reduce viral loads in patients with pure red cell aplasia related to parvovirus B19 infection 4.
- However, IVIG treatment can also cause side effects such as acute reversible renal failure and pulmonary edema 4.