What is the workup for nucleated red blood cells (NRBCs)?

From the Guidelines

Nucleated red blood cells (NRBCs) in peripheral blood require prompt evaluation with a complete blood count (CBC) with differential, peripheral blood smear, and reticulocyte count, as indicated by the American Society of Clinical Oncology (ASCO) guideline 1. The presence of NRBCs in adults typically indicates significant underlying pathology, such as severe bone marrow stress or disruption of the blood-bone marrow barrier.

• Key initial tests include:
  • CBC with differential to confirm the presence and quantify NRBCs
  • Peripheral blood smear review to assess for other abnormalities
  • Reticulocyte count to evaluate bone marrow response
• Additional testing may be necessary based on clinical presentation and initial findings, such as:
  • Comprehensive metabolic panel
  • Lactate dehydrogenase and haptoglobin to assess for hemolysis
  • Bone marrow examination if myelophthisic processes are suspected
  • Imaging studies like chest X-ray or CT scan to evaluate for potential malignancy or extramedullary hematopoiesis The ASCO guideline 1 provides a framework for evaluating cytopenias, including anemia, neutropenia, and thrombocytopenia, which may be associated with NRBCs in peripheral blood.
• The guideline recommends grading the severity of cytopenias and providing supportive care, corticosteroids, or critical care support as needed, with consideration of growth factor support for neutrophil recovery in severe cases 1.

From the Research

Nucleated Red Blood Cells Work Up

• Nucleated red blood cells (NRBCs) are present in the peripheral blood of several hematological and non-hematological conditions, usually associated with bad prognosis 2.
• The presence of NRBCs on an adult peripheral blood smear indicates that there is an extremely high demand for the bone marrow to manufacture RBCs and that immature red blood cells are being released into the bloodstream 3.
• NRBCs can be used to predict changes in clinical condition and mortality in critically ill patients, including those with sepsis, trauma, ARDS, acute pancreatitis, or severe cardiovascular disease 4.

Clinical Significance of NRBCs

• The incidence of NRBCs in ICU-admitted patients was 62.5% (500/800), and the overall mortality of NRBC-positive patients was 30% (150/500), which was significantly higher than that of NRBC-negative patients (14%; 44/300) 3.
• A cutoff of NRBCs of 2.50 showed a high risk of mortality with a sensitivity of 91% 3.
• Elevated levels of NRBCs in infants with blood group incompatibilities could alert clinicians about the severity of jaundice and should increase awareness in terms of hemolysis 5.

Reference Intervals for NRBCs

• The original launch of the Sysmex XN analyzer verified the previously used nRBC reference interval of 0.00 to 0.01 × 106/μL, but this interval may not be clinically relevant 6.
• A prospective analysis of 405 300 specimens from nonhospitalized individuals found that the upper limit of the reference interval for nRBCs could be updated from 0.01 × 106/μL to 0.10 × 106/μL 6.

Diagnostic Value of NRBCs

• NRBCs can be used as a biomarker in the diagnosis and clinical outcome prognosis of preterm infants or severely ill adult patients 4.
• An NRBC count is a cost-effective laboratory test that can be used in the diagnosis of hematological diseases/disorders relating to erythropoiesis, anemia, or hemolysis 4.
• The presence of NRBCs may predict mortality in critically ill ICU-admitted patients, and their presence in the blood may be regarded as a marker of severity suggesting a high risk of ICU death 3.