What are the implications of elevated immature granulocytes (IGs)?

From the Guidelines

Elevated immature granulocytes are a concerning finding that requires prompt evaluation and treatment of the underlying cause, which may be a sign of a serious infection, inflammation, or bone marrow disorder, as indicated by the presence of 10%–19% blast cells in the blood or bone marrow, according to the WHO criteria for accelerated phase chronic myeloid leukemia 1. The presence of elevated immature granulocytes in a blood test is a significant finding that warrants further investigation. This occurs when the bone marrow releases immature cells into the peripheral blood in response to increased demand, which can be due to various causes such as:

• Bacterial infections, particularly severe ones like sepsis
• Inflammation
• Tissue damage
• Bone marrow disorders, such as chronic myeloid leukemia (CML)
• Certain medications According to the European LeukemiaNet (ELN) recommendations 1, the presence of < 15% blasts in blood and bone marrow is associated with chronic phase (CP) disease, while 10%–19% blast cells are indicative of accelerated phase (AP) CML. Key points to consider when evaluating elevated immature granulocytes include:
• The clinical context, such as the presence of symptoms like fever, fatigue, or pain
• The results of additional tests, such as blood cultures, imaging studies, or bone marrow examination
• The need for prompt treatment of the underlying cause, which may involve antibiotics, targeted therapies, or other interventions It is essential to consult with a healthcare provider promptly if elevated immature granulocytes are detected, as this finding can be a sign of a serious underlying condition that requires prompt attention and treatment 1.

From the Research

Elevated Immature Granulocytes

• Elevated immature granulocytes have been studied as a potential marker for infection and sepsis in various research papers 2, 3, 4, 5, 6
• A study published in the American Journal of Clinical Pathology in 2003 found that the percentage of immature granulocytes was significantly higher in infected patients than in non-infected patients, and that a percentage of immature granulocytes of more than 3 was a very specific predictor of sepsis 2
• Another study published in BMC Immunology in 2013 found that the immature granulocyte count was a useful early diagnostic marker of sepsis, with a sensitivity of 89.2% and a specificity of 76.4% within the first 48 hours after the onset of systemic inflammatory response syndrome (SIRS) 3
• A study published in Clinical Biochemistry in 2017 found that lactate had the highest odds ratio for the prediction of sepsis, while immature granulocyte count had an odds ratio of less than 1.00, indicating limited utility in the prediction of sepsis 4
• However, a study published in the Indian Journal of Critical Care Medicine in 2022 found that automated immature granulocyte count and immature granulocyte percentage were the earliest biomarkers to have a significant discriminating value for the prediction of sepsis, with an area under the curve of 0.81 and 0.82, respectively, as early as 24 hours before clinical sepsis is diagnosed by Sepsis-3 criteria 5
• A study published in the International Journal of Laboratory Hematology in 2019 found that an immature granulocyte percentage cutoff point of 2.0% was able to exclude sepsis based on clinical diagnosis with a specificity of 90.9% and a sensitivity of 38.5% 6

Diagnostic Value

• The diagnostic value of elevated immature granulocytes for sepsis has been evaluated in various studies, with some finding it to be a useful marker 2, 3, 5, 6 and others finding it to have limited utility 4
• The sensitivity and specificity of elevated immature granulocytes for sepsis vary depending on the study, with some finding a sensitivity of 89.2% and a specificity of 76.4% 3 and others finding a sensitivity of 38.5% and a specificity of 90.9% 6

Comparison to Other Markers

• Elevated immature granulocytes have been compared to other markers for sepsis, such as lactate, white blood cell count, neutrophil count, procalcitonin, and C-reactive protein 3, 4, 5
• Some studies have found that elevated immature granulocytes are a better predictor of sepsis than other markers 2, 3, 5, while others have found that lactate is a better predictor 4