Fluorescence of neutrophil granulocytes as a biomarker for clozapine use

Man, Wai Hong; Berg, Maarten ten; Wilting, Ingeborg; Huisman, Albert; Cahn, Wiepke; Douma, Jan Willem; Breeijen, Hanneke den; Heerdink, Eibert R.; Egberts, Toine C. G.; Solinge, Wouter W. van

doi:10.1016/j.euroneuro.2013.08.005

Cited by 6 publications

(7 citation statements)

References 27 publications

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“…Previously, we performed a cross ‐ sectional observational study reporting a significant association between clozapine use and FL3‐fluorescence . FL3‐fluorescence was elevated in clozapine users and found to increase with increasing clozapine dose.…”

Section: Discussionmentioning

confidence: 99%

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Development of a nomogram for the estimation of long‐term adherence to clozapine therapy using neutrophil fluorescence

Man

Pérez-Pitarch

Wilting

et al. 2018

Brit J Clinical Pharma

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Section: Discussionmentioning

confidence: 99%

“…Elevated FL3‐fluorescence has been serendipitously observed in patients using clozapine . In a previous study, our group assessed the association between clozapine use and FL3‐fluorescence . FL3‐fluorescence was significantly higher in clozapine users than in nonusers.…”

Section: Introductionmentioning

confidence: 99%

Development of a nomogram for the estimation of long‐term adherence to clozapine therapy using neutrophil fluorescence

Man

Pérez-Pitarch

Wilting

et al. 2018

Brit J Clinical Pharma

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“…The structure and content of UPOD have been described in more detail elsewhere ( 16 ). The blood cell analyzer is equipped with an integrated 488-nm blue diode laser and uses spectrophotometry, electrical impedance, laser light scattering (multi angle polarized scatter separation), and 3-color fluorescent technologies to measure morphological parameters of leukocytes, red blood cells, and platelets for classification and enumeration ( 17 , 18 ). Details on the blood cell parameters measured by the Cell-Dyn Sapphire analyzer is provided in Supplementary Table S1 .…”

Section: Methodsmentioning

confidence: 99%

Central Multifocal Choroiditis: Platelet Granularity as a Potential Marker for Treatment With Steroid-Sparing Immunomodulatory Therapy

et al. 2021

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PurposeWe aimed to evaluate the blood cell composition in patients with central multifocal choroiditis (cMFC), a rare form of posterior uveitis predominantly affecting young myopic women.MethodsIn this retrospective observational case-control study, a 104-parameter automated hematocytometry was conducted by the Cell-Dyn Sapphire hematology analyzer for 122 cases and 364 age- and sex-matched controls. Cox proportional regression analysis was used to assess the relation between the blood cell composition and the time between disease onset (first visit) and the start of systemic corticosteroid-sparing immunomodulatory therapy (IMT).ResultsAt a false discovery rate of 5% (Padj), we identified a decrease of blood monocytes in cases with cMFC, which could be attributed to disease activity. Cox proportional hazard analysis including age and sex revealed that increased platelet granularity (measured by mean intermediate angle scatter) was an independent risk factor for treatment with IMT (hazard ratio = 2.3 [95% confidence interval = 1.28 - 4.14], Padj = 0.049). The time between the first presentation and the start of IMT was 0.3 years in the group with an increased platelet granularity and 3.4 years in the group without increased platelet granularity.ConclusionsPatients with cMFC demonstrated a decrease in blood monocytes. Moreover, platelet granularity could potentially be used as a marker for treatment with IMT.

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“…These patients were recruited from the departments of general surgery, trauma surgery, vascular surgery, surgical oncology, the surgical intermediate care unit and intensive care unit (ICU) KG. Exclusion criteria were present or recent (< 3 months) use of immunosuppressive or cytotoxic medication, a known HIV-positive status or other immunosuppressive diseases, and the use of clozapine, since this is associated with an increased FL3 signal [ 35 ]. Control blood samples were provided by anonymous, sex and age matched healthy volunteers.…”

Section: Methodsmentioning

confidence: 99%

Fragile neutrophils in surgical patients: A phenomenon associated with critical illness

et al. 2020

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Leukocyte viability (determined by e.g. propidium iodide [PI] staining) is automatically measured by hematology analyzers to check for delayed bench time. Incidental findings in fresh blood samples revealed the existence of leukocytes with decreased viability in critically ill surgical patients. Not much is known about these cells and their functional and/or clinical implications. Therefore, we investigated the incidence of decreased leukocyte viability, the implications for leukocyte functioning and its relation with clinical outcomes. An automated alarm was set in a routine hematology analyzer (Cell-Dyn Sapphire) for the presence of non-viable leukocytes characterized by increased fluorescence in the PI-channel (FL3:630 ±30nm). Patients with non-viable leukocytes were prospectively included and blood samples were drawn to investigate leukocyte viability in detail and to investigate leukocyte functioning (phagocytosis and responsiveness to a bacterial stimulus). Then, a retrospective analysis was conducted to investigate the incidence of fragile neutrophils in the circulation and clinical outcomes of surgical patients with fragile neutrophils hospitalized between 2013-2017. A high FL3 signal was either caused by 1) neutrophil autofluorescence which was considered false positive, or by 2) actual non-viable PI-positive neutrophils in the blood sample. These two causes could be distinguished using automatically generated data from the hematology analyzer. The non-viable (PI-positive) neutrophils proved to be viable (PInegative) in non-lysed blood samples, and were therefore referred to as 'fragile neutrophils'. Overall leukocyte functioning was not impaired in patients with fragile neutrophils. Of the 11 872 retrospectively included surgical patients, 75 (0.63%) were identified to have fragile neutrophils during hospitalization. Of all patients with fragile neutrophils, 75.7% developed an infection, 70.3% were admitted to the ICU and 31.3% died during hospitalization. In conclusion, fragile neutrophils occur in the circulation of critically ill surgical patients. These cells can be automatically detected during routine blood analyses and are an indicator of critical illness.

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Fluorescence of neutrophil granulocytes as a biomarker for clozapine use

Cited by 6 publications

References 27 publications

Development of a nomogram for the estimation of long‐term adherence to clozapine therapy using neutrophil fluorescence

Development of a nomogram for the estimation of long‐term adherence to clozapine therapy using neutrophil fluorescence

Central Multifocal Choroiditis: Platelet Granularity as a Potential Marker for Treatment With Steroid-Sparing Immunomodulatory Therapy

Fragile neutrophils in surgical patients: A phenomenon associated with critical illness

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