International Journal of Laboratory Hematology

ORIGINAL ARTICLE

Significance of serum ferritin level in hemophagocytic lymphohistiocytosis diagnosis

Xiao-Xi Zhao

orcid.org/0000-0003-3657-6661

Beijing Key Laboratory of Pediatric Hematology Oncology, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

National Key Discipline of Pediatrics (Capital Medical University), Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Hematology Oncology Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

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Hong-Yun Lian,

Hong-Yun Lian

Beijing Key Laboratory of Pediatric Hematology Oncology, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

National Key Discipline of Pediatrics (Capital Medical University), Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Hematology Oncology Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

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Li Zhang,

Li Zhang

Beijing Key Laboratory of Pediatric Hematology Oncology, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

National Key Discipline of Pediatrics (Capital Medical University), Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Hematology Oncology Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

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Hong-Hao Ma,

Hong-Hao Ma

Beijing Key Laboratory of Pediatric Hematology Oncology, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

National Key Discipline of Pediatrics (Capital Medical University), Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Hematology Oncology Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

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Dong Wang,

Dong Wang

Beijing Key Laboratory of Pediatric Hematology Oncology, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

National Key Discipline of Pediatrics (Capital Medical University), Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Hematology Oncology Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

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Yun-Ze Zhao,

Yun-Ze Zhao

Beijing Key Laboratory of Pediatric Hematology Oncology, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

National Key Discipline of Pediatrics (Capital Medical University), Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Hematology Oncology Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

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Zeng-Wu Liu,

Zeng-Wu Liu

National Key Discipline of Pediatrics (Capital Medical University), Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

Department of medical laboratory, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

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Tian-You Wang,

Tian-You Wang

Beijing Key Laboratory of Pediatric Hematology Oncology, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

National Key Discipline of Pediatrics (Capital Medical University), Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Hematology Oncology Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

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Rui Zhang,

Corresponding Author

Rui Zhang

[email protected]

Beijing Key Laboratory of Pediatric Hematology Oncology, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

National Key Discipline of Pediatrics (Capital Medical University), Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Hematology Oncology Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Correspondence

Rui Zhang, Beijing Key Laboratory of Pediatric Hematology Oncology, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing 100045, China.

Email: [email protected]

and

Zhi-Gang Li, Laboratory of Hematologic diseases, Beijing Pediatric Research Institute, National Center for Children’s Health, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China.

Email: [email protected]

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Zhi-Gang Li,

Corresponding Author

Zhi-Gang Li

[email protected]

orcid.org/0000-0001-5334-9706

Laboratory of Hematologic diseases, National Center for Children’s Health, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China

Correspondence

Rui Zhang, Beijing Key Laboratory of Pediatric Hematology Oncology, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing 100045, China.

Email: [email protected]

and

Email: [email protected]

Search for more papers by this author

Xiao-Xi Zhao,

Xiao-Xi Zhao

orcid.org/0000-0003-3657-6661

Beijing Key Laboratory of Pediatric Hematology Oncology, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

National Key Discipline of Pediatrics (Capital Medical University), Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Hematology Oncology Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Search for more papers by this author

Hong-Yun Lian,

Hong-Yun Lian

Beijing Key Laboratory of Pediatric Hematology Oncology, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

National Key Discipline of Pediatrics (Capital Medical University), Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Hematology Oncology Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Search for more papers by this author

Li Zhang,

Li Zhang

Beijing Key Laboratory of Pediatric Hematology Oncology, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

National Key Discipline of Pediatrics (Capital Medical University), Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Hematology Oncology Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Search for more papers by this author

Hong-Hao Ma,

Hong-Hao Ma

Beijing Key Laboratory of Pediatric Hematology Oncology, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

National Key Discipline of Pediatrics (Capital Medical University), Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Hematology Oncology Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Search for more papers by this author

Dong Wang,

Dong Wang

Beijing Key Laboratory of Pediatric Hematology Oncology, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

National Key Discipline of Pediatrics (Capital Medical University), Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Hematology Oncology Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Search for more papers by this author

Yun-Ze Zhao,

Yun-Ze Zhao

Beijing Key Laboratory of Pediatric Hematology Oncology, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

National Key Discipline of Pediatrics (Capital Medical University), Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Hematology Oncology Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Search for more papers by this author

Zeng-Wu Liu,

Zeng-Wu Liu

National Key Discipline of Pediatrics (Capital Medical University), Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

Department of medical laboratory, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Search for more papers by this author

Tian-You Wang,

Tian-You Wang

Beijing Key Laboratory of Pediatric Hematology Oncology, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

National Key Discipline of Pediatrics (Capital Medical University), Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Hematology Oncology Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Search for more papers by this author

Rui Zhang,

Corresponding Author

Rui Zhang

[email protected]

Beijing Key Laboratory of Pediatric Hematology Oncology, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

National Key Discipline of Pediatrics (Capital Medical University), Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Hematology Oncology Center, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing, China

Correspondence

Rui Zhang, Beijing Key Laboratory of Pediatric Hematology Oncology, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing 100045, China.

Email: [email protected]

and

Email: [email protected]

Search for more papers by this author

Zhi-Gang Li,

Corresponding Author

Zhi-Gang Li

[email protected]

orcid.org/0000-0001-5334-9706

Laboratory of Hematologic diseases, National Center for Children’s Health, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China

Correspondence

Rui Zhang, Beijing Key Laboratory of Pediatric Hematology Oncology, National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing 100045, China.

Email: [email protected]

and

Email: [email protected]

Search for more papers by this author

First published: 25 April 2019

https://doi.org/10.1111/ijlh.13032

Citations: 7

Funding information

This work was supported by National Science and Technology Key Projects (No. 2017ZX09304029004), Beijing Municipal Science and Technology Commission (No. Z171100001017050), National Natural Science Foundation of China (No. 81700186), Scientific Research Common Program of Beijing Municipal Commission of Education (No. KM201710025019), Pediatric Project of Ai You Foundation (No. AYEK201802), Talent Training Project- Fostering Fund of National Natural Science Foundation of Beijing Children's Hospital, Capital Medical University (No. GPY201713), the Special Fund of The Pediatric Medical Coordinated Development Center of Beijing Municipal Administration of hospitals (No. XTZD20180202), Beijing Municipal Administration of Hospitals' Youth Programme (No. QML20181205).

Data Availability Statement: All data generated or analyzed during this study are included in this published article.

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Abstract

Introduction

The threshold of serum ferritin (SF) level listed in diagnostic guidelines for hemophagocytic lymphohistiocytosis (HLH) of HLH-2004 has a low specificity. The goal of this research was to evaluate the role of admission SF in HLH diagnostic procedure and to find an appropriate threshold for a HLH suspected cohort with fever.

Methods

All patients admitted to Beijing Children's Hospital during the period of September 1, 2015 and July 31, 2016 with fever and SF tested at admission were included in this study. The significance of SF in HLH diagnosis and its relationships with HLH-relevant clinical characteristics were studied.

Results

Among 357 patients, 39 HLH cases were diagnosed (24 EBV-related HLH, 13 unknown etiologies triggered HLH, and two familial HLH).

The best cutoff value of admission SF was 934 ng/mL, with sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) being 87.2%, 88.4%, 47.9%, and 98.3%, respectively. Compared to 500 ng/mL, specificity and PPV of the new SF standard in HLH diagnose increased by 11.7% and 14.0%, which indicated improvements in diagnostic ability of “non-HLH” and in veracity of “HLH” identification. Among four HLH patients whose admission SF was between 500 ng/mL and 934 ng/mL, HLH diagnosis was guaranteed by other laboratory results in two patients; however, possible misdiagnosis was made in the rest two patients.

Conclusion

Elevated cutoff value of admission SF level seems to be more appropriate for distinguishing HLH in patients with fever. The exact cutoff value of SF level at diagnosis needs to be determined.

CONFLICT OF INTEREST

The authors have no conflicts of interest to disclose.

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Volume41, Issue4

August 2019

Pages 503-508

Significance of serum ferritin level in hemophagocytic lymphohistiocytosis diagnosis

Abstract

Introduction

Methods

Results

Conclusion

CONFLICT OF INTEREST

REFERENCES

Citing Literature

References

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Significance of serum ferritin level in hemophagocytic lymphohistiocytosis diagnosis

Abstract

Introduction

Methods

Results

Conclusion

CONFLICT OF INTEREST

REFERENCES

Citing Literature

References

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