PMID- 38199058
OWN - NLM
STAT- MEDLINE
DCOM- 20240129
LR  - 20240206
IS  - 1873-376X (Electronic)
IS  - 1570-0232 (Linking)
VI  - 1233
DP  - 2024 Feb 1
TI  - Characterization of complexes of PF4 and heparins by size-exclusion 
      chromatography coupled with multi-angle light scattering detector.
PG  - 124004
LID - S1570-0232(24)00012-6 [pii]
LID - 10.1016/j.jchromb.2024.124004 [doi]
AB  - Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin 
      therapy. Antibodies binding to complexes of platelet factor 4 (PF4) and heparin 
      is the trigger of HIT. A method using size exclusion chromatography with 
      multi-angle laser light scattering detector (SEC-MALS) was developed in this 
      work. The soluble ultra-large complex (ULC) was separated from the small complex 
      (SC) and their molecular weights (MWs) were firstly measured. The complexes of 
      PF4 and three heparins with different MW, including unfractionated heparin (UFH), 
      dalteparin (Daltep) and enoxaparin (Eno) were characterized using this method. 
      The contents and the sizes of ULC increased gradually when heparins were added to 
      PF4 to certain amounts. While, they reduced after more heparins were added. It is 
      the first time to measure the MWs of the biggest ULC of PF4-heparins as millions 
      of Dalton. at the proper ratios of PF4 to heparin (PHR). Meanwhile, those 
      mixtures at those certain PHRs induced the higher expression of CD83 and CD14 
      markers on dendritic cells (DCs) suggesting that they had stronger immunogenicity 
      and is critical for HIT.
CI  - Copyright (c) 2024 Elsevier B.V. All rights reserved.
FAU - Zhao, Jingwen
AU  - Zhao J
AD  - Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical 
      Sciences, Soochow University, Suzhou, Jiangsu 215021, China.
FAU - Xue, Yiting
AU  - Xue Y
AD  - Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical 
      Sciences, Soochow University, Suzhou, Jiangsu 215021, China; School of Biology 
      and Food Engineering, Changshu Institute of Technology, Suzhou, Jiangsu 215500, 
      China.
FAU - Tian, He
AU  - Tian H
AD  - Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical 
      Sciences, Soochow University, Suzhou, Jiangsu 215021, China.
FAU - Qiu, Piaopiao
AU  - Qiu P
AD  - Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical 
      Sciences, Soochow University, Suzhou, Jiangsu 215021, China.
FAU - Ouyang, Yilan
AU  - Ouyang Y
AD  - Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical 
      Sciences, Soochow University, Suzhou, Jiangsu 215021, China.
FAU - Liu, Haiying
AU  - Liu H
AD  - Haihe Biopharma Co., Ltd., Shanghai, Pudong 201203, China. Electronic address: 
      haiying.liu@haihepharma.com.
FAU - Yi, Lin
AU  - Yi L
AD  - Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical 
      Sciences, Soochow University, Suzhou, Jiangsu 215021, China. Electronic address: 
      yilin@suda.edu.cn.
FAU - Zhang, Zhenqing
AU  - Zhang Z
AD  - Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical 
      Sciences, Soochow University, Suzhou, Jiangsu 215021, China. Electronic address: 
      z_zhang@suda.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20240106
PL  - Netherlands
TA  - J Chromatogr B Analyt Technol Biomed Life Sci
JT  - Journal of chromatography. B, Analytical technologies in the biomedical and life 
      sciences
JID - 101139554
RN  - 9005-49-6 (Heparin)
RN  - 37270-94-3 (Platelet Factor 4)
RN  - 0 (Anticoagulants)
RN  - 0 (Immunologic Factors)
SB  - IM
MH  - Humans
MH  - *Heparin/pharmacology
MH  - Platelet Factor 4/chemistry/metabolism
MH  - Anticoagulants/chemistry
MH  - *Thrombocytopenia/chemically induced
MH  - Immunologic Factors
MH  - Chromatography, Gel
OTO - NOTNLM
OT  - Heparin
OT  - Heparin induced thrombocytopenia (HIT)
OT  - Multi-angle light scattering detector (MALS)
OT  - Platelet factor 4 (PF4)
OT  - Size-exclusion chromatography (SEC)
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2024/01/11 00:41
MHDA- 2024/01/29 06:43
CRDT- 2024/01/10 19:51
PHST- 2023/11/09 00:00 [received]
PHST- 2023/12/24 00:00 [revised]
PHST- 2024/01/05 00:00 [accepted]
PHST- 2024/01/29 06:43 [medline]
PHST- 2024/01/11 00:41 [pubmed]
PHST- 2024/01/10 19:51 [entrez]
AID - S1570-0232(24)00012-6 [pii]
AID - 10.1016/j.jchromb.2024.124004 [doi]
PST - ppublish
SO  - J Chromatogr B Analyt Technol Biomed Life Sci. 2024 Feb 1;1233:124004. doi: 
      10.1016/j.jchromb.2024.124004. Epub 2024 Jan 6.