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Blood：PF4-VWF-HIT抗体复合物在肝素诱导的血小板减少症发病过程中的作用

2020-02-21 不详 MedSci原创

Blood：PF4-VWF-HIT抗体复合物在肝素诱导的血小板减少症发病过程中的作用
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中心点：PF4与VWF结合形成抗原复合物，被HIT抗体识别。PF4-VWF-HIT抗体复合物通过血小板FcγRIIA和GPIb-IX受体 增强血小板粘附。摘要：肝素诱导的血小板减少症(HIT)是一种由血小板因子4 (PF4)和肝素或其他多阴离子之间的复合物介导的血栓前期疾病，但血栓形成的风险高于与其他PF4伴侣相关的肝素暴露的。近期，Johnston等发现血栓周围内皮细胞被HIT抗体攻击，但结合位

中心点：

PF4与VWF结合形成抗原复合物，被HIT抗体识别。

PF4-VWF-HIT抗体复合物通过血小板FcγRIIA和GPIb-IX受体 增强血小板粘附。

摘要：

肝素诱导的血小板减少症(HIT)是一种由血小板因子4 (PF4)和肝素或其他多阴离子之间的复合物介导的血栓前期疾病，但血栓形成的风险高于与其他PF4伴侣相关的肝素暴露的。近期，Johnston等发现血栓周围内皮细胞被HIT抗体攻击，但结合位点尚未明确。

在本研究中，Johnston等人发现，在流动的内皮化微流体系统中，光化学损伤后，PF4与内皮细胞释放的VWF的延伸链表面上的多个离散位点结合。HIT样单克隆抗体KKO和HIT患者抗体可识别PF4-VWF复合物，促进血小板粘附和微流体通道内血栓的增大。

血小板对PF4-VWF-HIT抗体复合物的粘附被可封闭FcgRIIA或血小板上的糖蛋白Ib-IX复合物的抗体所抑制。用可阻断或封闭VWF寡聚作用的药物破坏PF4-VWF-HIT抗体复合物可减少HIT小鼠模型的血栓形成。

总而言之，本研究表明，HIT免疫复合物沿受损内皮细胞释放的VWF延伸链组装，可能会增加HIT血栓形成的风险。破坏PF4-VWF复合物的形成或可为HIT的治疗提供新的思路。

原始出处：


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    2021-06-16 shengdai3

    学习了

    0

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    2020-08-20 sunmin0229

    #PF4#

    0

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    2020-04-07 yang0210

    #复合物#

    0

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    2020-04-29 yuandd

    #HIT#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=974134, encodeId=70bf9e413422, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=fd521314318, createdName=shengdai3, createdTime=Wed Jun 16 16:40:42 CST 2021, time=2021-06-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1702903, encodeId=aefe1e0290371, content=<a href='/topic/show?id=6d5414113d5' target=_blank style='color:#2F92EE;'>#PF4#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14113, encryptionId=6d5414113d5, topicName=PF4)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=217830458022, createdName=sunmin0229, createdTime=Thu Aug 20 03:05:00 CST 2020, time=2020-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1910655, encodeId=d8191910655df, content=<a href='/topic/show?id=b45b426195e' target=_blank style='color:#2F92EE;'>#复合物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42619, encryptionId=b45b426195e, topicName=复合物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ad7f282, createdName=yang0210, createdTime=Tue Apr 07 10:05:00 CST 2020, time=2020-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1894504, encodeId=c9c0189450412, content=<a href='/topic/show?id=7e2688e517' target=_blank style='color:#2F92EE;'>#HIT#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8875, encryptionId=7e2688e517, topicName=HIT)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=583c133, createdName=yuandd, createdTime=Wed Apr 29 17:05:00 CST 2020, time=2020-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1302838, encodeId=01221302838af, content=<a href='/topic/show?id=9c72890153c' target=_blank style='color:#2F92EE;'>#血小板减少#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89015, encryptionId=9c72890153c, topicName=血小板减少)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e07307, createdName=lingaifan, createdTime=Sun Feb 23 03:05:00 CST 2020, time=2020-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1372599, encodeId=7f6e13e2599a5, content=<a href='/topic/show?id=afaa185637c' target=_blank style='color:#2F92EE;'>#vWF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18563, encryptionId=afaa185637c, topicName=vWF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5462342, createdName=sunmin0219, createdTime=Sun Feb 23 03:05:00 CST 2020, time=2020-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1540610, encodeId=ab47154061076, content=<a href='/topic/show?id=4aa88133972' target=_blank style='color:#2F92EE;'>#肝素诱导的血小板减少症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81339, encryptionId=4aa88133972, topicName=肝素诱导的血小板减少症)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=43b613270021, createdName=kkunny, createdTime=Sun Feb 23 03:05:00 CST 2020, time=2020-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=379481, encodeId=ba8b3e9481b8, content=学习了，学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzTetibytbqFDmFITWHyBWbxU7S9MYibgPSqvu0sYteH0N6zXqbU0Kf3Mbdb7yWM1Kud3zPgYBibE2SZ/0, createdBy=da7696924, createdName=qingfengqishi5, createdTime=Fri Feb 21 13:38:40 CST 2020, time=2020-02-21, status=1, ipAttribution=)]
    2020-02-23 lingaifan

    #血小板减少#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=974134, encodeId=70bf9e413422, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=fd521314318, createdName=shengdai3, createdTime=Wed Jun 16 16:40:42 CST 2021, time=2021-06-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1702903, encodeId=aefe1e0290371, content=<a href='/topic/show?id=6d5414113d5' target=_blank style='color:#2F92EE;'>#PF4#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14113, encryptionId=6d5414113d5, topicName=PF4)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=217830458022, createdName=sunmin0229, createdTime=Thu Aug 20 03:05:00 CST 2020, time=2020-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1910655, encodeId=d8191910655df, content=<a href='/topic/show?id=b45b426195e' target=_blank style='color:#2F92EE;'>#复合物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42619, encryptionId=b45b426195e, topicName=复合物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ad7f282, createdName=yang0210, createdTime=Tue Apr 07 10:05:00 CST 2020, time=2020-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1894504, encodeId=c9c0189450412, content=<a href='/topic/show?id=7e2688e517' target=_blank style='color:#2F92EE;'>#HIT#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8875, encryptionId=7e2688e517, topicName=HIT)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=583c133, createdName=yuandd, createdTime=Wed Apr 29 17:05:00 CST 2020, time=2020-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1302838, encodeId=01221302838af, content=<a href='/topic/show?id=9c72890153c' target=_blank style='color:#2F92EE;'>#血小板减少#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89015, encryptionId=9c72890153c, topicName=血小板减少)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e07307, createdName=lingaifan, createdTime=Sun Feb 23 03:05:00 CST 2020, time=2020-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1372599, encodeId=7f6e13e2599a5, content=<a href='/topic/show?id=afaa185637c' target=_blank style='color:#2F92EE;'>#vWF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18563, encryptionId=afaa185637c, topicName=vWF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5462342, createdName=sunmin0219, createdTime=Sun Feb 23 03:05:00 CST 2020, time=2020-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1540610, encodeId=ab47154061076, content=<a href='/topic/show?id=4aa88133972' target=_blank style='color:#2F92EE;'>#肝素诱导的血小板减少症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81339, encryptionId=4aa88133972, topicName=肝素诱导的血小板减少症)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=43b613270021, createdName=kkunny, createdTime=Sun Feb 23 03:05:00 CST 2020, time=2020-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=379481, encodeId=ba8b3e9481b8, content=学习了，学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzTetibytbqFDmFITWHyBWbxU7S9MYibgPSqvu0sYteH0N6zXqbU0Kf3Mbdb7yWM1Kud3zPgYBibE2SZ/0, createdBy=da7696924, createdName=qingfengqishi5, createdTime=Fri Feb 21 13:38:40 CST 2020, time=2020-02-21, status=1, ipAttribution=)]
    2020-02-23 sunmin0219

    #vWF#

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=974134, encodeId=70bf9e413422, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=fd521314318, createdName=shengdai3, createdTime=Wed Jun 16 16:40:42 CST 2021, time=2021-06-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1702903, encodeId=aefe1e0290371, content=<a href='/topic/show?id=6d5414113d5' target=_blank style='color:#2F92EE;'>#PF4#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14113, encryptionId=6d5414113d5, topicName=PF4)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=217830458022, createdName=sunmin0229, createdTime=Thu Aug 20 03:05:00 CST 2020, time=2020-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1910655, encodeId=d8191910655df, content=<a href='/topic/show?id=b45b426195e' target=_blank style='color:#2F92EE;'>#复合物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42619, encryptionId=b45b426195e, topicName=复合物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ad7f282, createdName=yang0210, createdTime=Tue Apr 07 10:05:00 CST 2020, time=2020-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1894504, encodeId=c9c0189450412, content=<a href='/topic/show?id=7e2688e517' target=_blank style='color:#2F92EE;'>#HIT#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8875, encryptionId=7e2688e517, topicName=HIT)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=583c133, createdName=yuandd, createdTime=Wed Apr 29 17:05:00 CST 2020, time=2020-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1302838, encodeId=01221302838af, content=<a href='/topic/show?id=9c72890153c' target=_blank style='color:#2F92EE;'>#血小板减少#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89015, encryptionId=9c72890153c, topicName=血小板减少)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e07307, createdName=lingaifan, createdTime=Sun Feb 23 03:05:00 CST 2020, time=2020-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1372599, encodeId=7f6e13e2599a5, content=<a href='/topic/show?id=afaa185637c' target=_blank style='color:#2F92EE;'>#vWF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18563, encryptionId=afaa185637c, topicName=vWF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5462342, createdName=sunmin0219, createdTime=Sun Feb 23 03:05:00 CST 2020, time=2020-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1540610, encodeId=ab47154061076, content=<a href='/topic/show?id=4aa88133972' target=_blank style='color:#2F92EE;'>#肝素诱导的血小板减少症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81339, encryptionId=4aa88133972, topicName=肝素诱导的血小板减少症)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=43b613270021, createdName=kkunny, createdTime=Sun Feb 23 03:05:00 CST 2020, time=2020-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=379481, encodeId=ba8b3e9481b8, content=学习了，学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzTetibytbqFDmFITWHyBWbxU7S9MYibgPSqvu0sYteH0N6zXqbU0Kf3Mbdb7yWM1Kud3zPgYBibE2SZ/0, createdBy=da7696924, createdName=qingfengqishi5, createdTime=Fri Feb 21 13:38:40 CST 2020, time=2020-02-21, status=1, ipAttribution=)]
    2020-02-23 kkunny

    #肝素诱导的血小板减少症#

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=974134, encodeId=70bf9e413422, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=fd521314318, createdName=shengdai3, createdTime=Wed Jun 16 16:40:42 CST 2021, time=2021-06-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1702903, encodeId=aefe1e0290371, content=<a href='/topic/show?id=6d5414113d5' target=_blank style='color:#2F92EE;'>#PF4#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14113, encryptionId=6d5414113d5, topicName=PF4)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=217830458022, createdName=sunmin0229, createdTime=Thu Aug 20 03:05:00 CST 2020, time=2020-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1910655, encodeId=d8191910655df, content=<a href='/topic/show?id=b45b426195e' target=_blank style='color:#2F92EE;'>#复合物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42619, encryptionId=b45b426195e, topicName=复合物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ad7f282, createdName=yang0210, createdTime=Tue Apr 07 10:05:00 CST 2020, time=2020-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1894504, encodeId=c9c0189450412, content=<a href='/topic/show?id=7e2688e517' target=_blank style='color:#2F92EE;'>#HIT#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8875, encryptionId=7e2688e517, topicName=HIT)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=583c133, createdName=yuandd, createdTime=Wed Apr 29 17:05:00 CST 2020, time=2020-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1302838, encodeId=01221302838af, content=<a href='/topic/show?id=9c72890153c' target=_blank style='color:#2F92EE;'>#血小板减少#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89015, encryptionId=9c72890153c, topicName=血小板减少)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e07307, createdName=lingaifan, createdTime=Sun Feb 23 03:05:00 CST 2020, time=2020-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1372599, encodeId=7f6e13e2599a5, content=<a href='/topic/show?id=afaa185637c' target=_blank style='color:#2F92EE;'>#vWF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18563, encryptionId=afaa185637c, topicName=vWF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5462342, createdName=sunmin0219, createdTime=Sun Feb 23 03:05:00 CST 2020, time=2020-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1540610, encodeId=ab47154061076, content=<a href='/topic/show?id=4aa88133972' target=_blank style='color:#2F92EE;'>#肝素诱导的血小板减少症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81339, encryptionId=4aa88133972, topicName=肝素诱导的血小板减少症)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=43b613270021, createdName=kkunny, createdTime=Sun Feb 23 03:05:00 CST 2020, time=2020-02-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=379481, encodeId=ba8b3e9481b8, content=学习了，学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=105, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzTetibytbqFDmFITWHyBWbxU7S9MYibgPSqvu0sYteH0N6zXqbU0Kf3Mbdb7yWM1Kud3zPgYBibE2SZ/0, createdBy=da7696924, createdName=qingfengqishi5, createdTime=Fri Feb 21 13:38:40 CST 2020, time=2020-02-21, status=1, ipAttribution=)]
    2020-02-21 qingfengqishi5

    学习了，学习了

    0

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