Datta Payel, Zhang Fuming, Dordick Jonathan S, Linhardt Robert J
Heparin Applied Research Center, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA.
Thromb J. 2021 Sep 15;19(1):66. doi: 10.1186/s12959-021-00318-2.
This is a review article on heparin-induced thrombocytopenia, an adverse effect of heparin therapy, and vaccine-induced immune thrombotic thrombocytopenia, occurring in some patients administered certain coronavirus vaccines.
MAIN BODY/TEXT: Immune-mediated thrombocytopenia occurs when specific antibodies bind to platelet factor 4 /heparin complexes. Platelet factor 4 is a naturally occurring chemokine, and under certain conditions, may complex with negatively charged molecules and polyanions, including heparin. The antibody-platelet factor 4/heparin complex may lead to platelet activation, accompanied by other cascading reactions, resulting in cerebral sinus thrombosis, deep vein thrombosis, lower limb arterial thrombosis, myocardial infarction, pulmonary embolism, skin necrosis, and thrombotic stroke. If untreated, heparin-induced thrombocytopenia can be life threatening. In parallel, rare incidents of spontaneous vaccine-induced immune thrombotic thrombocytopenia can also occur in some patients administered certain coronavirus vaccines. The role of platelet factor 4 in vaccine-induced thrombosis with thrombocytopenia syndrome further reinforces the importance the platelet factor 4/polyanion immune complexes and the complications that this might pose to susceptible individuals. These findings demonstrate, how auxiliary factors can complicate heparin therapy and drug development. An increasing interest in biomanufacturing heparins from non-animal sources has driven a growing interest in understanding the biology of immune-mediated heparin-induced thrombocytopenia, and therefore, the development of safe and effective biosynthetic heparins.
In conclusion, these findings further reinforce the importance of the binding of platelet factor 4 with known and unknown polyanions, and the complications that these might pose to susceptible patients. In parallel, these findings also demonstrate how auxiliary factors can complicate the heparin drug development.
这是一篇关于肝素诱导的血小板减少症（肝素治疗的一种不良反应）以及疫苗诱导的免疫性血栓性血小板减少症（在接种某些新冠病毒疫苗的部分患者中出现）的综述文章。
当特异性抗体与血小板因子4/肝素复合物结合时，就会发生免疫介导的血小板减少症。血小板因子4是一种天然存在的趋化因子，在某些情况下，它可能与带负电荷的分子和聚阴离子（包括肝素）形成复合物。抗体 - 血小板因子4/肝素复合物可能导致血小板活化，并伴有其他级联反应，从而引发脑窦血栓形成、深静脉血栓形成、下肢动脉血栓形成、心肌梗死、肺栓塞、皮肤坏死和血栓性中风。如果不进行治疗，肝素诱导的血小板减少症可能会危及生命。与此同时，在接种某些新冠病毒疫苗的部分患者中也可能会罕见地自发出现疫苗诱导的免疫性血栓性血小板减少症。血小板因子4在疫苗诱导的血栓形成伴血小板减少症综合征中的作用进一步凸显了血小板因子4/聚阴离子免疫复合物的重要性以及这可能给易感个体带来的并发症。这些发现表明了辅助因素如何使肝素治疗和药物研发变得复杂。对非动物来源肝素生物制造的兴趣日益浓厚，这推动了人们对理解免疫介导的肝素诱导的血小板减少症生物学的兴趣增加，进而推动了安全有效的生物合成肝素的研发。
总之，这些发现进一步强化了血小板因子4与已知和未知聚阴离子结合的重要性以及这可能给易感患者带来的并发症。与此同时，这些发现也展示了辅助因素如何使肝素药物研发变得复杂。
