Chaudhary Ranjit K, Khanal Nabin, Giri Smith, Pathak Ranjan, Bhatt Vijaya R
University of Nebraska Medical Center, Department of Internal Medicine, Division of Hematology- Oncology, 987680 Nebraska Medical Center, Omaha, NE, USA, 68198-7680.
Cardiovasc Hematol Agents Med Chem. 2014;12(1):50-8. doi: 10.2174/1871525712666141106100803.
Heparin-induced thrombocytopenia (HIT) is a life and limb-threatening thrombotic complication of heparin, which is the result of platelet activation by anti-PF4/heparin antibodies. With lepirudin and danaparoid no longer available in the US, treatment options are limited to argatroban, fondaparinux (off-label use) and bivalirudin (for patients undergoing percutaneous coronary intervention). Both argatroban and bivalirudin are parenteral drugs and require close monitoring and hospitalization. Fondaparinux is contraindicated in patients with significant renal impairment and is associated with a small risk of HIT. Anticoagulants approved for thromboprophylaxis and management of thromboembolic conditions such as rivaroxaban, dabigatran, and apixaban have fixed oral dose, rapid onset of action and does not require monitoring. These novel agents do not interact with anti-PF4/heparin antibody and offer attractive therapy options for HIT. Their utility in HIT has been supported by a few clinical reports, however, larger studies are needed before they can be utilized in clinical practice. Therapeutic plasma exchange has been utilized with some success in patients with HIT, who need heparin reexposure for cardiac surgery but their safety and efficacy needs further exploration. 2-O, 3-O desulfated heparin, which lacks any anticoagulant effect, has been shown to reduce the development of HIT in murine models. Finally, novel targets based on the molecular pathogenesis of HIT are being studied for therapeutic drug development. We hope that the availability of novel therapies in the future will expand the options available for the management of HIT.
肝素诱导的血小板减少症（HIT）是一种危及生命和肢体的肝素血栓形成并发症，它是抗PF4/肝素抗体激活血小板的结果。由于在美国不再有lepirudin和达那肝素可用，治疗选择仅限于阿加曲班、磺达肝癸钠（标签外使用）和比伐卢定（用于接受经皮冠状动脉介入治疗的患者）。阿加曲班和比伐卢定都是胃肠外给药的药物，需要密切监测并住院治疗。磺达肝癸钠在有严重肾功能损害的患者中禁用，并且与HIT的小风险相关。已批准用于血栓预防和血栓栓塞性疾病管理的抗凝剂，如利伐沙班、达比加群和阿哌沙班，具有固定的口服剂量、起效迅速且不需要监测。这些新型药物不与抗PF4/肝素抗体相互作用，为HIT提供了有吸引力的治疗选择。它们在HIT中的效用得到了一些临床报告的支持，然而，在它们能够用于临床实践之前，还需要更大规模的研究。治疗性血浆置换在需要因心脏手术再次使用肝素的HIT患者中已取得了一些成功，但它们的安全性和有效性需要进一步探索。2-O、3-O去硫酸化肝素没有任何抗凝作用，已被证明在小鼠模型中可减少HIT的发生。最后，基于HIT分子发病机制的新型靶点正在被研究用于治疗药物开发。我们希望未来新型疗法的可用性将扩大HIT管理的可用选择。
