Gupta Naresh, Seth Tulika, Aggarwal Sunita, Atri Sudhir, Shaikh Bilal Ahmed, Nigam Rajendra K, Jain Ankur, Baveja Avriti, Digra Sanjeev Kumar, Vyas Bhadresh, Sharma Vishnu
Chairperson, Haemophilia and Health Collective of North®; Ex-Director-Professor, Department of Medicine, Maulana Azad Medical College, Delhi, India, Corresponding Author.
Professor, Department of Hematology, All India Institute of Medical Sciences, Delhi, India.
J Assoc Physicians India. 2025 Apr;73(4):e47-e54. doi: 10.59556/japi.73.0928.
Hemophilia, an X-linked genetic bleeding disorder, is caused by the deficiency of coagulation factors VIII (hemophilia A) or IX (hemophilia B). Regular replacement therapy with the missing clotting factor is an effective standard-of-care treatment. However, it comes with a significant fallout of frequent intravenous dosing with poor compliance, the risk of inhibitor development, and a substantial treatment burden. Research has progressed from missing clotting factors and factor VIII mimetics to the most recent rebalancing therapy that suppresses tissue factor pathway inhibitor (TFPI). Thrombin generation is restricted by TFPI, which inhibits the tissue factor-mediated activation of factor VII. This promising therapeutic approach rebalances hemostasis by inhibiting TFPI, a critical regulator of the extrinsic coagulation pathway, thereby increasing thrombin generation. Novel monoclonal antibodies (concizumab and marstacimab) enhance thrombin generation by blocking TFPI to restore hemostasis. Clinical trials have demonstrated good clinical efficacy and safety of these anti-TFPI, besides their convenient subcutaneous administration using pen devices. These innovative therapies have the potential to enhance the quality of life (QoL) of people with hemophilia. This review provides a comprehensive overview of the clinical development, therapeutic potential, challenges, and prospects of anti-TFPI in the management of hemophilia.
血友病是一种X连锁遗传性出血性疾病，由凝血因子VIII（A型血友病）或IX（B型血友病）缺乏引起。用缺失的凝血因子进行定期替代疗法是一种有效的标准治疗方法。然而，它伴随着频繁静脉给药的严重后果，包括依从性差、产生抑制剂的风险以及巨大的治疗负担。研究已从缺失的凝血因子和VIII因子模拟物发展到最近的重新平衡疗法，即抑制组织因子途径抑制剂（TFPI）。凝血酶的产生受TFPI限制，TFPI抑制组织因子介导的VII因子激活。这种有前景的治疗方法通过抑制TFPI（外源性凝血途径的关键调节因子）来重新平衡止血，从而增加凝血酶的产生。新型单克隆抗体（康齐珠单抗和马司他昔单抗）通过阻断TFPI来增强凝血酶的产生以恢复止血。临床试验已证明这些抗TFPI药物具有良好的临床疗效和安全性，而且它们使用笔式装置进行皮下给药很方便。这些创新疗法有可能提高血友病患者的生活质量（QoL）。本综述全面概述了抗TFPI在血友病管理中的临床开发、治疗潜力、挑战和前景。
