Department of Genetic, Physiology and Microbiology, Biology School, Complutense University of Madrid, Spain.
Osteoarticular Surgery Research, Hospital La Paz Institute for Health Research-IdiPAZ (La Paz University Hospital-Autonomous University of Madrid), Spain.
Thromb Res. 2023 Nov;231:99-111. doi: 10.1016/j.thromres.2023.10.001. Epub 2023 Oct 6.
Congenital coagulopathies have, throughout the history of medicine, been a focus of scientific study and of great interest as they constitute an alteration of one of the most important and conserved pathways of evolution. The first therapeutic strategies developed to address them were aimed at restoring the blood components lost during hemorrhage by administering whole blood or plasma. Later on, the use of cryoprecipitates was a significant breakthrough as it made it possible to decrease the volumes of blood infused. In the 1970' and 80', clotting factor concentrates became the treatment and, from the 1990's to the present day, recombinant factors -with increasingly longer half-lives- have taken over as the treatment of choice for certain coagulopathies in a seamless yet momentous transition from biological to biotechnological drugs. The beginning of this century, however, saw the emergence of new advanced (gene and cell) treatments, which are currently transforming the therapeutic landscape. The possibility to use cells and viruses as well as specific or bispecific antibodies as medicines is likely to spark a revolution in the world of pharmacology where therapies will be individualized and have long-term effects. Specifically, attention is nowadays focused on the development of gene editing strategies, chiefly those based on CRISPR/Cas technology. Rare coagulopathies such as hemophilia A and B, or even ultra-rare ones such as factor V deficiency, could be among those deriving the greatest benefit from these new developments.
先天性凝血障碍在医学史上一直是科学研究的重点，并且非常有趣，因为它们构成了对进化过程中最重要和最保守的途径之一的改变。为解决这些问题而开发的最初的治疗策略旨在通过输注全血或血浆来恢复在出血过程中丢失的血液成分。后来，使用冷沉淀是一个重大突破，因为它可以减少输注的血量。在 20 世纪 70 年代和 80 年代，凝血因子浓缩物成为治疗方法，而从 90 年代到现在，重组因子——半衰期越来越长——已成为某些凝血障碍的首选治疗方法，这是从生物药物到生物技术药物的无缝但意义重大的转变。然而，本世纪初出现了新的先进（基因和细胞）治疗方法，目前正在改变治疗领域。使用细胞和病毒以及特异性或双特异性抗体作为药物的可能性可能引发药理学领域的革命，其中治疗方法将具有个体化和长期效果。具体来说，人们现在关注的是基因编辑策略的发展，主要是基于 CRISPR/Cas 技术的策略。罕见的凝血障碍，如血友病 A 和 B，甚至是非常罕见的因子 V 缺乏症，都可能从这些新发展中受益最多。
