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Thromb Haemost 2021; 121(03): 261-269
DOI: 10.1055/s-0040-1716751
Review Article

Serpins, New Therapeutic Targets for Hemophilia

Karen Aymonnier‡   ∗
1   INSERM U1148-LVTS, Université de Paris, Paris, France
2   CHU Xavier Bichat, Paris, France
,
Charlotte Kawecki‡   ∗
1   INSERM U1148-LVTS, Université de Paris, Paris, France
3   INSERM U1176-HITh, Université Paris-Sud (Université Paris-Saclay), Le Kremlin-Bicêtre, France
,
Véronique Arocas
1   INSERM U1148-LVTS, Université de Paris, Paris, France
2   CHU Xavier Bichat, Paris, France
,
Yacine Boulaftali
1   INSERM U1148-LVTS, Université de Paris, Paris, France
2   CHU Xavier Bichat, Paris, France
,
Marie Christine Bouton
1   INSERM U1148-LVTS, Université de Paris, Paris, France
2   CHU Xavier Bichat, Paris, France
› Author Affiliations Funding This work was supported by INSERM, Université de Paris, and grants from CSL Behring-SFH, the Agence Nationale de la Recherche (ANR-14-OHRI-0013), the Bayer Hemophilia Award Program, and the National Blood Foundation. K.A. was the recipient of a PhD fellowship from the Société Française d'Hématologie (SFH).
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Abstract

Hemostasis is a tightly regulated process characterized by a finely tuned balance between procoagulant and anticoagulant systems. Among inherited hemostatic conditions, hemophilia is one of the most well-known bleeding disorders. Hemophilia A (HA) and B (HB) are due to deficiencies in coagulation factor VIII (FVIII) or FIX, respectively, leading to unwanted bleeding. Until recently, hemophilia treatment has consisted of prophylactic replacement therapy using plasma-derived or recombinant FVIII in cases of HA or FIX in cases of HB. Because FVIII and FIX deficiencies lead to an imbalance between procoagulant and anticoagulant systems, a recent upcoming strategy implies blocking of endogenous anticoagulant proteins to compensate for the procoagulant factor deficit, thus restoring hemostatic equilibrium. Important physiological proteins of the anticoagulant pathways belong to the serpin (serine protease inhibitor) family and, recently, different experimental and clinical studies have demonstrated that targeting natural serpins could decrease bleeding in hemophilia. Here, we aim to review the different, recent studies demonstrating that blocking serpins such as antithrombin, protein Z-dependent protease inhibitor, and protease nexin-1 or modifying a serpin like α1-antitrypsin could rebalance coagulation in hemophilia. Furthermore, we underline the potential therapeutic use of serpins for the treatment of hemophilia.

Keywords

coagulation inhibitors - hemophilia A/B - Serpins

∗ K.A. and C.K. contributed equally to this article.




Publication History

Received: 14 February 2020

Accepted: 07 August 2020

Article published online:
28 September 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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