China
Africa
Explore chapters and articles related to this topic
Haematological Disease
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
Activated partial thromboplastin time (APTT) tests the contact activated ‘intrinsic’ clotting pathway (factors VIII, IX, XI and XII) and final common pathway. It is usually expressed as a ratio, the APTTr. Prolongation indicates a deficiency of any or all of coagulation factors XII, XI, IX, VIII, X, V, II and fibrinogen. Note that deficiency of factor XII does not result in bleeding.
Spontaneous (Unexplained) Thrombosis: The Inherited Basis for the Thrombohemorrhagic Balance
Published in E. Nigel Harris, Thomas Exner, Graham R. V. Hughes, Ronald A. Asherson, Phospholipid-Binding Antibodies, 2020
The potential importance for thrombophilia due to the parameters set out in the last line of Table 1 remains to be established, since so far no inherited anomaly, except for the intrinsic fibrinolytic pathway, has been found. Although some reports have suggested a relationship between thrombophilia and factor XII deficiency, the connection remains obscure.61,79
Coagulation Theory, Principles, and Concepts
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
The lack of factor XII does not predispose a patient to even a modest bleeding risk, but rather a thrombotic risk. This observation, coupled with the fact that it has been very difficult to describe an in-vivo system which clearly produces the “surface” activation of factor XII similar to the artificial activation seen in vitro, continually questions the relevance of factor XII to normal in-vivo coagulation. It is likely that factor XII activation is important as a general defense mechanism which either preactivates or triggers a number of physiologic, cascade-based defense mechanisms, rather than being a primary event in coagulation (67–69).
Antibodies to watch in 2023
Published in mAbs, 2023
Hélène Kaplon, Silvia Crescioli, Alicia Chenoweth, Jyothsna Visweswaraiah, Janice M. Reichert
Garadacimab (CSL312) is a hinge-stabilized (S228P mutation), human anti-Factor XIIa IgG4λ antibody developed by CSL for hereditary angioedema, a rare disorder characterized potentially life-threatening, recurrent episodes of severe swelling. Factor XII is the principal initiator of the plasma contact system, a protease cascade that results in inflammation, increased vascular permeability, vasodilation, and chemotaxis, as well as activation of the intrinsic coagulation pathway. Garadacimab was granted Orphan Drug designations in the EU for hereditary angioedema and in the US for the prevention of bradykinin-mediated angioedema and for idiopathic pulmonary fibrosis. CSL aims to begin filing with global health authorities at the end of their current fiscal year, i.e., by July 2023, for full approval.126
Factor XII(a) inhibitors: a review of the patent literature
Published in Expert Opinion on Therapeutic Patents, 2021
Being an integral part of the contact activation system, blood coagulation factor XII plays an important role in pathophysiological processes such as blood coagulation and thrombosis, HAE, and (neuro)inflammation. As FXII-deficiency is practically asymptomatic, FXII zymogen, as well as its active form FXIIa, represent emerging and potentially safe drug targets. The current analysis of the patents filed by industrial and academic institutions revealed structurally and mechanistically diverse anti-FXII(a) therapeutics. These agents include small molecules [39,42–48], peptides [54,56], proteins [63,68,71–73,76,80], oligonucleotides [84], siRNAs [85,91], and mAbs [95–97,99,100,107,110]. Some of these chemical entities are active site FXIIa inhibitors, whereas others target FXII zymogen or disrupt its biosynthesis. Although many FXII(a) inhibitors are in the early preclinical stage, several already showed their efficacy in vivo animal models of thrombosis, sepsis, HAE, AD, MS, and even progressed into human clinical trials [78,103,106]. It is expected that further studies of pathophysiological functions of FXII(a) will encourage the development of new FXII(a)-targeting agents. A boost in the number of FXII(a)-related patents should be expected upon successful clinical trials of the aforementioned FXII(a)-addressing agents.
Complement activation and coagulopathy - an ominous duo in COVID19
Published in Expert Review of Hematology, 2021
Sojit Tomo, Kiran Pvsn Kumar, Dipayan Roy, Shrimanjunath Sankanagoudar, Purvi Purohit, Dharamveer Yadav, Mithu Banerjee, Praveen Sharma, Sanjeev Misra
Existing evidence supports a procoagulant effect of the complement system in COVID-19. It can be mediated directly by mannose-associated serine protease-2 (MASP-2), a critical component of the lectin pathway, which activates thrombin and subsequent fibrin mesh formation. Indirectly, complement effectors can bring about changes in the endothelium which modulates the clotting cascade. Again, in addition to modulating the cascade proteins, complements are also actively involved in aggregation of platelets, a coagulation-initiating effect. On the other hand, the complement system can be activated by the coagulation pathway by activation of Factor XIIa which can activate complement complex C1 in the classical pathway [20]. Thus, there is a clear cross-talk of the two pathways and there may be a synergistic activation of these two pathways in the COVID-19 patients, which amounts to an enhanced rate of coagulopathy.