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Reduced alpha-2-antiplasmin activity

MedGen UID:
904513
•Concept ID:
C4280703
•
Finding
HPO: HP:0040245

Definition

Reduced activity of alpha-2-antiplasmin. This protein inactivates the protease plasmin that drives fibrinolysis. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVReduced alpha-2-antiplasmin activity

Professional guidelines

PubMed

Fibrinogen, factor XIII and α(2)-antiplasmin genotypes are associated with inflammatory activity and anti-citrullinated protein antibodies.
Hoppe B, Schwedler C, Edelmann A, Pistioli A, Poddubnyy D, Burmester GR, Häupl T
Thromb Res 2020 Jul;191:90-96. Epub 2020 May 3 doi: 10.1016/j.thromres.2020.04.043. PMID: 32408093
Recent advances in understanding endogenous fibrinolysis: implications for molecular-based treatment of vascular disorders.
Bodary PF, Wickenheiser KJ, Eitzman DT
Expert Rev Mol Med 2002 Mar 26;4(7):1-10. doi: 10.1017/S1462399402004362. PMID: 14987391
Current status of pulmonary thromboembolism--incidence, diagnosis, classification, pathogenesis, and treatment.
Hasegawa H
Jpn Circ J 1984 Jan;48(1):100-10. doi: 10.1253/jcj.48.100. PMID: 6198531

Recent clinical studies

Etiology

Fibrinogen and Antifibrinolytic Proteins: Interactions and Future Therapeutics.
Pechlivani N, Kearney KJ, Ajjan RA
Int J Mol Sci 2021 Nov 21;22(22) doi: 10.3390/ijms222212537. PMID: 34830419Free PMC Article
α2-Antiplasmin: New Insights and Opportunities for Ischemic Stroke.
Reed GL, Houng AK, Singh S, Wang D
Semin Thromb Hemost 2017 Mar;43(2):191-199. Epub 2016 Jul 29 doi: 10.1055/s-0036-1585077. PMID: 27472428Free PMC Article
Evaluation of Fibrinolytic Inhibitors: Alpha-2-Antiplasmin and Plasminogen Activator Inhibitor 1 in Patients with Obstructive Sleep Apnoea.
Zakrzewski M, Zakrzewska E, Kiciński P, Przybylska-Kuć S, Dybała A, Myśliński W, Pastryk J, Tomaszewski T, Mosiewicz J
PLoS One 2016;11(11):e0166725. Epub 2016 Nov 18 doi: 10.1371/journal.pone.0166725. PMID: 27861608Free PMC Article
Natural heterogeneity of α2-antiplasmin: functional and clinical consequences.
Abdul S, Leebeek FW, Rijken DC, Uitte de Willige S
Blood 2016 Feb 4;127(5):538-45. Epub 2015 Dec 1 doi: 10.1182/blood-2015-09-670117. PMID: 26626994
Proteolytic and genetic variation of the alpha-2-antiplasmin C-terminus in myocardial infarction.
Uitte de Willige S, Miedzak M, Carter AM, Lisman T, Rosendaal FR, Grant PJ, Philippou H, Ariëns RA
Blood 2011 Jun 16;117(24):6694-701. Epub 2011 Apr 19 doi: 10.1182/blood-2010-11-320325. PMID: 21505192

Diagnosis

Management of disseminated intravascular coagulation associated with aortic aneurysm and vascular malformations.
Yamada S, Asakura H
Int J Hematol 2021 Jan;113(1):15-23. Epub 2020 Nov 11 doi: 10.1007/s12185-020-03028-z. PMID: 33175341
Application of a plasmin generation assay to define pharmacodynamic effects of tranexamic acid in women undergoing cesarean delivery.
Miszta A, Ahmadzia HK, Luban NLC, Li S, Guo D, Holle LA, Berger JS, James AH, Gobburu JVS, van den Anker J, de Laat B, Wolberg AS
J Thromb Haemost 2021 Jan;19(1):221-232. Epub 2020 Dec 26 doi: 10.1111/jth.15114. PMID: 33001565Free PMC Article
Defective α(2) antiplasmin cross-linking and thrombus stability in a case of acquired factor XIII deficiency.
Mitchell JL, Wright S, Kazi S, Watson HG, Mutch NJ
Br J Haematol 2017 Sep;178(5):794-799. Epub 2017 May 17 doi: 10.1111/bjh.14759. PMID: 28516512
Evaluation of Fibrinolytic Inhibitors: Alpha-2-Antiplasmin and Plasminogen Activator Inhibitor 1 in Patients with Obstructive Sleep Apnoea.
Zakrzewski M, Zakrzewska E, Kiciński P, Przybylska-Kuć S, Dybała A, Myśliński W, Pastryk J, Tomaszewski T, Mosiewicz J
PLoS One 2016;11(11):e0166725. Epub 2016 Nov 18 doi: 10.1371/journal.pone.0166725. PMID: 27861608Free PMC Article
Lonomia genus caterpillar envenomation: clinical and biological aspects.
Arocha-Piñango CL, Guerrero B
Haemostasis 2001 May-Dec;31(3-6):288-93. doi: 10.1159/000048075. PMID: 11910197

Therapy

Termination of bleeding by a specific, anticatalytic antibody against plasmin.
Zhao T, Houng A, Reed GL
J Thromb Haemost 2019 Sep;17(9):1461-1469. Epub 2019 Jun 23 doi: 10.1111/jth.14522. PMID: 31136076Free PMC Article
α2-Antiplasmin: New Insights and Opportunities for Ischemic Stroke.
Reed GL, Houng AK, Singh S, Wang D
Semin Thromb Hemost 2017 Mar;43(2):191-199. Epub 2016 Jul 29 doi: 10.1055/s-0036-1585077. PMID: 27472428Free PMC Article
Alpha2-antiplasmin: potential therapeutic roles in fibrin survival and removal.
Lee KN, Jackson KW, Christiansen VJ, Chung KH, McKee PA
Curr Med Chem Cardiovasc Hematol Agents 2004 Oct;2(4):303-10. doi: 10.2174/1568016043356228. PMID: 15320781
Acquired alpha-2-antiplasmin deficiency in acute promyelocytic leukaemia.
Avvisati G, ten Cate JW, Sturk A, Lamping R, Petti MG, Mandelli F
Br J Haematol 1988 Sep;70(1):43-8. doi: 10.1111/j.1365-2141.1988.tb02432.x. PMID: 2460126
Circular dichroism studies on alpha 2-antiplasmin and its interactions with plasmin and plasminogen.
Nilsson T, Sjöholm I, Wiman B
Biochim Biophys Acta 1982 Jul 26;705(2):264-70. doi: 10.1016/0167-4838(82)90187-x. PMID: 6214280

Prognosis

Persistent hypofibrinolysis in severe COVID-19 associated with elevated fibrinolysis inhibitors activity.
Okazaki E, Barion BG, da Rocha TRF, Di Giacomo G, Ho YL, Rothschild C, Fatobene G, de Carvalho Moraes BDG, Stefanello B, Villaça PR, Rocha VG, Orsi FA
J Thromb Thrombolysis 2024 Apr;57(4):721-729. Epub 2024 Mar 25 doi: 10.1007/s11239-024-02961-8. PMID: 38523179
Pregnancy outcome and fibrinolytic, endothelial and coagulation markers in women undergoing uterine artery Doppler screening at 23 weeks.
Hunt BJ, Missfelder-Lobos H, Parra-Cordero M, Fletcher O, Parmar K, Lefkou E, Lees CC
J Thromb Haemost 2009 Jun;7(6):955-61. Epub 2009 Mar 13 doi: 10.1111/j.1538-7836.2009.03344.x. PMID: 19320824
Implications of excessive fibrinolysis and alpha(2)-plasmin inhibitor deficiency in patients with severe head injury.
Kushimoto S, Yamamoto Y, Shibata Y, Sato H, Koido Y
Neurosurgery 2001 Nov;49(5):1084-9; discussion 1089-90. doi: 10.1097/00006123-200111000-00011. PMID: 11846901
Acquired alpha-2-antiplasmin deficiency in acute promyelocytic leukaemia.
Avvisati G, ten Cate JW, Sturk A, Lamping R, Petti MG, Mandelli F
Br J Haematol 1988 Sep;70(1):43-8. doi: 10.1111/j.1365-2141.1988.tb02432.x. PMID: 2460126
Inactivation of factor XII active fragment in normal plasma. Predominant role of C-1-inhibitor.
de Agostini A, Lijnen HR, Pixley RA, Colman RW, Schapira M
J Clin Invest 1984 Jun;73(6):1542-9. doi: 10.1172/JCI111360. PMID: 6725552Free PMC Article

Clinical prediction guides

Fibrinogen, factor XIII and α(2)-antiplasmin genotypes are associated with inflammatory activity and anti-citrullinated protein antibodies.
Hoppe B, Schwedler C, Edelmann A, Pistioli A, Poddubnyy D, Burmester GR, Häupl T
Thromb Res 2020 Jul;191:90-96. Epub 2020 May 3 doi: 10.1016/j.thromres.2020.04.043. PMID: 32408093
Efficacy of SMTP-7, a small-molecule anti-inflammatory thrombolytic, in embolic stroke in monkeys.
Suzuki E, Nishimura N, Yoshikawa T, Kunikiyo Y, Hasegawa K, Hasumi K
Pharmacol Res Perspect 2018 Dec;6(6):e00448. Epub 2018 Dec 5 doi: 10.1002/prp2.448. PMID: 30546909Free PMC Article
α2-Antiplasmin: New Insights and Opportunities for Ischemic Stroke.
Reed GL, Houng AK, Singh S, Wang D
Semin Thromb Hemost 2017 Mar;43(2):191-199. Epub 2016 Jul 29 doi: 10.1055/s-0036-1585077. PMID: 27472428Free PMC Article
Neutralization of alpha(2)-antiplasmin by microplasmin: a randomized, double-blind, placebo-controlled, ascending-dose study in healthy male volunteers.
Pakola S, Cahillane G, Stassen JM, Lijnen HR, Verhamme P
Clin Ther 2009 Aug;31(8):1688-706. doi: 10.1016/j.clinthera.2009.08.019. PMID: 19808128
Acquired alpha-2-antiplasmin deficiency in acute promyelocytic leukaemia.
Avvisati G, ten Cate JW, Sturk A, Lamping R, Petti MG, Mandelli F
Br J Haematol 1988 Sep;70(1):43-8. doi: 10.1111/j.1365-2141.1988.tb02432.x. PMID: 2460126

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