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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
Plasma proteinase inhibitor activity and hemostasis tests in children with nephrotic syndrome. Effect of prednisone alone and prednisone plus epsilon-aminocaproic acid treatment regimens: a preliminary report.
Prandota J, Pankow-Prandota L, Kotecki L, Noga L
Am J Ther 2001 Mar-Apr;8(2):97-107. doi: 10.1097/00045391-200103000-00004. PMID: 11304663

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

Impaired fibrinolysis and increased clot strength are potential risk factors for thrombosis in lymphoma.
Bønløkke ST, Fenger-Eriksen C, Ommen HB, Hvas AM
Blood Adv 2023 Nov 28;7(22):7056-7066. doi: 10.1182/bloodadvances.2023011379. PMID: 37756519Free PMC Article
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
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
Quality of therapeutic plasma-requirements for marketing authorization.
Heiden M, Seitz R
Thromb Res 2002 Oct 31;107 Suppl 1:S47-51. doi: 10.1016/s0049-3848(02)00152-4. PMID: 12379293
Alpha 2-antiplasmin supplementation inhibits tissue plasminogen activator-induced fibrinogenolysis and bleeding with little effect on thrombolysis.
Weitz JI, Leslie B, Hirsh J, Klement P
J Clin Invest 1993 Apr;91(4):1343-50. doi: 10.1172/JCI116335. PMID: 7682569Free PMC Article

Prognosis

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
The regulation of human factor XIIa by plasma proteinase inhibitors.
Pixley RA, Schapira M, Colman RW
J Biol Chem 1985 Feb 10;260(3):1723-9. PMID: 2578463
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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