Hyperfibrinolysis

The fibrinolysis system is responsible for removing blood clots. Hyperfibrinolysis describes a situation with markedly enhanced fibrinolytic activity, resulting in increased, sometimes catastrophic bleeding. Hyperfibrinolysis can be caused by acquired or congenital reasons. Among the congenital conditions for hyperfibrinolysis, alpha-2-plasmin inhibitor deficiency{{cite journal | author = Carpenter SL, Mathew P | year = 2008 | title = Alpha-2-antiplasmin and its deficiency: fibrinolysis out of balance | journal = Haemophilia | volume = 14 | issue = 6 | pages = 1250–4 | doi=10.1111/j.1365-2516.2008.01766.x | pmid=19141165| doi-access = free }} or plasminogen activator inhibitor type 1 (PAI-1){{cite journal | vauthors = Takahashi Y, Tanaka T, Minowa H, Ookubo Y, Sugimoto M, Nakajima M, Miyauchi Y, Yoshioka A | title = Hereditary partial deficiency of plasminogen activator inhibitor-1 associated with a lifelong bleeding tendency | journal = International Journal of Hematology | volume = 64 | issue = 1 | pages = 61–8 | date = July 1996 | doi = 10.1016/0925-5710(96)00460-4 | pmid = 8757969}} are very rare. The affected individuals show a hemophilia-like bleeding phenotype. Acquired hyperfibrinolysis is found in liver disease,{{cite journal | vauthors = Görlinger K | title = [Coagulation management during liver transplantation] | language = de | journal = Hamostaseologie | volume = 26 | issue = 3 Suppl 1 | pages = S64–76 | date = August 2006 | doi = 10.1055/s-0037-1617084 | pmid = 16953295 }} in patients with severe trauma,{{cite journal | vauthors = Levrat A, Gros A, Rugeri L, Inaba K, Floccard B, Negrier C, David JS | year = 2008 | title = Evaluation of rotation thrombelastography for the diagnosis of hyperfibrinolysis in trauma patients | journal = Br J Anaesth | volume = 100 | issue = 6 | pages = 792–7 | doi=10.1093/bja/aen083| pmid = 18440953 | doi-access = free }} during major surgical procedures,{{cite journal | vauthors = Vanek T, Jares M, Snircova J, Maly M | title = Fibrinolysis in coronary artery surgery: detection by thromboelastography | journal = Interactive Cardiovascular and Thoracic Surgery | volume = 6 | issue = 6 | pages = 700–4 | date = December 2007 | pmid = 17709365 | doi = 10.1510/icvts.2007.161463 | doi-access = free }} and other conditions.{{cite journal | vauthors = Chapin JC, Hajjar KA | title = Fibrinolysis and the control of blood coagulation | journal = Blood Reviews | volume = 29 | issue = 1 | pages = 17–24 | date = January 2015 | pmid = 25294122 | pmc = 4314363 | doi = 10.1016/j.blre.2014.09.003 }} A special situation with temporarily enhanced fibrinolysis is thrombolytic therapy with drugs which activate plasminogen, e.g. for use in acute ischemic events or in patients with stroke. In patients with severe trauma, hyperfibrinolysis is associated with poor outcome.{{cite journal | author = Schöchl H | year = 2008 | title = Hyperfibrinolysis:a prognostic marker of poor survival following major trauma? | journal = Haemostaseologie | volume = 28 | page = A57 }} Moreover, hyperfibrinolysis may be associated with blood brain barrier impairment, a plasmin-dependent effect due to an increased generation of bradykinin.{{Cite journal|last1=Marcos-Contreras|first1=Oscar A.|last2=Lizarrondo|first2=Sara Martinez de|last3=Bardou|first3=Isabelle|last4=Orset|first4=Cyrille|last5=Pruvost|first5=Mathilde|last6=Anfray|first6=Antoine|last7=Frigout|first7=Yvann|last8=Hommet|first8=Yannick|last9=Lebouvier|first9=Laurent|date=2016-01-01|title=Hyperfibrinolysis increases blood brain barrier permeability by a plasmin and bradykinin-dependent mechanism|journal=Blood|language=en|pages=blood–2016-03-705384|doi=10.1182/blood-2016-03-705384|issn=0006-4971|pmid=27531677|volume=128|issue=20 |doi-access=free}}

Bleeding is caused by the generation of fibrinogen degradation products which interfere with regular fibrin polymerization and inhibit platelet aggregation. Moreover, plasmin which is formed in excess in hyperfibrinolysis can proteolytically activate or inactivate many plasmatic or cellular proteins involved in hemostasis. Especially the degradation of fibrinogen, an essential protein for platelet aggregation and clot stability, may be a major cause for clinical bleeding.