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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, deficiency of alpha-2-antiplasmin[1] (alpha-2-plasmin inhibitor) or plasminogen activator inhibitor type 1 (PAI-1)[2] are very rare. The affected individuals show a hemophilia-like bleeding phenotype. Acquired hyperfibrinolysis is found in liver disease,[3] in patients with severe trauma,[4] during major surgical procedures,[5] and other conditions.[6] 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.[7] Moreover, hyperfibrinolysis may be associated with blood brain barrier impairment, a plasmin-dependent effect due to an increased generation of bradykinin.[8]

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.


The diagnosis of hyperfibrinolysis is made indirectly with immunochemical methods which detect the elevation of biomarkers such as D-Dimer (cross-linked fibrin degradation products), fibrinogen split products (FSP), complexes of plasmin and alpha-2-antiplasmin (PAP). However, the sensitivity and specificity of these methods is limited because elevation of these biomarkers can also occur induced in other clinical conditions. The classical coagulation tests such as PT (prothrombin time), aPTT (activated partial thromboplastin time) or thrombin time are not very sensitive for hyperfibrinolysis, and influenced by numerous other variables. The euglobulin lysis time test is very time consuming and complex. Viscoelastic methods in whole blood, especially thromboelastometry (TEM) when performed with special reagents detect hyperfibrinolysis very sensitively in a functional approach. The APTEM test, a tissue factor activated, heparin insensitive test performed in the presence of aprotinin (fibrinolysis inhibitor, confirms hyperfibrinolysis by comparing the TEM result of this assay with the EXTEM test (same activator, but without aprotinin). A normalization or improvement of the TEMogram in APTEM versus EXTEM confirms hyperfibrinolysis.[9] This in vitro approach can predict to a certain level if normal clot formation can be restored by use of an antifibrinolytic drug.


Since the use of aprotinin has been abandoned due to major side effects, the treatment or prophylaxis of hyperfibrinolysis is made with synthetic drugs such as tranexamic acid, epsilon-aminocaproic acid or other lysine analogues. When used appropriately, antifibriolytic drugs may avoid unnecessary transfusions.[10]


  1. ^ Carpenter SL, Mathew P (2008). "Alpha-2-antiplasmin and its deficiency: fibrinolysis out of balance". Haemophilia. 14: 1250–4. doi:10.1111/j.1365-2516.2008.01766.x. PMID 19141165.
  2. ^ Takahashi Y, Tanaka T, Minowa H, Ookubo Y, Sugimoto M, Nakajima M, Miyauchi Y, Yoshioka A (July 1996). "Hereditary partial deficiency of plasminogen activator inhibitor-1 associated with a lifelong bleeding tendency". International Journal of Hematology. 64 (1): 61–8. PMID 8757969.
  3. ^ Görlinger K (August 2006). "[Coagulation management during liver transplantation]". Hamostaseologie (in German). 26 (3 Suppl 1): S64–76. PMID 16953295.
  4. ^ Levrat A, Gros A, Rugeri L, Inaba K, Floccard B, Negrier C, David JS (2008). "Evaluation of rotation thrombelastography for the diagnosis of hyperfibrinolysis in trauma patients". Br J Anaesth. 100: 792–7. doi:10.1093/bja/aen083.
  5. ^ Vanek T, Jares M, Snircova J, Maly M (December 2007). "Fibrinolysis in coronary artery surgery: detection by thromboelastography". Interactive Cardiovascular and Thoracic Surgery. 6 (6): 700–4. doi:10.1510/icvts.2007.161463. PMID 17709365.
  6. ^ Chapin JC, Hajjar KA (January 2015). "Fibrinolysis and the control of blood coagulation". Blood Reviews. 29 (1): 17–24. doi:10.1016/j.blre.2014.09.003. PMC 4314363. PMID 25294122.
  7. ^ Schöchl H (2008). "Hyperfibrinolysis:a prognostic marker of poor survival following major trauma?". Haemostaseologie. 28: A57.
  8. ^ Marcos-Contreras, Oscar A.; Lizarrondo, Sara Martinez de; Bardou, Isabelle; Orset, Cyrille; Pruvost, Mathilde; Anfray, Antoine; Frigout, Yvann; Hommet, Yannick; Lebouvier, Laurent (2016-01-01). "Hyperfibrinolysis increases blood brain barrier permeability by a plasmin and bradykinin-dependent mechanism". Blood. 128: blood–2016-03-705384. doi:10.1182/blood-2016-03-705384. ISSN 0006-4971. PMID 27531677.
  9. ^ Vorweg M, Hartmann B, Knüttgen D, Jahn MC, Doehn M (December 2001). "Management of fulminant fibrinolysis during abdominal aortic surgery". Journal of Cardiothoracic and Vascular Anesthesia. 15 (6): 764–7. doi:10.1053/jcan.2001.28337. PMID 11748531.
  10. ^ Diprose P, Herbertson MJ, O'Shaughnessy D, Deakin CD, Gill RS (March 2005). "Reducing allogeneic transfusion in cardiac surgery: a randomized double-blind placebo-controlled trial of antifibrinolytic therapies used in addition to intra-operative cell salvage". British Journal of Anaesthesia. 94 (3): 271–8. doi:10.1093/bja/aei044. PMID 15591329.