Clinical Significance of Accelerated Fibrinolysis in Liver Disease

Francis, Robert B.; Feinstein, Donald I.

doi:10.1159/000215106

Cited by 44 publications

(45 citation statements)

References 10 publications

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“…Irrespective of the etiology, in cases of severe cirrhosis, hyperfibrinolysis occurs when plasminogen activation by tissue plasminogen activator is accelerated on the fibrin surface, which remains unbalanced by decreased levels of plasminogen activator inhibitor type 1 and alpha2-antiplasmin (31). Since no standardized global test is currently available to measure both profibrinolytic and antifibrinolytic activators (32), previous studies have been based on individual fibrinolysis tests (33)(34)(35). Meanwhile, Hu et al demonstrated hyperfibrinolysis (defined as a shortened euglobulin lysis time of < 120 minutes) in 31.3% (27/75) of patients with cirrhosis; this condition was found to be positively correlated with the severity of liver disease, such as a high Child-Pugh score (35).…”

Section: Discussionmentioning

confidence: 99%

Alcoholic Liver Disease Complicated by Deep Bleeding into the Muscles or Retroperitoneum: Report of Three Cases and a Review of the Literature

et al. 2014

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We herein report three cases of alcoholic cirrhosis complicated by deep bleeding. In two of the three cases, intramuscular or retroperitoneal hematomas developed spontaneously. In contrast, in the remaining case, an intramuscular hematoma developed after trauma. In the former two patients, the intramuscular hematomas recurred at other sites during hospitalization. All three patients received conservative therapy, and one patient with a retroperitoneal hematoma underwent transcatheter arterial embolization. All of the patients eventually died of liver failure. The occurrence of severe alcoholic liver disease with deep bleeding has recently been reported with increasing frequency, and clinicians should bear this condition in mind as a life-threatening complication of alcoholic liver disease.

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Section: Discussionmentioning

confidence: 99%

Alcoholic Liver Disease Complicated by Deep Bleeding into the Muscles or Retroperitoneum: Report of Three Cases and a Review of the Literature

et al. 2014

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“…Indeed, patients with severe liver cirrho sis (but not primary biliary cirrhosis) usually undergo OLT with a deeply altered clotting mechanism, including low-grade intravascu lar coagulation [18][19][20] and enhanced fibrinolytic activity [21,22]. Increased plas minogen activators [23], reduced PAI and a 2-antiplasmin [24], and increased plasmin ogen-independent proteases secreted by mononuclear cells [25] may all concur to activate fibrinolysis in this clinical condi tion.…”

Section: Discussionmentioning

confidence: 99%

Coagulation and Fibrinolysis in Orthotopic Liver Transplantation: Role of the Recipient’s Disease and Use of Antithrombin III Concentrates

Palareti¹,

Legnani²,

Maccaferri³

et al. 1991

Pathophysiol Haemos Thromb

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In this study we report the data obtained from extensive haemostatic testing of 25 patients undergoing orthotopic liver transplantation and the results of an open randomized pilot trial of antithrombin III concentrate administration during surgery. Marked differences in transfusional needs and in pre- and intraoperative blood coagulation and fibrinolytic changes were observed between recipients with liver cirrhosis and those with primary biliary cirrhosis. In the former, the increases in tissue-type plasminogen activator activity, total euglobulin fibrinolytic activity, and fibrin-derived degradation products occurred earlier and were more marked, as were the signs of increased thrombin formation. Supplementation of antithrombin III concentrate during surgery failed to induce significant changes in the main parameters studied and in the transfusional needs.

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“…[1][2][3] In addition, some patients with cirrhosis show hyperfibrinolysis [4][5][6] or, less frequently, chronic intravascular coagulation, 7 which may combine to further reduce plasma coagulation factors. These complex defects can be documented through the measurement of coagulation factors which are, with the only exception of factor VIII, 8 below normal limits, or through the prolongation of such global tests as the prothrombin time (PT) and the activated partial thromboplastin time (APTT).…”

mentioning

confidence: 99%

Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests

et al. 2005

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The role played by coagulation defects in the occurrence of bleeding in cirrhosis is still unclear. This is partly due to the lack of tests that truly reflect the balance of procoagulant and anticoagulant factors in vivo. Conventional coagulation tests such as prothrombin time and activated partial thromboplastin time are inadequate to explore the physiological mechanism regulating thrombin, because they do not allow full activation of the main anticoagulant factor, protein C, whose levels are considerably reduced in cirrhosis. We used a thrombin generation test to investigate the coagulation function in patients with cirrhosis. Thrombin generation measured without thrombomodulin was impaired, which is consistent with the reduced levels of procoagulant factors typically found in cirrhosis. However, when the test was modified by adding thrombomodulin (i.e., the protein C activator operating in vivo), patients generated as much thrombin as controls. Hence, the reduction of procoagulant factors in patients with cirrhosis is compensated by the reduction of anticoagulant factors, thus leaving the coagulation balance unaltered. These findings help clarify the pathophysiology of hemostasis in cirrhosis, suggesting that bleeding is mainly due to the presence of hemodynamic alterations and that conventional coagulation tests are unlikely to reflect the coagulation status of these patients. In conclusion, generation of thrombin is normal in cirrhosis.

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Clinical Significance of Accelerated Fibrinolysis in Liver Disease

Cited by 44 publications

References 10 publications

Alcoholic Liver Disease Complicated by Deep Bleeding into the Muscles or Retroperitoneum: Report of Three Cases and a Review of the Literature

Alcoholic Liver Disease Complicated by Deep Bleeding into the Muscles or Retroperitoneum: Report of Three Cases and a Review of the Literature

Coagulation and Fibrinolysis in Orthotopic Liver Transplantation: Role of the Recipient’s Disease and Use of Antithrombin III Concentrates

Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests

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