Download PDF
Semin Thromb Hemost 2008; 34(8): 772-778
DOI: 10.1055/s-0029-1145259
© Thieme Medical Publishers

Hemostatic Abnormalities and Liver Diseases

Hideo Wada1 , Masanobu Usui2 , Nobuo Sakuragawa3 , 4
  • 1Departments of Molecular and Laboratory Medicine, Mie University Graduate School of Medicine, Tsu-city, Japan
  • 2First Department of Surgery, Mie University Graduate School of Medicine, Tsu-city, Japan
  • 3Toyama University, School of Medicine, Toyama City, Toyama, Japan
  • 4Toyoura Hospital, Toyoura, Japan
Further Information

Publication History

Publication Date:
12 February 2009 (online)

   Permissions and Reprints

ABSTRACT

Professor Eberhard F. Mammen greatly contributed to the understanding of the relationship between hemostatic abnormalities and liver diseases. The physiology of the hemostatic system is closely linked to liver function because the liver parenchymal cells produce most of the factors of the clotting and fibrinolytic systems. Acute or chronic hepatocellular diseases and hepatic failure including liver cirrhosis, vitamin K deficiency, liver surgery including liver transplantation, and sclerotherapy of bleeding esophageal varices, which were classified by Prof. Mammen, show various hemostatic abnormalities in the coagulation system, fibrinolytic system, platelets, and the reticuloendothelial system. Hemostatic abnormalities in patients with hepatic failure or in those that have undergone liver surgery are similar to those in disseminated intravascular coagulation. Prof. Mammen also contributed to the study of vitamin K–dependent clotting factors, antithrombin, and hemostatic molecular markers. Partly based on this work, the prothrombin time–international normalized ratio, several hemostatic molecular markers, and antithrombin therapy have been recently developed for the diagnosis and treatment of thrombosis.

KEYWORDS

Liver disease - hemostasis - vitamin K deficiency - disseminated intravascular coagulation

REFERENCES

  • 1 Mammen E F. Coagulopathies of liver disease.  Clin Lab Med. 1994;  14 769-780
    PubMedGoogle Scholar
  • 2 Mammen E F. Coagulation defects in liver disease.  Med Clin North Am. 1994;  78 545-554
    PubMedGoogle Scholar
  • 3 Mammen E F. Coagulation abnormalities in liver disease.  Hematol Oncol Clin North Am. 1992;  6 1247-1257
    PubMedGoogle Scholar
  • 4 Mammen E F. Blood coagulation disorders in liver diseases.  Dtsch Med Wochenschr. 1970;  95 2241-2242
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Carlier M, Van Obbergh L J, Veyckemans F et al.. Hemostasis in children undergoing liver transplantation.  Semin Thromb Hemost. 1993;  19 218-222
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Matsumoto T, Wada H, Nishiyama H et al.. Hemostatic abnormalities and changes following bone marrow transplantation.  Clin Appl Thromb Hemost. 2004;  10 341-350
    CrossrefPubMedGoogle Scholar
  • 7 Stafford D W. The vitamin K cycle.  J Thromb Haemost. 2005;  3 1873-1878
    CrossrefPubMedGoogle Scholar
  • 8 Aljabiri M R, Lodato F, Burroughs A K. Surveillance and diagnosis for hepatocellular carcinoma.  Liver Transpl. 2007;  13 S2-S12
    CrossrefPubMedGoogle Scholar
  • 9 Tripodi A, Chantarangkul V, Mannucci P M. The international normalized ratio to prioritize patients for liver transplantation: problems and possible solutions.  J Thromb Haemost. 2008;  6 243-248
    CrossrefPubMedGoogle Scholar
  • 10 Akiyama K, Nakamura K, Makino I et al.. Antithrombin III producing hepatocellular carcinoma.  Thromb Res. 1993;  72 193-201
    CrossrefPubMedGoogle Scholar
  • 11 Koike C, Hayakawa Y, Niiya K, Sakuragawa N, Sasaki H. The production of heparin cofactor II is not regulated by inflammatory cytokines in human hepatoma cells: comparison with plasminogen activator inhibitor type-1.  Thromb Haemost. 1996;  75 298-302
    PubMedGoogle Scholar
  • 12 Mammen E F. Antithrombin: its physiological importance and role in DIC.  Semin Thromb Hemost. 1998;  24 19-25
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Mammen E F. Clinical relevance of antithrombin deficiencies.  Semin Hematol. 1995;  32(Suppl 2) 2-6
    PubMedGoogle Scholar
  • 14 Wada H, Sakuragawa N, Shiku H. Hemostatic molecular markers before onset of disseminated intravascular coagulation in leukemic patients.  Semin Thromb Hemost. 1998;  24 293-297
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Hirose K, Okajima K, Uchiba M, Nakano K Y, Utoh J, Kitamura N. Antithrombin reduces the ischemia/reperfusion-induced spinal cord injury in rats by attenuating inflammatory responses.  Thromb Haemost. 2004;  91 162-170
    PubMedGoogle Scholar
  • 16 Warren B L, Eid A, Singer P et al.. KyberSept Trial Study Group: caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial.  JAMA. 2001;  286 1869-1878
    CrossrefPubMedGoogle Scholar
  • 17 Kienast J, Juers M, Wiedermann C J et al.. KyberSept investigators: treatment effects of high-dose antithrombin without concomitant heparin in patients with severe sepsis with or without disseminated intravascular coagulation.  J Thromb Haemost. 2006;  4 90-97
    CrossrefPubMedGoogle Scholar
  • 18 Sakuragawa N. Regulation of thrombosis and hemostasis by antithrombin.  Semin Thromb Hemost. 1997;  23 557-562
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Okabayashi K, Wada H, Ohta S, Shiku H, Nobori T, Maruyama K. Hemostatic markers and the sepsis-related organ failure assessment score in patients with disseminated intravascular coagulation in an intensive care unit.  Am J Hematol. 2004;  76 225-229
    CrossrefPubMedGoogle Scholar
  • 20 Griffin G C, Mammen E F, Sokol R J, Perrotta A L, Stoyanovich A, Abildgaard C F. Alpha 2-antiplasmin deficiency. An overlooked cause of hemorrhage.  Am J Pediatr Hematol Oncol. 1993;  15 328-330
    PubMedGoogle Scholar
  • 21 Koyama T, Kakishita E, Nakai Y, Okamoto E. Significance of hemostatic molecular markers during disseminated intravascular coagulation in patients with liver cirrhosis treated by endoscopic embolization for esophageal varices.  Am J Hematol. 1991;  38 90-94
    CrossrefPubMedGoogle Scholar
  • 22 Kuter D J, Begley C G. Recombinant human thrombopoietin: basic biology and evaluation of clinical studies.  Blood. 2002;  100 3457-3469
    CrossrefPubMedGoogle Scholar
  • 23 Fujikawa K, Suzuki H, McMullen B, Chung D. Purification of human von Willebrand factor-cleaving protease and its identification as a new member of the metalloproteinase family.  Blood. 2001;  98 1662-1666
    CrossrefPubMedGoogle Scholar
  • 24 Faeh M, Hauser S P, Nydegger U E. Transient thrombopoietin peak after liver transplantation for end-stage liver disease.  Br J Haematol. 2001;  112 493-498
    CrossrefPubMedGoogle Scholar
  • 25 Fujimura Y, Matsumoto M, Yagi H, Yoshioka A, Matsui T, Titani K. Von Willebrand factor-cleaving protease and Upshaw-Schulman syndrome.  Int J Hematol. 2002;  75 25-34
    CrossrefPubMedGoogle Scholar
  • 26 Ko S, Okano E, Kanehiro H et al.. Plasma ADAMTS13 activity may predict early adverse events in living donor liver transplantation: observations in 3 cases.  Liver Transpl. 2006;  12 859-869
    CrossrefPubMedGoogle Scholar
  • 27 Taylor Jr F B, Toh C H, Hoots K, Wada H, Levi M. Towards a definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation.  Thromb Haemost. 2001;  86 1327-1330
    Article in Thieme ConnectPubMedGoogle Scholar
  • 28 Wada H. Disseminated intravascular coagulation.  Clin Chim Acta. 2004;  344 13-21
    CrossrefPubMedGoogle Scholar
  • 29 Soria J, Soria C, Ryckewaert J J, Samama M, Thomson J M, Poller L. Study of acquired dysfibrinogenaemia in liver disease.  Thromb Res. 1980;  19 29-41
    CrossrefPubMedGoogle Scholar
  • 30 Hoak D R, Mammen E F, Banerjee S K, Kaldor G. A fully automated immuno-turbidimetric determination of fibrin(ogen) degradation products.  Thromb Res. 1986;  44 1-10
    CrossrefPubMedGoogle Scholar
  • 31 Wada H, Kobayashi T, Abe Y et al.. Elevated levels of soluble fibrin or D-dimer indicate high risk of thrombosis.  J Thromb Haemost. 2006;  4 1253-1258
    CrossrefPubMedGoogle Scholar
  • 32 de Moerloose P, Palareti G, Aguilar C, Legnani C, Reber G, Peetz D. A multicenter evaluation of a new quantitative highly sensitive D-dimer assay for exclusion of venous thromboembolism.  Thromb Haemost. 2008;  100 505-512
    PubMedGoogle Scholar
  • 33 Roffi L, Colloredo G, Pioltelli P et al.. Gruppo Epatologico Lombardo. Pegylated interferon-alpha2b plus ribavirin: an efficacious and well-tolerated treatment regimen for patients with hepatitis C virus related histologically proven cirrhosis.  Antivir Ther. 2008;  13 663-673
    PubMedGoogle Scholar
  • 34 Wilson R F, Mammen E, Walt A J. Eight years of experience with massive blood transfusions.  J Trauma. 1971;  11 275-285
    PubMedGoogle Scholar
  • 35 Jones A L, Hulett M D, Parish C R. Histidine-rich glycoprotein: a novel adaptor protein in plasma that modulates the immune, vascular and coagulation systems.  Immunol Cell Biol. 2005;  83 106-118
    CrossrefPubMedGoogle Scholar
  • 36 Gando S, Iba T, Eguchi Y for the Japanese Association for Acute Medicine Disseminated Intravascular Coagulation et al. (JAAM DIC) Study Group: a multicenter, prospective validation of disseminated intravascular coagulation diagnostic criteria for critically ill patients: comparing current criteria.  Crit Care Med. 2006;  34 625-631
    CrossrefPubMedGoogle Scholar
  • 37 Dargaud Y, Desmurs-Clavel H, Marin S, Bordet J C, Poplavsky J L, Negrier C. Comparison of the capacities of two prothrombin complex concentrates to restore thrombin generation in plasma from orally anticoagulated patients: an in vitro study.  J Thromb Haemost. 2008;  6 962-968
    CrossrefPubMedGoogle Scholar
  • 38 Walenga J M, Hoppensteadt D A. Monitoring the new antithrombotic drugs.  Semin Thromb Hemost. 2004;  30 683-695
    Article in Thieme ConnectPubMedGoogle Scholar
  • 39 Rost S, Fregin A, Ivaskevicius V et al.. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2.  Nature. 2004;  427 537-541
    CrossrefPubMedGoogle Scholar
  • 40 Wadelius M, Chen L Y, Lindh J D et al.. The largest prospective warfarin-treated cohort supports genetic forecasting.  Blood. 2008;  , June 23 [Epub ahead of print]
    PubMedGoogle Scholar
  • 41 Wilson R F, Mammen E F, Robson M C, Heggers J P, Soullier G, DePoli P A. Antithrombin, prekallikrein, and fibronectin levels in surgical patients.  Arch Surg. 1986;  121 635-640
    PubMedGoogle Scholar
  • 42 Senzolo M, Burra P, Cholongitas E, Burroughs A K. New insights into the coagulopathy of liver disease and liver transplantation.  World J Gastroenterol. 2006;  12 7725-7736
    PubMedGoogle Scholar
  • 43 Bezeaud A, Denninger M H, Dondero F et al.. Hypercoagulability after partial liver resection.  Thromb Haemost. 2007;  98 1252-1256
    PubMedGoogle Scholar
  • 44 Porte R J. Coagulation and fibrinolysis in orthotopic liver transplantation: current views and insights.  Semin Thromb Hemost. 1993;  19 191-196
    Article in Thieme ConnectPubMedGoogle Scholar
  • 45 Abe Y, Wada H, Yamada E et al.. The effectiveness of measuring for fragmented red cells using an automated hematology analyzer in patients with thrombotic microangiopathy.  Clin Appl Thromb Hemost. 2008;  ,  July 3 [Epud ahead of print]
    PubMedGoogle Scholar
  • 46 Cerutti E, Stratta C, Romagnoli R et al.. Thromboelastogram monitoring in the perioperative period of hepatectomy for adult living liver donation.  Liver Transpl. 2004;  10 289-294
    CrossrefPubMedGoogle Scholar
  • 47 Wada H, Wakita Y, Shiku H. Tissue factor expression in endothelial cells in health and disease.  Blood Coagul Fibrinolysis. 1995;  6 S26-S31
    CrossrefPubMedGoogle Scholar
  • 48 Fujii Y, Sugawa C, Ozawa T, Nakumura R, Brown-Castillo J, Mammen E F. Hemostasis activation during esophageal variceal sclerotherapy with thrombin in cirrhotics.  Am Surg. 1991;  57 222-225
    PubMedGoogle Scholar

Prof. Hideo WadaM.D. Ph.D. 

Department of Laboratory Medicine, Mie University School of Medicine

2-174 Edobashi, Tsu-city, Mie-ken 514-8507, Japan

Email: wadahide@clin.medic.mie-u.ac.jp

      >