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Thromb Haemost 1993; 69(01): 025-028
DOI: 10.1055/s-0038-1651542
Original Article
Coagulation
Schattauer GmbH Stuttgart

Intravascular Coagulation in Liver Transplantation – Is It Present or Not?

A Comparison between Orthotopic and Heterotopic Liver Transplantation
C M Bakker
1   The Department of International Medicine, University Hospital Dijkzigt, Rotterdam, The Netherlands
2   The Department of Hematology, University Hospital Dijkzigt, Rotterdam, The Netherlands
,
H J Metselaar
1   The Department of International Medicine, University Hospital Dijkzigt, Rotterdam, The Netherlands
,
M J Gomes
2   The Department of Hematology, University Hospital Dijkzigt, Rotterdam, The Netherlands
,
R J Porte
1   The Department of International Medicine, University Hospital Dijkzigt, Rotterdam, The Netherlands
,
Th N Groenland
3   The Department of Anesthesiology, University Hospital Dijkzigt, Rotterdam, The Netherlands
,
S W Schalm
1   The Department of International Medicine, University Hospital Dijkzigt, Rotterdam, The Netherlands
,
O T Terpstra
4   The Department of Surgery, University Hospital Dijkzigt, Rotterdam, The Netherlands
,
J Stibbe
2   The Department of Hematology, University Hospital Dijkzigt, Rotterdam, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 12 June 1992

Accepted after revision 19 August 1992

Publication Date:
04 July 2018 (online)

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Summary

It is still not clear whether disseminated intravascular coagulation (DIC) contributes to the hemostatic disturbances in orthotopic liver transplantation (OLT). Theoretically the lack of hepatic clearance of procoagulant factors during the anhepatic period and the release of thromboplastic material from the graft might trigger DIC. During heterotopic liver transplantation (HLT) the host liver is left in situ and procoagulant factors may still be cleared; DIC, if present, may not occur until after reperfusion. The aim of the present study was to gain more insight into the underlying mechanism of the coagulation changes during liver transplantation by comparison of OLT and HLT. Thrombin-antithrombin-III complexes (TAT), and indicator of thrombin generation, fibrin degradation products (FbDP) and routine clotting times were assayed in 12 OLTs, 18 HLTs and in a control group of 10 partial hepatic resections (PHR).

TAT increased dramatically after reperfusion to 136 μg/l in OLT and to 94 μg/l in HLT (p n.s.). In contrast, FbDP levels increased only in OLT, to a maximum of 13.8 μg/ml. Routine clotting times changed mildly and similarly in both OLT and HLT.

Conclusions: Graft reperfusion triggers excessive thrombin formation, but there are no other signs of subsequent DIC. Any thrombin formed is probably rapidly inhibited by antithrombin-III. The rise in FbDP during OLT is the result of increased fibrinolysis, which occurred only in OLT and not in HLT.

 

  • References

  • 1 Maddrey WC, van Thiel DH. Liver transplantation: An Overview. Hepatology 1988; 8: 948-959
    CrossrefPubMedGoogle Scholar
  • 2 Starzl TE, Iwatsuki S, van Thiel DH, Gartner JC, Zitelli BJ, Malatack JJ, Schade RR, Shaw Jr BW, Hakala TR, Rosenthal JT, Porter KA. Evolution of liver transplantation. Hepatology 1982; 2: 614-636
    PubMedGoogle Scholar
  • 3 Porte RJ, Knot EAR, Bontempo FA. Hemostasis in liver transplantation. Gastroenterology 1989; 97: 488-501
    CrossrefPubMedGoogle Scholar
  • 4 Dzik WH, Arkin CF, Jenkins RL, Stump DC. Fibrinolysis during liver transplantation in humans: role of tissue-type plasminogen activator. Blood 1988; 71: 1090-1095
    CrossrefPubMedGoogle Scholar
  • 5 Porte RJ, Bontempo FA, Knot EAR, Lewis JH, Kang YG, Starzl TE. Tissue�type-plasminogen-activator-associated fibrinolysis in orthotopic liver transplantation. Transplant Proc 1989; 21: 3542
    PubMedGoogle Scholar
  • 6 Böhmig HJ. The coagulation disorder or orthotopic hepatic transplantation. Semin Thromb Hemostas 1977; 4: 57-82
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Palaretti G, Legagni C, Maccaferri M, Grozetti G, Mazziotti A, Martinelli G, Zanello M, Sama C, Coccheri S. Coagulation and fibrinolysis in orthotopic liver transplantation: The role of the recipient’s disease and the use of antithrombin-III concentrates. Haemostasis 1991; 21: 68-76
    PubMedGoogle Scholar
  • 8 Owen CA, Rettke SR, Bowie EJW, Cole TL, Jensen CC, Wiesner RH, Krom RAF. Hemostatic evaluation of patients undergoing liver transplantation. Mayo Clin Proc 1987; 62: 761-772
    CrossrefPubMedGoogle Scholar
  • 9 Porte RJ, de Jong E, Knot EAR, de Maat MPM, Terpstra OT, van Urk H, Groenland THN. Monitoring heparin and hemostasis during reconstructions of the abdominal aorta. Eur J Vase Surg 1987; 1: 397-402
    CrossrefPubMedGoogle Scholar
  • 10 Homatas J, Wasantapruek S, van Kaulla KN, Eiseman B. Clotting abnormalities following orthotopic and heterotopic transplantation of marginally preserved pig livers. Acta Hepato-splenol 1969; 2: 14-27
    PubMedGoogle Scholar
  • 11 Wasantapruek S, Homatas J, von Kaulla KN, Eiseman B. Clotting abnormalities including intravascular coagulation following transplantation of preserved livers in pigs. Thromb Diath Haemorrh 1969; 36 suppl 319-332
    PubMedGoogle Scholar
  • 12 Perkins HA, May RE, Belzer FO. Cause of abnormal bleeding after transplantation of pig liver stored by a perfusion technique. Arch Surg 1970; 101: 62-68
    CrossrefPubMedGoogle Scholar
  • 13 Hutchison DE, Genton E, Porter KA, Daloze PM, Huguet C, Brettschneider L, Groth CG, Starzl TE. Platelet changes following clinical and experimental hepatic homotransplantation. Arch Surg 1968; 97: 27-33
    CrossrefPubMedGoogle Scholar
  • 14 Porter KA. Pathology of the orthotopic homograft and heterograft. In: Experience in hepatic transplantation. Starzl TE, Putman CW. (eds). Philadelphia, PA: W. B. Saunders; 1969: 422-472
    Google Scholar
  • 15 Terpstra OT, Reuvers CB, Schalm SW. Auxiliary heterotopic liver transplantation. Transplantation 1988; 45: 1003-1007
    CrossrefPubMedGoogle Scholar
  • 16 Metselaar HJ, Hesselink EJ, de Rave S, ten Kate FJW, Laméris JS, Groenland THN, Reuvers CB, Weimar W, Terpstra OT, Schalm SW. Recovery of failing liver after auxiliary heterotopic transplantation. Lancet 1990; 1: 1156-1157
    PubMedGoogle Scholar
  • 17 Pelzer H, Schwarz A, Heimburger N. Determination of thrombin-antithrombin III complex in plasma with an enzyme-linked immunosorbent assay. Thromb Haemostas 1988; 59: 101-106
    PubMedGoogle Scholar
  • 18 Iwatsuki S, Shaw BW Jr, Starzl TE. Current status of hepatic transplantation. Semin Liver Dis 1983; 3: 173-180
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Terpstra OT, Schalm SW, Weimar W, Willemse PJA, Baumgartner D, Groenland THN, ten Kate FJW, Porte RJ, de Rave S, Reuvers CB, Stibbe J, Terpstra JL. Auxiliary partial liver transplantation for end-stage chronic liver disease. N Engl J Med 1988; 319: 1507-1511
    CrossrefPubMedGoogle Scholar
  • 20 Koppert PW, Hoegee-de NobelE, Nieuwenhuizen W. A monoclonal antibody-based enzyme immunoassay for fibrin degradation products in plasma. Thromb Haemostas 1988; 59: 310-315
    PubMedGoogle Scholar
  • 21 Abildgaard U, Lie M, Odegaard OR. Antithrombin (heparin cofactor) assay with "new" chromogenic substrates (S-2238 and Chromozym TH). Thromb Res 1977; 11: 549-553
    CrossrefPubMedGoogle Scholar
  • 22 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol (Basel) 1957; 17: 237-246
    CrossrefPubMedGoogle Scholar
  • 23 Pugh RNH, Murray-Lyon IM, Dawson JL, Pietroni MC, Wiliams R. Transection of the oesophagus for bleeding of oesophageal varices. Br J Surg 1973; 60: 646-649
    CrossrefPubMedGoogle Scholar
  • 24 Thurman RG, Marzi I, Seitz J, Lemasters JJ, Zimmermann FA. Hepatic reperfusion injury following orthotopic liver transplantation in the rat. Transplantation 1988; 46: 502-506
    CrossrefPubMedGoogle Scholar
  • 25 Caldwell-Kenkel JC, Currin RT, Tanaka Y, Thurman RG, Lemasters JJ. Reperfusion injury to endothelial cells following cold ischemic storage of rat livers. Hepatology 1989; 10: 292-299
    CrossrefPubMedGoogle Scholar
  • 26 McCord JM. Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med 1985; 312: 159-163
    CrossrefPubMedGoogle Scholar
  • 27 McKeown CMB, Edwards V, Philips MJ, Harvey PRC, Petrunka CN, Strasberg SM. Sinusoidal lining cell damage: the critical injury in cold preservation of liver allografts in the rat. Transplantation 1988; 46: 178-182
    CrossrefPubMedGoogle Scholar
  • 28 Takei Y, Marzi I, Kauffman FC, Currin RT, Lemasters JJ, Thurman RG. Increase in survival time of liver transplants by protease inhibitors and a calcium channel blocker, nisoldipine. Transplantation 1990; 50: 14-20
    CrossrefPubMedGoogle Scholar
  • 29 Nawroth PP, Handley D, Stern DM. The multiple levels of endothelial cell-coagulation factor interactions. Clin Haematol 1986; 15: 293-321
    PubMedGoogle Scholar
  • 30 Riess H, Jochum M, Machleidt W, Himmelreich G, Blumhardt G, Roissaint R, Neuhaus P. Possible role of extracellularly released phagocyte proteinases in coagulation disorder during liver transplantation. Transplantation 1991; 52: 482-490
    CrossrefPubMedGoogle Scholar
  • 31 Kim YI, Kawano K, Nakashima K, Goto S, Kobayshi M. Alleviation of 3.5-hour warm ischemic injury of the liver in pigs by cyclosporine pretherapy. Transplantation 1991; 51: 731-733
    CrossrefPubMedGoogle Scholar
  • 32 Bakker CM, Metselaar HJ, Groenland THN, Terpstra OT, Stibbe J. Increased fibrinolysis in orthotopic but not in heterotopic liver transplantation; the role of the anhepatic phase. Transplant Int 1992; 5 (Suppl. 01) 173-174
    CrossrefPubMedGoogle Scholar
  • 33 Bakker CM, Metselaar HJ, Gorenland THN, Gomes M, Knot EAR, Hesselink EJ, Schalm SW, Stibbe J, Terpstra OT. Increased tissue-type plasminogen activator activity in orthotopic but not in heterotopic liver transplantation: The role of the anhepatic period. Hepatology. 1992 (in press).
    PubMedGoogle Scholar
  • 34 Bakker CM, Knot EAR, Stibbe J, Wilson JHP. Disseminated intravascular coagulation in liver cirrhosis. J Hepatol. 1992 (in press).
    PubMedGoogle Scholar
  • 35 Blankert B, Nekek S, Vinazzer H, Beymann H. Substitution therapy with an antithrombin-III in shock and DIC. Thromb Res 1982; 27: 271
    CrossrefPubMedGoogle Scholar
  • 36 Vinazzer H. Clinical use of antithrombin concentrate. Vox Sang 1987; 53: 193-198
    PubMedGoogle Scholar
  • 37 Schipper HG, Ten Cate JW. Antithrombin III transfusion in patients with hepatic cirrhosis. Br J Haematol 1982; 52: 25-33
    CrossrefPubMedGoogle Scholar