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Erschienen in: International Journal of Hematology 4/2014

01.04.2014 | Original Article

Prolonged thrombocytopenia after living donor liver transplantation is a strong prognostic predictor irrespective of history of splenectomy: the significance of ADAMTS13 and graft function

verfasst von: Yu Nobuoka, Hideo Wada, Shugo Mizuno, Masashi Kishiwada, Masanobu Usui, Hiroyuki Sakurai, Masami Tabata, Toshihiko Kobayashi, Tsutomu Nobori, Shinji Uemoto, Shuji Isaji

Erschienen in: International Journal of Hematology | Ausgabe 4/2014

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Abstract

The precise mechanism of prolonged thrombocytopenia following living donor liver transplantation (LDLT) remains unclear. To determine risk factors associated with prolonged thrombocytopenia following LDLT, with a focus on the activity of ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs member 13) and the influence of splenectomy. Adult LDLT patients were divided into two groups on the basis of platelet counts (100 × 103/μL) on POD 14: high and low platelet (HP and LP) groups. Survival analysis was performed in the 100 patients, and ADAMTS13 activity and von Willebrand factor (VWF) levels in the plasma were measured in 65 adult recipients. The 6-month survival rate was significantly lower in the LP group (n = 36) than in the HP group (n = 62) (61.1 vs. 93.5 %). ADAMTS13 activity had been significantly lower in the LP group (n = 23) than in the HP group (n = 42). The VWF/ADAMTS13 ratio was significantly higher in the LP group than in the HP group. The independent risk factors for thrombocytopenia on POD14 were preoperative AT levels and ADAMTS13 activity on POD14. TPO levels on POD14 were significantly higher in the LP group than in the HP group, while those on POD28 in the LP group were significantly decreased, despite the low platelet levels. Irrespective of splenectomy history, platelet counts and ADAMTS13 activity in the LP group remained low until POD28, while VWF/ADAMTS13 ratio significantly increased until POD28. These results suggest that prolonged thrombocytopenia after LDLT was associated with not only a decrease in ADAMTS13 due to sinusoidal endothelial cell injury, but also low TPO production due to hepatocyte dysfunction, irrespective of history of splenectomy.
Literatur
1.
Zurück zum Zitat Kishi Y, Sugawara Y, Akamatsu N, Kaneko J, Tamura S, Kokudo N, et al. Splenectomy and preemptive interferon therapy for hepatitis C patients after living- donor liver transplantation. Clin Transpl. 2005;19(6):769–72.CrossRef Kishi Y, Sugawara Y, Akamatsu N, Kaneko J, Tamura S, Kokudo N, et al. Splenectomy and preemptive interferon therapy for hepatitis C patients after living- donor liver transplantation. Clin Transpl. 2005;19(6):769–72.CrossRef
2.
Zurück zum Zitat Marubashi S, Dono K, Miyamoto A, Takeda Y, Nagano H, Umeshita K, et al. Impact of graft size on postoperative thrombocytopenia in living donor liver transplant. Arch Surg. 2007;142(11):1054–8.CrossRefPubMed Marubashi S, Dono K, Miyamoto A, Takeda Y, Nagano H, Umeshita K, et al. Impact of graft size on postoperative thrombocytopenia in living donor liver transplant. Arch Surg. 2007;142(11):1054–8.CrossRefPubMed
3.
Zurück zum Zitat Yoshizumi T, Taketomi A, Soejima Y, Ikegami T, Uchiyama H, Kayashima H, et al. The beneficial role of simultaneous splenectomy in living donor liver transplantation in patients with small-for-size graft. Transpl Int. 2008;21(9):833–42.CrossRefPubMed Yoshizumi T, Taketomi A, Soejima Y, Ikegami T, Uchiyama H, Kayashima H, et al. The beneficial role of simultaneous splenectomy in living donor liver transplantation in patients with small-for-size graft. Transpl Int. 2008;21(9):833–42.CrossRefPubMed
4.
Zurück zum Zitat Kobayashi T, Wada H, Usui M, Sakurai H, Matsumoto T, Nobori T, et al. Decreased ADAMTS13 levels in patients after living donor liver transplantation. Thromb Res. 2009;124(5):541–5.CrossRefPubMed Kobayashi T, Wada H, Usui M, Sakurai H, Matsumoto T, Nobori T, et al. Decreased ADAMTS13 levels in patients after living donor liver transplantation. Thromb Res. 2009;124(5):541–5.CrossRefPubMed
5.
Zurück zum Zitat Soejima K, Mimura N, Hirashima M, Maeda H, Hamamoto T, Nakagaki T, et al. A novel human metalloprotease synthesized in the liver and secreted into the blood: possibly, the von Willebrand factor-cleaving protease? J Biochem. 2001;130(4):475–80.CrossRefPubMed Soejima K, Mimura N, Hirashima M, Maeda H, Hamamoto T, Nakagaki T, et al. A novel human metalloprotease synthesized in the liver and secreted into the blood: possibly, the von Willebrand factor-cleaving protease? J Biochem. 2001;130(4):475–80.CrossRefPubMed
6.
Zurück zum Zitat Levy GG, Nichols WC, Lian EC, Foroud T, McClintick JN, McGee BM, et al. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature. 2001;413(6855):488–94.CrossRefPubMed Levy GG, Nichols WC, Lian EC, Foroud T, McClintick JN, McGee BM, et al. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature. 2001;413(6855):488–94.CrossRefPubMed
7.
Zurück zum Zitat Zheng X, Chung D, Takayama TK, Majerus EM, Sadler JE, Fujikawa K. Structure of von Willebrand factor-cleaving protease (ADAMTS 13), metalloproteinase involved in thrombotic thrombocytopenic purpura. J Biol Chem. 2001;276(44):41059–63.CrossRefPubMed Zheng X, Chung D, Takayama TK, Majerus EM, Sadler JE, Fujikawa K. Structure of von Willebrand factor-cleaving protease (ADAMTS 13), metalloproteinase involved in thrombotic thrombocytopenic purpura. J Biol Chem. 2001;276(44):41059–63.CrossRefPubMed
8.
Zurück zum Zitat Plaimauer B, Zimmermann K, Völkel D, Antoine G, Kerschbaumer R, Jenab P, et al. Cloning, expression and characterization of the von Willebrand factor-cleaving pro- tease (ADAMTS 13). Blood. 2002;100(10):3626–32.CrossRefPubMed Plaimauer B, Zimmermann K, Völkel D, Antoine G, Kerschbaumer R, Jenab P, et al. Cloning, expression and characterization of the von Willebrand factor-cleaving pro- tease (ADAMTS 13). Blood. 2002;100(10):3626–32.CrossRefPubMed
9.
Zurück zum Zitat Furlan M, Robles R, Galbusera M, Remuzzi G, Kyrle PA, Brenner B, et al. von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. New Engl J Med. 1998;339(22):1578–84.CrossRefPubMed Furlan M, Robles R, Galbusera M, Remuzzi G, Kyrle PA, Brenner B, et al. von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. New Engl J Med. 1998;339(22):1578–84.CrossRefPubMed
10.
Zurück zum Zitat Tsai HM, Lian EC. Antibody to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med. 1998;339(22):1585–94.CrossRefPubMedPubMedCentral Tsai HM, Lian EC. Antibody to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med. 1998;339(22):1585–94.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Uemura M, Fujimura M, Matsumoto M, Ishizashi H, Kato S, Matsuyama T, et al. Comprehensive analysis of ADAMTS13 in patients with liver cirrhosis. Thromb Haemost. 2008;99:1019–29.PubMed Uemura M, Fujimura M, Matsumoto M, Ishizashi H, Kato S, Matsuyama T, et al. Comprehensive analysis of ADAMTS13 in patients with liver cirrhosis. Thromb Haemost. 2008;99:1019–29.PubMed
12.
Zurück zum Zitat Hyun J, Kim HK, Kim JE, Lim MG, Jung JS, Park S, et al. Correlation between plasma activity of ADAMTS-13 and coagulopathy, and prognosis in disseminated intravascular coagulation. Thromb Res. 2009;124(1):75–9.CrossRefPubMed Hyun J, Kim HK, Kim JE, Lim MG, Jung JS, Park S, et al. Correlation between plasma activity of ADAMTS-13 and coagulopathy, and prognosis in disseminated intravascular coagulation. Thromb Res. 2009;124(1):75–9.CrossRefPubMed
13.
Zurück zum Zitat McCaughan GW, Herkes R, Powers B, Rickard K, Gallagher ND, Thompson JF, et al. Thrombocytopenia post liver transplantation. Correlations with pre-operative platelet count, blood transfusion requirements, allograft function and outcome. J Hepatol. 1992;16(1–2):16–22.CrossRefPubMed McCaughan GW, Herkes R, Powers B, Rickard K, Gallagher ND, Thompson JF, et al. Thrombocytopenia post liver transplantation. Correlations with pre-operative platelet count, blood transfusion requirements, allograft function and outcome. J Hepatol. 1992;16(1–2):16–22.CrossRefPubMed
14.
Zurück zum Zitat Chatzipetrou MA, Tsaroucha AK, Weppler D, Pappas PA, Kenyon NS, Nery JR, et al. Thrombocytopenia after liver transplantation. Transplantation. 1999;67(5):702–6.CrossRefPubMed Chatzipetrou MA, Tsaroucha AK, Weppler D, Pappas PA, Kenyon NS, Nery JR, et al. Thrombocytopenia after liver transplantation. Transplantation. 1999;67(5):702–6.CrossRefPubMed
15.
Zurück zum Zitat Chang FY, Singh N, Gayowski T, Wagener MM, Mietzner SM, Stout JE, et al. Thrombocytopenia in liver transplant recipients: predictors, impact on fungal infections, and role of endogenous thrombopoietin. Transplantation. 2000;69(1):70–5.CrossRefPubMed Chang FY, Singh N, Gayowski T, Wagener MM, Mietzner SM, Stout JE, et al. Thrombocytopenia in liver transplant recipients: predictors, impact on fungal infections, and role of endogenous thrombopoietin. Transplantation. 2000;69(1):70–5.CrossRefPubMed
16.
Zurück zum Zitat Ben Hamida C, Lauzet JY, Rézaiguia-Delclaux S, Duvoux C, Cherqui D, Duvaldestin P, et al. Effect of severe thrombocytopenia on patient outcome after liver transplantation. Intensive Care Med. 2003;29(5):756–62.CrossRefPubMed Ben Hamida C, Lauzet JY, Rézaiguia-Delclaux S, Duvoux C, Cherqui D, Duvaldestin P, et al. Effect of severe thrombocytopenia on patient outcome after liver transplantation. Intensive Care Med. 2003;29(5):756–62.CrossRefPubMed
17.
18.
Zurück zum Zitat Iu S, Harvey PRC, Makowka L, Petrunka CN, Ilson RG, Strasberg SM. Markers of allograft viability in the rat: relationship between transplant viability and liver function in the isolated perfused liver. Transplantation. 1987;44(4):562–9.CrossRefPubMed Iu S, Harvey PRC, Makowka L, Petrunka CN, Ilson RG, Strasberg SM. Markers of allograft viability in the rat: relationship between transplant viability and liver function in the isolated perfused liver. Transplantation. 1987;44(4):562–9.CrossRefPubMed
19.
Zurück zum Zitat Alkozai EM, Nijsten MW, de Jong KP, de Boer MT, Peeters PM, Slooff MJ, et al. Immediate postoperative low platelet count is associated with delayed liver function recovery after partial liver resection. Ann Surg. 2010;251(2):300–6.CrossRefPubMed Alkozai EM, Nijsten MW, de Jong KP, de Boer MT, Peeters PM, Slooff MJ, et al. Immediate postoperative low platelet count is associated with delayed liver function recovery after partial liver resection. Ann Surg. 2010;251(2):300–6.CrossRefPubMed
20.
Zurück zum Zitat Kokame K, Nobe Y, Kokubo Y, Okayama A, Miyata T. FRETS-VWF73, a first fluorogenic substrate for ADAMTS13 assay. Br J Haematol. 2005;129(1):93–100.CrossRefPubMed Kokame K, Nobe Y, Kokubo Y, Okayama A, Miyata T. FRETS-VWF73, a first fluorogenic substrate for ADAMTS13 assay. Br J Haematol. 2005;129(1):93–100.CrossRefPubMed
21.
Zurück zum Zitat Buss DH, Cashell AW, O’Connor ML, Richards F 2nd, Case LD. Occurrence, etiology, and clinical significance of extreme thrombocytosis: a study of 280 cases. Am J Med. 1994;96(3):247–53.CrossRefPubMed Buss DH, Cashell AW, O’Connor ML, Richards F 2nd, Case LD. Occurrence, etiology, and clinical significance of extreme thrombocytosis: a study of 280 cases. Am J Med. 1994;96(3):247–53.CrossRefPubMed
22.
Zurück zum Zitat Ichikawa N, Kitano K, Shimodaira S, Ishida F, Ito T, Kajikawa S, et al. Changes in serum thrombopoietin levels after splenectomy. Acta Haematol. 1998;100(3):137–41.CrossRefPubMed Ichikawa N, Kitano K, Shimodaira S, Ishida F, Ito T, Kajikawa S, et al. Changes in serum thrombopoietin levels after splenectomy. Acta Haematol. 1998;100(3):137–41.CrossRefPubMed
23.
Zurück zum Zitat Richards EM, Alexander GJ, Calne RY, Baglin TP. Thrombocytopenia following liver transplantation is associated with platelet consumption and thrombin generation. Br J Haematol. 1997;98(2):315–21.CrossRefPubMed Richards EM, Alexander GJ, Calne RY, Baglin TP. Thrombocytopenia following liver transplantation is associated with platelet consumption and thrombin generation. Br J Haematol. 1997;98(2):315–21.CrossRefPubMed
24.
Zurück zum Zitat Hernandez LA, Grisham MB, Twohig B, Arfors KE, Harlan JM, Granger DN. Role of neutrophils in ischemia-reperfusion induced microvascular injury. Am J Physiol. 1987;253:H699–703.PubMed Hernandez LA, Grisham MB, Twohig B, Arfors KE, Harlan JM, Granger DN. Role of neutrophils in ischemia-reperfusion induced microvascular injury. Am J Physiol. 1987;253:H699–703.PubMed
25.
Zurück zum Zitat Absher E, Labarrere CA, Carter C, Haag B, Faulk WP. The endothelial heparan sulfate-antithrombin III natural anticoagulant pathway in normal and transplanted human kidneys. Transplantation. 1992;53(4):828–34.CrossRefPubMed Absher E, Labarrere CA, Carter C, Haag B, Faulk WP. The endothelial heparan sulfate-antithrombin III natural anticoagulant pathway in normal and transplanted human kidneys. Transplantation. 1992;53(4):828–34.CrossRefPubMed
26.
27.
Zurück zum Zitat Iu S, Harvey PRC, Makowka L, Petrunka CN, Ilson RG, Strasberg SM. Markers of allograft viability in the rat: relationship between transplant viability and liver function in the isolated perfused liver. Transplantation. 1987;44(4):562–9.CrossRefPubMed Iu S, Harvey PRC, Makowka L, Petrunka CN, Ilson RG, Strasberg SM. Markers of allograft viability in the rat: relationship between transplant viability and liver function in the isolated perfused liver. Transplantation. 1987;44(4):562–9.CrossRefPubMed
28.
Zurück zum Zitat Claus RA, Bockmeyer CL, Budde U, Kentouche K, Sossdorf M, Hilberg T, et al. Variations in the ratio between von Willebrand factor and its cleaving protease during systemic inflammation and association with severity and prognosis of organ failure. Thromb Haemost. 2009;101(2):239–47.PubMed Claus RA, Bockmeyer CL, Budde U, Kentouche K, Sossdorf M, Hilberg T, et al. Variations in the ratio between von Willebrand factor and its cleaving protease during systemic inflammation and association with severity and prognosis of organ failure. Thromb Haemost. 2009;101(2):239–47.PubMed
29.
Zurück zum Zitat Claus RA, Bockmeyer CL, Sossdorf M, Lösche W. The balance between von-Willebrand factor and its cleaving protease ADAMTS13: biomarker in systemic inflammation and development of organ failure? Curr Mol Med. 2010;10(2):236–48.CrossRefPubMed Claus RA, Bockmeyer CL, Sossdorf M, Lösche W. The balance between von-Willebrand factor and its cleaving protease ADAMTS13: biomarker in systemic inflammation and development of organ failure? Curr Mol Med. 2010;10(2):236–48.CrossRefPubMed
30.
Zurück zum Zitat Ko S, Okano E, Kanehiro H, Matsumoto M, Ishizashi H, Uemura M, et al. Plasma ADAMTS13 activity may predict early adverse events in living donor liver transplantation: observations in 3 cases. Liver Transpl. 2006;12(5):859–69.CrossRefPubMed Ko S, Okano E, Kanehiro H, Matsumoto M, Ishizashi H, Uemura M, et al. Plasma ADAMTS13 activity may predict early adverse events in living donor liver transplantation: observations in 3 cases. Liver Transpl. 2006;12(5):859–69.CrossRefPubMed
31.
Zurück zum Zitat Pereboom ITA, Adelmeijer J, van Leeuwen Y, Hendriks HGD, Porte RJ, Lisman T. Development of a severe von Willebrand factor/ADAMTS13 dysbalance during orthotopic liver transplantation. Am J Transpl. 2009;9(5):1189–96.CrossRef Pereboom ITA, Adelmeijer J, van Leeuwen Y, Hendriks HGD, Porte RJ, Lisman T. Development of a severe von Willebrand factor/ADAMTS13 dysbalance during orthotopic liver transplantation. Am J Transpl. 2009;9(5):1189–96.CrossRef
32.
Zurück zum Zitat Mizuno S, Wada H, Hamada T, Nobuoka Y, Tabata M, Nobori T, et al. Lethal hepatic infarction following plasma exchange in living donor liver transplant patients. Transpl Int. 2011;24(7):e57–8.CrossRefPubMed Mizuno S, Wada H, Hamada T, Nobuoka Y, Tabata M, Nobori T, et al. Lethal hepatic infarction following plasma exchange in living donor liver transplant patients. Transpl Int. 2011;24(7):e57–8.CrossRefPubMed
33.
Zurück zum Zitat Hori T, Kaido T, Oike F, Ogura Y, Ogawa K, Yonekawa Y, et al. Thrombotic microangiopathy-like disorder after living-donor liver transplantation: a single-center experience in Japan. World J Gastroenterol. 2011;17(14):1848–57.CrossRefPubMedPubMedCentral Hori T, Kaido T, Oike F, Ogura Y, Ogawa K, Yonekawa Y, et al. Thrombotic microangiopathy-like disorder after living-donor liver transplantation: a single-center experience in Japan. World J Gastroenterol. 2011;17(14):1848–57.CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Nomura S, Ogami K, Kawamura K, Tsukamoto I, Kudo Y, Kanakura Y, et al. Cellular localization of thrombopoietin mRNA in the liver by in situ hybridization. Exp Hematol. 1997;25:565.PubMed Nomura S, Ogami K, Kawamura K, Tsukamoto I, Kudo Y, Kanakura Y, et al. Cellular localization of thrombopoietin mRNA in the liver by in situ hybridization. Exp Hematol. 1997;25:565.PubMed
36.
Zurück zum Zitat Kaushansky K. Thrombopoietin: the primary regulator of megakaryocyte and platelet production. Thromb Haemost. 1995;74:521–5.PubMed Kaushansky K. Thrombopoietin: the primary regulator of megakaryocyte and platelet production. Thromb Haemost. 1995;74:521–5.PubMed
37.
Zurück zum Zitat Kaushansky K. Thrombopoietin: the primary regulator of platelet production. Blood. 1995;86:419–31.PubMed Kaushansky K. Thrombopoietin: the primary regulator of platelet production. Blood. 1995;86:419–31.PubMed
39.
Zurück zum Zitat Kuter DJ. The biology of thrombopoietin and thrombopoietin receptor agonists. Int J Hematol. 2013;98:10–23.CrossRefPubMed Kuter DJ. The biology of thrombopoietin and thrombopoietin receptor agonists. Int J Hematol. 2013;98:10–23.CrossRefPubMed
40.
Zurück zum Zitat Li J, Xia Y, Kuter DJ. Interaction of thrombopoietin with the platelet c-mpl receptor in plasma: binding, internalization, stability and pharmacokinetics. Br J Haematol. 1999;106(2):345–56.CrossRefPubMed Li J, Xia Y, Kuter DJ. Interaction of thrombopoietin with the platelet c-mpl receptor in plasma: binding, internalization, stability and pharmacokinetics. Br J Haematol. 1999;106(2):345–56.CrossRefPubMed
41.
Zurück zum Zitat Fielder PJ, Gurney AL, Stefanich E, Marian M, Moore MW, Carver-Moore K, et al. Regulation of thrombopoietin levels by c-mpl-mediated binding to platelets. Blood. 1996;87(6):2154–61.PubMed Fielder PJ, Gurney AL, Stefanich E, Marian M, Moore MW, Carver-Moore K, et al. Regulation of thrombopoietin levels by c-mpl-mediated binding to platelets. Blood. 1996;87(6):2154–61.PubMed
Metadaten
Titel
Prolonged thrombocytopenia after living donor liver transplantation is a strong prognostic predictor irrespective of history of splenectomy: the significance of ADAMTS13 and graft function
verfasst von
Yu Nobuoka
Hideo Wada
Shugo Mizuno
Masashi Kishiwada
Masanobu Usui
Hiroyuki Sakurai
Masami Tabata
Toshihiko Kobayashi
Tsutomu Nobori
Shinji Uemoto
Shuji Isaji
Publikationsdatum
01.04.2014
Verlag
Springer Japan
Erschienen in
International Journal of Hematology / Ausgabe 4/2014
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-014-1543-9

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