Severe bleeding tendency caused by a rare complication of excessive fibrinolysis with disseminated intravascular coagulation in a 51-year-old Japanese man with prostate cancer: a case report

Journal of Medical Case Reports

Takahisa Imamura¹  Masatoshi Eto³  Yoji Murakami³  Yoshihiro Maeda³  Ken-ichiro Tanoue³  Jiro Honda³  Wataru Takahashi³  Nobuyuki Kai³  Yoshiaki Kawano³  Mitsuhiro Uchiba²  Yoshihiro Wada³ 

[1] Department of Molecular Pathology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan;Department of Blood Transfusion and Cell Therapy, Kumamoto University Hospital, 1-1-1 Honjo, Kumamoto, 860-8556, Japan;Department of Urology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan

关键词: Tranexamic acid;    Low-molecular-weight heparin;    Excessive fibrinolysis;    Disseminated intravascular coagulation;    Castration-resistant prostate cancer;   

Others  :  1195270
DOI  :  10.1186/1752-1947-6-378

 received in 2012-06-28, accepted in 2012-10-03,  发布年份 2012

【 摘 要 】

Introduction

Disseminated intravascular coagulation causes thrombotic tendency leading to multiple organ failure and occurs in a wide variety of diseases including malignancy. Disseminated intravascular coagulation is a latent complication in people with prostate cancer.

Case presentation

A 51-year-old Japanese man with advanced castration-resistant prostate cancer was admitted to our hospital because of extensive purpura and severe anemia. Prolonged plasma coagulation time, hypofibrinogenemia and normal platelet count suggested that a decrease in fibrinogen induced a bleeding tendency causing purpura. However, elevated plasma levels of thrombin-antithrombin complex, fibrin and/or fibrinogen degradation products and D-dimers, with positive fibrin monomer test, manifested disseminated intravascular coagulation and subsequent fibrinolysis. Plasma levels of thrombin-antithrombin complex, fibrin and/or fibrinogen degradation products and D-dimers decreased after administration of low-molecular-weight heparin. However, low fibrinogen and α₂-antiplasmin levels were not improved and plasmin-antiplasmin complex did not decrease, which revealed excessive fibrinolysis complicated with disseminated intravascular coagulation. We suspected that prostate cancer cell-derived urokinase-type plasminogen activator caused excessive fibrinolysis. Administration of tranexamic acid for fibrinogenolysis was added together with high-dose anti-androgen therapy (fosfestrol) for prostate cancer. Thereafter, prostate-specific antigen and plasmin-antiplasmin complex decreased, followed by normalized fibrinogen and α₂-antiplasmin levels, and the patient eventually recovered from the bleeding tendency. Immunohistochemical staining of the biopsied prostate tissue exhibited that the prostate cancer cells produced tissue factor, the coagulation initiator, and urokinase-type plasminogen activator.

Conclusion

This patient with rare complications of disseminated intravascular coagulation and excessive fibrinolysis is a warning case of potential coagulation disorder onset in patients with prostate cancer. We propose that combined administration of tranexamic acid and low-molecular-weight heparin together with high-dose anti-androgen therapy is a useful therapeutic option for patients with this complicated coagulation disorder.

【 授权许可】

   
2012 Wada et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Smith JA Jr, Soloway MS, Young MJ: Complications of advanced prostate cancer. Urology 1999, 54:8-14.
• [2]Abdulkadir SA, Carvalhal GF, Kaleen Z, Kisiel W, Humphrey PA, Catalona WJ, Milbrandt J: Tissue factor expression and angiogenesis in human prostate carcinoma. Hum Pathol 2000, 31:443-447.
• [3]Nemerson Y: Tissue factor and hemostasis. Blood 1998, 71:1-8.
• [4]Levi M: Disseminated intravascular coagulation. Crit Care Med 2007, 35:2191-2195.
• [5]Cozzi PJ, Wang J, Delprado W, Madigan MC, Fairy S, Russell PJ, Li Y: Evaluation of urokinase plasminogen activator and its receptor in different grades of human prostate cancer. Hum Pathol 2006, 37:1442-1451.
• [6]Castelline JC, Violand BN: The mechanism of activation of human plasminogen by urokinase. J Biol Chem 1976, 251:3906-3912.
• [7]Duran I, Tannock IF: Disseminated intravascular coagulation as the presenting sign of metastatic prostate cancer. J Gen Intern Med 2006, 21:C6-C8.
• [8]Akashi T, Furuya Y, Ohta S, Fuse H: Tissue factor expression and prognosis in patients with metastatic prostate cancer. Urology 2003, 62:1078-1082.
• [9]Pulukuri SM, Gondi CS, Lakka SS, Jutla A, Estes N, Gujrati M, Rao JS: RNA interference-directed knockdown of urokinase plasminogen activator and urokinase plasminogen activator receptor inhibits prostate cancer cell invasion, survival, and tumorigenicity in vivo. J Biol Chem 2005, 280:36529-36540.
• [10]Imamura T, Kaneda H, Nakamura S: New functions of neutrophils in the Arthus reaction: expression of tissue factor, the clotting initiator, and fibrinolysis by elastase. Lab Invest 2002, 282:1287-1295.
• [11]Levi M, de Jonge E, van der Poll T, ten Cate H: Disseminated intravascular coagulation. Thromb Haemost 1999, 82:695-705.
• [12]Okajima K, Kohno I, Soe G, Okabe H, Takatsuki K, Binder BR: Direct evidence for systemic fibrinogenolysis in patients with acquired alpha 2-plasmin inhibitor deficiency. Am J Hematol 1994, 45:16-24.
• [13]Okajima K, Kohno I, Tsuruta J, Okabe H, Takatsuki K, Binder BR: Direct evidence for systemic fibrinogenolysis in a patient with metastatic prostatic cancer. Thromb Res 1992, 66:717-727.
• [14]Koo JR, Lee YK, Kim YS, Cho WY, Kim HK, Won NH: Acute renal cortical necrosis caused by an antifibrinolytic drug (tranexamic acid). Nephrol Dial Transplant 1999, 14:750-752.
• [15]Festuccia C, Dolo V, Guerra F, Violini S, Muzi P, Pavan A, Bologna M: Plasminogen activator system modulates invasive capacity and proliferation in prostatic tumor cells. Clin Exp Metastasis 1998, 16:513-528.