Hypercoagulable state in patients with advanced gastrointestinal cancer: Evidence for an acquired resistance to activated protein C

Domenico De Lucia, Ferdinando De Vita, Michele Orditura, Valter Renis, Antonello Belli, Mario Conte, Maria Di Grazia, Licia Lacoviello, Maria Benedetta Donati, Giuseppe Catalano

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Aims and background: Thromboembolic complications are common in patients with cancer and represent the second cause of death in patients with overt malignant disease. The aim of this study was to investigate the activated protein C pathway in cancer. Methods: We studied the coagulation cascade, natural clotting inhibitors, fibrinolytic proteins and resistance to activated protein C in 20 patients with advanced gastrointestinal cancer and 84 volunteers by measuring PT, APTT, fibrinogen, AT III, PC, PS, APC resistance, fibrinolytic system (PLG, ANPL, PAl-1 and t-PA) and activation peptides (D-Dimers, prothrombin 0 fragment 1+2/F1+2). Results: Laboratory tests confirmed coagulation abnormalities in cancer patients. Fibrinogen, D- Dimers and F1+2 were increased, while t-PA activity was significantly lower than that of controls. APC resistance was higher in cancer patients compared to the control group (55% vs 2%; P<0.0001). Excess thrombin generation was manifested by increased F1+2 plasma levels in APC-resistant cancer patients. Genetic analyses showed that only one patient with a poor response to APC carried a factor V R506Q mutation in exon 10. Conclusions: Our findings show a high prevalence of APC resistance in cancer, compatible with an acquired defect in the APC pathway.

Original languageEnglish
Pages (from-to)948-952
Number of pages5
JournalTumori
Volume83
Issue number6
Publication statusPublished - Nov 1997

Fingerprint

Activated Protein C Resistance
Gastrointestinal Neoplasms
Neoplasms
Fibrinogen
Factor V
Second Primary Neoplasms
Protein C
Thrombin
Cause of Death
Volunteers
Exons
Control Groups
Peptides
Mutation

Keywords

  • APC resistance
  • Cancer
  • Hypercoagulable state

ASJC Scopus subject areas

  • Cancer Research

Cite this

De Lucia, D., De Vita, F., Orditura, M., Renis, V., Belli, A., Conte, M., ... Catalano, G. (1997). Hypercoagulable state in patients with advanced gastrointestinal cancer: Evidence for an acquired resistance to activated protein C. Tumori, 83(6), 948-952.

Hypercoagulable state in patients with advanced gastrointestinal cancer : Evidence for an acquired resistance to activated protein C. / De Lucia, Domenico; De Vita, Ferdinando; Orditura, Michele; Renis, Valter; Belli, Antonello; Conte, Mario; Di Grazia, Maria; Lacoviello, Licia; Donati, Maria Benedetta; Catalano, Giuseppe.

In: Tumori, Vol. 83, No. 6, 11.1997, p. 948-952.

Research output: Contribution to journalArticle

De Lucia, D, De Vita, F, Orditura, M, Renis, V, Belli, A, Conte, M, Di Grazia, M, Lacoviello, L, Donati, MB & Catalano, G 1997, 'Hypercoagulable state in patients with advanced gastrointestinal cancer: Evidence for an acquired resistance to activated protein C', Tumori, vol. 83, no. 6, pp. 948-952.
De Lucia D, De Vita F, Orditura M, Renis V, Belli A, Conte M et al. Hypercoagulable state in patients with advanced gastrointestinal cancer: Evidence for an acquired resistance to activated protein C. Tumori. 1997 Nov;83(6):948-952.
De Lucia, Domenico ; De Vita, Ferdinando ; Orditura, Michele ; Renis, Valter ; Belli, Antonello ; Conte, Mario ; Di Grazia, Maria ; Lacoviello, Licia ; Donati, Maria Benedetta ; Catalano, Giuseppe. / Hypercoagulable state in patients with advanced gastrointestinal cancer : Evidence for an acquired resistance to activated protein C. In: Tumori. 1997 ; Vol. 83, No. 6. pp. 948-952.
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abstract = "Aims and background: Thromboembolic complications are common in patients with cancer and represent the second cause of death in patients with overt malignant disease. The aim of this study was to investigate the activated protein C pathway in cancer. Methods: We studied the coagulation cascade, natural clotting inhibitors, fibrinolytic proteins and resistance to activated protein C in 20 patients with advanced gastrointestinal cancer and 84 volunteers by measuring PT, APTT, fibrinogen, AT III, PC, PS, APC resistance, fibrinolytic system (PLG, ANPL, PAl-1 and t-PA) and activation peptides (D-Dimers, prothrombin 0 fragment 1+2/F1+2). Results: Laboratory tests confirmed coagulation abnormalities in cancer patients. Fibrinogen, D- Dimers and F1+2 were increased, while t-PA activity was significantly lower than that of controls. APC resistance was higher in cancer patients compared to the control group (55{\%} vs 2{\%}; P<0.0001). Excess thrombin generation was manifested by increased F1+2 plasma levels in APC-resistant cancer patients. Genetic analyses showed that only one patient with a poor response to APC carried a factor V R506Q mutation in exon 10. Conclusions: Our findings show a high prevalence of APC resistance in cancer, compatible with an acquired defect in the APC pathway.",
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AU - Renis, Valter

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