Hypercoagulability in patients with Cushing disease detected by thrombin generation assay is associated with increased levels of neutrophil extracellular trap-related factors

作者: Armando Tripodi , Concetta T. Ammollo , Fabrizio Semeraro , Mario Colucci , Elena Malchiodi

DOI: 10.1007/S12020-016-1027-1

关键词: ThrombosisProtein CAntithrombinThrombomodulinImmunologyInternal medicineAnticoagulantAntithromboticGastroenterologyNeutrophil extracellular trapsThrombinMedicine

摘要: Patients with Cushing disease (CD) are at increased risk of venous thromboembolism (VTE). It was surmised, but not conclusively shown that the is related to plasma hypercoagulability secondary glucocorticoids effect. This study aimed detecting in patients CD. Case-control 48 CD and controls enrolled two Italian clinics for whom we assessed thrombin-forming-potential presence optimal activation protein C obtained by adding into assay system its main endothelial activator, thrombomodulin. These experimental conditions mimic more closely than any other test vivo situation. We observed enhanced thrombin-generation patients, as modification parameters [i.e., shortened lag-time time-to-peak, thrombin peak endogenous potential (ETP)]. Moreover, ETP ratio (with/without thrombomodulin), recognized an index hypercoagulability, compared controls. attempted explain such measuring both procoagulant anticoagulant factors, some non-coagulation (i.e., neutrophil extracellular traps (NET), recently associated VTE and/or hypercoagulability. showed levels factor VIII NET-related variables. detected found explanation occurrence. Whether this can entirely occurrence should be investigated ad-hoc clinical trials. However, until these studies will available evidence supports concept candidates antithrombotic prophylaxis.

参考文章(48)
C. R. Bishop, J. W. Athens, D. R. Boggs, H. R. Warner, G. E. Cartwright, M. M. Wintrobe, Leukokinetic studies Journal of Clinical Investigation. ,vol. 47, pp. 249- 260 ,(1968) , 10.1172/JCI105721
Marialuisa Zilio, Linda Mazzai, Maria Teresa Sartori, Mattia Barbot, Filippo Ceccato, Viviana Daidone, Alessandra Casonato, Graziella Saggiorato, Franco Noventa, Laura Trementino, Paolo Prandoni, Marco Boscaro, Giorgio Arnaldi, Carla Scaroni, A venous thromboembolism risk assessment model for patients with Cushing's syndrome. Endocrine. ,vol. 52, pp. 322- 332 ,(2016) , 10.1007/S12020-015-0665-Z
Mark J. Bolland, Ian M. Holdaway, Juliet E. Berkeley, Sarina Lim, Will J. Dransfield, John V. Conaglen, Michael S. Croxson, Greg D. Gamble, Penny J. Hunt, Robyn J. Toomath, Mortality and morbidity in Cushing's syndrome in New Zealand. Clinical Endocrinology. ,vol. 75, pp. 436- 442 ,(2011) , 10.1111/J.1365-2265.2011.04124.X
Shamim Ejaz, Rena Vassilopoulou-Sellin, Naifa L. Busaidy, Mimi I. Hu, Steven G. Waguespack, Camilo Jimenez, Anita K. Ying, Maria Cabanillas, Maher Abbara, Mouhammed Amir Habra, Cushing syndrome secondary to ectopic adrenocorticotropic hormone secretion: the University of Texas MD Anderson Cancer Center Experience. Cancer. ,vol. 117, pp. 4381- 4389 ,(2011) , 10.1002/CNCR.26029
C. T. AMMOLLO, F. SEMERARO, J. XU, N. L. ESMON, C. T. ESMON, Extracellular histones increase plasma thrombin generation by impairing thrombomodulin‐dependent protein C activation Journal of Thrombosis and Haemostasis. ,vol. 9, pp. 1795- 1803 ,(2011) , 10.1111/J.1538-7836.2011.04422.X
Caterina Bressi, Marigrazia Clerici, Armando Tripodi, Peter L A Giesen, Veena Chantarangkul, Thrombin generation assessed as endogenous thrombin potential in patients with hyper- or hypo-coagulability. Haematologica. ,vol. 88, pp. 547- 554 ,(2003) , 10.3324/%X
Hiba Masri-Iraqi, Eyal Robenshtok, Gloria Tzvetov, Yossi Manistersky, Ilan Shimon, Elevated white blood cell counts in Cushing’s disease: association with hypercortisolism Pituitary. ,vol. 17, pp. 436- 440 ,(2014) , 10.1007/S11102-013-0522-0
CİHANGİR Erem, I Nuhoglu, MUSTAFA Yilmaz, MUSTAFA Kocak, ADEM Demirel, O Ucuncu, H Onder Ersoz, Blood coagulation and fibrinolysis in patients with Cushing’s syndrome: Increased plasminogen activator inhibitor-1, decreased tissue factor pathway inhibitor, and unchanged thrombin-activatable fibrinolysis inhibitor levels Journal of Endocrinological Investigation. ,vol. 32, pp. 169- 174 ,(2009) , 10.1007/BF03345709
Marco Boscaro, Nicoletta Sonino, Alessandro Scarda, Luisa Barzon, Francesco Fallo, Maria T. Sartori, Giovanni M. Patrassi, Antonio Girolami, Anticoagulant prophylaxis markedly reduces thromboembolic complications in Cushing's syndrome. The Journal of Clinical Endocrinology and Metabolism. ,vol. 87, pp. 3662- 3666 ,(2002) , 10.1210/JCEM.87.8.8703