title: Reference values for thromboelastometry (ROTEM®) in cynomolgus monkeys (Macaca fascicularis).
abstract: BACKGROUND
  The imbalance in clotting homeostasis, tending towards hypercoagulation, is recognized as the real barrier to the long-term survival of porcine xenografts in pig-to-primate xenotransplatation. The present study aimed to validate in primate blood the applicability of whole blood rotation thromboelastometry, performed by ROTEM®, which evaluates the characteristics of clot formation by dynamic monitoring.
  
  
  METHODS
  ROTEM® (Pentapharm GmbH, Munich, Germany) was used to investigate native coagulation (NATEM®), the intrinsic (INTEM®) and extrinsic (EXTEM®) pathways, the function of fibrinogen (FIBTEM®), and the presence of fibrinolysis in 40 naïve cynomolgus monkeys. Using classic validation approaches, the normal thromboelastographic profile was defined and the influence of haematocrit (Hct,%), platelet count (x10(9)/L), fibrinogen (mg/dl), and factor VIII (FVIII,%) was evaluated.
  
  
  RESULTS
  In all four (NATEM®, INTEM®, EXTEM®, FIBTEM®) assays considered, Clotting Time (CT, sec) and Clot Formation Time (CFT, sec) were shorter in primates than humans. Moreover, α-angle (°), Maximum Clot Firmness (MCF, mm), and MaxVel (mm/min) were also higher in primates than humans. No substantial difference was observed for Hct and platelet count between the two species. On the contrary, FVIII was higher in primates than in humans whereas, interestingly enough, fibrinogen levels were lower in monkeys than in humans.
  
  
  CONCLUSIONS
  ROTEM® depicts a hypercoagulable profile in primates as compared to humans. Taken together these data suggest that, with regard to coagulation, xenotransplantation in cynos may represent a much more difficult situation than xenotransplantation in humans.
authors: Department of Cardiologic, Thoracic, and Vascular Sciences, 2nd Chair of Internal Medicine, University of Padua Medical School, Padua, Italy.
authors: Luca
authors: L
authors: Spiezia
authors: Diana
authors: D
authors: Bertini
authors: Massimo
authors: M
authors: Boldrin
authors: Claudia
authors: C
authors: Radu
authors: Cristiana
authors: C
authors: Bulato
authors: Sabrina
authors: S
authors: Gavasso
authors: Emanuele
authors: E
authors: Cozzi
authors: Paolo
authors: P
authors: Simioni
mesh_terms: D000818:Animals; D001779:Blood Coagulation Factors / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis; D006400:Hematocrit; D006801:Humans; D008252:Macaca fascicularis; D010976:Platelet Count; D012016:Reference Values; D013916:Thrombelastography / Q000592:standards*
chemical_list: D001779:Blood Coagulation Factors; D005340:Fibrinogen