Hyper-coagulability in obese patients accurately identified by combinations of global coagulation assay parameters. Issue 187 (March 2020)

• Record Type: Journal Article
• Authors: Bertaggia Calderara, Debora; Aliotta, Alessandro; Zermatten, Maxime G.; Kröll, Dino; Stirnimann, Guido; Alberio, Lorenzo
• Is Part Of: Thrombosis research. Issue 187(2020)
• Page Start: 91
• Page End: 102
• Publication Date: 2020-03
• Subjects: AMC 7-amino-4-methylcoumarin -- aPTT Activated partial thromboplastin time -- Ast Stationary amplitude of the moving peak of thrombin concentration (thrombin generation, TD) -- CAT Calibrated Automated Thrombogram -- Cmax_ATG Maximum concentration of Activator Thrombin Generation (thrombin generation TD) -- CS Clot size (fibrin formation, TD) -- D Density (fibrin formation, TD) -- ETP Endogenous thrombin potential (thrombin generation, CAT) -- ETP_ATG Thrombin potential of Activator Thrombin Generation (thrombin generation, TD) -- HV Healthy volunteers -- IQR Interquartile range -- Lag time_ATG Lag-time of Activator Thrombin Generation (thrombin generation, TD) -- LMWH Low molecular weight heparin -- LT Lag time (thrombin generation, CAT) -- OP Obese patients -- PFP platelet free plasma -- PT Prothrombin time -- ROC Receiver operating characteristics -- TD Thrombodynamics -- TG Thrombin generation -- Tlag Lag-time (fibrin formation, TD) -- Tmax_ATG Time to peak of Activator Thrombin Generation (thrombin generation, TD) -- Tsp Spontaneous clot formation time (fibrin formation, TD) -- TTP Time to peak (thrombin generation, CAT) -- V Rate of clot growth (fibrin formation, TD) -- Vi Initial rate of clot growth (fibrin formation, TD) -- VI Velocity index (thrombin generation, CAT and TD) -- VKA Vitamin K antagonist -- Vt Rate of thrombin peak propagation (thrombin generation, TD); Global hemostasis test -- Hyper-coagulation -- Thrombin generation -- Thrombotic risk -- Thrombodynamics; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2020.01.012
• Languages: English
• ISSNs: 0049-3848

Abstract

Abstract: Background: Routine laboratory methods are insensitive to hyper-coagulation, which may be detected by global hemostasis tests. Calibrated Automated Thrombogram (CAT) is a gold standard method to measure thrombin generation and coagulation potential. Thrombodynamics (TD) is a new global assay that monitors the spatio-temporal propagation of blood coagulation, separating initiation from amplification/propagation phases of coagulation and visualizing fibrin clot formation. Aim: We investigated whether CAT and/or TD can identify hyper- and hypo-coagulable states in patients with well-characterized phenotypes and which parameters could be used as potential predictors of thrombotic risk. Methods: Blood was collected from: (1) forty healthy volunteers; (2) twelve obese patients scheduled for bariatric surgery (BMI ≥ 35 kg/m 2 ); (3) nine patients under therapy with vitamin K-antagonists (median INR 2.7); (4) eight patients treated with low molecular weight heparins (anti-Xa activity between 0.5 and 0.7 U anti-Xa/ml); (5) ten patients with hemophilia A or B. Tissue factor induced thrombin generation was measured with CAT. Propagation of thrombin generation and clot growth from a tissue factor coated surface were monitored with TD. Results: Thrombin generation and fibrin clot formation parameters were significantly higher in obese patients compared to healthy volunteers and anticoagulated or hemophilic patients. ROC analysis of combined CAT or CAT/TD parameters (integrating thrombin generation and fibrin clot formation) demonstrated an excellent accuracy in detecting hyper-coagulability. Conclusion: Combinations of CAT assay parameters and of parameters of thrombin generation burst with final fibrin clot properties allow recognizing accurately hyper-coagulable plasma and may represent predictive markers for thrombotic events. Highlights: Routine coagulation assays are insensitive to hyper-coagulation. Global assays visualizing thrombin generation and fibrin clot formation give a better assessment of hemostatic potential. A model integrating thrombin generation and fibrin clot formation is proposed to identify hypercoagulable plasma.