The Effect of Dilution on Plasma Coagulation Kinetics Determined by Thrombelastography Is Dependent on Antithrombin Activity and Mode of Activation
Case Report: Hemodilution-associated hypercoagulability has been the focus of several investigations because significant morbidity and mortality have been associated with perioperative thrombophilia. Because most investigations implicate imbalances in procoagulant/anticoagulant activity as the etiology of hemodilution-associated hypercoagulability, we determined the effects of dilution on coagulation kinetics and clot strength with thrombelastography (TEG®). Control plasma (±celite activation) and antithrombin (AT)-deficient (<10% activity) plasma were diluted 0%, 10%, 20%, and 30% with saline. TEG® variables measured included time to clot initiation (reaction time, R), speed of clot propagation (angle, 
), and clot strength (amplitude, A; or shear elastic modulus, G). Dilution of control plasma (10%–30%) resulted in a significant (P < 0.05) 16% decrease in R values, no change in values, and decrease in A and G values. AT-deficient plasma had significantly smaller R values compared with control, and dilution did not change R values in AT-deficient plasma. Celite activation eliminated dilution-associated changes in R values in control plasma but resulted in linear decreases (R2 = 0.88–0.96, P < 0.0001) in , A, and G in response to dilution. Thus, our data indirectly support the concept that decreases in AT activity cause dilution-mediated hypercoagulability in plasma. Finally, celite activation permits quantification of dilution with TEG®.
Implications: Hemodilution-associated hypercoagulability is of clinical interest, given the morbidity and mortality associated with perioperative thrombophilia. We determined that decreased antithrombin activity is responsible for accelerated clot initiation via thrombelastography with in vitro plasma-based experiments. Celite activation of plasma resulted in a linear relationship between degree of dilution and thrombelastographic variables.
