Carroll Roger C, Craft Robert M, Whitaker Gregory L, Snider Carolyn C, Kirby Ryan K, Elder Robert F, Hennessey Mark D
Department of Anesthesiology, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN 37920, United States.
Thromb Res. 2007;120(3):367-70. doi: 10.1016/j.thromres.2006.10.011. Epub 2006 Dec 5.
The anticoagulant effect of enoxaparin is readily observed by Thrombelastography (TEG), particularly on the reaction time (R) to form a clot, and is completely reversed by heparinase. In this study, recalcified citrated whole blood with heparinase (CNHR) and without (CNR), along with TEG R time, was used to derive a delta R (CNR-CNHR). This delta R (DeltaR) was then used to measure enoxaparin anticoagulation, which was correlated by linear regression (r(2)=0.806) with plasma anti-Xa in 48 thrombophilic pregnancy patients. In a follow up study whole blood from 15 thrombophilic and 15 normal pregnancy subjects was titrated ex vivo with enoxaparin and TEG DeltaR determined. Linear dose responses (all r(2)>0.9) of DeltaR versus plasma enoxaparin concentration were obtained for each subject. A large variation in slope was observed for both thrombophilic (>7 fold, 217 to 1,588 s DeltaR/unit anti-Xa) and normal (>3 fold, 788 to 2,758) pregnancy subjects. The average slope for the thrombophilic group (710 s DeltaR/unit anti-Xa) was significantly (P=0.002) lower than the normal pregnancy group (1,354 s), indicating resistance to enoxaparin anticoagulation in the thrombophilic group. This technique may help gauge the appropriate dose of enoxaparin for each individual, check for residual anticoagulation before invasive procedures, and perhaps help screen for thrombophilic subjects.
通过血栓弹力图（TEG）很容易观察到依诺肝素的抗凝作用，尤其是对形成凝块的反应时间（R）的影响，并且肝素酶可完全逆转这种作用。在本研究中，使用含有肝素酶的重新钙化枸橼酸盐全血（CNHR）和不含肝素酶的重新钙化枸橼酸盐全血（CNR），以及TEG R时间，来得出ΔR（CNR - CNHR）。然后用这个ΔR来测量依诺肝素的抗凝作用，在48例血栓形成倾向的妊娠患者中，它与血浆抗Xa通过线性回归相关（r² = 0.806）。在一项后续研究中，对15例血栓形成倾向的妊娠受试者和15例正常妊娠受试者的全血进行体外依诺肝素滴定，并测定TEG ΔR。为每个受试者获得了ΔR与血浆依诺肝素浓度的线性剂量反应（所有r²>0.9）。观察到血栓形成倾向的妊娠受试者（>7倍，217至1588 s ΔR/单位抗Xa）和正常妊娠受试者（>3倍，788至2758）的斜率都有很大差异。血栓形成倾向组的平均斜率（710 s ΔR/单位抗Xa）显著低于正常妊娠组（1354 s）（P = 0.002），表明血栓形成倾向组对依诺肝素抗凝有抵抗作用。这项技术可能有助于为每个个体确定合适的依诺肝素剂量，在侵入性操作前检查残留抗凝情况，并且可能有助于筛查血栓形成倾向的受试者。
