Virtanen Lauri, Salmela Birgitta, Leinonen Jari, Lemponen Marja, Huhtala Jukka, Joutsi-Korhonen Lotta, Lassila Riitta
aCoagulation Disorders, Department of Hematology bDepartment of Clinical Chemistry (HUSLAB Laboratory Services), Helsinki University Central Hospital cCoxa Hospital for Joint Replacement, Tampere, Finland.
Blood Coagul Fibrinolysis. 2014 Sep;25(6):597-603. doi: 10.1097/MBC.0000000000000116.
Fondaparinux, indirect factor Xa (FXa) inhibitor, is recommended for thromboprophylaxis for high-risk patients undergoing major orthopedic surgery. We evaluated the prothrombotic state and anticoagulant intensity of fondaparinux (2.5 mg daily) after total hip replacement (THR). Twenty patients underwent THR - seven bilateral and 13 unilateral. Blood samples were collected preoperatively and at 6 h, 8 h (2 h after fondaparinux), 1 day (12-14 h after fondaparinux), and 4 weeks (12-14 h after fondaparinux) postoperatively. Antithrombin (AT), fibrinogen, factor VIII activity, coagulation times, thrombin-AT (TAT) complex, D-dimer, C-reactive protein, prothrombinase-induced clotting time (PiCT) and anti-Xa activity were measured. The latter two were also tested after plasma spiking with fondaparinux 0-1.25 μg/ml. In spiked prophylactic fondaparinux samples (0-0.25 μg/ml), PiCT and anti-Xa activity correlated (r = 0.84) better than in the patient samples (r = 0.35). On the first day, anti-Xa activity and PiCT dissociated, and PiCT lost sensitivity for fondaparinux. AT decreased but stayed within the normal range, whereas TAT complex and D-dimer peaked at 6 h as signs of thrombin generation. On the first postoperative day, TAT and D-dimer halved. Bilateral THR associated with higher TAT and D-dimer levels up to 4 weeks. Perioperative FVIII levels were not affected, but were elevated in both groups (range 191-211%) after 4 weeks. Anti-Xa activity detected prophylactic fondaparinux with higher sensitivity than PiCT in vitro, but even more so in vivo. Thus, PiCT is not the method of choice to assess fondaparinux at least in association with THR. THR, bilateral more than unilateral, increased thrombin generation and D-dimer 7-11-fold early after surgery. Factor VIII activity and D-dimer remained elevated even after 4 weeks despite the compliant thromboprophylaxis with fondaparinux.
磺达肝癸钠是一种间接的Xa因子（FXa）抑制剂，推荐用于接受大型骨科手术的高危患者的血栓预防。我们评估了全髋关节置换术（THR）后磺达肝癸钠（每日2.5毫克）的促血栓形成状态和抗凝强度。20例患者接受了THR，其中7例为双侧置换，13例为单侧置换。术前以及术后6小时、8小时（磺达肝癸钠给药后2小时）、1天（磺达肝癸钠给药后12 - 14小时）和4周（磺达肝癸钠给药后12 - 14小时）采集血样。检测抗凝血酶（AT）、纤维蛋白原、凝血因子VIII活性、凝血时间、凝血酶 - AT（TAT）复合物、D - 二聚体、C反应蛋白、凝血酶原酶诱导的凝血时间（PiCT）和抗Xa活性。在血浆中加入0 - 1.25μg/ml磺达肝癸钠后也对后两者进行了检测。在加样的预防性磺达肝癸钠样本（0 - 0.25μg/ml）中，PiCT与抗Xa活性的相关性（r = 0.84）优于患者样本（r = 0.35）。在术后第一天，抗Xa活性与PiCT出现解离，PiCT对磺达肝癸钠失去敏感性。AT降低但仍在正常范围内，而TAT复合物和D - 二聚体在6小时达到峰值，作为凝血酶生成的指标。术后第一天，TAT和D - 二聚体减半。双侧THR在术后4周内TAT和D - 二聚体水平较高。围手术期凝血因子VIII水平未受影响，但4周后两组均升高（范围为191 - 211%）。在体外，抗Xa活性检测预防性磺达肝癸钠的敏感性高于PiCT，在体内更是如此。因此，至少在与THR相关的情况下，PiCT不是评估磺达肝癸钠的首选方法。THR，双侧置换比单侧置换更易在术后早期使凝血酶生成和D - 二聚体增加7 - 11倍。尽管使用磺达肝癸钠进行了规范的血栓预防，但凝血因子VIII活性和D - 二聚体在4周后仍保持升高。
