Department of Cardio-thoracic Surgery, Institute for Cardiovascular Research, VU University Medical Centre, Amsterdam, The Netherlands.
Department of Anaesthesiology, Institute for Cardiovascular Research, VU University Medical Centre, Amsterdam, The Netherlands.
Eur J Vasc Endovasc Surg. 2017 Oct;54(4):534-541. doi: 10.1016/j.ejvs.2017.07.006. Epub 2017 Aug 9.
To investigate whether a fixed heparin dose results in adequate heparinisation levels and consequent inhibition of haemostatic activation in all patients.
This prospective clinical pilot study included 24 patients undergoing arterial vascular surgery. Individual heparin responsiveness was assessed using the Heparin Dose Response (HDR) test, while the activated clotting time (ACT) and heparin concentration were measured to monitor the peri-procedural degree of anticoagulation. Finally, peri-operative haemostasis was evaluated with rotational thromboelastometry (ROTEM).
Eight patients were identified with reduced heparin sensitivity (RS group) and 16 patients with normal heparin sensitivity (NS group). Compared with the NS group, the RS group showed less prolonged ACTs after heparinisation with heparin concentrations below the calculated target heparin concentration. ROTEM revealed shorter clot formation times in the intrinsically activated coagulation test (INTEM) 3 min (114 ± 48 s vs. 210 ± 128 s) and 30 min after the initial heparin bolus (103 ± 48 s vs. 173 ± 81 s) in the RS group compared with the NS group. In the RS group, one patient developed a major thromboembolic complication.
This study shows that a third of the study population had reduced heparin sensitivity, which was associated with lower levels of heparinisation, and lower inhibition levels of clot initiation and clot formation. Identifying patients with reduced heparin sensitivity by monitoring the anticoagulant effect of heparin could decrease the risk of thrombotic complications after arterial vascular surgery.
研究固定剂量肝素是否能使所有患者达到充分的肝素化水平，并由此抑制止血激活。
这是一项前瞻性临床初步研究，纳入了 24 例行动脉血管手术的患者。采用肝素剂量反应（HDR）试验评估个体肝素反应性，同时监测活化凝血时间（ACT）和肝素浓度，以评估围手术期抗凝程度。最后，采用旋转血栓弹性测定法（ROTEM）评估围手术期止血情况。
确定 8 例患者存在肝素敏感性降低（RS 组），16 例患者存在肝素敏感性正常（NS 组）。与 NS 组相比，肝素浓度低于计算目标肝素浓度时，RS 组肝素化后 ACT 延长程度较小。ROTEM 显示，在固有激活凝血试验（INTEM）中，RS 组凝血块形成时间较短，初始肝素推注后 3 分钟为（114±48）s，30 分钟为（103±48）s，而 NS 组分别为（210±128）s 和（173±81）s。在 RS 组中，1 例患者发生了主要的血栓栓塞并发症。
本研究表明，研究人群中有三分之一存在肝素敏感性降低，这与肝素化水平较低以及凝血起始和凝血形成的抑制水平较低有关。通过监测肝素的抗凝作用来识别肝素敏感性降低的患者，可能会降低动脉血管手术后发生血栓并发症的风险。
