Oncology Division, Rambam Health Care Campus, The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
Thrombosis and Hemostasis Unit, Rambam Health Care Campus, The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
J Thromb Thrombolysis. 2020 Jul;50(1):112-122. doi: 10.1007/s11239-020-02128-1.
Hospitalized cancer patients are at increased risk of thrombosis and prophylaxis with heparin is recommended. Heparanase is a protein capable of degrading heparan sulfate (HS) chains. The first objective of the study was to examine the effects of weight on anti-Xa levels in cancer patients treated with a fixed dose of enoxaparin as thromboprophylaxis. The second aim was to assess a potential correlation between plasma pre-treatment coagulation parameters and anti-Xa levels in an assumption that heparanase degradation activity towards heparins and HS chains could affect anti-Xa levels. Two blood samples (prior to and 3 h after drug injection) of 76 cancer patients with an indication for prophylaxis with enoxaparin (40 mg) were evaluated for coagulation markers. Sub-prophylactic levels of anti-Xa (< 0.2 U/ml) were found in 16/76 (21%) patients; in 13/76 (13%) patients the values were supra-prophylactic (> 0.5 U/ml). In the subgroup of patients weighing > 80 kg, 7/14 (50%) individuals had a sub-prophylactic level. Overall, anti-Xa levels appeared to correlate with patient's weight (r = - 0.48, p < 0.0001), pre-treatment partial thromboplastin time (PTT), D-dimer, HS, heparanase levels and procoagulant activity. We concluded that plasma anti-Xa levels correlated with patient's weight. A substantial portion of cancer patients receiving enoxaparin prophylaxis was undertreated. For patients > 80 kg, a weight-adjusted prophylactic dose of enoxaparin could be considered. Elevated enoxaparin anti-Xa levels correlated with pre-treatment parameters of coagulation system activation. High pre-treatment HS and elevated plasma anti-Xa levels may potentially serve as biomarkers for the identification of patients at increased thrombosis risk.
住院癌症患者有血栓形成的风险增加，建议使用肝素进行预防。肝素酶是一种能够降解肝素硫酸酯（HS）链的蛋白质。研究的首要目标是检查体重对接受固定剂量依诺肝素进行血栓预防治疗的癌症患者抗 Xa 水平的影响。第二个目的是评估血浆预处理凝血参数与抗 Xa 水平之间的潜在相关性，假设肝素酶对肝素和 HS 链的降解活性可能会影响抗 Xa 水平。对 76 例有依诺肝素（40mg）预防指征的癌症患者的 2 个血液样本（用药前和用药后 3 小时）进行了凝血标志物评估。在 76 例患者中，有 16 例（21%）患者抗 Xa 水平低于亚预防水平（<0.2U/ml）；有 13 例（13%）患者抗 Xa 水平高于超预防水平（>0.5U/ml）。在体重>80kg 的患者亚组中，有 7/14（50%）个体的抗 Xa 水平处于亚预防水平。总体而言，抗 Xa 水平似乎与患者体重（r=-0.48，p<0.0001）、预处理部分凝血活酶时间（PTT）、D-二聚体、HS、肝素酶水平和促凝活性相关。我们得出结论，血浆抗 Xa 水平与患者体重相关。接受依诺肝素预防治疗的癌症患者中，相当一部分患者治疗不足。对于体重>80kg 的患者，可考虑使用依诺肝素进行剂量调整的预防治疗。升高的依诺肝素抗 Xa 水平与凝血系统激活的预处理参数相关。较高的预处理 HS 和升高的血浆抗 Xa 水平可能潜在用作识别血栓形成风险增加患者的生物标志物。
