Fuentes Amaris, Gordon-Burroughs Sherilyn, Hall Jeffrey B, Putney David R, Monsour Howard P
Departments of *Pharmacy; †Medicine; and ‡Surgery, Houston Methodist Hospital, TX.
Ther Drug Monit. 2015 Feb;37(1):40-4. doi: 10.1097/FTD.0000000000000105.
Cirrhosis of the liver results in complex hemostatic changes that place patients at risk for both bleeding and thrombotic events. This study evaluates the adverse effects of anticoagulation with unfractionated heparin among patients with cirrhosis and analyzes the discrepancy between anti-Xa and activated partial thromboplastin time (aPTT) values for heparin monitoring among cirrhotics.
Patients with cirrhosis receiving unfractionated heparin were matched 2:1 to patients without evidence of cirrhosis anticoagulated with unfractioned heparin. Markers of bleeding events including blood product administration and use of heparin reversal were analyzed between groups. Patients from both groups with aPTT and anti-Xa values obtained at the same time were also analyzed.
A higher incidence of blood product administration or use of heparin reversal was observed among patients with cirrhosis [35/105 (33.3%) versus 37/210 (17.6%), P = 0.002]. This finding was consistent among those receiving anticoagulation through an established anti-Xa-based heparin dosing protocol [23/62 (37.1%) versus 25/124 (20.2%), P = 0.013]. A decrease in hemoglobin greater than 2 g/dL or a platelet decrease 50% or greater from baseline was also more frequently identified among cirrhotics when receiving heparin therapy [20/105 (19%) versus 23/210 (11%), P = 0.049 and 21/105 (20%) versus 12/210 (6%), P < 0.001, respectively]. A total of 88 correlated anti-Xa and aPTT values from 35 patients with cirrhosis demonstrated supratherapeutic aPTT values for anti-Xa levels within the therapeutic range (P < 0.001). This discrepancy was not observed among controls.
A greater use of blood products among the cirrhotic population may indicate potential bleeding events on therapy. A discrepancy in correlated anti-Xa and aPTT values among patients with cirrhosis may explain the propensity for adverse effects. Further study is required to identify effective heparin anticoagulation monitoring strategies in liver disease.
肝硬化会导致复杂的止血变化，使患者面临出血和血栓形成事件的风险。本研究评估了普通肝素抗凝对肝硬化患者的不良影响，并分析了肝硬化患者在肝素监测中抗Xa与活化部分凝血活酶时间（aPTT）值之间的差异。
接受普通肝素治疗的肝硬化患者与接受普通肝素抗凝且无肝硬化证据的患者按2:1进行匹配。分析两组之间包括血液制品输注和肝素逆转使用情况在内的出血事件标志物。还对两组同时获得aPTT和抗Xa值的患者进行了分析。
肝硬化患者中血液制品输注或肝素逆转使用的发生率更高[35/105（33.3%）对37/210（17.6%），P = 0.002]。在通过既定的基于抗Xa的肝素给药方案进行抗凝的患者中，这一发现是一致的[23/62（37.1%）对25/124（20.2%），P = 0.013]。在接受肝素治疗时，肝硬化患者中血红蛋白下降大于2 g/dL或血小板较基线下降50%或更多的情况也更常见[分别为20/105（19%）对23/210（11%），P = 0.049；21/105（20%）对12/210（6%），P < 0.001]。来自35例肝硬化患者的总共88个相关抗Xa和aPTT值显示，在治疗范围内抗Xa水平对应的aPTT值高于治疗水平（P < 0.001）。对照组未观察到这种差异。
肝硬化人群中更多地使用血液制品可能表明治疗中存在潜在出血事件。肝硬化患者抗Xa与aPTT值之间的差异可能解释了不良反应的倾向。需要进一步研究以确定肝病中有效的肝素抗凝监测策略。
