Lasocki Sigismond, Piednoir Pascale, Ajzenberg Nadine, Geffroy Arnaud, Benbara Abdel, Montravers Philippe
Département d'Anesthésie - Réanimation Chirurgicale, APHP, CHU Bichat-Claude Bernard, Université Paris 7, Paris, France.
Crit Care. 2008;12(3):R84. doi: 10.1186/cc6937. Epub 2008 Jun 25.
Heparin-induced thrombocytopenia is an immune-mediated adverse drug reaction that is associated with a procoagulant state and both arterial and venous thrombosis. After observing two cases of repeated hemofiltration-filter clotting associated with high anti-PF4/heparin antibody concentrations, we systematically measured the anti-PF4/heparin antibody concentration in all cases of unexpected and repeated hemofiltration-filter clotting during continuous veno-venous hemofiltration (CVVH). The aim of this study was to identify factors associated with positive anti-PF4/heparin antibody in the case of repeated hemofiltration-filter clotting.
We reviewed the charts of all patients who had an anti-PF4/heparin antibody assay performed for repeated hemofiltration-filter clotting between November 2004 and May 2006 in our surgical intensive care unit. We used an enzyme-linked immunoabsorbent assay (heparin-platelet factor 4-induced antibody) with an optical density (OD) of greater than 1 IU considered positive.
During the study period, anti-PF4/heparin antibody assay was performed in 28 out of 87 patients receiving CVVH. Seven patients were positive for anti-PF4/heparin antibodies (OD 2.00 [1.36 to 2.22] IU) and 21 were antibody-negative (OD 0.20 [0.10 to 0.32] IU). Baseline characteristics, platelet counts, and activated partial thromboplastin time ratios were not different between the two groups. CVVH duration was significantly decreased in antibody-positive patients (5.0 [2.5 to 7.5] versus 12.0 [7.5 to 24.0] hours; P = 0.007) as was CVVH efficiency (urea reduction ratio 17% [10% to 37%] versus 44% [30% to 52%]; P = 0.04) on heparin infusion. Anti-PF4/heparin antibody concentration was inversely correlated with CVVH duration. The receiver operating characteristic curve showed that a 6-hour cutoff was the best CVVH session duration to predict a positive antibody test (sensitivity 71%, specificity 85%, and area under the curve 0.83). CVVH duration (32 [22 to 37] hours; P < 0.05) and urea reduction (55% [36% to 68%]; P < 0.03) were restored by danaparoid sodium infusion.
Repeated hemofiltration-filter clotting in less than 6 hours was often associated with the presence of anti-PF4/heparin antibodies, regardless of the platelet count. In antibody-positive patients, replacement of heparin by danaparoid sodium allowed the restoration of CVVH duration and efficiency.
肝素诱导的血小板减少症是一种免疫介导的药物不良反应，与促凝状态以及动脉和静脉血栓形成有关。在观察到两例与高抗PF4/肝素抗体浓度相关的重复血液滤过器凝血病例后，我们系统地测量了连续性静脉-静脉血液滤过（CVVH）期间所有意外和重复血液滤过器凝血病例中的抗PF4/肝素抗体浓度。本研究的目的是确定重复血液滤过器凝血情况下与抗PF4/肝素抗体阳性相关的因素。
我们回顾了2004年11月至2006年5月在我们外科重症监护病房因重复血液滤过器凝血而进行抗PF4/肝素抗体检测的所有患者的病历。我们使用酶联免疫吸附测定法（肝素-血小板因子4诱导抗体），光密度（OD）大于1 IU被认为是阳性。
在研究期间，87例接受CVVH的患者中有28例进行了抗PF4/肝素抗体检测。7例患者抗PF4/肝素抗体呈阳性（OD 2.00 [1.36至2.22] IU），21例抗体阴性（OD 0.20 [0.10至0.32] IU）。两组之间的基线特征、血小板计数和活化部分凝血活酶时间比值无差异。抗体阳性患者的CVVH持续时间显著缩短（5.0 [2.5至7.5]小时对12.0 [7.5至24.0]小时；P = 0.007），肝素输注时的CVVH效率（尿素清除率17% [10%至37%]对44% [30%至52%]；P = 0.04）也显著降低。抗PF4/肝素抗体浓度与CVVH持续时间呈负相关。受试者工作特征曲线显示，6小时的截断值是预测抗体检测阳性的最佳CVVH疗程持续时间（敏感性71%，特异性85%，曲线下面积0.83）。输注达那肝素钠后，CVVH持续时间（32 [22至37]小时；P < 0.05）和尿素清除率（55% [36%至68%]；P < 0.03）恢复正常。
无论血小板计数如何，6小时内的重复血液滤过器凝血通常与抗PF4/肝素抗体的存在有关。在抗体阳性患者中，用达那肝素钠替代肝素可使CVVH持续时间和效率恢复正常。
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