Williams R D, D'Ambra M N, Maione T E, Lynch K E, Keene D F
Department of Anesthesia Massachusetts General Hospital, Harvard Medical School, Boston.
J Thorac Cardiovasc Surg. 1994 Nov;108(5):975-83.
The ability of recombinant platelet factor 4, a protein of human origin with high heparin affinity, and the present clinical heparin reversal agent, protamine, to neutralize heparin in human whole blood was studied by means of three standard whole blood coagulation tests: whole blood clotting time, heparin assay, and activated clotting time. Ten subjects were chosen at random among patients undergoing cardiopulmonary bypass operations. Heparinized blood, free of protamine, was obtained from the bypass reservoir for testing. Whole blood aliquots, without reversal agents (controls) or with either protamine (10, 20, 30, or 40 micrograms/ml) or recombinant platelet factor 4 (10, 20, 40, or 80 micrograms/ml), were analyzed. The quantity of each agent required to reverse the ten samples, using 95% upper confidence bounds (t distribution) was determined for each method. Recombinant platelet factor 4 reversed heparin at 40 micrograms/ml and protamine at 20 micrograms/ml, suggesting a reversal ratio for recombinant platelet factor 4/protamine of 2:1 on a milligram basis. Further, currently available methods for testing coagulation should be reliable, without modification, to monitor the restoration of normal coagulation parameters with recombinant platelet factor 4 after cardiopulmonary bypass.
全血凝固时间、肝素测定和活化凝血时间，研究了重组血小板因子4（一种具有高肝素亲和力的人源蛋白）和目前临床使用的肝素中和剂鱼精蛋白在人全血中中和肝素的能力。在接受体外循环手术的患者中随机选择10名受试者。从体外循环储液器中获取不含鱼精蛋白的肝素化血液进行检测。分析了不含中和剂（对照）或含有鱼精蛋白（10、20、30或40微克/毫升）或重组血小板因子4（10、20、40或80微克/毫升）的全血样本。对于每种方法，使用95%置信上限（t分布）确定逆转十个样本所需的每种试剂的量。重组血小板因子4在40微克/毫升时可逆转肝素，鱼精蛋白在20微克/毫升时可逆转肝素，这表明重组血小板因子4与鱼精蛋白在毫克基础上的逆转比例为2:1。此外，目前可用的凝血检测方法应可靠，无需修改，以监测体外循环后使用重组血小板因子4恢复正常凝血参数的情况。
