Lindblad B, Wakefield T W, Whitehouse W M, Stanley J C
Department of Surgery, University of Michigan Medical School, Ann Arbor.
Scand J Thorac Cardiovasc Surg. 1988;22(1):55-9. doi: 10.3109/14017438809106052.
The adverse effects of protamine sulfate, used to neutralize the anticoagulant action of heparin, include systemic hypotension, pulmonary artery hypertension, thrombocytopenia and leukopenia. For further evaluation of protamine's mechanism of action, a three-part investigation was performed. In part I platelet-rich plasma (PRP) was prepared from canine blood samples (n = 6) taken before and 2 minutes after injection of protamine. In part II human PRP (n = 5) was preincubated with protamine or distilled water. Adenosine diphosphate-induced aggregation of protamine-treated platelets was unchanged, but thrombin-induced aggregation was inhibited in both canine and human preparations (p less than 0.05). In part III thrombocytopenia was produced in splenectomized dogs (n = 5), using microporous filters, to 4.5-8.4% of the initial platelet count. Protamine reversal of the heparinization caused hypotension (maximally -29 mmHg 90 s after protamine), but not pulmonary arterial hypertension. Leukopenia developed before additional thrombocytopenia appeared. Protamine-platelet interaction inhibits thrombin-induced platelet aggregation. Platelets may play an important role in the pulmonary pressure rise during protamine reversal, but do not mediate the systemic hypotension.
用于中和肝素抗凝作用的硫酸鱼精蛋白的不良反应包括全身性低血压、肺动脉高压、血小板减少和白细胞减少。为了进一步评估鱼精蛋白的作用机制，进行了一项分为三个部分的研究。在第一部分中，从注射鱼精蛋白前和注射后2分钟采集的犬血样本（n = 6）中制备富含血小板血浆（PRP）。在第二部分中，将人PRP（n = 5）与鱼精蛋白或蒸馏水预孵育。二磷酸腺苷诱导的经鱼精蛋白处理的血小板聚集未发生变化，但在犬和人样本中凝血酶诱导的聚集均受到抑制（p < 0.05）。在第三部分中，使用微孔滤器使脾切除的犬（n = 5）产生血小板减少，降至初始血小板计数的4.5 - 8.4%。鱼精蛋白逆转肝素化导致低血压（鱼精蛋白注射后90秒时最大降至 -29 mmHg），但未导致肺动脉高压。白细胞减少在进一步的血小板减少出现之前就已发生。鱼精蛋白与血小板的相互作用抑制凝血酶诱导的血小板聚集。血小板可能在鱼精蛋白逆转过程中肺压力升高方面起重要作用，但不介导全身性低血压。
