Cook J J, Niewiarowski S, Yan Z, Schaffer L, Lu W, Stewart G J, Mosser D M, Myers J A, Maione T E
Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140.
Circulation. 1992 Mar;85(3):1102-9. doi: 10.1161/01.cir.85.3.1102.
It has been observed that the reversal of heparin anticoagulation in humans by protamine sulfate (PS) results in various adverse reactions including leukopenia, thrombocytopenia, activation of complement, increased vascular permeability, systemic hypotension, pulmonary vasoconstriction, and pulmonary edema. The purpose of this study was to compare the efficacy and effects of native platelet factor 4 (PF4) and recombinant platelet factor 4 (rPF4) with those of PS in heparin neutralization in vivo, using a rat model.
Sprague-Dawley rats were anesthetized with sodium pentobarbital, and the right femoral vein and carotid artery were cannulated. For determination of activated partial thromboplastin time, platelet count, white blood cell count, and complement titer, arterial blood samples were taken before and immediately after heparin (10 units/100 g) infusion and at several time points after the infusion of the neutralizing agent (PS, 0.1 mg/100 g; PF4, 0.5 mg/100 g). In separate groups of animals, mean arterial blood pressure was monitored throughout identical protocols and the lungs were prepared for histological examination. The anticoagulant activity of heparin was effectively reversed by all of the neutralizing agents (PS, PF4, and rPF4). Platelet count (48% of initial), white blood cell count (52% of initial), complement titer (60% of initial), and mean arterial pressure (20% decrease) decreased significantly in heparinized animals receiving PS but not in those receiving PF4 or rPF4. Lung interstitium appeared normal when heparin was followed by PF4; however, interstitial edema and hemorrhage were observed with heparin-PS.
These results suggest that PF4 efficiently reverses heparin anticoagulation in the rat without the adverse effects of heparin-protamine complexes. Therefore, rPF4 may be an appropriate substitute for PS in patients undergoing cardiovascular surgery and other procedures that require heparin anticoagulation.
据观察，硫酸鱼精蛋白（PS）逆转人体肝素抗凝作用会导致各种不良反应，包括白细胞减少、血小板减少、补体激活、血管通透性增加、全身性低血压、肺血管收缩和肺水肿。本研究的目的是使用大鼠模型比较天然血小板因子4（PF4）和重组血小板因子4（rPF4）与PS在体内中和肝素的疗效和效果。
用戊巴比妥钠麻醉Sprague-Dawley大鼠，将右股静脉和颈动脉插管。为了测定活化部分凝血活酶时间、血小板计数、白细胞计数和补体滴度，在输注肝素（10单位/100克）之前和之后立即以及在输注中和剂（PS，0.1毫克/100克；PF4，0.5毫克/100克）后的几个时间点采集动脉血样本。在单独的动物组中，按照相同方案全程监测平均动脉血压，并准备肺组织进行组织学检查。所有中和剂（PS、PF4和rPF4）均有效逆转了肝素的抗凝活性。接受PS的肝素化动物的血小板计数（初始值的48%）、白细胞计数（初始值的52%）、补体滴度（初始值的60%）和平均动脉压（降低20%）显著下降，但接受PF4或rPF4的动物则未出现这种情况。肝素后接PF4时肺间质看起来正常；然而，肝素-PS组观察到间质水肿和出血。
这些结果表明，PF4可有效逆转大鼠体内的肝素抗凝作用，而无肝素-鱼精蛋白复合物的不良反应。因此，rPF4可能是心血管手术和其他需要肝素抗凝的手术患者中PS的合适替代品。
Zotero 插件