Weiss H J, Turitto V T, Baumgartner H R
J Lab Clin Med. 1978 Nov;92(5):750-64.
Previous studies have demonstrated impaired adhesion of platelets to the subendothelium in von Willebrand's disease. These studies were performed by circulating (in a closed system) citrated whole blood through a chamber containing everted segments of rabbit aorta from which the endothelium had been removed by balloon catheter. The average wall shear rate was 800 sec-1, and the perfusion time was 10 min. In the present study we measured the interaction of platelets with subendothelium in native (nonanticoagulated) blood, using a recently described technique in which the vessel segments are perfused with directly sampled venous blood. The system was open; that is, the blood was not recirculated. We used blood flow rates of 20, 40, and 50 ml/min, which correspond to calculated shear rates of 1300, 2600, and 3300 sec-1 and perfusion times of 3, 2, and 2 min, respectively. For comparison, parallel studies at 1300 sec-1 were also obtained with citrated blood. In normal subjects, at a shear rate of 1300 sec-1, platelet adhesion was less in native blood than in citrated blood, but thrombus formation was greater. Platelet adhesion in five patients with von Willebrand's disease was decreased in both citrated and native blood. The magnitude of the adhesion defect was strongly dependent on the shear rate. Thus, in citrated blood studied at a shear rate of 1300 sec-1, adhesion was 75% less than in normal subjects, whereas in previous studies at 800 sec-1 the reduction in adhesion was 29%. In native blood, adhesion in von Willebrand's disease was normal at a shear rate of 1300 sec-1, whereas 53% and 77% reductions in adhesion were obtained at shear rates of 2600 and 3300 sec-1, respectively. The latter shear rates studied, adhesion of platelets in native blood was also decreased in the Bernard-Soulier syndrome but was normal in hemophilia and afibrinogenemia. Our findings with native blood provide further evidence that impaired adhesion of platelets to the vessel wall accounts for the hemostatic defect in von Willebrand's disease. In addition, this adhesion defect is shear rate-dependent.
以往研究已证实，血管性血友病患者的血小板与内皮下层的黏附功能受损。这些研究是通过在一个封闭系统中使枸橼酸化全血循环通过一个装有经球囊导管去除内皮的兔主动脉外翻段的腔室来进行的。平均壁切变率为800秒-1，灌注时间为10分钟。在本研究中，我们使用一种最近描述的技术，即向血管段灌注直接采集的静脉血，来测量天然（未抗凝）血液中血小板与内皮下层的相互作用。该系统是开放的，也就是说，血液不循环。我们使用的血流速度分别为20、40和50毫升/分钟，对应的计算切变率分别为1300、2600和3300秒-1，灌注时间分别为3、2和2分钟。为作比较，还对枸橼酸化血液在1300秒-1切变率下进行了平行研究。在正常受试者中，在1300秒-1的切变率下，天然血液中的血小板黏附比枸橼酸化血液中的少，但血栓形成更多。5例血管性血友病患者的血小板黏附在枸橼酸化血液和天然血液中均降低。黏附缺陷的程度强烈依赖于切变率。因此，在切变率为1300秒-1的枸橼酸化血液中进行研究时，黏附比正常受试者减少了75%，而在以往切变率为800秒-1的研究中，黏附减少了29%。在天然血液中，血管性血友病患者在1300秒-1的切变率下黏附正常，而在2600和3300秒-1的切变率下，黏附分别减少了53%和77%。在所研究的后一切变率下，伯纳德-索利尔综合征患者天然血液中的血小板黏附也降低，但血友病和无纤维蛋白原血症患者的黏附正常。我们对天然血液的研究结果进一步证明，血小板与血管壁的黏附受损是血管性血友病止血缺陷的原因。此外，这种黏附缺陷是切变率依赖性的。
