John Paul II Hospital, Krakow, Poland.
Heart. 2011 Dec;97(24):2023-8. doi: 10.1136/hrt.2010.217273. Epub 2011 May 10.
High molecular weight von Willebrand factor (vWF) multimers (HMWM) are often deficient in patients with severe aortic stenosis (AS) owing to shear stress-enhanced proteolysis of vWF. It has also been reported that AS is associated with increased activation of blood coagulation.
To investigate whether patients with AS with a deficiency in vWF HMWM have enhanced thrombin generation and platelet activation in vivo.
Based on the analysis of vWF HMWM performed using immunolocalisation, 11 subjects with vWF HMWM deficiency (low %HMWM group) were identified and compared with 42 patients with AS with a normal distribution of vWF HMWM (normal %HMWM group). Plasma thrombin markers thrombin-antithrombin complexes (TAT) and prothrombin factor 1+2 (F1.2) plus platelet activation markers soluble CD40 ligand (sCD40L), β-thromboglobulin and P-selectin were also measured.
48 consecutive patients with severe AS and five with moderate AS, free of angiographically-proven coronary artery disease and clinically overt bleeding, were studied.
Patients in the low %HMWM group had 34.8% higher maximal transvalvular gradient (p = 0.0003) and 44.8% higher mean gradient (p = 0.0002) than those in the normal %HMWM group. Thrombin formation was enhanced in the low %HMWM group (F1.2, 284.5 ± 63.7 vs 216.9 ± 62.5 pmol/l, p = 0.004; thrombin-antithrombin, 4.89 ± 1.3 vs 4.06 ± 0.9 μg/l, p = 0.02) and both markers showed inverse correlations with the percentage of vWF HMWM (r = -0.59, p = 0.002; r = -0.42, p = 0.03, respectively). In the low %HMWM group sCD40L (279.4 ± 60.7 vs 221.4 ± 41.7 pmol/l, p = 0.003) and β-thromboglobulin (73.1 ± 9.2 vs 64.5 ± 8.5 IU/ml, p = 0.04), but not P-selectin, were also higher than in the remaining patients with AS.
Patients with advanced AS deficient in vWF HMWM are characterised by enhanced thrombin formation and platelet activation. This observation indicates the ambivalent impact of high shear stress in AS on haemostasis and might help explain two aspects of AS-Heyde syndrome and increased risk of thromboembolism.
由于剪切应力增强了 vWF 的蛋白水解，患有严重主动脉瓣狭窄（AS）的患者通常缺乏高分子量 vWF（HMWM）。也有报道称，AS 与血液凝固的激活增加有关。
研究 vWF HMWM 缺乏的 AS 患者体内是否存在增强的凝血酶生成和血小板激活。
根据免疫定位分析 vWF HMWM，确定了 11 例 vWF HMWM 缺乏（低 %HMWM 组）的患者，并与 42 例 vWF HMWM 分布正常的 AS 患者（正常 %HMWM 组）进行比较。还测量了血浆凝血酶标志物凝血酶-抗凝血酶复合物（TAT）和凝血酶原因子 1+2（F1.2）以及血小板活化标志物可溶性 CD40 配体（sCD40L）、β-血栓球蛋白和 P-选择素。
研究了 48 例连续的严重 AS 患者和 5 例中度 AS 患者，这些患者均无血管造影证实的冠状动脉疾病和明显的临床出血。
低 %HMWM 组的最大跨瓣梯度比正常 %HMWM 组高 34.8%（p=0.0003），平均梯度高 44.8%（p=0.0002）。低 %HMWM 组凝血酶生成增强（F1.2，284.5±63.7 对 216.9±62.5 pmol/l，p=0.004；凝血酶-抗凝血酶，4.89±1.3 对 4.06±0.9 μg/l，p=0.02），这两个标志物均与 vWF HMWM 的百分比呈负相关（r=-0.59，p=0.002；r=-0.42，p=0.03）。在低 %HMWM 组中，sCD40L（279.4±60.7 对 221.4±41.7 pmol/l，p=0.003）和β-血栓球蛋白（73.1±9.2 对 64.5±8.5 IU/ml，p=0.04）也高于其余 AS 患者，但 P-选择素除外。
vWF HMWM 缺乏的晚期 AS 患者表现为凝血酶生成和血小板激活增强。这一观察结果表明，高剪切应力对 AS 中止血的双重影响可能有助于解释 AS-He yde 综合征和血栓栓塞风险增加的两个方面。
