Center for Haemorrhagic and Thrombotic Diseases, Department of Medical Sciences, Catholic University School of Medicine, 'A. Gemelli' Hospital, Rome, Italy.
Center for Haemorrhagic, Thrombotic and Rare Hematologic Diseases, Spirito Santo Hospital, Pescara, Italy.
J Thromb Haemost. 2015 Jul;13(7):1226-37. doi: 10.1111/jth.12967. Epub 2015 May 22.
Essential thrombocythemia (ET) is characterized by increased platelets and prevalent thrombosis. An acquired von Willebrand factor (VWF) disease has been hypothesized and inconsistently associated with extreme thrombocytosis or rare bleeding in ET. Whether VWF is modified in ET patients with controlled platelet count remains unclear.
We studied different VWF- and platelet-associated parameters in ET patients treated according to current recommendations.
PATIENTS/METHODS: Sixty-nine ET patients (M = 29; median age, 62 [48-70] years; platelets, 432 [337-620] × 10(3) μL(-1) ), 69 matched controls and 10 subjects with reactive thrombocytosis (RT) were studied. VWF:antigen (Ag), activity (act), electrophoretic patterns, VWF:propeptide, plasma glycocalycin (GC), glycoproteinV (GpV), ADAMTS-13, elastase, C-reactive protein and serum thromboxane (TX)B2 were measured.
In ET patients, VWF:Ag was increased by 31 ± 13% vs. controls (P < 0.01), without dependence of blood groups, while VWF:act was reduced by 21 ± 12% vs. controls and by 50 ± 24% vs. RT (P < 0.01). The VWF:act/VWF:Ag ratios in ET were reduced by 35 ± 17% vs. controls and RT patients (P < 0.001) and significantly associated with: immature or total platelet counts, GC, GpV and TXB2 . In multivariable analysis, only GC inversely predicted ET patients' VWF:act/VWF:Ag ratios (β = -0.42, P = 0.01). By electrophoresis analyses, high-molecular-weight VWF multimers were variably reduced with atypical cleavage bands in ET only. VWF:propeptide, ADAMTS-13 and elastase levels were normal in ET patients. Platelet-associated ADAM-10 and ADAM-17 hydrolyzed VWFm in vitro, showing patterns similar to those in ET samples.
In ET patients with controlled platelet counts, the VWF:act/VWF:Ag ratio is decreased and predicted by GC, a product of platelet activation. ADAM-10 and/or ADAM-17 might be involved. In vivo platelet activation, which characterizes ET, might contribute to disease-specific VWF alterations.
特发性血小板增多症（ET）的特征是血小板增多和普遍存在血栓形成。已经假设获得性血管性血友病因子（VWF）疾病与 ET 中的极端血小板增多或罕见出血有关，但血小板计数得到控制的 ET 患者的 VWF 是否发生改变尚不清楚。
我们研究了根据当前建议治疗的 ET 患者中不同的 VWF 和血小板相关参数。
患者/方法：研究了 69 名 ET 患者（M=29；中位年龄，62[48-70]岁；血小板计数，432[337-620]×103μL-1）、69 名匹配对照和 10 名反应性血小板增多症（RT）患者。测量了 VWF：抗原（Ag）、活性（act）、电泳模式、VWF：前肽、血浆糖胺聚糖（GC）、糖蛋白 V（GpV）、ADAMTS-13、弹性蛋白酶、C 反应蛋白和血清血栓烷 B2（TXB2）。
与对照组相比，ET 患者的 VWF：Ag 增加了 31±13%（P<0.01），而与血型无关，而 VWF：act 则降低了 21±12%与对照组相比，与 RT 患者相比降低了 50±24%（P<0.01）。与对照组和 RT 患者相比，ET 患者的 VWF：act/VWF：Ag 比值降低了 35±17%（P<0.001），并与不成熟或总血小板计数、GC、GpV 和 TXB2 显著相关。在多变量分析中，只有 GC 反向预测 ET 患者的 VWF：act/VWF：Ag 比值（β=-0.42，P=0.01）。通过电泳分析，仅在 ET 中观察到高相对分子质量 VWF 多聚体减少，伴有典型的切割带。ET 患者的 VWF：前肽、ADAMTS-13 和弹性蛋白酶水平正常。血小板相关的 ADAM-10 和 ADAM-17 在体外水解 VWFm，表现出与 ET 样本相似的模式。
在血小板计数得到控制的 ET 患者中，VWF：act/VWF：Ag 比值降低，并受 GC 预测，GC 是血小板激活的产物。ADAM-10 和/或 ADAM-17 可能参与其中。特征为 ET 的体内血小板激活可能导致疾病特异性 VWF 改变。
