Whole blood tissue factor procoagulant activity is elevated in patients with sickle cell disease
Whole blood tissue factor procoagulant activity is elevated in patients with sickle cell disease
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DOI：
10.1182/blood.v91.11.4216.411k15_4216_4223
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发表时间：
1998-06-01
期刊：
影响因子：
20.3
通讯作者：
Bach, RR
中科院分区：
文献类型：
--
作者：
Key, NS;Slungaard, A;Bach, RR
我们开发了一种简单的测定全血样品中的组织因子促凝活性（TF PCA），避免了对单核细胞分离的需要。该方法结合了样品采集和处理的便利性以及对TF的高度灵敏度和特异性。使用这种方法，我们已经确定TF PCA在正常个体的全血样本中是可检测的，这本身就是一个新的观察结果。基本上所有五氯苯甲醚都可以定位于血液的单核细胞部分。与对照组相比，无论血红蛋白病的亚型（SS或SC疾病）如何，镰状细胞病（SCD）患者的全血IF水平均显著升高（P <0.00001）。疼痛危象组与稳态组相比，TF PCA无显著性差异。由于TF在体外FVII向FVIIa的蛋白水解转化中起辅因子的作用，因此预期循环TF PCA的增加将导致体内FVIIa产生的增加。相反，在SCD患者的血浆中，FVIIa水平实际上降低。SCD患者血浆TF途径抑制物（TFPI）抗原水平正常，表明TFPI途径加速清除FVIIa不是FVIIa水平降低的原因。我们认为，循环TF PCA水平升高可能在触发已知发生在SCD患者的凝血激活中起重要作用。由于TF是FVIIa的主要细胞配体，因此可能与TF结合的增加导致血浆FVIIa水平降低。(C)1998年，美国血液学会。
We developed a simple assay for the measurement of tissue factor procoagulant activity (TF PCA) in whole blood samples that avoids the need for mononuclear cell isolation. This method combines convenience of sample collection and processing with a high degree of sensitivity and specificity for TF. Using this method, we have determined that TF PCA is detectable in whole blood samples from normal individuals, which is itself a novel observation. Essentially all PCA could be shown to be localized in the mononuclear cell fraction of blood. Compared with controls, whole blood if levels were significantly (P < .000001) elevated in patients with sickle cell disease (SCD), regardless of the subtype of hemoglobinopathy (SS or SC disease). No significant difference in TF PCA was observed between patients in pain crisis compared with those in steady-state disease. Because TF functions as cofactor in the proteolytic conversion of FVII to FVIIa in vitro, it was expected that an increase in circulating TF PCA would lead to an increased in vivo generation of FVIIa. On the contrary, FVIIa levels were actually decreased in the plasma of patients with SCD. Plasma TF pathway inhibitor (TFPI) antigen levels were normal in SCD patients, suggesting that accelerated clearance of FVIIa by the TFPI pathway was not responsible for the reduced FVIIa levels. We propose that elevated levels of circulating TF PCA may play an important role in triggering the activation of coagulation known to occur in patients with SCD. Because TF is the principal cellular ligand for FVIIa, it is possible that increased binding to TF accounts for the diminished plasma FVIIa levels. (C) 1998 by The American Society of Hematology.