Background: Blood viscoelasticity and plasma protein levels can play an important role in the diagnosis and prognosis of cancer. However, the role of histones and DNA in modulating blood clot properties remains to be investigated. This study investigates the differences in blood viscoelasticity and plasma protein levels among cancer patients, individuals with other diseases, and healthy individuals. Methods: Blood samples were collected from 101 participants, including 45 cancer patients, 22 healthy individuals, and 34 individuals with other diseases. Rheological properties of clots formed in vitro by reconstituted elements of fibrinogen or plasma were analyzed with an Anton Paar Rheometer, USA. Plasma protein levels of D-dimer, TPA, EPCR, fibrinogen, and histone H3 were measured through ELISA. Blood clots were formed with or without DNA and histones (H3) by adding thrombin and calcium to plasma samples, and were evaluated for viscoelasticity, permeability, and degradation. Results: Cancer patients show higher blood viscoelasticity and plasma D-dimer levels compared to healthy individuals and individuals with other diseases. Our in vitro analysis showed that the addition of histone to the plasma results in a significant decrease in viscoelasticity and mean fiber thickness of the clot formed thereafter. In parallel studies, using plasma from patients, DNA and histones were detected in fibrin clots and were associated with less degradation by t-PA. Moreover, our results show that the presence of DNA and histones not only increases clots’ permeability, but also makes them more prone to degradation. Conclusions: Plasma histones and DNA affect the structure of the clot formed and induce defective fibrinolysis. Moreover, the increased viscoelastic properties of plasma from cancer patients can be used as potential biomarkers in cancer prognosis.
背景：血液粘弹性与血浆蛋白水平在癌症的诊断和预后评估中具有重要作用。然而，组蛋白和DNA在调节血栓特性中的作用仍有待研究。本研究旨在探讨癌症患者、其他疾病患者及健康人群在血液粘弹性与血浆蛋白水平方面的差异。方法：研究共纳入101名参与者，包括45名癌症患者、22名健康个体及34名其他疾病患者。采用美国安东帕流变仪对纤维蛋白原或血浆重组成分体外形成的血栓进行流变学特性分析。通过酶联免疫吸附法测定血浆中D-二聚体、组织型纤溶酶原激活剂、内皮细胞蛋白C受体、纤维蛋白原及组蛋白H3的水平。通过向血浆样本中添加凝血酶和钙离子，在有无DNA及组蛋白（H3）的条件下形成血栓，并评估其粘弹性、渗透性和降解性。结果：与健康个体及其他疾病患者相比，癌症患者的血液粘弹性及血浆D-二聚体水平显著升高。体外分析显示，向血浆中添加组蛋白会显著降低随后形成血栓的粘弹性及平均纤维厚度。在平行研究中，通过对患者血浆的分析，在纤维蛋白血栓中检测到DNA和组蛋白的存在，且这些血栓经组织型纤溶酶原激活剂降解的程度较低。此外，研究结果表明DNA和组蛋白的存在不仅会增加血栓的渗透性，还会使其更易发生降解。结论：血浆组蛋白与DNA会影响血栓的结构并导致纤溶功能缺陷。此外，癌症患者血浆粘弹性的增强可作为癌症预后评估的潜在生物标志物。
Blood Clot Dynamics and Fibrinolysis Impairment in Cancer: The Role of Plasma Histones and DNA
肿瘤(癌症)患者之家