Mohren Martin, Jentsch-Ullrich Kathleen, Koenigsmann Michael, Kropf Siegfried, Schalk Enrico, Lutze Gerd
Department of Hematology/Oncology, Magdeburg University Hospital, Magdeburg, Germany.
Klinik für Hämatologie/Onkologie, Johanniter-Krankenhaus Stendal, Wendstr. 31, 39576, Stendal, Germany.
Int J Hematol. 2016 Feb;103(2):189-95. doi: 10.1007/s12185-015-1913-y. Epub 2015 Nov 26.
The risk of venous thromboembolism is increased in patients with lymphoma and leukemia; however, little is known about the potential underlying hereditary or acquired thrombophilia. We prospectively analyzed procoagulant markers and gene mutations in patients with lymphoma (n = 35) and leukemia (n = 10) at diagnosis and over the course of treatment. Global coagulation tests were normal in all patients, as were antithrombin and protein S. Activated protein C resistance caused by the factor V Leiden mutation was found in four patients, one patient had the G20210A mutation of the prothrombin gene, and one patient had protein C deficiency. The most striking findings were sustained very high levels of factor VIII (>150 %) in 30 patients (68 %), which correlated with high von Willebrand factor. An acute phase response in these patients was ruled out by absence of fever and normal IL-6 and -α. Elevated factor VIII is an independent thrombophilic risk factor and may play an etiologic role in thromboembolic complications in patients with malignant lymphoma. Since high von Willebrand factor is most likely caused by endothelial cell injury, an additional, unknown pathophysiological association with malignant lymphoma and acute leukemia is possible.
淋巴瘤和白血病患者发生静脉血栓栓塞的风险增加；然而，对于潜在的遗传性或获得性易栓症知之甚少。我们对35例淋巴瘤患者和10例白血病患者在诊断时及治疗过程中进行了前瞻性促凝标志物和基因突变分析。所有患者的全血凝固试验均正常，抗凝血酶和蛋白S也正常。4例患者发现由因子V Leiden突变引起的活化蛋白C抵抗，1例患者有凝血酶原基因的G20210A突变，1例患者有蛋白C缺乏。最显著的发现是30例患者（68%）的因子VIII水平持续非常高（>150%），这与高血管性血友病因子相关。这些患者不存在发热且白细胞介素-6和-α正常从而排除了急性期反应。因子VIII升高是一个独立的易栓危险因素，可能在恶性淋巴瘤患者的血栓栓塞并发症中起病因学作用。由于高血管性血友病因子很可能是由内皮细胞损伤引起的，因此恶性淋巴瘤和急性白血病可能存在另一种未知的病理生理关联。
