Department of Hematology/Oncology, Sint Franciscus Gasthuis, Rotterdam, The Netherlands.
Department of Hematology, Erasmus University Medical Center (Erasmus MC), Rotterdam, The Netherlands.
Blood. 2016 Oct 6;128(14):1854-1861. doi: 10.1182/blood-2016-02-701094. Epub 2016 Jun 28.
Venous thromboembolism is a common complication in patients with cancer, but only limited data are available in acute myeloid leukemia (AML). In a prospective study in a cohort of 272 adult patients (aged 18-65) and an independent validation cohort of 132 elderly adults (aged >60) with newly diagnosed AML, we assessed markers of disseminated intravascular coagulation (DIC) (fibrinogen, D-dimer, α-2-antiplasmin, antitrombin, prothrombin time, and platelet count) and the DIC score according the International Society of Thrombosis and Haemostasis and their associations with the occurrence of venous and arterial thrombosis during follow-up. The prevalence of thrombosis was 8.7% (4.7% venous, 4.0% arterial) in the younger adults over a median follow-up of 478 days and 10.4% (4.4% venous, 5.9% arterial) in elderly patients. Most thrombotic events (66%) occurred before the start of the second course of chemotherapy. The calculated DIC score significantly predicted venous and arterial thrombosis with a hazard ratio (HR) for a high DIC score (≥5) of 4.79 (1.71-13.45). These results were confirmed in the validation cohort of elderly patients with AML (HR 11.08 [3.23-38.06]). Among all DIC parameters, D-dimer levels are most predictive for thrombosis with an HR of 12.3 (3.39-42.64) in the first cohort and an HR of 7.82 (1.95-31.38) in validation cohort for a D-dimer >4 mg/L vs ≤4 mg/L. It is concluded that venous and arterial thrombosis may develop in ∼10% of AML patients treated with intensive chemotherapy, which to a large extent can be predicted by the presence of DIC at time of AML diagnosis.
静脉血栓栓塞症是癌症患者的常见并发症，但在急性髓系白血病（AML）中仅有有限的数据。在一项前瞻性研究中，我们评估了 272 名成年患者（年龄 18-65 岁）和 132 名新诊断为 AML 的老年患者（年龄>60 岁）队列中的弥漫性血管内凝血（DIC）标志物（纤维蛋白原、D-二聚体、α2-抗纤溶酶、抗凝血酶、凝血酶原时间和血小板计数）和 DIC 评分，以及国际血栓和止血学会（International Society of Thrombosis and Haemostasis）的评分，并根据其与随访期间静脉和动脉血栓形成的发生的相关性进行分析。在中位随访 478 天内，年轻患者的血栓形成患病率为 8.7%（4.7%为静脉血栓形成，4.0%为动脉血栓形成），老年患者为 10.4%（4.4%为静脉血栓形成，5.9%为动脉血栓形成）。大多数血栓形成事件（66%）发生在第二个化疗疗程开始之前。计算得出的 DIC 评分显著预测了静脉和动脉血栓形成，高 DIC 评分（≥5）的危险比（HR）为 4.79（1.71-13.45）。这些结果在 AML 老年患者的验证队列中得到了证实（HR 11.08 [3.23-38.06]）。在所有 DIC 参数中，D-二聚体水平对血栓形成的预测性最高，在第一队列中 HR 为 12.3（3.39-42.64），在验证队列中 HR 为 7.82（1.95-31.38），D-二聚体>4 mg/L 与≤4 mg/L 相比。总之，约 10%接受强化化疗的 AML 患者可能会发生静脉和动脉血栓形成，在 AML 诊断时 DIC 的存在在很大程度上可以预测这种情况。
