Yang Hua, Zhu Cheng-Ying, Wang Quan-Shun, Niu Jian-Hua, Zhang Qi, Zhu Hai-Yan, Yao Zi-Long, Xu Yuan-Yuan, Jing Yu, Yu Li
Department of Hematology, Chinese PLA General Hospital, Beijing 100853, China.
Department of Hematology and Oncology, The Forth People's Hospital of Jinan City, Jinan 250031, Shandong Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2014 Apr;22(2):315-22. doi: 10.7534/j.issn.1009-2137.2014.02.010.
This study was aimed to explore the clinical characteristics and optimal therapeutic methods for newly diagnosed acute promyelocytic leukemia (APL) combined with disseminated intravascular coagulation (DIC) so as to guide the clinical therapy. The clinical date and therapeutic outcome of 25 cases of APL combined with DIC treated from January 2008 to March 2013 in our department were analysed retrospectively. The 25 patients were given ATRA 20 mg orally twice a day and arsenic trioxide (ATO) 10 mg intravenously once a day to induce differentiation therapy, the chemotherapy was added after degranulation of promyelocytes. At the same time the platelets, fresh frozen plasma, fibrinogen, cryoprecipitate,prothrombin complex and amino methylbenzoic acid, low molecular weight heparin were given to treat DIC. According to the laboratorial examination of coagulation and fibrinolysis, the medication was adjusted.The white blood cell count, platelet level, prothrombin time (PT), partial thromboplastin time of plasma (APTT), fibrinogen level were detected, and the relation of those factors and age with bleeding severity was analyzed by multivariate manner. The results showed that among 25 patients with APL (low-risk 5 cases, intermediate risk 13 cases and high risk 7 cases), 22 cases combined with DIC, incidence of DIC was 88%. Out of 22 patients with DIC 21 patients (95.5%) were corrected, except 1 case death. After the first course of treatment, 23 cases (92%) gained complete remission (CR) with average CR time 31.8 ± 7.2 days. During the induction of CR, the average platelet transfusion level was 75.68 ± 55.88 U, the RBC level was 8.90 ± 5.69 U, the average level of fresh frozen plasma transfusion of APL patients with DIC was 21.92 ± 19.32 U. The recovery time of platelet level to normal was 29.3 ± 9.3 days, the recovery time of PT, APTT, FDP and fibrinogen to normal were 12.7 ± 9.5 days, 11.6 ± 8.6 days, 16.0 ± 9.3 days and 125.3 ± 85.3 days respectively. The multivariate analysis showed that WBC count at onset was >10 × 10(9)/L and APTT was prolonged. These two factors were main reasons resulting in severe bleeding. It is concluded that the newly diagnosed APL always combined with DIC, therefore in the early phase of disease active transfusion of blood products, application of anti-coagulation and anti-fibrinolytic drugs as well as heparin should be performed; the coagulation function should be as soon as recovered to normal so as to early correct DIC. These measures can significantly decrease the mortality of APL patients resulting from DIC. The hyperleukocytosis and prolonged APTT are the main factors for severe bleeding.
本研究旨在探讨初诊急性早幼粒细胞白血病（APL）合并弥散性血管内凝血（DIC）的临床特点及最佳治疗方法，以指导临床治疗。回顾性分析了2008年1月至2013年3月在我科治疗的25例APL合并DIC患者的临床资料及治疗结果。25例患者给予全反式维甲酸（ATRA）20mg口服，每日2次，三氧化二砷（ATO）10mg静脉滴注，每日1次，进行诱导分化治疗，早幼粒细胞脱颗粒后加用化疗。同时给予血小板、新鲜冰冻血浆、纤维蛋白原、冷沉淀、凝血酶原复合物、氨甲环酸、低分子量肝素治疗DIC。根据凝血及纤溶实验室检查结果调整用药。检测白细胞计数、血小板水平、凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、纤维蛋白原水平，并采用多因素分析方法分析这些因素及年龄与出血严重程度的关系。结果显示，25例APL患者中（低危5例，中危13例，高危7例），22例合并DIC，DIC发生率为88%。22例DIC患者中，21例（95.5%）纠正，1例死亡。第1疗程治疗后，23例（92%）获得完全缓解（CR），平均CR时间为31.8±7.2天。诱导CR期间，平均血小板输注量为75.68±55.88U，红细胞输注量为8.90±5.69U，APL合并DIC患者新鲜冰冻血浆平均输注量为21.92±19.32U。血小板水平恢复正常时间为29.3±9.3天，PT、APTT、纤维蛋白降解产物（FDP）及纤维蛋白原恢复正常时间分别为12.7±9.5天、11.6±8.6天、16.0±9.3天及125.3±85.3天。多因素分析显示，发病时白细胞计数>10×10⁹/L及APTT延长是导致严重出血的主要原因。结论：初诊APL常合并DIC，因此在疾病早期应积极输注血液制品，应用抗凝及抗纤溶药物以及肝素；尽快使凝血功能恢复正常，以早期纠正DIC。这些措施可显著降低APL患者因DIC导致的死亡率。白细胞增多及APTT延长是严重出血的主要因素。
