【作者】 王彤；

【导师】 许莲蓉；

【作者基本信息】 山西医科大学 ， 内科学， 2020， 硕士

【摘要】 目的:讨论新诊断初发急性白血病(Acute Leukemia,AL)凝血指标及各亚型之间的对比方法:共纳入105例新诊断的急性淋巴细胞白血病(Acute Lymphoblastic Leukemia,ALL)患者、212例急性髓性白血病(Acute Myeloid Leukemia,AML)患者。其中105例ALL病人包括47名费城染色体(Philadelphia Chromosome,Ph)阳性ALL患者和58名Ph阴性ALL患者。进行凝血试验,包括凝血酶原时间(Prothrombin Time,PT),活化部分凝血活酶时间(Activated Partial Thromboplastin Time,APTT),纤维蛋白原(Fibrinogen,FIB-C)试验和D-二聚体(D-dimer,D-D)试验。在化疗开始前,评估弥散性血管内凝血(Disseminated intravascular coagulation,DIC)相关实验室指标(1)D-二聚体(2)PT(3)纤维蛋白原(4)血小板计数。结果:研究发现Ph阳性ALL患者年龄较阴性ALL患者高,外周血白细胞计数和血红蛋白水平中位数显著高于后者,与正常核型急性髓系白血病(Normal Karyotype Acute Myeloid Leukemia,NK-AML)变异阴性患者相比,具有t(8;21)变异的AML患者更年轻并且具有更低的血红蛋白水平。NK-AML突变阳性患者弥散性血管内凝血(DIC)发生率显著增加,其中核仁磷酸蛋白(NuclearPhosphoprotein,NPM1)和酪氨酸激酶III型受体串联重复(Fms-like tyrosine kinase-3 internal tandem repeat,FLT3-ITD)突变患者的DIC发生率极高。达到DIC诊断标准的急性白血病患者的ISTH DIC评分在APL和非APL AML(P=0.001),APL和B-ALL(P=0.002)以及非APL AML和B-ALL(P=0.009)之间明显不同。多变量logistic回归分析表明,NPM1突变和FLT3-ITD突变是正常核型非APL AML发生DIC的独立因素,特征是PT显著延长,D-二聚体明显升高。P210BCR-ABL转录提示可能发生低纤维蛋白原血症。结论:ALL病人中Ph阴性是D-二聚体升高的危险因素,OR为4.812(1.433-16.16)(P=0.011)。Ph阳性ALL患者具有较低血小板中位数较低(P=0.01)和较低的D-二聚体中位数(P=0.002)。2、在AML患者中,最常用的ISTH-DIC评分的4个参数中的两个指标(血小板、纤维蛋白原水平)参考意义不大。首先,低血小板计数在急性白血病中非常常见,而且血小板减少与凝血异常无关。更多还原

【Abstract】 Objective:To discuss the coagulatory indicators(or indexes)of newly diagnosed acute leukemia and compare them between AL subtypes Methods:A total of 105 newly diagnosed patients with acute lymphoblastic leukemia and 212 patients with acute myeloid leukemia were enrolled in this study.All patients’ diagnosis were confirmed by bone marrow smear and biopsy morphology,immunophenotyping,cytogenetics and molecular biology.Of these 105 ALL patients 47 were Philadelphia chromosome-positive(Ph-positive)and 58 Ph-negative.Coagulation tests including prothrombin time(PT),activated partial thromboplastin time(APTT),fibrinogen(FIB-C),and D-dimer(D-D)were performed for all patients.Diffuse intravascular coagulation(DIC)related indexes such as(1)D-dimer(2)PT(3)fibrinogen(4)platelet counts were assessed prior to initiation of chemotherapy.Results:Philadelphia chromosome-positive ALL patients were older than negative ALL patients,and the median white blood cell count and hemoglobin levels were significantly higher than the latter,with t(8;21)variation compared with normal karyotype(NK-AML)variant negative patients.AML patients are younger and have lower hemoglobin levels.Compared with NK-AML mutation-positive patients,the incidence of DIC was significantly increased.The DIC incidence of nucleolar phosphoprotein(NPM1)and tyrosine kinase type III receptor tandem repeat(FLT3-ITD)mutations is extremely high.Among patients with acute leukemia who meet the diagnostic criteria for DIC,patients with acute promyelocytic leukemia(APL)have severe hypofibrinogenemia that is significantly higher than patients with non-APL AML.Patients with ALL and non-APL AML with significant DIC have significantly higher levels of D-dimer.However,there was no significant difference in the level of D-dimer in patients with acute early-stage cellular leukemia with and without disseminated intravascular coagulation(DIC).The incidence of elevated D-dimer levels in the Ph-positive ALL group was significantly lower than in Ph-negative ALL patients.Conclusion:1.Ph negative in ALL patients was a risk factor for D-dimer elevation,with an OR of 4.812(1.433-16.16)(P = 0.011).P210BCR-ABL positive in ALL patients suggested a low fibrinogenemia(OR: 16.667 [CI: 1.565-177.494])(P = 0.02).The Ph-positive ALL group had a lower platelet median(P = 0.01)and a lower D-dimer median(P = 0.002)compared with Ph-negative ALL patients.2.In AML patients,two of the four parameters of the most commonly used ISTH-DIC score(platelet,fibrinogen levels)are of little value.First,low platelet counts are very common in acute leukemia and are not due to coagulation activation.In addition,as recorded in our study,fibrinogen levels rarely decrease <1 g / L in AML.When the fibrinogen level was excluded,the DIC score hardly changed,so the fibrinogen index was of little significance.更多还原