Study On Coagulation Indexes And Related Gene Polymorphism In Acute Leukemia

Acute leukemia(AL)is a malignant blood disease originating from hematopoietic stem cells.Abnormal primordial cells and immature cells(leukemia cells)in the bone marrow proliferate in a large amount,accumulate in the bone marrow and inhibit normal hematopoiesis,and extensively infiltrate the extra medullary organs such as liver,spleen and lymph nodes.The patients showed signs of anemia,hemorrhage,infection and infiltration.AL is divided into two categories: acute myeloid leukemia(AML)and acute lymphoblastic leukemia(ALL).AL patients often have varying degrees of bleeding tendency,and the invasion and metastasis of cancer cells to surrounding tissues can lead to changes in the coagulation mechanism of patients.Coagulation and anticoagulation in normal human body are in a dynamic equilibrium.The enhancement or decrease of coagulation activity will lead to bleeding or hypercoagulability due to the imbalance of this dynamic balance.In patients with AL,due to the consumption of coagulation factors or the presence of the coagulation factor inhibitors,the content or the activity of some coagulation factors is decreased,causing a disorder of coagulation mechanism.The abnormal blood coagulation is one of the most common clinical symptoms in patients with acute leukemia.This article analyzes retrospectively the relationship between bleeding and related coagulation parameters and platelet count(PLT)in patients with newly diagnosed acute leukemia.Moreover,the relationship between associatate coagulation genes and AL patients or bleeding symptom was analyzed from genetics perspective.Objective: To retrospectively analyze the relationship between bleeding in patients with primary acute leukemia and coagulation indicators and platelet count.To explore the relationship between gene polymorphism of coagulation-related gene FV Leiden,FII G20210 A,F11 rs2289252,F12 rs1801020 and acute leukemia patients and their clinical symptoms of bleeding.Methods: 92 patients with primary acute leukemia(excluding acute promyelocytic leukemia)were divided into bleeding group(43 cases)and non-bleeding group(49cases)according to whether bleeding occurred or not.Platelet(PLT)count and levels of blood coagulation indicators,including prothrombin time(PT),activated partial thromboplastin time(APTT),plasma fibrinogen(FIB),thrombin time(TT)and D-dimer(D-D),were measured at initial diagnosis stage.Abnormal status and level differences of these indicators was analyzed between the two groups.The bleeding diagnostic value of PLT and FIB was analyzed by using receiver operating characteristic(ROC)curve.90 cases of acute leukemia(70 cases of acute myeloid leukemia(AML)and 20 cases of acute lymphoblastic leukemia(ALL))and 104 healthy peoples(normal control group)were selected from September 2016 to September 2018 in Jingzhou Central Hospital.The patients with acute leukemia were divided into two subgroups: the non-bleeding group and the bleeding group according to the clinical symptoms of the bleeding at the time of admission.The single nucleotide polymorphisms(SNP)of FV Leiden,FII G20210 A,F11 rs2289252,F12 rs1801020 were analyzed using Sanger sequencing method in all subjects.Then,Clinical data,genotype frequencies and allele frequencies were compared between the AL group and its subgroups(AML group,ALL group)and the control group.The relationship and susceptibility between F11 rs2289252,F12rs1801020 genotype frequency or,allele frequencies and patient bleeding were further analyzed.Results: 1.There were no significant differences in gender,age,white blood cell count at the time of initial diagnosis and leukemia type between the bleeding group and the non-bleeding group(all P>0.05).Statistically significant difference of patient coagulation index abnormal rate never existed between the bleeding group and the non-bleeding group(P>0.05).There was a statistically significant difference in PLT count between the two groups at initial diagnosis stage(P<0.01),and patients with lower PLT count were more likely to bleed.FIB in patients with bleeding group were significantly lower than that in patient with non-bleeding group(P<0.05).Other four blood coagulation indicators were no significantly different between the two groups(all P>0.05).When the diagnosis cut-off point of PLT count was 39.5×109/L,the sensitivity of the diagnosis of acute leukemia was 0.633 and the specificity was 0.814.The value of FIB in diagnosing bleeding was not good.2.There were no significant differences in gender ratio,age,prothrombin time(PT)and activated partial thromboplastin time(APTT)between the acute leukemia group and the control group(P>0.05),while the number of red blood cells(RBC),white blood cell count(WBC),platelet count(PLT)as well as level of hemoglobin(HB),plasma thrombin time(TT)and fibrinogen(FIB)were statistically significant differences between the case group and the control group(P<0.05).The results of FV Leiden gene and FII G20210 A gene were all GG genotype,no mutation was detected;F11rs2289252 gene detection results were 34 CC genotype,46 TC genotype,10 TT genotype;F12 rs1801020 gene test result was 3 Case CC genotype,33 cases of TC genotype,54 cases of TT genotype.F11 rs2289252 and F12 rs1801020 genotype and allele frequency were not significantly different between the two groups(P>0.05).In the non-bleeding group and the bleeding group of acute leukemia patients,the distribution of F11 rs2289252 genotype and the allele were statistically significant(P<0.05).In the bleeding group,the genotype frequency of F11 rs2289252(TT+TC)and T allele was significantly lower than in the non-bleeding group.In acute leukemia patients,the bleeding risk of patients carrying F11 rs2289252 TC was 0.313 times of CC(95%CI:0.121~0.802,P=0.014),and the bleeding risk of patients of F11 rs2289252 T allele carrier(TT+TC)was 0.296 times of CC(95%CI:0.122~0.734,P=0.007).3.Aanlyzed among AML group,ALL group and control group,F11 rs2289252 genotype and allele frequency were significantly different(P<0.05).In the non-bleeding group and the bleeding group of AML patients,the distribution of F11 rs2289252 genotype and the allele were statistically significant(P<0.05),but the distribution of F12 rs1801020 genotype and the allele were not statistically significant(P>0.05).In the bleeding group of AML patients,the genotype frequency of rs2289252(TT+TC)and T allele was significantly lower than in the non-bleeding group.In the non-bleeding group and the bleeding group of ALL patients,the genotype frequency of rs2289252(TT+TC),CC and allele frequency were not statistically significant(P>0.05).In AML patients,the bleeding risk of patients carrying rs2289252 TC was 0.256 times of CC(95%CL: 0.081-0.808,P=0.020),and the bleeding risk of patients of rs2289252 T allele carrier(TT+TC)was 0.263 times of CC(95%CI:0.091~0.763,P=0.011).Conclusion: 1.The number of platelets and plasma fibrinogen levels in patients with primary acute leukemia are associated with bleeding symptom.2.PLT is sensitive to the diagnosis of bleeding symptom to some extent in patients with primary acute leukemia.3.The F11 rs2289252 gene polymorphism is associated with acute leukemia hemorrhage,and the T allele is a protective factor for acute leukemia bleeding.4.The F11 rs2289252 gene polymorphism is associated with acute myeloid leukemia hemorrhage,and the T allele is a protective factor for acute myeloid leukemia bleeding.