Effect of recombinant human coagulation factor Ⅶa combined with Bakri balloon compression on oxidative stress and coagulation in patients with refractory postpartum hemorrhage / 中国输血杂志

【Objective】 To investigate the effects of recombinant human coagulation factor Ⅶa combined with Bakri balloon compression on oxidative stress and coagulation in patients with refractory postpartum hemorrhage. 【Methods】 Prospectively, 80 patients with refractory postpartum hemorrhage in Chengdu Fifth People′s Hospital from June 2019 to June 2022 were selected and grouped according to the random number table method. The control group (n=40) was treated with Bakri balloon compression, and the observation group (n=40) was treated with recombinant human coagulation factor Ⅶa combined with Bakri balloon compression. The bleeding-related indexes and adverse effects were observed in both groups, and the prenatal and 24 h postpartum oxidative stress, coagulation function and inflammatory factors were compared between the two groups. 【Results】 The blood loss in the observation group and the control group was (683.96±146.52) vs(796.63±152.41)mL during operation, (812.46±161.53) vs(965.39±166.22)mL in 2 h after delivery, (899.53±178.74) vs(1 084.31±203.67)mL in 24 h after delivery, and the transfusion volume was (512.31±104.76) vs(683.25±113.52)mL, and the onset time of hemostasis was (14.63±3.18) vs (21.72±5.29) min (P0.05). At 24 h postpartum, NE, Cor, SOD and MDA were higher than those before delivery in both groups, but the observation group was lower than the control group (P<0.05); TT, APTT and PT were longer and Fib was lower in both groups than before delivery, but TT, APTT and PT were shorter and Fib was higher in the observation group than in the control group (P<0.05); CRP, IL-8 and TNF-α were higher in both groups than before delivery, but the observation group was lower than in the control group (P<0.05). 【Conclusion】 Hemostasis in patients with refractory postpartum hemorrhage treated with recombinant human coagulation factor Ⅶa combined with Bakri balloon compression was effective, which can improve coagulation, reduce transfusion, decrease oxidative stress injury and inflammatory response without increasing adverse effects.

Effect evaluation of blood component transfusion combined with recombinant activated factorⅦa in treatment of severe active hemorrhage after cardiac surgery / 中国综合临床

Objective To evaluate the efficacy and complications of component blood transfusion combined with recombinant activated factorⅦa(rFⅦa)in treatment of severe active hemorrhage after cardiac surgery??Methods Fifty patients who suffered from severe active hemorrhage after cardiac surgery were selected from the First Affiliated Hospital of Dalian Medical University from July 2015 to May 2017??All patients were divided into GR group ( component blood transfusion combined with rFⅦa) and GA group (component blood transfusion combined with tranexamic acid) by random number table method,25 cases in each group??The changes of disseminated intravascular coagulation (DIC) were screened on admission(D1), after cessation of cardiopulmonary bypass ( D2 ), and 2 h ( D3 ), 6 h ( D4 ) and 12 h ( D5 ) after medication??The difference of activated partial thromboplastin time (APTT), international normalized ratio (INR),fibrinogen,hemoglobin and platelet of the two groups at each time point of D1,D2,D3,D4 and D5 were analyzed??Meanwhile, the postoperative drainage, postoperative blood transfusion, postoperative plasma transfusion volume, postoperative mechanical ventilation time, ICU retention time, the 30 d mortality and complications were compared between the two groups??Results There were significant differences in APTT, INR,fibrinogen,hemoglobin and platelet between the two groups ( all P＜0??05)??There was no significant difference in the indices of DIC screening between the two groups at D1, D2 and D5 time points ( all P＞0??05),but at D3 time point,APTT in GR group was significantly shorter than that in GA group((50??3 ±6??6)s vs??(60??1±6??5)s,P＝0??027),and INR in GR group at D4 time point was also significantly lower ((1??3 ± 0??3) vs??( 1??5 ± 0??3), P＝0??041)??In addition, the amount of red blood cells transfusion after treatment in GR group and GA group (( 3??2± 1??0) U vs??(4??1 ± 1??0) U,P＝0??005),the amount of fresh plasma transfusion ((303??2±98??5) ml vs??(469??6± 190??5) ml,P＝0??000),the amount of 24 h drainage after operation ((519??9±107??5) ml vs??(657??2±100??1) ml, P＝0??000) were significantly decreased,the differences were statistically significant??Conclusion Blood component transfusion combined with rFⅦa can significantly improve APTT and INR of severe active hemorrhage after cardiac surgery,at the same time,it can reduce the amount of red blood cells transfusion and plasma transfusion??

Clinical efficacy of recombinant activated factor Ⅶ a for 16 hematonosis with moderate or severe bleeding / 中华血液学杂志

Objective@#To analyze the efficacy of recombinant activated factor Ⅶ a (rF Ⅶ a) on hematonosis with moderate or severe bleeding signs.@*Methods@#Of total 16 cases with rF Ⅶ a treatment from May 2013 to May 2016, 8 cases received allogeneic hematopoietic stem cells transplantation (allo-HSCT) and the other were non-transplantation patients. In two groups, there was no significant difference on rF Ⅶ a usage and dosage. 15 patients with acute graft-versus-host disease (aGVHD) after allo-HSCT were control group (without rF Ⅶ a) .@*Results@#①The total response rate was 75.0% (6/8) in non-transplantation group and 37.5% (3/8) in transplantation group, respectively. Median interval for hemorrhage stop was 38.5 hours in non-transplantation group and 63.0 hours in transplantation group. The median overall survival (OS) was 201.0 and 29.0 days for non-transplantation group and transplantation group, respectively, and the OS rate was 50.0% (4/8) and 25.0% (2/8) , respectively. The bleeding-related mortality rate was 50.0% (2/4) and 83.3% (5/6) , respectively. ②Of the 16 cases, 9 showed response to rF Ⅶ a treatment and the other 7 cases’bleeding signs did not alleviate. The median OS was 268.0 in 9 cases with response and 24.0 days in 7 cases without response, respectively. ③In patients with intestinal aGVHD complicated with intestinal hemorrhage, the median OS of observation group (n=6) and control group (n=15) were 25.5 days and 20.0 days, respectively.@*Conclusion@#Patients with hematological diseases, especially patients after allo-HSCT, had high bleeding-related mortality, and rFⅦa therapy had a obvious hemostatic efficacy. The survival rate of patients with response was higher than that of cases without response. The causes of poor hemostasis efficacy of rF Ⅶ a therapy were associated with unsatisfactory control of complications in patients with intestinal bleeding after allo-HSCT.

Mechanism of cross talk between tissue factor/active coagulation factor Ⅶ and epidermal growth factor receptor signalings in colon cancer cells in culture / 北京大学学报(医学版)

Objective:To preliminarily verify the cross talk between tissue factor/active coagulation factor Ⅶ (TF/FⅦa) and epidermal growth factor receptor (EGFR) pathways in human colon cancer cells in culture.Methods:FⅦa was treated to HT-29 (KRAS-wild type) and LoVo (KRAS-mutant) colon cancer cells to activate TF/F Ⅶa pathway,qRT-PCR and Western blot were used to detect the expressions of amphiregulin (AREG) and epiregulin (EREG),ligands of EGFR on mRNA and protein levels,respectively.After knocking down expression of TF by TF-targeted siRNA transfection,FⅦa was treated and mRNA expressions of AREG and EREG were detected to see whether the FⅦa-induced effects were dependent on TF.Expressions of mRNA of TF and FⅦwere detected by qRT-PCR following the activation of EGFR pathway by treatment with epidermal growth factor (EGF) to HT-29 and LoVo cells.Results:After TF/FⅦa pathway was activated,for HT-29 cells,expressions of AREG (on mRNA level) and EREG (both on mRNA and protein level) were significantly down-regulated versus those of control group,gene expressions of AREG and EREG were 0.55 ± 0.09 vs.0.99 ± 0.09,0.67 ± 0.10 vs.1.02 ± 0.02,protein expressions of EREG were 0.54 ± 0.09 vs.1.04 ± 0.13,all P ＜ 0.05.For LoVo cells,expressions of AREG (both on mRNA and protein level) and EREG (on protein level) were significantly up-regulated versus those of control group,gene expression of AREG were 1.87 ± 0.39 vs.0.93 ± 0.23,protein expressions of AREG and EREG were 3.09 ±0.73 vs.1.11 ±0.21,1.53 ±0.19 vs.0.97 ± 0.23,all P ＜0.05.The regulating effect of AREG and EREG mRNA expression by FⅦa in HT-29 and LoVo cells could both be partly blocked by knocking down TF expression.For HT-29 cells,activation of EGFR pathway induced no significant TF mRNA expression,F Ⅶ mRNA expression was not detected.However,for LoVo cells,activation of EGFR pathway induced significantly higher mRNA expressions of both TF and FⅦ,expressions were 1.53 ± 0.23 vs.1.00 ± 0.23,53.20 ± 6.08 vs.1.00 ± 0.15,all P ＜0.05.Conclusion:In colon cancer cell LoVo,when activated,TF/FⅦa pathway and EGFR pathway could interact through upregulating the other pathway's effectors,and mutant KRAS might play a critical role in the two pathways'cross talk.

A successful experience of using recombinant human coagulation factor Ⅶ a for treatment of a patient with pernicious placenta previa and massive postpartum hemorrhage / 中国中西医结合急救杂志

Massive postpartum hemorrhage is one of the most severe complications of pregnant women during deliveries, especially, on the basis of a scarred uterus with placenta previa and placenta implantation, the risk of occurrence of massive hemorrhage after delivery will be obviously increased. The recombinant human coagulation factorⅦa (rFⅦa) can be used to significantly reduce the incidence of delutional coagulopathy and the necessary amount of blood products in patients after major abdominal surgery. One patient with massive postpartum hemorrhage resulted from scarred uterus with placenta previa and previa accreta was administered into Guizhou Medical University Affiliated Hospital, whose hemorrhage was successfully stopped by using rFⅦa in case of surgical indication being excluded. It is suggested that rFⅦa can be regarded as an effective drug for postpartum hemorrhage on the basis of indication being strictly controlled.

A successful experience of using recombinant human coagulation factor Ⅶ a for treatment of a patient with pernicious placenta previa and massive postpartum hemorrhage / 中国中西医结合急救杂志

Massive postpartum hemorrhage is one of the most severe complications of pregnant women during deliveries, especially, on the basis of a scarred uterus with placenta previa and placenta implantation, the risk of occurrence of massive hemorrhage after delivery will be obviously increased. The recombinant human coagulation factorⅦa (rFⅦa) can be used to significantly reduce the incidence of delutional coagulopathy and the necessary amount of blood products in patients after major abdominal surgery. One patient with massive postpartum hemorrhage resulted from scarred uterus with placenta previa and previa accreta was administered into Guizhou Medical University Affiliated Hospital, whose hemorrhage was successfully stopped by using rFⅦa in case of surgical indication being excluded. It is suggested that rFⅦa can be regarded as an effective drug for postpartum hemorrhage on the basis of indication being strictly controlled.

Levels of plasma D-dimer, activated coagulation factor Ⅶ and Ⅻ in patients with chronic urticaria / 中华皮肤科杂志

Objective To measure the levels of plasma D-dimer,activated coagulation factor Ⅶ (FⅦa) and activated clotting factor Ⅻ (FⅫa) in patients with chronic urticaria (CU),and to investigate their relationship with the occurrence of CU.Methods Venous blood samples were collected from 50 patients with CU and 50 healthy human controls.Dry-column immune scattering chromatography was performed to detect the plasma level of D-dimer,and enzyme-linked immunosorbent assay (ELISA) to measure the levels of FⅦa and FⅫa.In addition,autologous plasma skin test (APST) was conducted in 43 patients with CU,and autologous serum skin test (ASST) in 41 patients with CU.A correlation analysis was carried out between the above three parameters and disease severity as well as between the results of APST and ASST and plasma level of D-dimer.Results The levels of plasma D-dimer and F Ⅶa were significantly higher in patients with CU than in healthy human controls (both P ＜ 0.05),while no significant difference was found in FⅫa level between the two groups (P ＞ 0.05).Moreover,the degree of increase in D-dimer plasma level was positively correlated with disease severity in the patients with CU.The plasma level of D-dimer was significantly higher in APST-positive patients than in APST-negative patients (P ＜ 0.05),but not significantly different between ASST-positive and-negative patients (P ＞ 0.05).Conclusions Coagulation mechanism,especially the extrinsic coagulation pathway,is related to the occurrence of CU.Studies on coagulation mechanism are beneficial to the evaluation of severity,and clinical treatment,of CU.

γFⅦa for the treatment of intraoperaflve bleedings in abdominal surgery / 中华普通外科杂志

Objective To investigate the efficacy of recombinant activated factor Ⅶ (γFⅦa)in the management or prevention of intraoporative bleeding in general surgery. Methods A retrospective analysis was made to investigate the effect of FⅦa in 56 surgical cases.There were 56 cases including 53 hepatobiliary cases,3 gastrointestinal surgical cflses.γFⅦa was used intraoperatively when bleeding was difficult to control in 12 patients,and in 30 liver transplant cases before a skin incision was made.γFⅦa was used in the other 14 cases postoperatively to control intraabdominal bleeding. Results Massive bleeding stopped in 11 out of 12 cases who used γFⅦa during the operation as a rescue regimen,though two of them eventually died intraoperatively for deteriorating hemedynamics,one died of intraoperative intractable bleeding in spite of the Use of γFⅦa.All the 30 liver transplant cases used γFⅦa in the prevention of intraoperative bleeding had a successful surgery.After γFⅦa was administered in 11 out of the 14 cases of postoperative bleeding,the drainage decreased by 50%.In 3 cases γFⅦa failed and hemodynamic and vital signs were still unstable.In brief,γFⅦa were safely used in bleeding control or prophylaxis.Its Successful rate reached 89% in 56 patients.No thrombus complication was found. Conclusion γFⅦ a controls perioperative hemorrhage complications.

Warfarin-associated intracerebral hemorrhage / 国际脑血管病杂志

The incidence of warfarin-associated intracerebral hemorrhage is increasing gradually. Its early mortality is as high as 50%. The risk factors include advanced age, international normalized ratio > 3.5, hypertension, previous stroke, leukoaraiosis, cerebral amyloid angiopathy, and concomitant antiplatelet therapy, etc. Its prognosis was poor and there is no optimal treatment.

Relationship of clinical symptom to plasmic levels of D-dimer, activated factor Ⅶ and tissue factor pathway inhibitor (TFPI)/Xa in patients with urticaria / 中华皮肤科杂志

Objective To evaluate the relationship of clinical symptom to plasmic levels of D-dimer, activated factorⅦ (FⅦa) and tissue factor pathway inhibitor (TFPI)/X a in patients with urticaria. Methods A total of 27 patients with chronic urticaria (CU), 27 patients with acute urticaria (AU) and 26 normal human controls were included in this study. Symptom score was determined and disease course was surveyed in these patients. ELISA was used to detect the plasma levels of D-dimer, FⅦa and (TFPI)/Xa in patients and controls. The relation of clinical symptom and disease course to plasma levels of these parameters was assessed. Results In patients with AU and normal controls, the plasma level of D-dimer was 450.57± 242.13 ng/mL and 266.81±40.68 ng/mL, respectively, the level of FⅦa, 2.23± 0.74 ng/mL and 5.23±1.35 ng/mL, respectively, and the level of TFPI/Xa 0.87±0.13 nmol/L and 0.88 ~ 0.12 nmol/L, respectively. There was a significant difference in the level of both D-dimer and FⅦa (both P < 0.01 ), whereas no differ-ence was observed in that of TFPI/X a (P > 0.05) between patients with AU and normal controls. In addi-tion, increased level of D-dimer and decreased level of FⅦa were noticed in patients with CU compared with those in normal controls (593.80±294.04 ng/mL vs 266.81±40.68 ng/mL, 3.98±0.35 ng/mL vs 5.23± 1.35 ng/mL, both P < 0.01 ), but there was no significant difference in the plasma level of TFPI/Xa (0.87± 0.16 nmol/L vs 0.88±0.12 nmol/L, P > 0.05). Significant difference was observed in the plasma level of D-dimer and FⅦa between patients with AU and CU (450.57±242.13 ng/mL vs 593.80 ±294.04 ng/mL, P < 0.05; 2.23± 0.74 ng/mL vs 3.98± 0.35 ng/mL, P<0.01 ). The plasma level of D-dimer positively corre-lated to the symptom score of patients with CU and those with AU (r= 0.68, P< 0.01; r= 0.82, P< 0.01),but was independent of discase course (P> 0.05). Neither the level of FⅦa nor that of TFPI/Xa correlated to symptom score or disease course of patients (all P > 0.05). Conclusions There is an overactivation of coagulation cascade, consumption of blood coagulation factors and secondary fibrinolysis in patients with urticaria, suggesting that plasma D-dimer and FⅦa may be associated with the clinical symptoms of urticaria.