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【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.
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A retrospective analysis of 7 patients of multiple myeloma (MM) with initial manifestation of bleeding and coagulation abnormalities were performed. Clinical manifestations, laboratory and imaging examinations were collected. The activity of coagulation factors was measured before the treatment. Single factor X deficiency was seen in one patient. Two cases had factor Ⅶ deficiency, while four other patients had multiple factor deficiency. The time from onset of symptoms to diagnosis ranged from 2 to 10 months. After anti-MM treatment started and plasma or coagulation factors were transfused, the prolonged coagulation time returned to normal from 28-84 days. Most of these patients presented large, deep and multiple sites of hematoma, which caused concerns of bone marrow puncture and may direct to other differential diagnoses. This is helpful to improve physicians′ understanding of the special clinical characteristics in MM patients.
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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??
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Objective@#To detect potential mutations of the coagulation factor Ⅶ (F7) gene in a pedigree affected with hereditary FⅦ deficiency and explore its molecular pathogenesis.@*Methods@#The FⅦ antigen (FⅦ∶Ag) was analyzed by an enzyme-linked immunosorbent assay (ELISA) method. Prothrombin time (PT), FⅦ activity (FⅦ∶C) and other coagulant parameters were quantified with an one-stage clotting assay. The F7 gene was amplified by PCR and sequenced. Mutational sites were confirmed by reverse sequencing. Impact of amino acid substitution was assessed using SIFT and PolyPhen-2 software. Structure of the mutant protein was analyzed using Swiss-pdb Viewer software based on the three-dimensional structure in the Protein Data Bank.@*Results@#The propositus had prolonged PT (36.3 s), with FⅦ∶C and FⅦ∶Ag significantly reduced to 2% and 44%, respectively. Her father, mother, younger sister and daughter had slightly prolonged PT and reduced FⅦ∶C (86%-120%). The FⅦ∶Ag of her father and younger sister were also reduced. DNA sequencing revealed that the propositus has carried compound heterozygous mutations (Lys341Glu and IVS6-1G>A) of the F7 gene. Her father and younger sister were heterozygous for the IVS6-1G>A mutation, while her mother and daughter were heterozygous for the Lys341Glu mutation. Bioinformatics analysis indicated that Lys341Glu mutation may affect the stability and function of the FⅦ protein.@*Conclusion@#The Lys341Glu and IVS6-1G>A mutations probably underlie the reduced activity of FⅦ in this pedigree.
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Objective@#To investigate the clinical value of blood coagulation and fibrinolysis index detection in lymphoma patients.@*Methods@#A total of 115 lymphoma patients hospitalized at Zhongshan Hospital of Xiamen University from January 2013 to September 2017 were retrospectively analyzed. According to the diagnostic and therapeutic criteria of lymphoma from World Health Organization (2008), these patients were divided into chemotherapy remission group (76 cases) and chemotherapy non-remission group (39 cases). A total of 138 healthy examination subjects at the same period were selected as the control group. Coagulation factor Ⅶ (FⅦ), D-dimer (D-D), von Willebrand factor antigen (vWF: Ag) and serum lactate dehydrogenase (LDH) levels were measured in all subjects. Kruskal-Wallis test was used to compare the differences of blood coagulation and fibrinolysis indicators in patients with different lymphoma staging and stratified treatment outcomes. Correlation test of D-D and LDH and disease staging was performed by using Spearman correlation analysis. The receiver operating characteristics (ROC) curve was used to analyze the efficacy of D-D in the assisted diagnosis of lymphoma with thrombosis.@*Results@#The plasma D-D, vWF: Ag levels and FⅦ activity [the median (interquartile range)] in lymphoma patients were higher than those in healthy controls [1 240 ng/ml (1 610 ng/ml) vs. 250 ng/ml (43 ng/ml), Z = -10.728, P < 0.01; 170 ng/ml (113 ng/ml) vs. 105 ng/ml (28 ng/ml), Z = -6.425, P < 0.01; 120% (26%) vs. 96% (26%), Z = -4.602, P < 0.01]. With the increase of Ann Arbor stage, plasma D-D, vWF: Ag levels and FⅦ activity were also increased gradually (all P < 0.05); plasma D-D, vWF: Ag levels and FⅦ activity in lymphoma with thrombosis group were higher than those in the group without thrombosis (all P < 0.01), D-D and vWF: Ag levels in the chemotherapy remission group were lower than those in the chemotherapy non-remission group (all P < 0.01). Plasma D-D levels were positively correlated with LDH level and Ann Arbor stage (r values were 0.414 and 0.530, respectively, all P < 0.01). When the plasma D-D level was 1 735 ng/ml, the sensitivity of diagnosis of thrombosis in patients with lymphoma was 81.8%, the specificity was 85.7%, the area under the ROC curve was 0.894, and the Youden index was the highest (0.675).@*Conclusions@#Clinically, blood coagulation and fibrinolysis in patients with lymphoma can be evaluated by detecting blood coagulation and fibrinolysis indexes such as plasma D-D. Real-time monitoring of plasma D-D level can determine the thrombosis trend of lymphoma patients, and it may play an important role in evaluating the efficacy and prognosis.
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Objective To study the effect of the promoter methylation of coagulation factor Ⅶ (FⅦ) on the coagulation factor Ⅶ activity (FⅦa) in traumatic brain injury (TBI) patients,and the correlation between the promoter methylation in FⅦ and intracranial progressive hemorrhagic injury (PHI).Methods A prospective analysis was conducted on 79 patients with moderate-severe TBI admitted to emergency department from August 2010 to August 2014.The peripheral venous blood samples were collected at admission and then were delivered for measurement of FⅦa.Genomic DNA was isolated from patient blood,and the promoter methylation in FⅦ (CpG2,CpG3,CpG4,CpG5,and CpG6) were analyzed.According to the level of plasma FⅦa,the patients were divided into FⅦa ≥90％ group and FⅦa ＜ 90％ group.Based on the presence of PHI,the patients were divided into PHI group and non-PHI group.The FⅦ promoter methylation,age,gender,systolic blood pressure,Glasgow Coma Scale (GCS),length of stay and mortality between FⅦa≥90％ group and FⅦa ＜ 90％ group,PHI group and non-PHI group were compared.Results There were no significant differences in age,gender,systolic blood pressure,GCS,LOS,and mortality between FⅦa ≥90％ group and FⅦa ＜90％,PHI group and non-PHI group (P ＞ 0.05).The methylation of CpG3 in FⅦa ≥90％ group was less than that in FⅦa ＜90％ group (0.83 ±0.05 vs.0.85 ±0.03) (P＜0.05),while there were no significant differences in other CpG sites between these two groups (P ＞ 0.05).No significant differences in all of methylation levels of the CpG sites between PHI group and non-PHI group were found (P ＞0.05).Conclusions The promoter methylation of FⅦ affects plasma FⅦa concentrations,and higher methylation results in lower FⅦa.The promoter methylation of FⅦ is not associated with PHI in TBI patients.
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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.
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Traumatic brain injury is always associated with hemorrhage and coagulopathy, leading the occurrence of anemia, platelet function inactivation, platelet and coagulation factor consumptive reduction. Theoretically, transfusion therapy should be given to supplement the missing component in an appropriate range. However, whether the transfusion therapy can improve the prognosis of patients with traumatic brain injury, and the indications of transfusion, have been the focus of academic debate for a long time. This article reviews the latest progress of transfusion therapy in traumatic brain injury, and provides reference for better guidance of transfusion in clinical treatment.
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Objective@#To investigate the treatment efficacy of recombinant activated factor Ⅶ (rFⅦa) for bleeding among patients with hematologic disorders.@*Methods@#A total of 38 times of bleeding in 31 patients with hematological disease treated with rFⅦa were analyzed retrospectively.@*Results@#The clinical effective rate of rFⅦa for bleeding management in acquired hemophilia A (AHA) patients/hemophilia patients with inhibitor, acute promyelocytic leukemia (APL) patients and patients with non-APL leukemia was 90% (9/10) , 71.4% (5/7) and 60.0% (3/5) , respectively, which was higher than that in patients following HSCT (30.8%) . The clinical effective rate of rFⅦa for patients with bleeding score of 2 (100.0%) was higher than that with 3 (66.7%) and 4 (54.1%) . The effective rate of rFⅦa was 25.0% (2/5) in 5 patients with cerebral hemorrhage, 66.7% (6/9) in 9 patients with hematuria and 41.7% in 12 patients with gastrointestinal hemorrhage. The curative effect for 3 patients with joints and muscle bleeding and 5 patients with skin, nasal, pharyngeal and gum bleeding was excellent. Following HSCT, among patients with bleeding score of 4 points, high dose and repeated use of rFⅦa did not necessarily achieve a good effect. Among AHA/hemophilia patients with inhibitors and patients with acute leukemia who had bleeding score of 4 points, the use of low dose FⅦa could achieve good therapeutic effect, however the efficacy of lowest dose (22.5 μg/kg) rFⅦa was poor.@*Conclusions@#The hemostasis efficacy of rFⅦa is affected by various factors such as diseases, bleeding sites, bleeding score and so on. The use of rFⅦa can achieve good efficacy for bleeding management in AHA patients/hemophilia patients with inhibitor, APL patients and patients with non-APL leukemia. However the efficacy of rFⅦa for bleeding of patients after HSCT is poor. Early use of rFⅦa is important for successful hemostatic treatment. Management of underlying condition is as important as hemostatic treatment.
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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.
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Objective To summarize analysis postpartum hemorrhage were treated by human recombinant coagulation factor Ⅶ, CARDS and other three amine butyl alcohol, psychological intervention treatment of clinical effects and the patient's quality of life.Methods Our hospital during July 2013 to December 2016, total 100 cases of postpartum hemorrhage patients treated with the control group of 50 patients with card other three amine butyl alcohol with psychological intervention therapy;observation group of 50 cases using human recombinant coagulation factor Ⅶ, CARDS and other three amine butyl alcohol, psychological intervention treatment, two groups of patients were reviewed treatment effect and postpartum quality of life.Results In the bleeding, bleeding time, postpartum anxiety score, depression score indicators, such as observation group is less than the control group, the difference to be markedly, with statistical significance (P<0.05);In the postpartum life quality score, the observation group is higher than the control group, the obvious differences, statistically significant (P<0.05);In terms of adverse reaction happening, observation group and control group difference is not obvious, not statistically significant .Conclusion Human recombinant coagulation factor Ⅶ, CARDS and other three amine butyl alcohol, psychological intervention treatment of postpartum hemorrhage, the clinical curative effect is distinct, can better improve the patients quality of life, improve patients' negative mood, is worthy of popularization and application.
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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.
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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.
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Objective To study plasma coagulation factor Ⅶ effects of intracerebral hemorrhage in patients with craniocerebral injury.Methods 120 cases of patients with traumatic brain injury were treated,for patients admitted to hospital,the hospital after 24 hours,48 hours of live clotting enzyme activation part (APlT),peripheral venous blood specimen testing international standardization ratio (INR)and the activity of platelet and F Ⅶ were detected.According to the intracranial bleeding lesions was expanded or the emergence of a new bleeding lesions,and so on and so forth were divided into research group and the control group,43 patients in the research group,77 cases in the control group.Results The study showed that the two groups of patients with injury to the first CT time, subarachnoid hemorrhage,epidural hematoma,there were no significant difference between the indexes of subdural hematoma,patients in the study group lost 48h PPSB was (653.2 ±489.8)IU,platelet (180.7 ±63.5)mL,plasma (582.7 ±411.3)mL and red blood cells (612.3 ±490.1)mL,which were higher than those of the control group [(465.7 ±278.8)IU,(0.0 ±0.0)mL,(335.1 ±261.9)mL,(378.3 ±46.3)mL],there were statistifically significant differences between the two groups(t =2.399,2.388,2.582,3.231,P =0.020,0.022,0.010,0.001), the platelet and F Ⅶ of the research group were (101.43 ±41.85)×109 /L,(93.04 ±20.98)%,which were lower than those of the control group[(128.37 ±51.49)×109 /L,(107.67 ±20.25)%],there were statistifically significant differences between the two groups(t =2.583,2.893,P =0.010,0.004).Conclusion Lower levels of platelet activity and F Ⅶ of closely associated with intracranial hemorrhage in patients with craniocerebral injury,according to the clinical indicators to predict whether patients with intracranial hemorrhage,in order to for the treatment of patients with timely and accurate to ensure the patient's life and health.
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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.
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Objective To study the correlation between the coagulation factor Ⅶ (F Ⅶ) and progressive hemorrhage after brain contusion in mice and provide the experimental evidence for the clinical application of recombinant human FⅦa.Methods Twelve male BALB/c mice were given liposomeencapsulated FⅦsiRNA via tail vein at doses of 1,3,5 and 10 mg/kg with 3 mice per dosage.The other 3 mice received equivalent volume of normal saline as controls.Two days after the injection,mice blood sampling was used to detect FⅦ mRNA expression in liver using real-time PCR,level of plasma FⅦ using ELISA method,and activity of plasma FⅦ using chromogenic substrate assay.The optimal dose at which F Ⅶ expression was inhibited was determined.Thirty BALB/c male mice were assigned to two groups (n =15 per group) according to the random number table:FⅦ-suppressing group,mice were injected with FⅦsiRNA at the optimal dose and control group,mice were injected with same volume of negative control vector.The model of brain contusion was established in both groups.Volume of hemorrhage following brain contusion was measured at 3,24 and 72 h postinjury,and hematoma volume at 24 and 48 h postinjury.Results Liposome-encapsulated siRNA delivery down-regulated FⅦ expression in the mouse liver.Level and activity of plasma FⅦ were also reduced significantly.The optimal siRNA dose was 3 mg/kg.At 3,24 and 72 h postinjury,relative volume of brain hemorrhage in FⅦ-suppressing group was 1.46 ± 0.10,1.82 ± 0.23 and 2.28 ± 0.15 respectively,significantly higher than that in control group (1.00 ± 0.25,1.20 ± 0.31 and 1.20 ± 0.22 respectively) (P ＜ 0.05).At 24 and 48 h postinju-ry,volume of hematoma in FⅦ-suppressing group was (6.7 ± 1.5)mm3 and (9.8 ± 1.0) mm3,significantly higher than that in control group [(5.2 ± 1.2) mm3 and (5.5 ± 1.5) mm3] (P ＜0.01).Conclusions Level of FⅦ in vivo relates closely to the progressive hemorrhage of brain contusion in mice.Administration of FⅦ is effective to reduce the incidence of progressive hemorrhage.
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Objective To study the pathogenesis, clinical characteristics, laboratory tests, treatments and prognosis of con-genital factorⅦdeficiency. Methods The clinical data of two cases of congenital factorⅦdeficiency diagnosed at the Chil-dren’s Hospital of Fudan University and 9 cases reported in the past 10 years retrieved from Pubmed, Web of Knowledge and CNKI, Wangfang database by using the factorⅦdeficiency , congenital, newborn and case report as keyword were reviewed and analyzed. Results All cases were full term birth with normal birth weight (>2 500 g), including 4 females and 7 males. Pa-rental consanguinity was found in 3 cases, and a family history was found in 3 cases. The laboratory tests were characterized by significantly prolonged prothrombin time, normal partial thromboplastin time, and decreased coagulation factorⅦactivity. The coagulation factorⅦactivity of 10 cases were less than 5%. Five cases (45.5%) were treated with human recombinant activated factorⅦ. Four cases (36.4%) treated with plasma or human recombinant activated factorⅦare currently in normal growth and development. Four cases (36.4%) died during the hospitalization. Conclusions A diagnosis of congenital factorⅦdeficiency should be considered in the neonates with severe bleeding, prolonged prothrombin time, normal partial thromboplastin time, and being intractable to vitamin K treatment. Human recombinant activated factorⅦis the first choice of the treatment of congenital factorⅦdeficiency. The further study of gene mutation type will be of great significance for disease screening, diagnosis, treat-ment and prognosis prediction.
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Objective To evaluate the effect of recombinant activated factor Ⅶ (rⅦa) in treatment of hemorrhagic shock after severe multiple injuries with coagulopathy.Methods Sixteen cases of coagulopathy after severe multiple injuries administered with rⅦa between July 2011 and June 2012 were reviewed.The requirements of blood product and coagulogram variation were comparatively studied before and after rⅦa therapy.Results After rⅦa therapy,bleeding was brought to a halt in 24 hours for nine cases and in 72 hours for seven cases.In the end,13 out of the 16 cases survived in the absence of myocardial infarct,cerebrovascular accident or deep vein thrombosis.Requirements of red blood cells,fresh frozen plasma,cryoprecipitate and platelet (PLT) were decreased at 48 hours after the final therapy as compared with those at 48 hours prior to the primary therapy,but statistical significance only existed in the reduction of fresh frozen plasma and cryoprecipitate (P ＜ 0.05).The coagulogram indices including prothrombin time (PT) and activated partial thromboplastin time (APTT) at 4 hours after the final therapy presented statistical differences from those prior to the primary therapy (P ＜ 0.05).Conclusion rⅦa is an important,effective and safe auxiliary means for surgical hemostasis of coagulopathy after severe multiple injuries.
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Objective To explore the associations between coagulation factor Ⅶ (FⅦ)polymorphisms and its haplotype with risk of ischemic cerebrovascular diseases (ICVD) in Henan Han population. Methods Five hundred and twelve cases with ICVD as patient group and 560 healthy subjects as control were recruited in the study. The polymorphisms of R353Q, 5'F7 and IVS7 were detected by PCR-RFLP. The genotype frequency and allele gene frequency were compared between ICVD group and control group. The haplotype was analyzed by SHEsis software. Results The RQ genotype frequencies and Q allele frequencies of ICVD group were significantly lower than those of control group. The distribution of H7 allele frequencies and H6H7 genotype frequencies of FⅦ/IVS7 polymorphisms had significant difference between ICVD group and control group. Finally, the prevalence of R-P0-H6 haplotype in ICVD group(53. 3% )was higher than that in control group (47.5%, OR = 1. 219, 95% CI 1. 028-1. 446,P =0.023). Conclusions In Henan Han population, the Q allele of F Ⅶ/R353Q polymorphisms and the H7 allele of F Ⅶ/IVS7 polymorphisms may be protective genetic factors against ischemic cerebrovascular disease, and the R-P0-H6 haplotype may be a risk factor of ischemic cerebrovascular disease.
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Objective To identify gene mutations and explore the molecular mechanism of a pedigree with inherited coagulation F Ⅶ deficiency. Methods The levels of F Ⅶ: Ag in the proband and other family members were measured by ELISA assay. The values of PT, F Ⅶ: C and other coagulant parameters were determined by one-stage clotting for laboratory phenotype diagnosis. All the exons,exon-intron boundaries and 5',3' untranslated sequences of F7 gene were amplified by direct sequencing. The detected mutations were further confirmed by sequencing the other stand. The CLC Protein Workbench software was used to analyze the species conservation of the mutated site and the protein secondary structure. 100 healthy individuals were selected to exclude gene polymorphism. Results PT, FⅦ∶C and FⅦ: Ag in the proband and his sister were abnormal, which were 36. 3 s, 5.0%, 40. 7% and 33.4 s,5. 0%, 37.4%, respectively. Both PT and FⅦ∶C in the proband's father, mother, daughter and niece were slightly abnormal, which were 14.9 s, 14. 6 s, 15.5 s, 14. 6 s and 70%, 85%, 59%, 79%, respectively.The heterozygous mutations c. 784T ＞ C and c. 964T ＞ G in exon 8 of F7 gene were found in the proband,resulting in the substitutions of Ser269Pro and Cys329Gly respectively. Compound heterozygous mutations c. 784T ＞ C and c. 964T ＞ G were found in the proband's sister. The proband's mother was heterozygous for c. 784T ＞ C. His father, daughter and niece were heterozygous for c. 964T ＞ G. The protein biological characteristics analysis revealed that the Cys329Gly caused the change of spatial configuration, and Ser269Pro led to the change of amino acid polarity and hydrophobicity. Conclusion Compound heterozygous mutations of Cys329Gly and Ser269 Pro in F7 gene may be the underlying molecule mechanism of FⅦ deficiency in this pedigree.