Effect of ion-exchange chromatography on removal of fibronectin in von Willebrand factor / 中国输血杂志

【Objective】 To study the removal effect of fibronectin(Fn) from von willebrand factor(vWF) by ion-exchange chromatography through processing human coagulation factor Ⅷ chromatographic washing products, in order to select a method that can effectively reduce Fn without compromising the activity yield. 【Methods】 In a multi-batch process development experiment, Fractogel® EMD TMAE(M) strong anion filler produced by Merck(Germany) was used to conduct chromatography to investigate vWF ristomycins titer (vWF: RCof), vWF recovery, protein content and Fn content. 【Results】 During the development of vWF pilot purification process, the content of Fn in the samples can be effectively reduced by ion-exchange chromatography, with removal rate more than 87%, titer recovery of vWF more than 80%, and no significant change in other quality indexes. 【Conclusion】 The use of ion-exchange chromatography to purify vWF can effectively reduce the content of Fn, which has positive significance for developing new product process and improving the product quality of blood products manufacturers.

Selection of sterilizing-grade filter for preparation of human coagulation factor Ⅷ/ von Willebrand factor complex / 中国输血杂志

【Objective】 To screen the sterilizing-grade filters applicable for production of human coagulation factor Ⅷ/von Willebrand factor complex(FⅧ/VWF)and study the sterilization filtration process. 【Methods】 Four sterilizing-grade filters for FⅧ/VWF were evaluated through indicators such as filtration capacity, filtration flux, recovery rate of FⅧ activity, recovery rate of VWF activity, recovery rate of VWF antigen, recovery rate of protein and VWF molecular distribution. The sterilizing-grade filter with the best filtration performance was selected for further study. The study was designed by general full-factor design to determine the appropriate filitered protein concentration and filitered speed range through evaluating the total filtered protein amount, recovery rate of protein and filtration efficiency, and then the process operation parameters was determined. 【Results】 The filtration flux of Sartobran P, Sartopore 2 XLG, Sartopore Platinum and Sartopore 2 XLI were 1.71±0.01, 1.80±0.01, 1.34±0.01, and 1.81±0.04 L·(m2)-1·min-1, respectively; the recovery rates (%) of FⅧ activity were 97.09±2.82, 99.22±0.99, 96.87±1.85 and 93.76±1.21, respectively; the recovery rates (%) of VWF activity were 98.12±1.42, 99.95±1.85, 94.80±1.62 and 92.09±1.67, respectively. Between Sartopore 2 XLG and Sartobran P, the difference of filtration flux (P<0.001) was statistically significant; between Sartopore 2 XLG and Sartopore Platinum, the differences of the filtration flux (P<0.001) and VWF potency recovery rate (P<0.05) were statistically significant; between Sartopore 2 XLG and Sartopore 2 XLI, the differences of FⅧ potency recovery rate (P<0.01) and VWF potency recovery rate (P<0.01) were statistically significant. The optimal process operating space of Sartopore 2 XLG was protein concentration of 0.45-0.58 mg/mL, and filtration rate of 1.48-2.95 L·(m2)-1·min-1. 【Conclusion】 Sartopore 2 XLG is the most suitable filter for the production of FⅧ/VWF and the DoE test proves that it has good process operation space.

A Teenage Boy with Systemic Lupus Erythematosus Complicated with Acquired von Willebrand Syndrome: A Rare Case and Challenging in Making Diagnosis

@#In systemic lupus erythematosus (SLE), haematological abnormalities are frequent, although they are an uncommon cause of acquired von Willebrand syndrome (AVWS). AVWS is a rare condition that can cause a bleeding disorder. We presented a case of AVWS in the early diagnosis of SLE. One month before admission, the patient had a history of recurrent epistaxis. He presented to the hospital with symptomatic anaemia and was noted to have severe anaemia with iron deficiency. During hospitalisation, recurrent epistaxis recurred and was found to have prolonged activated partial thromboplastin time (aPTT), presence of lupus anticoagulant (LA), and lower von Willebrand factor (VWF), and factor 8 (VIII) levels. Simultaneously, he was diagnosed with SLE based on Systemic Lupus International Collaborating Clinics (SLICC) criteria. He underwent blood transfusions and was treated with immunosuppressive drugs such as steroids, mycophenolate mofetil, and an anti-fibrinolytic agent; he subsequently stopped bleeding and showed clinical improvement.

VWF Damage Based on Novel Maglev Taylor-Couette Blood-Shearing Circulation Platform / 医用生物力学

Objective To study von Willebrand factor(VWF) damage based on a novel Maglev Taylor-Couette blood-shearing device. Methods The magnetic levitation (maglev) Taylor-Couette blood-shearing device was designed, and the blood-shearing platform was built. Fresh porcine blood was tested in circulation loop for 1 hour at laminar flow state. VWF damage was assessed by analyzing sample through Western blot and enzyme-linked immunosorbent assay. Results With the increase of exposure time and shear stress, a large number of high molecular weight VWF multimers were degraded into low molecular weight VWF. The maximum rate of degradation was 569%. When the shear stress increased from 18 Pa to 55 Pa, the ratio of VWF-Rco to VWF-Ag decreased from 45.7% to 32.8%. ConclusionsCompared with initial sample, the VWF damage was mainly manifested by the decrease of high molecular weight VWF and the decrease of VWF activity, and VWF-Ag did not change significantly. The novel maglev Taylor-Couette blood-shearing device can quantitatively control the flow parameters (exposure time and shear stress), and be used for blood damage research in vitro, thus providing references for the design and optimization of extracorporeal membrane oxygenation and blood pump.

Evaluation on Mechanical Damage of vWF Induced by Shear Stress in BPX-80 Centrifugal Blood Pump / 医用生物力学

Objective To evaluate the damage of von Willebrand factor (vWF) induced by shear stress in BPX-80 centrifugal blood pump, and determine whether it can be used as a reference pump for vWF damage research. Methods An in vitro hemolysis test platform was established according to the ASTM standards. The BPX-80 centrifugal blood pump was tested for 8 hours by using fresh porcine blood. The hemolysis level and vWF damage of hourly blood samples were then evaluated and compared with the static control group. ResultsThe hemolysis index of BPX-80 was stable and low during the test; vWF polymer with high molecular weight had a small amount of degradation, and showed no significant difference compared with the static control group; there was no significant change in the concentration of vWF antigen, which was basically consistent with the trend of the static control group. Conclusions BPX-80 centrifugal blood pump has good blood compatibility and can be used as the reference pump for vWF damage and hemolysis evaluation, thereby providing guidance for the design and optimization of new blood pumps.

Efficacy analysis of von Willebrand factor in human coagulation factor FⅧ concentrates in China / 中国输血杂志

【Objective】 To obtain the quality information of von Willebrand factor (vWF) in coagulation factor Ⅷ (FⅧ) concentrates in China. 【Methods】 FⅧ concentrates produced by 7 domestic blood product manufactures and 1 foreign manufacture were collected, then FⅧ and vWF contained in FⅧ concentrates were evaluated. 【Results】 The activity loss of vWF was more than 25% in 2 of the 7 domestic FⅧ concentrates. The ratio of vWF activity to FⅧ activity in FⅧ concentrates from different domestic manufactures was significantly different (P<0.05). The ratio in FⅧ concentrates prepared by C, D, F manufacturer was greater than 1, which was similar to that in willate@ approved abroad for the treatment of vWD. The ratio in FⅧ concentrates prepared by E manufacturer was greater than 0.7 and less than 1, and by A, B, G manufacturers was less than 0.5. In addition, the specific activities of FⅧ and vWF were significantly different among different FⅧ concentrates in China (P<0.05), and the specific activities of FⅧ and vWF were much lower than that of willate@. 【Conclusion】 The variation of vWF quality between domestic FⅧ concentrates and willate@ is mainly due to the different in vWF content. After the comprehensive consideration of various indicators, the FⅧ concentrates made by C and D manufacturers may be used in the treatment of vWD.

Nesiritide protects endothelial function after balloon-induced trauma in the iliac artery in rabbits

To assess the effect of nesiritide on the endothelial function of iliac arteries following endothelia trauma. Right iliac artery trauma was created with a balloon catheter. Ten rabbits were treated with a 4-week subcutaneous injection of nesiritide at a fixed daily dose of 0.1mg/kg. Ten rabbits received daily normal saline injection. Plasma endothelin 1 (ET-1), nitric oxide (NO), and Von Willebrand Factor (vWF) were measured before and after the therapies. Tissue proliferating cell nuclear antigen (PCNA) was measured after the treatment. After the treatment, in the therapeutic group, the area under internal elastic membrane and the residual lumen area were higher than in the normal saline group (P <0.05). The plasma levels of ET-1 (91.6±6.8 vs 114.9±6.3 ng/L, P =0.001), vWF (134.6±10.8% vs 188.8±10.4%, P =0.001) and the ratio of PCNA positive expression (11.7±4.2% vs 36.2±11.4%, P =0.005) in the therapeutic group was lower than in the normal saline group, while the plasma levels of NO was higher (89.7±9.3 vs 43.5±5.3 µmol/L, P =0.001). Nesiritide inhibited remodeling of rabbit iliac artery following endothelial trauma. The inhibition of vascular remodeling may be related to the alleviated endothelial dysfunction and reduced expression of tissue proliferating cell nuclear antigen

Adhesive Rolling of Neutrophils on the Immobilized Platelets under Flows / 医用生物力学

Objective To investigate the effects of fluid shear stress on rolling adhesion of neutrophils on immobilized platelets under flows. Methods Experiments were performed at the parallel plate flow chamber. Platelets were adhered to the functionalized flow chamber bottom which were coated with vWF-A1 first, and then washed with PBS under wall shear stress (WSS) of 1 Pa for different time (0 min, 2.5 min, 7.5 min). A high-speed camera was used to observe and record the rolling adhesion events of neutrophils on immobilized platelets under 50 mPa WSS, and the adhesion parameters such as the number of adhesion events, the tether lifetime of cells and rolling velocity. Results Neutrophils could specifically bind to the immobilized platelets on vWF-A1-coated bottom of the flow chamber. Mechanical stimulation on immobilized platelets had no effects on the tether lifetime of neutrophils on the platelets, but up-regulated the adhesive ratio of neutrophils on the platelets and slowed down the rolling of neutrophils on the platelets. Conclusions Mechanical stimulation on the immobilized platelets will significantly make the circulating neutrophils to be captured easily and promote the rolling adhesion of neutrophils on platelets.

Molecular Dynamics Study on Docking of A3/A1 and Interdomain Interactions / 医用生物力学

Objective To investigate the interaction between von Willebrand factor (vWF) A1 and A3 domain, and type 2 M mutant W1745C-A3 effect on thermal stability and mechanical stability of A3/A1. Methods The crystal structures of A1 and A3 were downloaded from Protein Data Base (PDB). The wild-type (WT) A3/A1 structure was obtained by using SwarmDock Server, then W1745C-A3/A1 mutant was constructed by replacing the Trp1745 with Cys1745 in A3/A1. Through steered molecular dynamics simulation, formation and evolution of hydrogen bond and salt bridge between A1 and A3 interfaces were observed, and the differences in conformation, disrupted force and dissociation time between WT-A3/A1 and W1745C-A3/A1 were compared. Results There were 5 pairs of hydrogen bonds with survival rate > 0-2 and 1 pair of salt bridge with survival rate > 0-5 between A1 and A2. The W1745C-A3/A1 complex could withstand greater disrupted force and longer dissociation time compared with WT-A3/A1, by improving the stability of hydrogen bonds and increasing 1 pair of stable salt bridge. Conclusions The interaction between A1 and A3 would hinder the binding sites of A1 to GPIbα, and the W1745C-A3 mutation would further reduce the affinity of A1 to platelets. These results provide references for revealing the molecular mechanism of von Willebrand diseases in the clinic and developing the corresponding drugs targeted to hemostasis disorders.

Analysis of survival and risk factors of DVT in patients with cervical cancer / 中国综合临床

Objective To investigate the relationship between vWF levels and ADAMTS13 levels of DVT (venous thrombosis) in patients with cervical cancer,and then to evaluate the predictive value of vWF levels and ADAMTS13 levels of cervical cancer patients with DVT. Methods A total of sixty-six patients diagnosed as cervical cancer and treated from June 2015 to June 2016 in Weinan Maternal and Child Health Hospital were enrolled,and their baseline data,pathological type,tumor classification,TNM staging,vWF, ADAMTS13 levels and Autar score were recorded. All patients were followed up for 1 year and the patients with adverse outcomes were defined as poor prognosis group during the follow-up period while the patients whose disease progression free were defined as good prognosis group. Univariate analysis showed that the incidence of venous thrombosis in patients with cervical cancer was affected; Cox proportional hazard model further assessed the impact of all statistically significant factors on the occurrence of venous thrombosis in patients; t test showed the distribution of influential factors between the two groups; ROC curve was used to analyze the sensitivity and specificity of vWF and ADAMTS13 levels in predicting the occurrence of venous thrombosis in cervical cancer patients. Results At the end of the follow-up,among the 66 patients,Six were not followed and 40 had good prognosis without venous thrombosis,which was a good prognosis group; Twenty had poor prognosis,i. e. venous thrombosis,which was a poor prognosis group,including 5 deaths. The poor prognosis rate was 30. 30%. Univariate Cox proportional hazard model results showed that vWF (P＝0. 023, (95%CI: 1. 743－1. 215)) and ADAMTS13 (P＝0. 037,(95%CI: 1. 158－1. 566)) had a significant effect on the patients with venous thrombosis. The levels of vWF (( 0. 535 ± 0. 075) μg/L) and ADAMTS13 ((69. 453±10. 284)%) in good prognosis group were significantly lower than those in poor prognosis group ((0. 592 ± 0. 082 ) μg/L, ( 79. 245 ± 11. 477 )%), and the differences between the two groups were statistically significant (t＝2. 690,3. 345,P＜0. 05). Under ROC curve,the AUC of vWF level was 0. 841,the sensitivity and specificity were 55% and 97. 5% respectively,and that of ADAMTS13 level was 0. 906,the sensitivity and specificity were 85% and 80%,respectively. Conclusion The levels of vWF and ADAMTS13 have a good predictive effect on the occurrence of venous thrombosis in patients with cervical cancer. It is expected to be used as a routine evaluation index to predict the occurrence of venous thrombosis in patients with cervical cancer after treatment.

von Willebrand Factor Profiles of the Different ABO Blood Groups Among the Malay Population

@#The National Blood Center, Kuala Lumpur interprets laboratory results for the von Willebrand factor (VWF) profile based on guidelines which were established based on the Caucasian population. The VWF profiles among the Malay population has not yet been established. The current study aims to determine the VWF profiles of the different ABO blood types among Malays and to evaluate their association with demographic characteristics and smoking habits. Methods: One hundred and forty Malay donors were involved. Factor VIII (FVIII:C), VWF antigen (VWF:Ag), and ristocetin cofactor (VWF:RiCof) levels and collagen binding activity (VWF:CBA) were measured by coagulometric clot detection, latex agglutination, and enzyme-linked immunosorbent assay. Results: The majority of donors (59.3%) were 30–49 years old, male (81.43%), non-smokers (74.3%), and overweight (71.4%). The Malay VWF:Ag were slightly higher than those of Caucasians, Indians, Thais, and Chinese, but the average ratios of VWF activity (i.e., VWF:RiCof level and VWF:CBA) to VWF:Ag were slightly lower than those of the other populations. The highest level of VWF:Ag was found among those with the B blood group, followed by types A and O. Conclusion: Malays with type O blood had lower values of the components of the VWF profile compared to subjects with non-O blood. The higher levels of these elements and lower VWF activity to VWF:Ag ratio in Malays compared to other populations suggest that ethnicity impacts the plasma VWF levels and their interaction with collagen and platelets.

Research progress of the relationship between von Willebrand factor and hepatic diseases / 中华肝脏病杂志

Hepatic diseases refer to acute and chronic liver disease linked to all kinds of hepatic pathological changes. Viral hepatitis, bacterial infections, endotoxins and other factors initiate the activation and injury of vascular endothelial cells in patients with liver diseases. Von Willebrand factor (vWF) represents a specific marker of endothelial dysfunction and plays a vital role in the occurrence and development of hepatic diseases. This paper reviews the research progress of the relationship between vWF and hepatic diseases.

Clinical significance of dynamic detecting TNF-α,HMBG-1,TF and vWF in peripheral blood from patients with sepsis / 实用医学杂志

Objective To investigate the clinical significance of dynamic detecting the levels of TNF-α, HMBG-1,TF and vWF in the peripheral blood from the patients with sepsis. Method The serum and plasma were collected from 39 patients with sepsis onset 24,48,72 and 120 h,and 15 health volunteers. The levels of TNF-α,HMBG-1,TF in serum and vWF in plasma were detected with ELISA.The septic patients were divided in-to death and survival groups.The relations were compared between the changes of the levels of TNF-α,HMBG-1, TF and vWF from septic patient peripheral blood with the illness severity.Results The levels of TNF-α,HMBG-1, TF and vWF in serums from different time point septic patient were significantly higher than health group(P <0.01).The peak time was 24 h for TNF-α,48 h for HMBG-1,TF and vWF,and the 24 h was lowest.By the mul-tivariate Logistic regression analysis,the death groups were significantly higher than survival groups(P < 0.05 &0.01).By ROC curve analysis,the 4 inflammatory factors have obvious judgment value from 72 and 120 h curves. Conclusion Firstly,the inflammatory immune response in the septic patient was excessive activated. Then the levels of detected inflammatory factors have a trend toward increased with the extension of the course and there may be a peak point. Moreover,the levels of detected inflammatory factors have a positively correlated with the course of the disease.Lastly,by dynamic detecting the changes of the levels of TNF-α,HMBG-1,TF and vWF in serum from septic patient,it can be served as a comprehensive evaluation index of the patient condition,treatment effect and prognostic judgment.

Status and advances of long-acting factor Ⅷ / 生物工程学报

Current treatment for hemophilia A is based on replacement therapy that is the most effective method by using recombinant clotting factor FⅧ (rFⅧ). Although the safety and effectiveness of replacement therapy has been proved by clinical practice for the last decades, FⅧ products are temporally limited because of a short half-life and requiring prophylactic injections frequently for most patients, usually three times per week or every other day. Frequent intravenous injection not only brings physical pain to the patient, but also produces FⅧ antibodies that seriously affect the treatment effect. In this paper, we review the present status, research progress and main problems of the long-acting recombinant factor Ⅷ.

Predictive and prognostic evaluation of surfactant protein D, von Willebrand factor and interleukin-8 for sepsis-induced acute respiratory distress syndrome / 临床检验杂志

Objective To select valuable biomarkers for diagnosis and predicting outcome of sepsis-related acute respiratory distress syndrome(ARDS) from D-dimmer (DD),yon Willebrand factor (vWF),platelet (PLT),N terminal-pro brain natriuretic peptide (NT-ProBNP),interleukin-6 (IL-6),interleukin-8 (IL-8) and surfactant protein D (SP-D).Methods A total of 48 sepsis accompanied with ARDS patients and 40 sepsis patients were prospectively studied with comparison.The clinical characteristics of all the patients were recorded in detail.The blood samples were obtained within 24 hours of ICU admission.The concentration or activity of the seven biomarkers was quantitatively assayed and the results were recorded.To select the most valuable biomarkers as clinical indices,diagnosis model and death predictive model were constructed by Logistic regression.Results Among the seven candidate biomarkers,SP-D,vWF and IL-8 showed the most value.Their area under the receiver operator characteristic curve (ROC) were 0.758 (P ＜ 0.01),0.783 (P ＜ 0.01) and 0.747 (P ＜ 0.01) respectively,and raised to 0.847 (P ＜ 0.001) when the three biomarkers were combined.IL-8,age greater than or equal to 60 years and APACHE Ⅱ score greater than or equal to 20 were related to ARDS death with 12.138(lnIL-8)(P=0.022),6.157(P=0.040) and7.415(P=0.014) of OR values respectively.Conclusion SP-D,vWF,IL-8 should be valuable for early prediction of sepsis-induced ARDS and the diagnostic accuracy raised through combined utilization.IL-8 may be predictable for prognosis of sepsis related ARDS and the comprehensive evaluation combining clinical indices with IL-8 should be suggested in clinical practice.

VWF-A1A2A3-mediated expression of P-selectin in platelets under flow shear stress / 医用生物力学

Objective To investigate the effect of fluid shear stress (FSS) on VWF-A1A2A3-mediated expression of platelet surface P-selectin.Methods Using a parallel plate flow chamber system and mouse anti-human CD62P:FITC as the indicator of P-selectin expression,the alteration of platelet P-selectin expression level with increasing exposure time under different FSS conditions (0,1,2 Pa) specifically mediated by VWF-A1A2A3 was observed and analyzed by fluorescence microscope to obtain the activation characteristics.Results FSS triggered platelet activation and P-selectin expression.The activation ratio of platelet was positively regulated by FSS and their exposure time,reaching the maximum value,9.42％ and 14.59％ under FSS of 1 Pa and 2 Pa,respectively.The level of P-selectin expression exhibited two-phase tendency with the shear stress-exposure time increasing,uplifted at first,then decreased,with the best action time at 7.5 min.The fluorescence peak intensity increased when FSS was enhanced.Conclusions The level of platelet P-selectin expression is co-regulated by VWF-A1A2A3 and FSS,and is closely related to force-signaling exposure time.

VWF-A1A2A3-mediated expression of P-selectin in platelets under flow shear stress / 医用生物力学

Objective To investigate the effect of fluid shear stress (FSS) on VWF-A1A2A3-mediated expression of platelet surface P-selectin.Methods Using a parallel plate flow chamber system and mouse anti-human CD62P:FITC as the indicator of P-selectin expression,the alteration of platelet P-selectin expression level with increasing exposure time under different FSS conditions (0,1,2 Pa) specifically mediated by VWF-A1A2A3 was observed and analyzed by fluorescence microscope to obtain the activation characteristics.Results FSS triggered platelet activation and P-selectin expression.The activation ratio of platelet was positively regulated by FSS and their exposure time,reaching the maximum value,9.42％ and 14.59％ under FSS of 1 Pa and 2 Pa,respectively.The level of P-selectin expression exhibited two-phase tendency with the shear stress-exposure time increasing,uplifted at first,then decreased,with the best action time at 7.5 min.The fluorescence peak intensity increased when FSS was enhanced.Conclusions The level of platelet P-selectin expression is co-regulated by VWF-A1A2A3 and FSS,and is closely related to force-signaling exposure time.

Clinical Application of Detection of Plasma vWF:Ag and S100B in Ischemic Cerebral Apoplexy Disease / 现代检验医学杂志

Objective To explore the clinical application value of S100B and vWF:Ag levels in ischemic cerebral apoplexy disease.Methods The plasma and clinical data from 85 cases of patients with ischemic cerebral apoplexy were collected,extracted 38 cases of volunteer blood plasma from a random sample of the general population and quantitative detected S100B levels by ELISA method,using Sysmex CA-7000 automatic blood coagulation instrument to detect plasma vWF:Ag levels.The carotid artery diameter and intima-media thickness of all the participants were detected by GELOGIC9 color doppler ultrasonic diagnostic instrument.Results The levels of plasma vWF:Ag in the CS group,the NCS (％) group and the control group were 176.8±56.3,128.9±37.6 and 93.7±30.1,which of plasma S100B (μg/L) were 2.8±1.3,1.9±0.9 and 1.3 ±0.7.Stroke patients could be divided into CS group and NCS group,compared with control group,observed the changes and the relationship of ischemic stroke disease for plasma S100B and vWF:Ag levels.The levels of plasma vWF:Ag and called S100B in the two case groups were increased compared with those in controls,the differences had statistical significance (F=125.9,89.3,P＜0.01).In CS and NCS group,vWF:Ag and S100B were comparative differences and statistically significant (F=125.9,89.3,P＜0.01),the levels of the two markers in the CS group were higher than in replication group.In CS group,the plasma levels of vWF:Ag and S100B were positively correlated (r=0.836,P＜0.01).In CS group,plasma levels of vWF:Ag were associated with carotid artery diameter and intima-media thicknes (r=-0.853,0.923,P＜0.01 and r=-0.783,0.823,P＜0.01),which of S100B did so (r=-0.820,0.833,P＜0.01).Conclution Detection of the levels of vWF:Ag and S100B can predict the degree of danger of ischemic cerebral apoplexy disease and estimate the development of the disease.

VWF-A1A2A3-mediated expression of P-selectin in platelets under flow shear stress / 医用生物力学

Objective To investigate the effect of fluid shear stress (FSS) on VWF-A1A2A3-mediated expression of platelet surface P-selectin.Methods Using a parallel plate flow chamber system and mouse anti-human CD62P:FITC as the indicator of P-selectin expression,the alteration of platelet P-selectin expression level with increasing exposure time under different FSS conditions (0,1,2 Pa) specifically mediated by VWF-A1A2A3 was observed and analyzed by fluorescence microscope to obtain the activation characteristics.Results FSS triggered platelet activation and P-selectin expression.The activation ratio of platelet was positively regulated by FSS and their exposure time,reaching the maximum value,9.42％ and 14.59％ under FSS of 1 Pa and 2 Pa,respectively.The level of P-selectin expression exhibited two-phase tendency with the shear stress-exposure time increasing,uplifted at first,then decreased,with the best action time at 7.5 min.The fluorescence peak intensity increased when FSS was enhanced.Conclusions The level of platelet P-selectin expression is co-regulated by VWF-A1A2A3 and FSS,and is closely related to force-signaling exposure time.

The effect of heparin on endothelial function and prognosis in sepsis shock / 中华急诊医学杂志

Objective To detect the effect of low-dose heparin on endothelial function by detecting the change of yon Willebrand factor (vWF) in blood plasma of patients with sepsis shock after treatment with low-dose heparin in order to observe organ function and prognosis of patients.Methods A total of 118 patients with sepsis shock were randomized into low-dose heparin group and control group.In addition to the routine treatment,the patients in low-dose heparin group were given low-dose heparin,while those in control group were not.The levels of APTT,PT,platelet (PLT) count,hepatic function and renal function were determined before and after treatment in two groups,and hemorrhagic events or other complications were recorded.The lengths of stay in ICU and in hospital,the days of mechanical ventilation and the rates of acute respiratory distress syndrome (ARDS),disseminated intravascular coagulation (DIC) and multiple organ dysfunction syndrome (MODS) and 28-day survival rate in the two groups were documented.The levels of vWF in patients of two groups were determined by using immunoturbidimetry before and after treatment.Results The rates of DIC and MODS in low-dose heparin group decreased significantly after therapy (rate of DIC,10.6％ vs.26.7％,P ＜ 0.05;rate of MODS,19.3％ vs.32.0％,P ＜ 0.05).Hepatic function and renal function in low-dose heparin group were significantly improved than that in the control group (P ＜ 0.05),28-day survival rate in the low-dose heparin group was higher than that in the control group (78.3％ vs.69.1％,P ＜0.05),the differences between low-dose heparin group and control group were not statistically significant in the lengths of stay in ICU and hospital,the days of mechanical ventilation and the rate of ARDS (P ＞ 0.05).The differences in APTT,PT and PLT were not significant from pre-treatment to after treatment and between the two groups (P ＞ 0.05).The levels of vWF in low-dose heparin group decreased significantly after therapy rather than those in control group (P ＜ 0.05).Conclusions The endothelial function is improved in patients with sepsis shock after employment of lowdose heparin.Low-dose heparin alleviates the interaction between coagulation and inflammation,improves hepatic,renal and other important organs function,decreases the rate of MODS and increases 28-day survival rate patients with sepsis.The low-dose heparin therapy is a safe and promising treatment in sepsis patients without severe side effects.