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.

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.

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.

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

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.

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.

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.

Mechanism of affinity alterations in VWF-A1 domain mutant G561S studied by molecular dynamics simulation / 医用生物力学

Objective To investigate the mechanism of affinity down-regulation between Von Willebrand factor mutant G561S and its ligand. Methods Three molecular systems were constructed for WT-A1, G561S-A1, and R543Q-A1, respectively. G561S-A1 mutant was constructed by replacing the Gly561 with Ser561 in the wild-type A1 domain. The crystal structures of WT-A1 and R543Q-A1 were downloaded from Protein Data Base (PDB). Free molecular dynamics simulation was performed to observe the changes of conformation, alterations of flexibility, and the formation and evolution of hydrogen bond and/or salt bridge, among the three A1 domains (WT-A1, G561S-A1, and R543Q-A1). ResultsG561S mutation lowered the localized dynamic properties of α2 helix and increased the interactions between the N-terminal arm and body region in A1 domain, thus leading to the decreased binding affinity with its ligand GPIbα. However, the Gain-of-function mutation R543Q followed the pathway which was contrary to G561S. ConclusionsThe change of localized dynamic properties of α2 helix is a potential mechanism in the regulation of the binding affinity of A1, and this research finding is helpful in developing allosteric drugs against the activated A1 domain and relevant anti-thrombus drugs.

Endothelial dysfunction and lipid oxidation status after coronary artery bypass grafting procedure under cardio-pulmonary bypass / 解放军医学杂志

Objectives To evaluate the influence of cardio-pulmonary bypass (CPB) to the endothelial function and lipid oxidative status of the Coronary Artery Bypass Grafting (CABG) patients. Methods Thirty-five coronary patients (female 5 cases, male 30 cases, mean age 59.5±8. 6 years) who needed CABG operation therapy were included. The control group consisted of 20 health volunteers (female 5 cases, male 15 cases, mean age 49. 5 ± 7.3 years).Blood samples were taken at preoperative, 3 and 7 days postoperative. Serum von Willebrand factor (vWF) level, one of the endothelial dysfunction markers,and oxidized low density lipid (OxLDL) level, one of the lipid oxidization status markers were detected with ELISA kits. Results The levels of vWF and OxLDL in CABG patients' serum were elevated significantly compared with those of control group ( 139.60% ± 34. 39% vs 82. 79% ±13. 89% and 63. 7 ±18. 9U/ml vs 25.4± 15.2U/ml respectively). Three and 7 days after CABG significant increases in the vWF level (194. 30% ±37. 74%; 181.07% ±31.05%vs 139.60% ±34.39% at baseline, P＜0. 0001, respectively) and OxLDL level (79. 3±26. 7U/ml; 72.4±23.1U/ml vs 63.7±18. 9U/ml at baseline, P＜0. 01, respectively) were detected. Conclusion Compared with normal people, the endothelial system of CABG patients is impaired, and their lipids are in a more oxidative status. CABG procedure with CPB can further deteriorate the conditions, which may imply that the patients are predisposed to acute coronary accident shortly are the procedure.

Multiplication and differentiation into endothelial cells of bone marrow stromal cells of rats in vitro / 中国康复理论与实践

@#ObjectiveTo explore the feasibility of bone marrow stromal cells (BMSC) of rats differentiating into endothelial cells.MethodsBone marrow cells were obtained by an aseptic technique. Afterwards, the obtained cells were divided into two groups: cells in test group were propagated in 1640 medium with recombinant human GM-CSF (rhGM-CSF) (400ng/ml), and that in control group were propagated in medium with 1640 medium only. The differentiated cells were detected by specific immunology marker by immunocytochemistry and immunofluorescence at day 8.ResultsThe differentiated cells demonstrated the characters of endothelial cells under phase contrast microscopy. Cells of the test groups demonstrated specific characters by immunocytochemistry stain.ConclusionBone marrow stromal cells can multiply vigorously and differentiate into cells with endothelial cells characters in the medium with high concentration rhGM-CSF.