Study on pathogenesis and laboratory diagnosis of a family with von Willebrand disease caused by c.1117C＞T/c.7288-9T＞G compound heterozygous mutation / 临床检验杂志

Objective To explore the diagnosis of clinically suspicious von Willebrand disease(vWD)in a family and its pathogene-sis.Methods The pedigree information and the biological specimen were collected from the clinically suspected VWD patient and her family members(4 persons in total)in Peking University First Hospital.The levels of platelet count(PLT),activated partial thrombo-plastin time(APTT),vWF antigen(vWF:Ag),vWF activity(vWF:Ac)and FⅧ activity(FⅧ:C)were detected,and vWF risto-cetin cofactor(vWF:RCo)assay,ristocetin-induced platelet aggregation assay(RIPA)and vWF collagen binding(vWF:CB)assay were performed for phenotype diagnosis.The peripheral blood genomic DNAs were extracted from the proband and her family members to perform whole-exome sequencing for identifying the mutation of vWF gene,The mutation site was analyzed by using bioinformation tools to explore the pathogenesis of the proband.Results The APTT of proband(m 1)was slightly prolonged and her vWF:Ag,vWF:Ac,vWF:RCo and vWF:CB were significantly decreased.There was no obvious aggregation in RIPA assay(1.0 mg/mL and 1.25 mg/mL).In her father(Ⅱ3),APTT,FⅧ:C,vWF:Ag,vWF:Ac and vWF:CB were normal,but vWF:RCo was slightly decreased.In her mother(Ⅱ4),APTT,FⅧ:C,vWF:Ag,vWF:RCo and vWF:CB were all normal,but vWF:Ac significantly decreased.In her brother(Ⅲ2),APTT and FⅧ:C were normal,but vWF:Ag,vWF:Ac,vWF:RCo and vWF:CB were reduced to varying degrees.In all the family members(father,mother and brpther),no apparent aggregation in RIPA(1.0 mg/mL)was shown.Genetic analysis showed that the proband(Ⅲ1)carried a compound heterozygous mutation of vWF gene c.7288-9T＞G and c.1117C＞T,her father(Ⅱ3)carried vWF gene c.7288-9T＞G heterozygous mutation,and vWF gene c.1117C＞T heterozygous mutation was presented in both mother(Ⅱ4)and brother(Ⅲ2).Conclusion According to the results of laboratory tests,the proband was diagnosed as type 2A vWD.The hetero-zygous mutation in vWF gene c.1117C＞T and c.7288-9T＞G may be the molecular mechanism leading to type 2A vWD in the proband.

Predictive value of von Willebrand factor for venous thromboembolism in critically ill patients based on propensity score matching / 中华危重病急救医学

Objective:To analyze the predictive value of von Willebrand factor (vWF) for venous thromboembolism (VTE) of patients in intensive care unit (ICU) by using propensity score matching (PSM).Methods:Patients admitted to ICU of the Second Affiliated Hospital of Kunming Medical University from December 2020 to June 2022 who stayed in ICU for ≥72 hours and underwent daily bedside vascular ultrasound screening were included. Baseline data such as age, gender, primary disease, and chronic comorbidities were collected. Coagulation indexes before admission to ICU and 24 hours and 48 hours after ICU admission were collected, including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), international normalized ratio (INR), fibrinogen (Fib), fibrin monomer (FM), vWF, D-dimer, antithrombin Ⅲ (ATⅢ), etc. Patients were divided into VTE group and non-VTE group according to whether they had VTE or not [diagnosis of VTE: patients underwent daily ultrasound screening of bedside blood vessels (both upper and lower limbs, visceral veins), and those suspected of having thrombosis were confirmed by ultrasonographer or pulmonary angiography]. Using PSM analysis method, the VTE group was used as the benchmark to conduct 1 : 1 matching of age, whether there was malignant tumor, whether there was infection, whether there was diabetes, and coagulation indicators before admission to ICU. Finally, the cases with balanced covariates between the two groups were obtained. The risk factors of VTE were analyzed by multivariate Logistic regression analysis. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of vWF in the occurrence of VTE in critically ill patients.Results:A total of 120 patients were enrolled, of which 18 (15.0%) were diagnosed with VTE within 72 hours after admission to ICU, and 102 (85.0%) were not found to have thrombus in ICU. Before PSM, there were significant differences in age, gender, proportion of malignant tumor and infection, and coagulation indexes between VTE group and non-VTE group. After PSM, 14 pairs were successfully matched, and the unbalanced covariables between the two groups reached equilibrium. Multivariate Logistic regression analysis showed that vWF was an independent risk factor for VTE at 48 hours after ICU admission in critically ill patients [odds ratio ( OR) = 1.165, 95% confidence interval (95% CI) was 1.000-1.025, P = 0.004]. ROC curve analysis showed that the area under the ROC curve (AUC) of vWF at 48 hours after ICU admission for predicting VTE was 0.782, 95% CI was 0.618-0.945, P = 0.007. When the optimal cut-off value was 312.12%, the sensitivity was 67.7% and the specificity was 93.0%. Conclusion:Dynamic monitoring of vWF is helpful to predict the occurrence of VTE in ICU patients, and vWF at 48 hours after ICU admission has certain value in predicting the occurrence of VTE.

Effect of Shexiangbaoxin Pill on vascular endothelial function in patients with primary microvascular angina / 中国现代医生

@#Objective The plasma von Willebrand factor(vWF)level in patients with primary microvascular angina(PMVA)were measured to evaluate the vascular endothelial function of the patients.The change of vWF level in patients after the treatment with Shexiangbaoxin Pill were observeg.Methods Totally 69 patients who were definitely diagnosed as PMVA,They were randomly divided into conventional treatment group(33cases)and ShexiangBaoxin Pill group(36cases).The plasma vWF levels of the two groups were measured before and after treatment.Results The level of vWF before treatment in conventional treatment group was(50.93±32.98)μg/L.The level of vWF before treatment in ShexiangBaoxin Pill group was(27.45±25.02)μg/L.The level of vWF in conventional treatment group after treatment was(49.65±35.12)μg/L.The level of vWF after treatment in ShexiangBaoxin Pill group was(17.37±15.68)μg/L.The difference of vWF decrease in Baoxin Pill group after treatment(10.08±16.47)μg/L,was lower than that in conventional treatment group(1.28±12.37)μg/L,the difference is significant(P<0.05).Conclusion Shexiang Baoxin Pill has the function of protecting vascular endothelium,and PMVA patients can benefit from treatment.

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.

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.

Application Value of Plasma vWF and ADAMTS-13 in Evaluating Postoprative Vascular Endothelial Injury and Prognosis in Children with VSD / 中国实验血液学杂志

OBJECTIVE@#To dynamically observe the levels and activities of von Willebrand factor (vWF) and ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) in plasma of children with congenital ventricular septal defect (VSD) during perioperative period, and explore the value of plasma vWF antigen (vWF:Ag) and ADAMTS-13 activity (ADAMTS-13: AC) in evaluating vascular endothelial injury and prognosis in children with VSD.@*METHODS@#In this cross-sectional study, a total of 74 children with VSD who underwent surgical treatment in TEDA International Cardiovascular Hospital from September 2018 to March 2019 were enrolled in the observation group. Among them, there were 28 cases of pure VSD, 32 cases of VSD combined with pulmonary hypertension, and 14 cases of VSD combined with valvular heart disease. 31 healthy children who underwent physical examination in Tianjin Children's Hospital during the same period were collected as the control group. The biochemical indexes of the children at admission were recorded. Peripheral plasma was collected at admission, postsurgery day 0 and day 1, respectively, and the levels of vWF activity (vWF:AC), vWF:Ag, ADAMTS-13 antigen (ADAMTS-13:Ag) and ADAMTS-13:AC were detected.@*RESULTS@#The level of plasma vWF:Ag and vWF:AC in the observation group before surgery were significantly lower than those in the control group (P<0.001), and increased continuously, on postsurgery day 0 and day 1 (P<0.001). The level of ADAMTS-13:Ag in the observation group before surgery was significantly higher than that in the control group (P<0.001), which decreased significantly on postsurgery day 0 (P<0.001), and increased significantly on postsurgery day 1 compared with postsurgery day 0 (P=0.033). The level of ADAMTS-13:AC in the observation group before surgery was significantly lower than that in the control group (P=0.015), which decreased significantly on postsurgery day 0 (P=0.037), and increased on postsurgery day 1, but the difference was not statistically significant (P=0.051). The changes of vWF and ADAMTS-13 in the three subgroups were basically similar to the observation group. vWF: Ag/ADAMTS-13: AC ratio on postsurgery day 0 and day 1 had high diagnostic value in vascular endothelial injury (AUC=0.80, P<0.001; AUC=0.93, P<0.001). Preoperative vWF and ADAMTS-13 levels, and related baseline indicators were not correlated with postoperative infection, bleeding, thrombosis,etc.@*CONCLUSION@#Preoperative vWF: Ag, vWF: AC and ADAMTS-13: AC levels in children with VSD are low, while the level of ADAMTS-13: Ag is high. After surgery, the levels of vWF: Ag and vWF: AC are increased and the level of ADAMTS-13: Ag is decreased. The postoperative vWF: Ag/ADAMTS-13: AC ratio shows high diagnostic value in evaluating vascular endothelial injury. There is no correlation between preoperative vWF and ADAMTS-13 levels with perioperative clinical events.

Analysis of risk factors related to hemorrhagic fever with renal syndrome in children / 国际儿科学杂志

Objective:To investigate the related risk factors affecting the prognosis of hemorrhagic fever with renal syndrome(HFRS) in children.Methods:A retrospective study was carried out.We selected 182 pediatric patients who met the diagnostic criteria for pediatric HFRS while hospitalized in the Intensive Care Department of the Affiliated Children′s Hospital of Xi′an Jiaotong University between July 2014 and December 2021 as the research objects.The severe and critical patients were taken as the observation group(24 cases), and the mild and moderate pediatric patients were taken as the control group(158 cases). The demographic, epidemiological data and clinically relevant indicators within 8 hours of pediatric patients after admission were collected.The 28-day death was the primary endpoint.Renal failure and pulmonary edema were secondary endpoint.The differences of clinically relevant indicators between the two groups were observed.Logistic regression was used to analyze the risk factors and receiver operating characteristic(ROC) curve was used to determine the predictive efficacy of different outcome prediction models.Results:There were no statistically significant differences in age, gender, and BMI between the two groups (all P>0.05). Compared the control group with the observation group, coagulation function indicators such as activated partial thromboplastin time (APTT)[(134±21)s vs.(164±34)s], D-dimer [(6.31±3.20)mg/L vs.(12.43±5.67)mg/L], von Willebrand factor (vWF)[(352±45)μg/L vs.(465±103)μg/L], and platelet(PLT)[(87±35)×10 9/L vs.(45±24)×10 9/L], Lactate(Lac)[(2.6±1.1)mmol/L vs.(6.0±2.0)mmol/L]were different significantly(all P<0.05). Additionally, the lymphocyte characteristic analysis indicator lymphocytes [(2 749±686)×10 6/L vs.(2 374±851)×10 6/L], CD3 + [(1 821± 487)×10 6/L vs.(1 065±539)×10 6/L], CD4 + /CD8 + (1.65±0.73)vs.(1.00±0.25), CD19 + [(559±105)×10 6/L vs.(487± 133)×10 6/L]were different significantly(all P<0.05). The inflammatory index procalcitonin(PCT) [(22±15)ng/L vs.(56±21)ng/L, P<0.05]was different significantly in two groups.The rate of continuous renaly replacement therapy, ventilator-assisted ventilation, vasoactive drugs and other treatment measures increased significantly in observation group than those in control group(all P<0.05). Multivariate logistic regression analysis was performed on the included indicators.With death as the primary endpoint, Lac, CD8 + , D-dimer, vWF and PCT were significantly associated with mortality, which were risk factors for death, while PLT and CD4 + /CD8 + were protective factors.With renal failure and pulmonary edema as secondary endpoint, CD8 + , D-dimer, Lac and PCT were risk factors for secondary endpoint.ROC curve analysis showed that the sensitivity, specificity and AUC of the risk factor prediction model related to the primary endpoint variables were 77.91%, 81.22% and 0.769, and which related to secondary endpoint variables were 87.61%, 77.59% and 0.891, respectively. Conclusion:The combinations of CD8 + , D-dimer, Lac, PCT and vWF have good predictive value for poor prognosis in children with HFRS.

Analysis of subgingival plaque Streptococcus sanguinis levels of the oral cavity in middle-aged and elderly patients with primary microvascular angina / 中华老年医学杂志

Objective:To analyze levels of oral Streptococcus sanguinis( Ss)in middle-aged and elderly patients with primary microvascular angina(PMVA)and changes in vascular endothelial function. Methods:In this case-control study, 21 middle-aged and elderly patients diagnosed with PMVA at the Department of Cardiology, Hangzhou Red Cross Hospital between January 2019 and July 2022(the PMVA group)were recruited, with ages ranging from 45 to 80(63.4±12.3)years, while 23 healthy individuals receiving health checkups during the same period served as the control group, with ages ranging from 48-76(62.5±6.5)years.The 21 middle-aged and elderly PMVA patients underwent tests for the measurement of subgingival plaque Ss levels of the oral cavity and levels of plasma vascular von Willebrand factor(VWF)and homocysteine(Hcy). Pearson linear regression analysis was conducted.Results:Ss was not found in subgingival plaque of the oral cavity in the control group, but low levels of Ss were detected in patients from the PMVA group(percentage: 1.754×10 -4; 6.218×10 -5, 4.450×10 -4). The VWF level in the PMVA group was higher than in the control group[(20.22 ± 4.44)μg/L vs.(12.00 ± 6.60)μg/L, t=4.890, P<0.01]. There was no statistical difference in the Hcy level between the PMVA group and the control group[(15.28±6.40)μmol/L vs.(12.86±2.63)μmol/L, t=1.615, P>0.05]. There was no significant correlation between Ss levels and VWF levels in the PMVA group( r=0.038, P>0.05). Conclusions:Ss can be detected in subgingival plaque of the oral cavity in PMVA patients, but not in healthy middle-aged and elderly people.The VWF level in PMVA patients is significantly higher than in healthy people, indicating that vascular endothelial function is impaired in middle-aged and elderly PMVA patients.However, there is no correlation between subgingival plaque Ss levels of the oral cavity and VWF levels in PMVA patients.

Preparation and Application of Monoclonal Antibody Against Human von Willebrand Factor Propeptide / 中国实验血液学杂志

OBJECTIVE@#To develop monoclonal antibodies that can specifically recognize human von Willebrand factor (VWF) propeptide (VWFpp) in plasma, and establish a rapid and reliable method for the detection of VWFpp antigen in plasma by using the double-antibody sandwich ELISA with the obtained anti-VWFpp monoclonal antibody.@*METHODS@#The recombinant human VWFpp (D1 and D2 regions) protein expressed in eukaryotic cells was used as immunogen to immunize BALB/c mice with routine method, so as to obtain clones of fusion cells. After screening and identification, hybridoma cell lines secreting monoclonal antibodies against VWFpp were selected, and then double-antibody sandwich ELISA assay was used to construct VWFpp antigen detection kit for the determination of VWFpp in human plasma. The levels of VWFpp antigen in plasma of 12 leukemia patients who underwent bone marrow transplantation were dynamically detected.@*RESULTS@#Two hybridoma cell lines that can be subcultured continuously and secrete monoclonal antibodies against VWFpp were obtained and named SZ175 and SZ176 respectively. Identified by ELISA and Western blot, the antibodies could both specifically recognize VWFpp but couldn't recognize mature VWF (without propeptide). Based on the principle of double-antibody sandwich ELISA, monoclonal antibodies SZ175 and SZ176 were successfully made into a kit for detecting VWFpp antigen. The plasma VWFpp levels of leukemia patients before and after bone marrow transplantation were dynamically detected. The results showed that the plasma VWFpp levels of the patients after transplantation were significantly higher than those before transplantation.@*CONCLUSION@#Two monoclonal antibodies against VWFpp were successfully prepared, and a double-antibody sandwich ELISA detection kit for VWFpp antigen was constructed, which provides a powerful tool for further study on the biological function of VWFpp, the clinical diagnosis and classification of von Willebrand disease (VWD), and the prognostic monitoring of endothelial injury-related diseases.

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.

Microfluidics-based study on the damage pattern of red blood cells and VWF / 国际生物医学工程杂志

Objective:To investigate the effects of shear stress magnitude and exposure time on the damage of blood component erythrocytes and von willebrand factor (VWF) based on microfluidic technology.Methods:A blood shear platform was built based on a microfluidic chip, samples were prepared under different shear stress magnitudes and exposure time lengths, free hemoglobin assay experiments were performed on blood samples, the hemolysis indices of different samples were measured, and the relative molecular masses of different samples of VWF were analyzed by immunoblotting and chemiluminescence imaging.Results:The quantitative relationships between the hemolysis index and the degradation rate of high relative molecular mass VWF with shear stress and exposure time followed the power function model well.Conclusions:The microfluidic experimental platform has the advantages of a precise and controllable internal microenvironment and easy and rapid detection, which can be used for the quantitative study of blood damage patterns.

Diagnóstico de la enfermedad de von Willebrand / Diagnosis of von Willebrand disease

La enfermedad de von Willebrand (EVW) es el trastorno hemorrágico hereditario más común, y se caracteriza por presentar disminución de la capacidad del factor von Willebrand (FVW) de unirse a las plaquetas y al colágeno de la matriz extracelular durante la hemostasia primaria, debido a defectos cuantitativos o cualitativos. La EVW se clasifica en tres fenotipos principales: el 1 y el 3 que son trastornos cuantitativos, y el 2 que se subclasifica en 2A, 2B, 2M y 2N, y refleja los trastornos cualitativos. Para su diagnóstico son necesarios varios pasos: 1) la evaluación del historial de sangrado personal y familiar del paciente, 2) detección inicial de trastornos hemorrágicos, 3) pruebas para la detección de la EVW, 4) pruebas para la tipificación de la EVW, y 5) el análisis molecular. Tanto la subclasificación de la EVW como su diagnóstico continúan planteando desafíos importantes, motivo por el cual se realiza esta revisión, de manera que los profesionales de la salud tengan una guía que los oriente al momento de tener pacientes con algún trastorno hemorrágico que amerite descartar una EVW e implementar un tratamiento adecuado

von Willebrand disease (VWD) is the most common hereditary bleeding disorder, and is characterized by a decreased ability of the von Willebrand factor (VWF) to bind to platelets and extracellular matrix collagen during primary hemostasis, due to quantitative or qualitative defects. VWD is classified into three main phenotypes: 1 and 3, which are quantitative disorders, and 2 (2A, 2B, 2M and 2N) that reflects qualitative disorders. Several steps are necessary for its diagnosis: 1) evaluation of the patient's personal and family bleeding history, 2) initial screening tests for bleeding disorders, 3) tests for the detection of VWD, 4) tests for the classification of VWD, and 5) molecular analysis. Both the subclassification of VWD and its diagnosis continue to represent important challenges, which we aimed to describe in this review, so that health professionals have a guide to assist them when they have patients with a bleeding disorder that requires exclusion of VWD, and implementation of an appropriate treatment.

Enfermedad von Willebrand: consideraciones prácticas para el odontólogo. Revisión de literatura / von Willebrand disease: practical considerations for the dentist. Literature review

RESUMEN La enfermedad von Willebrand es el desorden hemorrágico hereditario más común, que se origina por la deficiencia del factor von Willebrand, la cual provoca una adhesión y agregación plaquetaria defectuosa. Se caracteriza por un tiempo de sangrado y tiempo parcial de tromboplastina prolongados, con bajos valores del factor VIII, y aumento de fragilidad capilar, pero con recuento normal de plaquetas. El tratamiento odontológico en un paciente con enfermedad von Willebrand, debe ser individualizado de acuerdo con la severidad de la condición del paciente, así como coordinado con el hematólogo, quien debe de determinar el tipo de enfermedad y la necesidad de la terapia de reemplazo del factor según diagnóstico específico previo al manejo de este. Mediante esta revisión bibliográfica se desea reforzar el conocimiento al odontólogo de este trastorno hemorrágico, ya que con ello se pueden evitar o minimizar posibles complicaciones de sangrado durante el tratamiento odontológico.

ABSTRACT von Willebrand disease is the most common inherited bleeding disorder, caused by von Willebrand factor deficiency, which causes defective platelet adhesion and aggregation. It is characterized by a prolonged bleeding time and partial thromboplastin time, with low levels of factor VIII, and increased capillary fragility, but with a normal platelet count. Dental treatment in a patient with von Willebrand disease must be individualized according to the severity of the patient's condition, as well as coordinated with the hematologist, who must determine the type of disease and the need for factor replacement therapy, prior to the patient management. Through this bibliographic review, it wants to reinforce the dentist's knowledge of this bleeding disorder, since this can prevent or minimize possible bleeding complications during dental treatment.

Clinical characteristics and outcome of 69 patients with thrombotic thrombocytopenic purpura / 中华内科杂志

To analyze the clinical characteristics, diagnosis, treatment and outcome of patients with thrombotic thrombocytopenic purpura (TTP). The clinical data of 69 adult patients with TTP were retrospectively analyzed. There were 19 males and 50 females with a median age of 42 (18-79) years. PLASMIC score 6-7 was recognized in 82.8% (53/64) patients. The activity of von Willebrand factor-cleaving protease (ADAMTS13), which was detected in 21 patients before treatment, was less than 5% in 17 patients and 5%-10% in 3 patients. All 69 patients were treated with plasma exchange (PEX) and/or fresh frozen plasma infusion (PI), 43 of whom were also given glucocorticoid. In addition to PEX/PI and glucocorticoid, rituximab and/or immunosuppressants were administrated in 20 patients. The median follow-up time was 12 (1-57) months. The remission rate was 69.6%, while the relapse rate was 11.6%. The 2-year overall survival (OS) rate was 69.6%±5.5%. The univariate and multivariate analysis showed that relapsed/refractory disease was an independent risk factor for OS. The 2-year OS rate of relapsed/refractory patients was significantly lower than that of the rest patients (41.5%±9.8% vs. 83.7%±5.6%, P<0.001). Regarding the unfavorable prognosis in relapsed/refractory patients, rituximab and/or immunosuppressants are strongly recommended for sake of improving the overall survival.

Analysis of laboratory parameters and death risk in patients with thrombotic thrombocytopenic purpura / 中华检验医学杂志

Objective:To analyze the laboratory parameters and clinical characteristics of TTP patients, so as to provide reference for the timely diagnosis and death risk assessment or TTP.Methods:83 patients with TTP from June 2016 to March 2022 in our hospital were analyzed retrospectively. They were divided into survival and death groups. The differences in general information, clinical symptoms and laboratory parameters were compared between the two groups. The prognostic prediction score was constructed by combining parameters which differ between the two groups to calculate the corresponding mortality risk.Results:83 patients were included in the study, of whom 81.1% (60/74), 91.1% (72/79) and 86.2% (50/58) had increased AST, IBIL and cTnI results, and all (78/78) had higher LDH at admission. Hb was decreased in 97.5% (79/81) patients, and PLT of 97.5% (79/81) patients was less than 30×10 9/L. There were no significant differences in gender, age, blood type, presence of fever, ADAMTS-13 activity and PLASMIC score between the survival group (58 cases) and the death group (25 cases), but the proportion of neurologic symptoms in the death group was significantly higher than that in the survival group. AST, IBIL, cTnI and APTT at admission were significantly higher in the death group than in the survival group ( P<0.05). The risk of death was 4.86, 9.74, 3.71, and 5.33 for those with high AST, IBIL, APTT, and cTnI levels, respectively, compared with those with low levels at admission. At last, AST, IBIL, APTT, cTnI and neurological symptoms were included to construct a score model. For each 1 point increase, the risk of short-term death in TTP patients was 3.24. Conclusions:Multiple laboratory markers have high negative exclusion value for TTP. For TTP patients with high AST, IBIL, cTnI and APTT and neurologic symptoms, more attention and active treatment should be paid to reduce mortality.

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.

Prospects for plasma protein products in China / 中国输血杂志

Plasma protein products, essential drugs for various clinical diseases, are therapeutic biological products extracted from healthy human plasma. The research and development of new plasma protein products, led by United States and European, has been widely deepened and enhanced. Therefore, accelerating the development of new plasma protein products in China is of great significance. This review summarizes the research and development of plasma protein products that have been marketed abroad but have not produced in China, as well as analyzes the difficulties and prospects of the development of plasma protein products in China.

Prediction study of main cardiovascular adverse events after percutaneous coronary intervention / 中国医师进修杂志

Objective:To investigate the relationship of von Willebrand factor cleaving enzyme(ADAMTS-13), ratio of mean platelet volume to platelet count (MPV/P), intelectin-1 (ITLN-1) and thrombolysis in myocardial infarction (TIMI) blood flow classification in acute myocardial infarction patients who performed percutaneous coronary intervention(PCI) and the value of predicting postoperative major cardiovascular adverse events (MACE).Methods:A total of 126 patients with acute myocardial infarction treated with PCI in Yuechi County People′s Hospital from January 2019 to January 2021 were selected and divided into MACE group (25 cases) and no MACE group (101 cases) according of the prognosis. The levels of ADAMTS-13, MPV/P and ITLN-1 were compared between the two groups, the correlation of above index and TIMI blood flow classification and the value of predicting postoperative MACE were analyzed.Results:The levels of ADAMTS-13 and ITLN-1 in the MACE group were lower than those in the MACE group, and the level of MPV/P was higher than that in the MACE group: (132.59 ± 43.05) μg/L vs. (186.33 ± 58.17) μg/L, (255.36 ± 80.24) mg/L vs. (342.65 ± 91.18) mg/L, (0.06 ± 0.02) fl/( × 10 9/L) vs. (0.04 ± 0.01) fl/( ×10 9/L), there were statistical differences ( P<0.05). The results of Spearman correlation analysis showed that the levels of ADAMTS-13 and ITLN-1 were positively correlated with TIMI blood flow classification ( r = 0.692, 0.622, P<0.01) , the level of MPV/P was negatively correlated with TIMI blood flow classification ( r = -0.665, P<0.01). The area under the curve of ADAMTS-13, MPV/P combined with ITLN-1 in protecting the MACE was 0.872. Conclusions:ADAMTS-13, MPV/P and ITLN-1 are related to the TIMI blood flow classification and MACE in patients with acute myocardial infarction after PCI, and the combined detection can be used as a reliable predictor of MACE.

Estudio de la relación entre el grupo sanguíneo eritrocitario ABO con los niveles del factor von Willebrand en pacientes diagnosticados con la enfermedad / Study of the relationship between the ABO erythrocyte blood group with the von Willebrand factor levels in patients diagnosed with the disease

Resumen La presencia o ausencia de los antígenos del sistema ABO entre otros factores se han relacionado con los niveles plasmáticos del factor von Willebrand (VWF) debido a su influencia en la proteólisis por la ADAMTS 13; la actividad de este sistema eritrocitario puede incidir en eventos trombóticos o hemorrágicos. El propósito de este estudio fue determinar si los pacientes diagnosticados con la enfermedad de von Willebrand pertenecían al grupo sanguíneo O y si los niveles de VWF y FVIII eran más bajos que los de los grupos no-O. El grupo sanguíneo fue identificado por un método directo en tubo y el VWF y FVIII se midieron mediante ensayos de coagulación. Se analizó un total de 64 pacientes, el 29,4% eran mayores de 40 años, el 100% presentaron valores más bajos del VWF que los grupos no-O, el 64% de los pacientes presentaron una concentración del FVIII de 6-49% inferior al rango normal establecido y el 78,51% fueron tipificados como del grupo sanguíneo O. El análisis estadístico demostró una relación estadísticamente significativa entre los niveles de VWF y el grupo sanguíneo. Se determinó que existe una relación entre el sistema ABO y el VWF-FVIII (p<0,05); sin embargo, esto no significa que sea la única causa de la existencia de un nivel bajo del factor. Estos datos indican la necesidad de mayores estudios en la población de pacientes con la enfermedad y la necesidad de determinar los tipos de von Willebrand y su relación con el grupo sanguíneo.

Abstract The presence or absence of antigens of the ABO system, among other factors, have been related to plasma levels of von Willebrand factor (VWF) due to its influence on proteolysis by ADAMTS 13. The activity of this erythrocyte system may influence on thrombotic or hemorrhagic events. The purpose of this study was to determine if the patients diagnosed with von Willebrand disease belonged to the O blood group and the VWF and FVIII levels were lower than those of the other blood groups. The blood group was identified by direct tube method and the VWF and FVIII were measured by coagulation tests. A total of 64 patients were analised, 29.4% were older than 40, 100% presented lower values of VWF than the non-O groups. A total of 64% of the patients presented a lower concentration of 6-49% in FVIII at the established normal range and 78.51% were typified as blood group O. Statistical analysis showed a statistically significant relationship between VWF levels and blood group. It was determined that there is a relationship between the ABO system and the VWF-FVIII (p<0.05). However, this does not mean that is the only cause of the existence of a low level of these factors. These data indicate the need for further studies in the population of patients with von Willebrand disease in order to determine the von Willebrand types and their relationship with the blood group.

Resumo A presença ou ausência dos antígenos do sistema ABO, entre outros fatores, tem sido relacionada aos níveis plasmáticos do fator de von Willebrand (VWF) devido à sua influência na proteólise pelo ADAMTS 13; a atividade desse sistema eritrocitário pode afetar eventos trombóticos ou hemorrágicos. O objetivo deste estudo foi determinar se os pacientes com diagnóstico de doença de von Willebrand pertenciam ao grupo sanguíneo O e se os níveis de VWF e FVIII eram inferiores aos dos grupos não-0. O grupo sanguíneo foi identificado por um método direto em tubo e o VWF e o FVIII foram medidos por testes de coagulação. Foram analisados 64 pacientes, 29,4% tinham idade superior a 40 anos, 100% apresentaram valores mais baixos do VWF que os grupos não-O e 64% dos pacientes apresentaram concentração de FVIII 6-49% menor à faixa normal estabelecida, e 78,51% foram tipificados como do grupo sanguíneo O. A análise estatística mostrou uma relação estatisticamente significativa entre os níveis de VWF e o grupo sanguíneo. Foi determinado que existe uma relação entre o sistema ABO e o VWF-FVIII (p<0,05), no entanto, isso não significa que seja a única causa da existência de um baixo nível do fator. Esses dados indicam a necessidade de novos estudos na população de pacientes com a doença e a necessidade de determinar os tipos de von Willebrand e sua relação com o grupo sanguíneo.

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.