Von Willebrand Factor In Patients Research Articles

A Feasibility Study Evaluating Von Willebrand Factor in Patients with Gastrointestinal Angiodysplasia

Background: Abnormalities of von Willebrand Factor (VWF), such as those found in von Willebrand Disease (VWD) are associated with the development of abnormal blood vessels known as angiodysplasia. Angiodysplasia occurs primarily in the gastrointestinal (GI) tract, particularly the small bowel. Among patients with VWD, angiodysplasia is significantly overrepresented as a cause of GI bleeding and occurs in all VWD subtypes although it is reported more frequently in those with loss of the high molecular weight multimer of VWF. Recent studies have demonstrated more than a third of patients with VWD and GI bleeding have angiodysplasia when systematically assessed with Video Capsule Endoscopy (VCE) to examine the small bowel. Given the relationship between angiodysplasia and VWD our objective was to assess the feasibility of evaluating patients with GI angiodysplasia for abnormalities of VWF. Methods: We undertook a prospective single center pilot study to assess patients over the age of 18 with GI angiodysplasia for underlying abnormalities of VWF. Patients were identified based on angiodysplasia being present on a VCE study. Patients who consented to enrollment completed a self-administered bleeding assessment tool (BAT) as well as baseline demographic data. VWF testing included VWF antigen (VWF:Ag), VWF functional assay (VWF:GPIbM), Factor VIII coagulant activity (FVIII:C), and VWF pro-peptide (VWFpp) levels. Results: After reviewing 190 consecutive VCE studies performed at our institution between April 2021 and April 2023, we identified 50 patients who had capsule endoscopies demonstrating angiodysplasia of the GI tract. Thirteen of these patients consented to enrollment in the study. The bleeding histories of included patients are detailed in Table 1 along with their baseline clinical, laboratory, and demographic data. Two patients endorsed lifelong bleeding symptoms and three reported a significant family history of bleeding - all in a female relative. ISTH-BAT scores ranged from 0 to 18 with a median score of 2. Since our population is older than other studies that report on bleeding scores, we considered an abnormal bleeding score to be >6 as recent evidence indicates normal BAT scores increase over time. Five patients (38.6%) in our study had an ISTH-BAT abnormal bleeding score. VWF levels were assessed (Table 1) and one patient aged 88 years old with a significant family and lifelong history of bleeding received a new diagnosis of Type 2A VWD. Severe iron deficiency anemia requiring ongoing IV iron was diagnosed in two patients. Conclusion: In our feasibility study, we demonstrated a feasible protocol for recruitment of patients with GI angiodysplasia for clinical and laboratory testing of VWF. A significant proportion of our patients (38.6%) had abnormal bleeding scores and one patient had an underlying Type 2A VWD diagnosis.

Utility of Assessing Primary Hemostasis By Determining Platelet Function and Von Willebrand Factor in Patients with Myeloproliferative Neoplasms

VWF Changes in primary hemostasis have been implicated in thrombotic and bleeding complications in myeloproliferative neoplasms (MPN), so their evaluation could be useful in the management of these patients. We studied primary hemostasis in 248 patients with essential thrombocythemia-type MPN (TE n=129), polycythemia vera (PV n=71) and myelofibrosis (MF n=48). Von Willebrand antigen (VWF:Ag) (normal: 60-160 U/dL), von Willebrand factor (VWF) activity (VWF:GPIbM) (normal: 60-160 U/dL) and closure time with the platelet function analyzer (PFA-200) (pathological: collagen-Epinephrine channel > 200 seconds; collagen-ADP channel > 140 seconds) were assessed. VWF:GPIbM < 60 U/dL and a VWF:GPIbM / VWF:Ag ratio < 0.7 were considered to be suggestive of acquired von Willebrand disease (aVWD). In antiplatelet patients with acetyl salicílic acid (ASA), we defined in vitro resistance as a PFA-200 Col-Epi time < 200 seconds. The results were correlated with the diagnosis, hematological values, conventional or NGS genotype (n=176) and treatment at the time of the study. Patients with thrombocytopenia < 50x10 9/L were excluded from the PFA-200 analysis. Table 1 describes the clinical variables of the patients. GPIbM was decreased in 14 cases, increased in 85 cases, and normal in the rest. We identified a direct correlation with age (β=0.29, R2=0.08, p=0.001), and an inverse correlation with the number of platelets (β=-0.45, R2=0.20, p<0.001), independent of the genotype. . We found elongated PFA-200 in the Col-Epi and Col-ADP channels in 129 (54%) and 63 (26%) cases, respectively. In 10 (4%) patients we found parameters suggestive of avWD. All of them had thrombocytosis. Elevated platelet count (>600x109/L) was associated with VWF values suggestive of aVWD, with a sensitivity and specificity of 90% and 83%, respectively (AUC: 0.938, 95%CI: 0.896-0.980). Of the 99 patients not on antiplatelet therapy, 31 (31%) had an elongated PFA-200. Elongated PFA-200 was associated with lower Hb, higher leukocytes, higher platelets, higher JAK2 mutational load, lower VWF:GPIbM, and CALR genotype. This alteration was observed in 71% of patients with the CALR genotype. In multivariate analysis, decreased VWF:GPIbM (OR: 0.98, 95%CI: 0.97-0.99, p=0.001) and CALR mutation (OR: 0.98, 95%CI: 0.97- 0.99, p=0.001), maintained their value. Of the 130 patients receiving ASA, in vitro resistance was found in 31 cases (24%) (PV 30%, TE 25%, MF 0%). ASA resistance was associated with a higher platelet count and higher VWF:GPIbM. 50% of the patients with increased VWF:GPIbM (>160 U/dL) had resistance to ASA, showing VWF:GPIbM as an independent variable in the multivariate analysis.

The level of adropin and von Willebrand factor in patients with arterial hypertension, excess body weight, and obesity

Objective. To investigate changes in adropin and von Willebrand factor (vWF) levels in patients with arterial hypertension (AH), excess body weight, and obesity.Material and methods. All patients were divided into two main groups: group 1 included 69 patients with AH and excess body weight; group 2 – 55 people with AH and obesity, and 20 healthy people of the control group. Anthropometric measurement, biochemical blood test, echocardiographic examination of the heart, and enzyme immunoassay (adropin, vWF) were performed.Results. The level of vWF was significantly higher in patients with AH, overweight, and obesity compared to healthy individuals (p=0,001). Meanwhile, the adropin level decreased with increasing BMI. The lowest adropin level was observed in individuals with AH and obesity (p=0,011). Additionally, a significant positive correlation was identified between vWF and the size of the LA (r=0,667; p=0,001), RV (r=0,487; p=0,021), MMLV (r=0,795; p=0,001) and IMMLV (r=0,731; p=0,001), whereas a negative correlation was found with EF (r=-0,461; p=0,031).Conclusions. An increase in vWF level was observed in patients with hypertension, overweight, and obesity which contributes to the emergence of endothelial dysfunction and structural myocardial changes, related to AH. The decrease in adropin level – a regulator of the cardiovascular system functions – was associated with an increase in BMI and elevated BP. Negative correlations were found between adropin and systolic and diastolic blood pressure values. It plays an important role in blood pressure and cardiovascular function regulation.

Effect of far-infrared radiation therapy on von Willebrand factor in patients with chronic kidney disease.

Hemostatic abnormality has contributed to vascular access thrombosis in patients with chronic kidney disease (CKD). Previous studies have demonstrated that far-infrared radiation (FIR) therapy can maintain the patency and maturity of arteriovenous fistulas of patients undergoing hemodialysis (HD). However, prolonged access bleeding is observed once FIR is conducted at the end of dialysis. FIR can block the binding of platelet and von Willebrand factor (vWF), a predictor of hemostatic abnormality and vascular access thrombosis. However, clinical studies exploring FIR and vWF are sparse. We recruited 20 HD patients, 21 CKD patients, and 20 controls to examine the alteration of vWF and a disintegrin and metalloproteinase with thrombospondin type 1 repeats 13 (ADAMTS13) following a single 40-min session of FIR therapy. In addition, the alteration of these factors in the HD group was examined following a 40-min FIR session thrice a week for 3 months. A decreasing trend in the vWF activity-antigen ratio of participants in all groups following a single FIR session was observed. In addition, the ratio in the HD group was significantly lower following 3 months of FIR therapy. The subgroup analysis revealed a consistent trend and multiple regression analysis showed that participants not taking hydroxymethylglutaryl-coenzyme A reductase inhibitor, diabetes mellitus, and higher hemoglobin levels were the significant factors. The alteration of the vWF activity-antigen ratio correlated moderately to that of ADAMTS13 antigen and activity. FIR may alter the ratio of ultra-large vWF multimers through ADAMTS13, contributing to inhibiting platelet-endothelium interactions of CKD patients.

Impact of transcatheter aortic valve implantation on circulating von Willebrand factor in patients with severe aortic stenosis.

Severe aortic stenosis (AS) can lead to degradation of high molecular weight (HMW) von Willebrand factor (VWF) which can result in haemostatic abnormalities. While studies have explored changes in VWF profiles before and after surgical aortic valve replacement (SAVR), the longer-term changes in VWF profiles pre- and post-transcatheter aortic valve implantation (TAVI) are less understood. Our primary objective was to identify differences in VWF multimer profiles and VWF function pre-TAVI and 1-month post-TAVI. Our secondary objective was to correlate VWF markers with measures of AS severity. Adult patients with severe AS referred for TAVI at our institution were prospectively enrolled in this cohort study. Blood samples were collected for plasma analysis at three time points for all patients: 1day pre-TAVI, 3days post-TAVI, and 1-month post-TAVI. VWF antigen, activity, propeptide, collagen binding, multimers, and factor VIII coagulant activity were determined at each time point. Correlations between VWF parameters and severity of AS were assessed. Twenty participants (15 males, five females) with severe AS were recruited for the study. There was a significant increase in HMW VWF between pre-procedure and 1-month post-TAVI (p<.05). There was a transient increase in VWF antigen levels and activity at 3-days post TAVI that decreased to pre-TAVI levels at 1-month. There were no statistically significant correlations between VWF markers and AS severity. This is the first study to elucidate longer-term (>1week) improvements in HMW VWF after a TAVI procedure in severe AS patients.

Primary hemostasis dysfunctions and bleeding risk in newly diagnosed acute myeloid leukemia.

Acute myeloid leukaemia carries the risk of complications associated with dysfunctions in haemostasis system. The purpose of this study was to investigate the factors associated with the risk of bleeding in patients with newly diagnosed acute myeloid leukaemia (AML). This study involved the methods of immunoenzymatic analysis and classical coagulation studies. The number of biochemical parameters important for establishing coagulative dysfunction in acute myeloid leukaemia was determined, the main ones being the level of von Willebrand factor, the Ristocetin-cofactor activity of von Willebrand factor and factor VIII activity, prothrombin time, platelet count, and fibrinogen concentration. According to the results of the present study, the reduced activity of von Willebrand factor in patients with AML was associated with severe bleeding. The authors observed an increase in the number of platelets count in patients with AML who experienced haemorrhages compared to patients with no bleeding signs. The study also established an increase in the concentration of fibrinogen in cancer patients, compared to the control sample. Symptoms and quantitative indicators for diagnosing the severity of haemorrhagic syndrome were grouped. The authors considered the advantages and disadvantages of many therapeutic preparations and focussed on specific markers of activated haemorrhage-predicting platelets. Further studies concern the search for effective markers and therapeutic approaches to minimize haemorrhagic syndrome. The results were statistically processed using the functions ANOVA, t test, CORREL, determination of the value of reliability, and mean square deviation.

Prophylaxis with recombinant von Willebrand factor in patients with type 3 von Willebrand disease: Results of a post hoc analysis from a phase 3 trial.

To describe efficacy/safety of recombinant von Willebrand factor (rVWF) prophylaxis in patients with type 3 von Willebrand disease (VWD). This post hoc analysis of a phase 3 open-label trial provides a more detailed analysis of adults with type 3 VWD, categorized based on prior treatment at screening: "Prior On-Demand (OD)" (OD VWF; ≥3 documented spontaneous bleeding events [BEs] requiring VWF in previous 12 months) or "Switch" (plasma-derived [pd] VWF prophylaxis for ≥12 months). Annualized bleeding rates (ABRs) were evaluated during 12 months of rVWF prophylaxis versus historical data from medical records. In the Prior OD group (n = 10), mean spontaneous ABR (sABR) for treated BEs was reduced by 91.6% (ratio, 0.08; 95% CI, 0.02-0.45) versus mean historical sABR. In the Switch group (n = 8), mean sABR for treated BEs was reduced by 47% (ratio, 0.53; 95% CI, 0.08-3.62). One non-serious adverse event (AE) was considered possibly related to rVWF. No treatment-related, fatal, or life-threatening serious AEs were reported, and no patient developed VWF inhibitors. rVWF prophylaxis reduced sABR in type 3 VWD patients previously treated with OD VWF therapy, and maintained a similar level of hemostatic control in those switching from pdVWF prophylaxis to rVWF prophylaxis.

(831) The Post-Operative Course of Von Willebrand Factor in Patients with Heartmate 3: A Longitudinal Study

(831) The Post-Operative Course of Von Willebrand Factor in Patients with Heartmate 3: A Longitudinal Study

Platelet adhesion mediated by von Willebrand factor in patients with premature coronary artery disease

Aim To study platelet adhesion mediated by von Willebrand factor (VWF) in patients with premature ischemic heart disease (IHD).Material and methods This study enrolled 58 patients with stable IHD, including 45 men younger than 55 years with the first manifestation of IHD at the age of &lt;50 years and 13 women younger than 65 years with the first manifestation of IHD at the age of &lt;60 years. The control group consisted of 33 patients, 13 men younger than 55 years and 20 women younger than 65 years without IHD. Platelet adhesion to the collagen surface at the shear rate of 1300 s-1 was studied by evaluating the intensity of scattered laser light from the collagen-coated optical substrate in a flow chamber of a microfluidic device after 15-min circulation of whole blood in the chamber. Decreases in platelet adhesion after addition to the blood of monoclonal antibodies (mAb) to platelet receptors glycoproteins Ib (GPIb) to inhibit the receptor interaction with VWF were compared for patients of both groups.Results In patients with premature IHD, the decrease in platelet adhesion following the platelet GPIb receptor inhibition was significantly less than in patients of the control group (74.8 % (55.6; 82.7) vs. 28.9 % (-9.8; 50,5), p &lt;0.001). For the entire sample, the median decrease in platelet adhesion following the GPIb receptor inhibition was 62.8 % (52.2; 71.2). With an adjustment for traditional risk factors of IHD, a decrease in platelet adhesion of &gt;62.8% after blocking GPIb receptors increased the likelihood of premature IHD (OR=9.84, 95 % CI: 2.80-34.59; p &lt;0.001).Conclusion Blocking the interaction of GPIb receptors with VWF in patients with premature IHD and increased shear rate induced a greater decrease in platelet adhesion than in patients without this disease. This suggested that an excessive interaction of VWF with platelets might contribute to the pathogenesis of premature IHD.

Levels and Activity of Von Willebrand Factor in Patients with Hereditary Thrombotic Thrombocytopenic Purpura

Background: Mutations in the ADAMTS-13 gene in patients with hereditary thrombotic thrombocytopenic purpura interfere with production or function of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) enzyme and increase levels of highly active large von Willebrand factor (vWF) multimers. Recent data from a cohort of hTTP patients carrying cDNA.4477_4477delA mutation in ADAMTS-13 gene suggested a discrepancy between ADAMTS13 activity and severity of clinical presentation. We proposed that the levels and activity of vWF might be elevated and associated with disease severity. In the present study we evaluated the levels and activity of vWF from homozygous cDNA.4477_4477delA mutation carriers in comparison to an historical cohort. Methods: In this retrospective cohort study all patients were diagnosed and treated at Soroka University Medical Center, Beer Sheba, Israel. Diagnosis of hTTP was confirmed by abnormal low levels of ADAMTS13, lack of anti-ADAMTS13 antibodies and positive testing for cDNA.4477_4477delA mutation. Patients' data were collected prospectively, while pre-enrollment data were collected retrospectively from the hospital records. The tests for von Willebrand factor activity (vWF:RCof) and von Willebrand factor antigen (vWF:Ag) were performed on non-pregnant patients and before FFP transfusions were initiated. Patients' vWF:RCof and vWF:Ag levels were compared to the values from previously published data of healthy subjects (Kilercik et al, Biological variations of ADAMTS13 and von Willebrand factor in human adults, Biochem. Medica. 24 [2014] 138-145). The data were analyzed using descriptive variables. vWF:RCof and vWF:Ag levels were compared using Mann-Whitney test. Results: Study population included 18 adults (15 female and three male patients) from two related families, all homozygous for c.3772 delA mutation. The age at initial presentation ranged from 18 to 48 years (mean 28.7±8.8). 17 patients were identified through episodes of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, vascular and pregnancy complications (see Figure 1B). One subject was detected due to family history as part of family screening. Symptomatic patients received FFP transfusions every two weeks. Pregnant patients received FFP transfusions at a dose of two units every two weeks until the week 20 and thereafter two units weekly until delivery. All patients responded well to FFP transfusions. We did not observe hTTP-related mortality among study participants. Figure 1A shows the comparison with an historic control group. The control group had similar size (19 vs. 18 subjects in the study group). The patients in our study group were slightly older and had a female predominance (83.3%), while the control group had 47% females and 53% males. All 18 patients in our cohort had blood group A, 15 (83%) have been Rh positive. 14 patients (82%, 12 females and two male) were thrombocytopenic on initial presentation (median, 28 x103/µL, interquartile range [IQR] 14 x103/µL - 144 x103/µL). 13 patients (73%) were anemic (median hemoglobin 10.2 gr/dL, IQR 7.6 gr/dL - 10.9 gr/dL). Lactate dehydrogenase (LDH) (median, 1425 U/L, IQR 915 U/L - 1912 U/L) was elevated in 16 patients (89%) during initial presentation. Seven patients (39%) had a schistocyte count ≥1% on peripheral blood smear. Values of vWF antigen (vWF:Ag) (median 209.3% [range 141.5-240.5%] vs. 104% [range 86-116%], p value <0.001) and vWF activity (vWF:RCof) (median 130.6% [range 102.6-139%] vs. 83% [range 77-99%], P value <0.001) were significantly higher in the study group than in healthy controls, respectively (Figure 1A, 1C). Conclusions: Our results demonstrate that the levels of vWF antigen and activity in patients with hTTP are significantly higher than in healthy controls. These findings prompt further evaluation of vWF as a possible biomarker for the severity of hTTP. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Changes in Plasma Levels of ADAMTS13 and von Willebrand Factor in Patients Undergoing Elective Joint Arthroplasty

Background: The risk of venous thromboembolic events (VTE) increases in patients undergoing total shoulder arthroplasty (TSA). However, there is no guidelines for prophylaxis. A decreased ratio of ADAMTS13 to VWF has been reported in patients with VTE. This study evaluates how TSA affects this ratio to better characterize timing of VTE risk and develop better guidelines for prophylactic treatment. Methods: Patients receiving TSA between 2016 and 2019 were recruited for this study following informed consent. Blood samples were collected at the clinic visit prior to surgery, postoperatively within one hour, at 24 h, 48 h, 2 and 6 weeks. Plasma levels of ADAMTS13 activity and VWF antigen were determined with a FRETS-VWF73 and an enzyme-linked immunoassay, respectively. Results: Of 22 patients included in the study, the mean age (± SD) was 68 ± 11 years. The most common diagnosis and surgery were osteoarthritis (68%) and reverse TSA (77%), respectively. Plasma ADAMTS13 activity was reduced immediately following surgery and remained lower than the baseline until postoperative day 2 (POD-2) (93.7 ± 28.5 IU/dL, p = 0.009). VWF antigen was the highest on POD-2 (253.2 ± 101.0%, p = 0.0034). The ADAMTS13/VWF ratio followed the same pattern, lowest on POD-2 (0.41 ± 0.20, p = 0.0016). All levels returned to baseline by two weeks. Conclusions: TSA resulted in low ADAMTS13 activity and high VWF acutely post-surgery day 2, suggesting that risk for VTE may be the highest during this period. ADAMTS13/VWF ratio is a useful marker to identify patients who may need proper anticoagulation after TSA.

Changes in the activity of metalloprotease ADAMTS13 antigen von Willebrand factor in patients with acute coronary syndrome

Introduction. Currently, considerable attention is being given to the study of the interaction of the von Willebrand factor (vWF) and its specific regulator of metalloprotease ADAMTS13 in various clinical conditions accompanied by the development of thrombosis.Aim — to assess the change in the activity of ADAMTS13 metalloprotease and vWF factor antigen in patients with acute coronary syndrome during the first five days after the onset of an anginal attack.Patients and methods: The study included 90 patients aged 42 to 86 years (Me — 61.5 y.o.) hospitalized with a diagnosis of acute coronary syndrome. Of these, 69 were men (Me — 59 y.o.) and 21 women (Me — 63 y.o.). All patients were tested for ADAMTS13 activity, ADAMTS13 antigen, and vWF antigen. Blood samples for the study were obtained upon admission to the hospital (arterial and venous blood), as well as 24, 72 and 120 hours after hospitalization (venous blood).Results. It was found that at all points of the study, in patients without coronary artery thrombosis, the average value of the ADAMTS13 activity indicator was significantly higher compared to the group of patients with coronary artery thrombosis. At the same time, there were no statistically significant differences in the average values of the ADAMTS13 antigen between the compared groups of patients. The mean value of vWF antigen in patients with coronary artery thrombosis was significantly higher compared to that of patients without coronary artery thrombosis.Conclusion. An increase in ADAMTS13 activity was noted more often in patients with acute coronary syndrome without coronary artery thrombosis than in patients with coronary artery thrombosis, which may indicate the antithrombotic effect of ADAMTS13 metalloprotease. No differences were found in ADAMTS13 antigen levels when comparing the study groups of patients, which indicates a greater significance for the anticoagulant activity of the functional characteristics of ADAMTS13. Significantly higher levels of the vWF antigen in patients with coronary artery thrombosis were due to the response to ischemic myocardial injury and stress but were not the primary cause of the thrombotic event.

PO-25: Elevated plasma von Willebrand Factor in patients with breast cancer may contribute to the early metastatic niche, promoting endothelial adhesion, invasion and angiogenic properties of circulating breast cancer cells

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Prognostic value of von-Willebrand factor in patients with liver cirrhosis and its relation to other prognostic indicators.

BACKGROUNDVon-Willebrand factor (vWF) disposes certain prognostic value in patients with liver cirrhosis, but its relation to other prognostic indicators has not been fully investigated. AIMTo analyze the relation between vWF and other prognostic indicators in cirrhotic patients and to evaluate its prognostic value for mortality. METHODSThis analytic prospective study was carried out in a tertiary center and initially enrolled 71 patients with liver cirrhosis and portal hypertension. It analyzed the relation between vWF and the stage of the disease and several inflammatory and prognostic indicators. The prospective analysis, performed on a sample of 63 patients, evaluated the association between the selected variables [vWF, Model for End-stage Liver Disease (MELD) score, C-reactive protein (CRP), ferritin, vitamin D, activated partial thromboplastin time, thrombin time, D-dimer concentration] and the survival time as well as their predictive value in terms of 3-mo, 6-mo and 1-year mortality.RESULTSvWF was significantly higher in patients with higher Child-Turcotte-Pugh class (P = 0.0045), MELD group (P = 0.0057), ferritin group (P = 0.0278), and D-dimer concentration (P = 0.0232). vWF significantly correlated with D-dimer concentration, ferritin, CRP, International Normalized Ratio, and MELD, Child-Turcotte-Pugh, Sequential Organ Failure Assessment, and CLIF-consortium organ failure (CLIF-C OF) scores. vWF, MELD score, and CRP were significantly associated with death and were significant predictors of 3-mo, 6-mo, and 1-year mortality. Each vWF unit significantly increased the probability for 3-mo mortality by 1.005 times (P = 0.008), for 6-mo mortality by 1.006 times (P = 0.005), and for 1-year mortality by 1.007 times (P = 0.002). There was no significant difference between the diagnostic performance of vWF and MELD score and also between vWF and CRP regarding the 3-mo, 6-mo, and 1-year mortality.CONCLUSIONIn patients with liver cirrhosis, vWF is significantly related to other prognostic indicators and is a significant predictor of 3-mo, 6-mo, and 1-year mortality similar to MELD score and CRP.

Von Willebrand factor in patients with peripheral artery disease who undergo invasive treatment

AIM: To evaluate the level and activity of von Willebrand factor (vWF) in patients with peripheral artery disease (PAD) who underwent endovascular or open bypass grafting.&#x0D; MATERIAL AND METHODS: The study included 115 patients with chronic lower limb ischemia due to PAD, stage IIb-IV according to A.V. PokrovskyFontaine. Fifty-five participants underwent endovascular treatment, while sixty underwent open bypass procedures using synthetic grafts. Peripheral blood samples were collected from all patients at baseline and three months after invasive treatment to determine the vWF antigen and activity. All patients were monitored every three months for a year to detect the development of unfavorable outcomes including disease progression, restenosis, graft thrombosis, oncology, myocardial infarction (MI), limb loss, stroke, and lethal outcomes.&#x0D; RESULTS: The highest values of vWF antigen in patients who underwent endovascular treatment were detected in patients with multilevel lesions1.25 g/mL (vs 0.2 g/mL, 95% confidence interval (CI) 0.723.21 mcg/mL p = 0.019); with a similar trend observed after a 3month follow-up. Baseline vWF antigen was higher in endovascular group patients who developed myocardial infarction (MI) within a year following the procedures as compared to those without MI: 1.15 mcg/mL (95% CI 1.051.175 mcg/mL) and 0.9 mcg/mL (95% CI 0.781.01 mcg/mL), respectively (p = 0.015). Moreover, vWF antigen was increased at the 3-month follow-up in patients with lethal outcomes1.06 mcg/mL (95% CI 0.961.18 mcg/mL, р = 0.031). vWF activity in endovascular group patients with developed MI was four times higher than those without MI (р = 0.022); a similar trend was detected in the development of lethal outcomes (р = 0.009). Those who underwent open bypass grafting presented with high activity of vWF with maximum values detected in participants with proximal iliofemoral lesions (1200%, 95% CI 640%1200%) and stage IV disease (770%, 95% CI 320%1200%, p 0.05). ROC analysis revealed that vWF activity at least 6.2 times higher in patients who underwent endovascular treatment associated with the development of lethal outcomes within one year after invasive treatments; sensitivity and specificity of the method were 83.3% and 75.5%, accordingly.&#x0D; CONCLUSION: Patients with PAD presented with increased vWF antigen and activity with maximum values detected in patients with multilevel lesions and critical lower limb ischemia. Increased vWF antigen and activity was associated with development of MI and lethal outcomes within one year following endovascular procedures on lower extremity arteries.

Severe COVID‐19 is associated with endothelial activation and abnormal glycosylation of von Willebrand factor in patients undergoing hemodialysis

BackgroundA major clinical feature of severe coronavirus diease 2019 (COVID‐19) is microvascular thrombosis linked to endothelial cell activation. Consistent with this, a number of studies have shown that patients with severe COVID‐19 have highly elevated plasma levels of von Willebrand Factor (VWF) that may contribute to the prothrombotic phenotype. In the current study, we investigated the extent of endothelial activation in patients receiving hemodialysis who had either mild or severe COVID‐19. MethodsPlasma VWF, ADAMTS‐13, angiopoietin‐2 (Ang2), and syndecan‐1 levels were determined by ELISA. The sialic acid content of VWF was investigated using a modified ELISA to measure elderberry bark lectin, specific for sialic acid residues, binding to VWF. ResultsPatients receiving hemodialysis with severe COVID‐19 had significantly higher plasma levels of VWF and lower ADAMTS‐13. VWF levels peaked and were sustained during the first 10 days after positive confirmation of infection. While Ang2 trended toward being higher in severely ill patients, this did not reach significance; however, severely ill patients had significantly higher soluble syndecan‐1 levels, with high levels related to risk of death. Finally, higher VWF levels in severely ill patients were correlated with lower VWF sialic acid content. ConclusionsSevere COVID‐19 in patients undergoing hemodialysis is associated with both acute and sustained activation of the endothelium, leading to alteration of the VWF/ADAMTS‐13 axis. Lower VWF sialic acid content represents altered VWF processing and further confirms the disturbance caused to the endothelium in COVID‐19.

Markers of Endothelial Dysfunction: E-selectin, Endothelin-1 and von Willebrand Factor in Patients with Coronary Heart Disease, Including in Combination with Type 2 Diabetes Mellitus

The prevalence of coronary heart disease (CHD) and type 2 diabetes mellitus (type 2 diabetes) in Russia and in the world continues to increase. Despite the prevention and optimization of therapy, CHD retains its leadership among all causes of death, and the mortality rate from type 2 diabetes and its complications gradually increases too. To improve the treatment of the above mentioned diseases, it is necessary to clarify the pathogenetic mechanisms of their development. The formation of endothelial dysfunction, characterized by an increase in the level of cell adhesion molecules and vasoconstriction, is a common link characteristic for the course and progression of CHD and type 2 diabetes. This article presents an analysis of preand clinical studies on the role of endothelial dysfunction markers: cell adhesion molecules (E-selectin), vasoconstriction (endothelin-1) and von Willebrand factor in patients with CHD, including those with type 2 diabetes mellitus.

Mitral valve regurgitation and clinical biochemistry: The role of von Willebrand factor in patients with transcatheter mitral valve repair

Mitral valve regurgitation and clinical biochemistry: The role of von Willebrand factor in patients with transcatheter mitral valve repair

Predictive and Prognostic Value of Von Willebrand Factor in Patients with Cirrhosis and Esophageal Varices

Background and study aim: Von Willebrand factor (vWF) is released by activated endothelial cells and plays a crucial role in the development of portal hypertension. vWF levels correlate with liver function and venous hepatic pressure gradient (VHPG) and independently predict clinical outcome. The aim was to evaluate serum vWF levels as a predictor for esophageal varices and prognosis in patients with liver cirrhosis. Patients and Methods: Sixty two patients with liver cirrhosis, divided into two groups according to presence (group I) or absence (group II) of varices were included, In addition, twenty healthy persons served as control group (group III). All patients were submitted to full history taking, clinical examination, laboratory investigations and abdominal ultrasonography. The severity of liver disease was estimated by Modified Child-Pugh and Model for End Stage Liver Disease (MELD) scores. All patients were underwent upper gastrointestinal endoscopy and vWF assay. Results: vWF values were significantly higher in group I (p1=0.001), than controls (p2=0.000), but no significant difference between group II and control group (p3= 0.59). Receiver operating characteristics (ROC) curve analysis of vWF revealed that, vWF at cutoff value of 173.8 µg/ml; the sensitivity for detection of esophageal varices was 80.8%, specificity 76.0%, positive predictive value (PPV) was 93.9%, negative predictive value (NPV) was 55.6%; area under the curve was 86.6.There was significant positive correlation between vWF and Child, MELD, esophageal varices grade and severity of portal hypertensive gastropathy. Conclusion: vWF is a good predictor for development of esophageal varices and correlated well with prognosis in patients with cirrhosis.

Phase 3 study of recombinant von Willebrand factor in patients with severe von Willebrand disease who are undergoing elective surgery

Summary Essentials Recombinant von Willebrand factor (rVWF) is effective in von Willebrand disease (VWD).A phase 3 study of rVWF, with/without recombinant factor VIII (rFVIII) before surgery in VWD.Overall rVWF's efficacy was rated excellent/good; rVWF was administered alone in most patients.rVWF was well‐tolerated and hemostasis was achieved in patients with severe VWD undergoing surgery. SummaryBackgroundRecombinant von Willebrand factor (rVWF) has demonstrated efficacy for on‐demand treatment of bleeding in severe von Willebrand disease (VWD), warranting evaluation in the surgical setting.ObjectivesThis study (NCT02283268) evaluated the hemostatic efficacy/safety profile of rVWF, with/without recombinant factor VIII (rFVIII), in patients with severe VWD undergoing surgery.Patients/MethodsPatients received rVWF 40–60 IU kg−1, VWF ristocetin cofactor activity was measured 12–24 h before surgery. If endogenous FVIII activity (FVIII:C) target levels were achieved 3 h before surgery, rVWF was administered alone 1 h before surgery; rVWF was co‐administered with rFVIII if target endogenous FVIII levels were not achieved. rVWF was infused postoperatively to maintain target trough levels. Overall and intraoperative hemostatic efficacy, the pharmacodynamics of rVWF administration and the incidence of adverse events (AEs) were assessed.ResultsAll patients treated with rVWF for major (n = 10), minor (n = 4) and oral (n = 1) surgery had overall and intraoperative hemostatic efficacy ratings of excellent (73.3% and 86.7%) or good (26.7% and 13.3%). Most rVWF infusions (89.4%) were administered alone, resulting in hemostatically effective levels of endogenous FVIII within 6 h, which were sustained for 72–96 h; 70% (n = 7/10) of major surgeries were performed without rFVIII co‐administration. Six patients reported 12 treatment‐emergent AEs. Two patients each had one serious AE: diverticulitis (not treatment related) and deep vein thrombosis (sponsor‐assessed as possibly treatment related). No severe allergic reactions or inhibitory antibodies were reported.ConclusionsThese data support the efficacy and safety profile of rVWF in patients with severe VWD undergoing elective surgery.