scholarly journals Blood Plasma Serotonin and von Willebrand Factor as Biomarkers of Unstable Angina Progression Toward Myocardial Infarction

2021 ◽  
Vol 28 (1) ◽  
pp. E202112
Author(s):  
Yuliya Tyravska ◽  
Oleksandr Savchenko ◽  
Viktor Lizogub ◽  
Nataliia Raksha ◽  
Olexiy Savchuk
Keyword(s):  
Myocardial Infarction ◽  
Blood Plasma ◽  
Von Willebrand Factor ◽  
Serotonin Concentration ◽  
Group 3 ◽  
Group 2 ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Plasma Serotonin ◽  
Group 1

Aim: To investigate the serotonin and von Willebrand factor (vWF) concentrations among unstable angina (UA) patients without and with progression toward myocardial infarction (outcome) and to assess the utility of both as prognostic markers of UA complications. Materials and methods: In observational cohort study, we recruited 103 patients with ischemic heart disease (the median age 65.0 (59.0-69.0) years, 45 females (43.7%)). After full set of investigations including high sensitive Troponin I test and 28-day follow-up period, we defined three groups: Group 1 - stable angina patients (n=22) as control, Group 2 - UA patients without outcome (n=71), Group 3 - UA patients with outcome (n=10). We analyzed the blood plasma serotonin content by the ion-exchange chromatography with measurement of serotonin on fluorescence spectrophotometer. VWF concentration was determined by ELISA. We compared the concentrations of observed parameters among the groups with the Kruskal-Wallis test (with post-hoc Mann-Whitney test with Bonferroni-Holm correction). We assessed binary logistic models, receiver operating characteristic curves, calculated sensitivity (Se), specificity (Sp), and positive likelihood ratio (LR+) for each indicator. Results: We registered elevation in serotonin concentration and decline in vWF concentration in Group 3 in comparison with Group 2 (22.670 (20.687-24.927) μg/ml vs 11.980 (8.120-15.000) μg/ml, p< 0.001, and 0.117 (0.109-0.120) rel.units/ml vs 0.134 (0.127-0.143) rel.units/ml, p < 0.001) and Group 1 (12.340 (10.052-13.619) μg/ml, p < 0.001, and 0.137 (0.127-0.156) rel.units/ml, p < 0.001), respectively. No significant differences in serotonin and vWF concentrations between Group 1 and Group 2 were detected (p=0.81 and p=0.36, respectively). The probability of outcome increased significantly (by 60.7% and 59.7%, LR+ 19.0 [6.0, 60.0] and 18.0 [3.9, 80.0]) if serotonin concentration was above 21.575 μg/ml (Se=80.0%, Sp=95.8%, AUC=0.975) and vWF concentration was below 0.114 rel.units/ml (Se=50.0%, Sp=97.2%, AUC=0.973), respectively. Conclusions: Serotonin and vWF as biomarkers are demonstrated promising results for rule-in the patients with risk of short-term UA progression toward myocardial infarction.

scholarly journals Effect of minimally invasive extracorporeal circulation on endothelial dysfunction in cardiac ­surgery patients

2020 ◽  
Vol 101 (2) ◽  
pp. 279-283
Author(s):  
V I Kornev ◽  
N M Kalinina ◽  
O N Startseva
Keyword(s):  
Cardiopulmonary Bypass ◽  
Endothelial Dysfunction ◽  
Minimally Invasive ◽  
Factor Viii ◽  
Von Willebrand Factor ◽  
Activated Platelets ◽  
Group 2 ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Group 1

Aim. To assess the changes in endothelial dysfunction in patients undergoing cardiac surgery with minimally invasive extracorporeal circulation (MiECC). Methods. The study included 50 patients who were undergoing coronary artery bypass grafting (CABG) surgery with cardiopulmonary bypass (CPB). The patients were divided assigned to either a minimally invasive cardiopulmonary bypass system (group 1, n=15) or standard extracorporeal circuit (group 2, n=35). Changes in the laboratory parameters were assessed 5 times: before the operation, 5 minutes after protamine sulfate administration, 12 hours after the operation, 7 days after the patient's discharged from the hospital and one month after the operation. The activity of von Willebrand factor, factor VIII, and the number of activated platelets were examined in all patients in venous blood. Results. After protamine sulfate administration, the activity of von Willebrand factor was increased to 164% in the group 1, and up to 193% in the group 2, with a tendency to increase the indicator after 12 hours. The peak of endothelial dysfunction, with the growth of von Willebrand factor and factor VIII, occurs on the 7th day after the operation. In patients of the group with MiECC, von Willebrand factor activity was decreased at the hospital discharge and returned to normal in 1 month. The number of activated platelets increases mainly in group 2 (6% versus 4% in group 1, p=0.29). The expression of P-selectin was significantly higher in group 2 at the hospital discharge (5.5% versus 3.1% in group 1, p 0.001), and in 1 month (4.5% versus 2.3% in group 1, p 0.001). Conclusion. In patients with minimally invasive cardiopulmonary bypass, platelet activation decreases, endothelial dysfunction, accompanied by an increase in the von Willebrand factor and factor VIII activity, is less pronounced; the seventh day after surgery is a period of the high risk of thrombogenic complications.

Intersection of Mechanisms of Type 2A Von Willebrand Disease through Defects in Von Willebrand Factor Multimerization, Secretion, ADAMTS-13 Susceptibility, and Regulated Storage

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 588-588 ◽  
Author(s):  
Paula M. Jacobi ◽  
Joan Cox Gill ◽  
Kenneth D. Friedman ◽  
Robert R. Montgomery ◽  
Sandra L. Haberichter
Keyword(s):  
Endothelial Cell ◽  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
Expression Studies ◽  
Sequence Variations ◽  
Group 2 ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Increased Susceptibility ◽  
Group 1

Abstract Type 2A von Willebrand disease (VWD) is characterized by the absence of large von Willebrand factor (VWF) multimers and decreased platelet binding function. These variants are classified as either group 1 (2A-1) with impaired assembly and secretion of VWF multimers, or group 2 (2A-2) with increased susceptibility to proteolysis by ADAMTS13. However, laboratory parameters in individual patients may not discriminate between 2A-1 and 2A-2; this must be established through expression studies. Type 2A VWD patients recruited through the TS Zimmerman Program For The Molecular And Clinical Biology Of VWD (ZPMCB VWD) were phenotypically identified based upon laboratory parameters. By sequencing genomic DNA we identified 13 potentially causative sequence variations in the VWF D2, D3, A1, and A2 domains of type 2A VWD patients. Expression studies were performed to examine the effect of these mutations on VWF processing and proteolysis, and VWF regulated storage. The VWF variants L1503R, S1506L, and V1607D demonstrated severely impaired secretion and lacked mid- and high-molecular weight multimers, consistent with a group 1 classification (2A – 1). Some variants including I1568N, G1579R, and G1631D were normally multimerized and secreted, but had an increased susceptibility to cleavage by ADAMTS13 cleavage, indicative of group 2 classification (2A – 2). Five variants involving cysteine residues (C1190S, C1099P, C1272R/S/Y) had multimer abnormalities, a modest reduction in secretion, and variably enhanced ADAMTS-13 cleavage. These variants did not easily fit the criteria for either 2A subgroup. We also identified sequence variations (M740I and I1380V) that had no effect on VWF secretion, structure, or proteolysis that are likely innocuous polymorphisms but are present in patients with a type 2A phenotype. VWF is stored for regulated release in endothelial cell Weibel-Palade bodies and in platelet alpha-granules. The effect of mutations on VWF regulated storage has been documented for few VWF variants. The 2A variants were expressed in HEK293 cells, immunostained, and examined by confocal microscopy. Several variants including C1272S/Y, L1503R, S1506L, and V1607D did not form storage granules. A loss or reduction in endothelial cell Weibel-Palade bodies may explain the diminished desmopressin response observed in many type 2A VWD patients. In sum, our data indicate that 2A-2 variants are associated with VWF A2 domain mutations and normal regulated storage, while 2A-1 mutations are not restricted to a particular domain and result in loss of regulated VWF storage. Mutations involving cysteines may not affect VWF secretion, but are likely to cause abnormalities in multimer structure. In summary, type 2A VWD appears to result from at least three intersecting mechanisms: intracellular retention, defective multimerization, or increased plasma proteolysis.

scholarly journals Characterization of guinea pig megakaryocyte subpopulations at different phases of maturation prepared with a Celsep separation system

Blood ◽  
1989 ◽  
Vol 73 (7) ◽  
pp. 1801-1808 ◽  
Author(s):  
PK Schick ◽  
BP Schick ◽  
K Williams-Gartner
Keyword(s):  
Guinea Pig ◽  
Stage I ◽  
Stage Iii ◽  
Ploidy Class ◽  
Group 3 ◽  
Group 2 ◽  
Von Willebrand ◽  
Immature Cells ◽  
Willebrand Factor ◽  
Group 1

Abstract We introduce a new method for preparing subpopulations of guinea pig megakaryocytes (MK). MK, partially purified by a density gradient, were separated according to size by sedimentation, starting as a monolayer, in an albumin gradient at unit gravity. Twenty-two fractions were collected. Cells were cytocentrifuged, ploidy was assessed by microdensitometry, and small MK were identified with anti-von Willebrand factor (vWF) immunoglobulin. Immaturity was assessed by uptake of 3H thymidine and synthesis of proteoglycans from 35S sulfate. About 88% of cells in fractions 2 through 18 were MK, of which 90% were viable. Fractions containing the largest cells were composed of 98% stage III and IV MK; fractions with the smallest cells contained up to 80% stage I and II MK. Six MK classes were isolated: immature cells, both stage I and II cells, at either the 8N, 16N or 32N ploidy class; mature cells, both stage III and IV cells, at either the 8N, 16N or 32N ploidy class. The fractions were pooled into three groups: (a) 8% of MK in group 1, fractions 2 through 11, were immature, and group 1 was composed of 92% of 16N and 32N mature classes; (b) 29% of MK in group 2, fractions 12 through 15, were immature, and group 2 was composed of 52% 16N mature, 24% 16N immature, and 13% 8N mature classes; 67% of MK in group 3, fractions 16 through 18, were immature, and group 3 contained 51% 8N immature, 14% 16N immature, and 18% mature 16N classes. The mean protein content of the three groups was 1.251, 0.624, and 0.284 mg/10(6) MK, respectively. Nine percent of cells in group 3 but no cells in group 1 took up large amounts of 3H thymidine. The synthesis of high-molecular-weight (high-mol-wt) proteoglycans in group 3 and synthesis of lower mol wt proteoglycans in groups 1 and 2 provided further evidence for differences in MK maturity. Thus, the method can isolate MK subpopulations that are viable and can be used to investigate the biochemical characteristics of MK at different phases of maturation.

scholarly journals Characterization of guinea pig megakaryocyte subpopulations at different phases of maturation prepared with a Celsep separation system

Blood ◽  
1989 ◽  
Vol 73 (7) ◽  
pp. 1801-1808
Author(s):  
PK Schick ◽  
BP Schick ◽  
K Williams-Gartner
Keyword(s):  
Guinea Pig ◽  
Stage I ◽  
Stage Iii ◽  
Ploidy Class ◽  
Group 3 ◽  
Group 2 ◽  
Von Willebrand ◽  
Immature Cells ◽  
Willebrand Factor ◽  
Group 1

We introduce a new method for preparing subpopulations of guinea pig megakaryocytes (MK). MK, partially purified by a density gradient, were separated according to size by sedimentation, starting as a monolayer, in an albumin gradient at unit gravity. Twenty-two fractions were collected. Cells were cytocentrifuged, ploidy was assessed by microdensitometry, and small MK were identified with anti-von Willebrand factor (vWF) immunoglobulin. Immaturity was assessed by uptake of 3H thymidine and synthesis of proteoglycans from 35S sulfate. About 88% of cells in fractions 2 through 18 were MK, of which 90% were viable. Fractions containing the largest cells were composed of 98% stage III and IV MK; fractions with the smallest cells contained up to 80% stage I and II MK. Six MK classes were isolated: immature cells, both stage I and II cells, at either the 8N, 16N or 32N ploidy class; mature cells, both stage III and IV cells, at either the 8N, 16N or 32N ploidy class. The fractions were pooled into three groups: (a) 8% of MK in group 1, fractions 2 through 11, were immature, and group 1 was composed of 92% of 16N and 32N mature classes; (b) 29% of MK in group 2, fractions 12 through 15, were immature, and group 2 was composed of 52% 16N mature, 24% 16N immature, and 13% 8N mature classes; 67% of MK in group 3, fractions 16 through 18, were immature, and group 3 contained 51% 8N immature, 14% 16N immature, and 18% mature 16N classes. The mean protein content of the three groups was 1.251, 0.624, and 0.284 mg/10(6) MK, respectively. Nine percent of cells in group 3 but no cells in group 1 took up large amounts of 3H thymidine. The synthesis of high-molecular-weight (high-mol-wt) proteoglycans in group 3 and synthesis of lower mol wt proteoglycans in groups 1 and 2 provided further evidence for differences in MK maturity. Thus, the method can isolate MK subpopulations that are viable and can be used to investigate the biochemical characteristics of MK at different phases of maturation.

scholarly journals Comparative analysis of prothrombotic activity in patients with myocardial infarction with non-obstructive and obstructive atherosclerotic lesions of the coronary arteries

2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
VV Ryabov ◽  
D Vorobyeva ◽  
YUG Lugacheva ◽  
IV Kulagina
Keyword(s):  
Myocardial Infarction ◽  
Coronary Arteries ◽  
Von Willebrand Factor ◽  
Protein C ◽  
Control Group ◽  
Moderate Correlation ◽  
Blood Tests ◽  
Group A ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The reported study was funded by RFBR, project number №19-315-90106 Aim To compare indicators of blood prothrombotic activity in patients with myocardial infarction with and without coronary arteries obstruction Material and methods. The study included 40 patients with AMI (19 patients in the main group and 21 patients in the control group). Three patients (15.7%) with acute myocarditis were excluded from the analysis. Hemostasiological and hematological blood tests were studied upon admission, on the 2nd, 4th, 7th days from hospitalization. Blood samples for protein C, antithrombin, von Willebrand factor (WF), plasminogen, homocysteine were performed on 4th ± 1 day from hospitalization. To determine the IgG / IgM antibodies to cardiolipin and β2-glycoprotein for the diagnosis of APS, the ORGENTEC Anti-β2-Glycoprotein I IgG / IgM ELISA enzyme immunoassay was used. Blood tests for lupus anticoagulant were performed using an ACL-Top 700 analyzer (Werfen) with HemosIL SynthASil dRVVT screen reagents / dRVVT confirm  and with a SCT screen / SCT confirm quartz activator. Results In patients with MINOCA a statistically higher level of homocysteine (p = 0.03) and a lower level of plasminogen (p = 0.007) are determined. Protein C, antithrombin, WF the presence of lupus anticoagulant, antibodies to cardiolipin and β2-glycoprotein no differences between the groups were detected, p &gt;0.05. MINOCA patients have a statistically higher platelet level on the 2nd and 4th day of AMI (p = 0.046 and p = 0.01 ) however the level of hemoglobin and hematocrit was statistically lower on the 4th day of AMI, (p = 0.008). In the main group, a moderate correlation was found between protein C and antithrombin (r = 0.65, p = 0.0001), antithrombin and von Willebrand factor (r = 0.54, p = 0.0001), between protein C and platelet level by 4th day (r = - 0.49, p = 0.04). In MINOCA patients a moderate negative correlation was found between homocysteine and plasminogen (r = -0.69, p = 0.002). In the control group, a high correlation was found between protein C and antithrombin (r = 0.96, p = 0.0001), a moderate correlation between protein C and plasminogen (r = 0.47, p = 0.03). In addition, a relationship was revealed between the presence of thrombosis according to ICAG data and the level of ejection fraction (r = 0.46, p = 0.04) in the control group, as well as between the presence of thrombosis and the level of fibrinogen upon admission (r = 0.55, p = 0.008). Conclusions Patients with MINOCA have a higher level of homocysteine and a lower level of plasminogen. For such indicators as protein C, antithrombin III, WF the presence of antibodies on the APS is not defined differences between groups. According to laboratory data patients with MINOCA showed higher levels of platelets but lower levels of hemoglobin and hematocrit in the early post-infarction period.

scholarly journals The von Willebrand factor Tyr2561 allele is a gain-of-function variant and a risk factor for early myocardial infarction

Blood ◽  
2019 ◽  
Vol 133 (4) ◽  
pp. 356-365 ◽  
Author(s):  
Reinhard Schneppenheim ◽  
Natalie Hellermann ◽  
Maria A. Brehm ◽  
Ulrike Klemm ◽  
Tobias Obser ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Von Willebrand Factor ◽  
Odds Ratio ◽  
Univariate Analysis ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Dependent Manner ◽  
Microfluidic Assays ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract The frequent von Willebrand factor (VWF) variant p.Phe2561Tyr is located within the C4 domain, which also harbors the platelet GPIIb/IIIa-binding RGD sequence. To investigate its potential effect on hemostasis, we genotyped 865 patients with coronary artery disease (CAD), 915 with myocardial infarction (MI), and 417 control patients (Ludwigshafen Risk and Cardiovascular Health Study) and performed functional studies of this variant. A univariate analysis of male and female carriers of the Tyr2561 allele aged 55 years or younger revealed an elevated risk for repeated MI (odds ratio, 2.53; 95% confidence interval [CI], 1.07-5.98). The odds ratio was even higher in females aged 55 years or younger, at a value of 5.93 (95% CI, 1.12-31.24). Cone and plate aggregometry showed that compared with Phe2561, Tyr2561 was associated with increased platelet aggregate size both in probands’ blood and with the recombinant variants. Microfluidic assays revealed that the critical shear rate for inducing aggregate formation was decreased to 50% by Tyr2561 compared with Phe2561. Differences in C-domain circular dichroism spectra resulting from Tyr2561 suggest an increased shear sensitivity of VWF as a result of altered association of the C domains that disrupts the normal dimer interface. In summary, our data emphasize the functional effect of the VWF C4 domain for VWF-mediated platelet aggregation in a shear-dependent manner and provide the first evidence that a functional variant of VWF plays a role in arterial thromboembolism.

scholarly journals Appropriate secondary prevention and clinical outcomes after acute myocardial infarction according to atherothrombotic risk stratification: The FAST-MI 2010 registry

2018 ◽  
Vol 26 (4) ◽  
pp. 411-419 ◽  
Author(s):  
Victoria Tea ◽  
Marc Bonaca ◽  
Chekrallah Chamandi ◽  
Marie-Christine Iliou ◽  
Thibaut Lhermusier ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
High Risk ◽  
Secondary Prevention ◽  
High Risk Patients ◽  
Risk Patients ◽  
St Elevation ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background Full secondary prevention medication regimen is often under-prescribed after acute myocardial infarction. Design The purpose of this study was to analyse the relationship between prescription of appropriate secondary prevention treatment at discharge and long-term clinical outcomes according to risk level defined by the Thrombolysis In Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS-2P) after acute myocardial infarction. Methods We used data from the 2010 French Registry of Acute ST-Elevation or non-ST-elevation Myocardial Infarction (FAST-MI) registry, including 4169 consecutive acute myocardial infarction patients admitted to cardiac intensive care units in France. Level of risk was stratified in three groups using the TRS-2P score: group 1 (low-risk; TRS-2P=0/1); group 2 (intermediate-risk; TRS-2P=2); and group 3 (high-risk; TRS-2P≥3). Appropriate secondary prevention treatment was defined according to the latest guidelines (dual antiplatelet therapy and moderate/high dose statins for all; new-P2Y12 inhibitors, angiotensin-converting-enzyme inhibitor/angiotensin-receptor-blockers and beta-blockers as indicated). Results Prevalence of groups 1, 2 and 3 was 46%, 25% and 29% respectively. Appropriate secondary prevention treatment at discharge was used in 39.5%, 37% and 28% of each group, respectively. After multivariate adjustment, evidence-based treatments at discharge were associated with lower rates of major adverse cardiovascular events (death, re-myocardial infarction or stroke) at five years especially in high-risk patients: hazard ratio = 0.82 (95% confidence interval: 0.59–1.12, p = 0.21) in group 1, 0.74 (0.54–1.01; p = 0.06) in group 2, and 0.64 (0.52–0.79, p < 0.001) in group 3. Conclusions Use of appropriate secondary prevention treatment at discharge was inversely correlated with patient risk. The increased hazard related to lack of prescription of recommended medications was much larger in high-risk patients. Specific efforts should be directed at better prescription of recommended treatment, particularly in high-risk patients.

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