THE Y2561 ALLELE OF A COMMON POLYMORPHISM IN THE C1 DOMAIN OF VON WILLEBRAND FACTOR APPEARS AS A NOVEL RISK FACTOR FOR MYOCARDIAL INFARCTION

2007 ◽  
Vol 5 ◽  
pp. O-M-032-O-M-032
Author(s):  
N. Hellermann ◽  
B.O. Boehm ◽  
W. Maerz ◽  
J. Rischewski ◽  
B.R. Winkelmann ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Risk Factor ◽  
Von Willebrand Factor ◽  
Common Polymorphism ◽  
C1 Domain ◽  
Von Willebrand ◽  
Willebrand Factor

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 >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.

ADAMTS13 and von Willebrand factor and the risk of myocardial infarction in men

Blood ◽  
2006 ◽  
Vol 109 (5) ◽  
pp. 1998-2000 ◽  
Author(s):  
Chan K. N. K. Chion ◽  
Carine J. M. Doggen ◽  
James T. B. Crawley ◽  
David A. Lane ◽  
Frits R. Rosendaal
Keyword(s):  
Myocardial Infarction ◽  
Von Willebrand Factor ◽  
Large Population ◽  
Population Based ◽  
Myocardial Infarctions ◽  
Enzyme Linked Immunosorbent Assay ◽  
Estimated Risk ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Adhesion Of Platelets

Abstract Von Willebrand factor (VWF) mediates the tethering/adhesion of platelets at sites of vascular injury. This function depends on its multimeric size, which is controlled by ADAMTS13. We measured plasma ADAMTS13 and VWF antigen levels by enzyme-linked immunosorbent assay (ELISA) in a large population-based case-control study (Study of Myocardial Infarctions Leiden [SMILE]), consisting of 560 men with a first myocardial infarction (MI) and 646 control subjects. Although ABO blood groups influenced VWF levels, they had no influence on ADAMTS13. Furthermore, there was no relationship between plasma ADAMTS13 and VWF levels. Similar to VWF, the estimated risk of MI was increased for every quartile of ADAMTS13 when compared to the lowest quartile (odds ratio, 1.5-1.6). If confirmed, the association of ADAMTS13 with MI may suggest an unexpected mechanistic action of ADAMTS13.

A novel cause of mild/moderate hemophilia A: mutations scattered in the factor VIII C1 domain reduce factor VIII binding to von Willebrand factor

Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 958-965 ◽  
Author(s):  
Marc Jacquemin ◽  
Renaud Lavend'homme ◽  
Abdellah Benhida ◽  
Beatrijs Vanzieleghem ◽  
Roseline d'Oiron ◽  
...  
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Cho Cells ◽  
Hemophilia A ◽  
Chinese Hamster ◽  
Expression Vectors ◽  
Scatchard Analysis ◽  
C1 Domain ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract The mechanisms responsible for the low factor VIII (fVIII) activity in the plasma of patients with mild/moderate hemophilia A are poorly understood. In such patients, we have identified a series of fVIII mutations (Ile2098Ser, Ser2119Tyr, Asn2129Ser, Arg2150His, and Pro2153Gln) clustered in the C1 domain and associated with reduced binding of fVIII to von Willebrand factor (vWf). For each patient plasma, the specific activity of mutated fVIII was close to that of normal fVIII. Scatchard analysis showed that the affinity for vWf of recombinant Ile2098Ser, Ser2119Tyr, and Arg2150His fVIII mutants was reduced 8-fold, 80-fold, and 3-fold, respectively, when compared with normal fVIII. Given the importance of vWf for the stability of fVIII in plasma, these findings suggested that the reduction of fVIII binding to vWf resulting from the above-mentioned mutations could contribute to patients' low fVIII plasma levels. We, therefore, analyzed the effect of vWf on fVIII production by Chinese hamster ovary (CHO) cells transfected with expression vectors for recombinant B domain-deleted normal, Ile2098Ser, Ser2119Tyr, and Arg2150His fVIII. These 3 mutations impaired the vWf-dependent accumulation of functional fVIII in culture medium. Analysis of fVIII production by transiently transfected CHO cells indicated that, in addition to the impaired stabilization by vWf, the secretion of functional Ile2098Ser and Arg2150His fVIII was reduced about 2-fold and 6-fold, respectively, by comparison to Ser2119Tyr and normal fVIII. These findings indicate that C1-domain mutations resulting in reduced fVIII binding to vWf are an important cause of mild/moderate hemophilia A.

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