Faculty Opinions recommendation of The von Willebrand factor Tyr2561 allele is a gain-of-function variant and a risk factor for early myocardial infarction.

Author(s):  
Imre Bodó
2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
VV Ryabov ◽  
D Vorobyeva ◽  
YUG Lugacheva ◽  
IV Kulagina

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.


Blood ◽  
2019 ◽  
Vol 133 (4) ◽  
pp. 356-365 ◽  
Author(s):  
Reinhard Schneppenheim ◽  
Natalie Hellermann ◽  
Maria A. Brehm ◽  
Ulrike Klemm ◽  
Tobias Obser ◽  
...  

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.


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

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.


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