scholarly journals Von Willebrand Factor, Factor VIII, and Other Acute Phase Reactants as Biomarkers of Inflammation and Endothelial Dysfunction in Chronic Graft-Versus-Host Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Antonela Lelas ◽  
Hildegard Theresia Greinix ◽  
Daniel Wolff ◽  
Günther Eissner ◽  
Steven Zivko Pavletic ◽  
...  

Chronic graft-versus-host disease (cGvHD) is an immune mediated late complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). Discovery of adequate biomarkers could identify high-risk patients and provide an effective pre-emptive intervention or early modification of therapeutic strategy, thus reducing prevalence and severity of the disease among long-term survivors of alloHSCT. Inflammation, endothelial injury, and endothelial dysfunction are involved in cGvHD development. Altered levels of acute phase reactants have shown a strong correlation with the activity of several immune mediated disorders and are routinely used in clinical practice. Since elevated von Willebrand factor (VWF) and factor VIII (FVIII) levels have been described as acute phase reactants that may indicate endothelial dysfunction and inflammation in different settings, including chronic autoimmune diseases, they could serve as potential candidate biomarkers of cGvHD. In this review we focused on reported data regarding VWF and FVIII as well as other markers of inflammation and endothelial dysfunction, evaluating their potential role in cGvHD.

2020 ◽  
Vol 101 (2) ◽  
pp. 279-283
Author(s):  
V I Kornev ◽  
N M Kalinina ◽  
O N Startseva

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.


1996 ◽  
Vol 76 (05) ◽  
pp. 749-754 ◽  
Author(s):  
Suzuki Suzuki ◽  
Morio Arai ◽  
Kagehiro Amano ◽  
Kazuhiko Kagawa ◽  
Katsuyuki Fukutake

SummaryIn order to clarify the potential role of von Willebrand factor (vWf) in attenuating the inactivation of factor VIII (fVIII) by those antibodies with C2 domain specificity, we investigated a panel of 14 human antibodies to fVIII. Immunoblotting analysis localized light chain (C2 domain) epitopes for four cases, heavy chain (A2 domain) epitopes in five cases, while the remaining five cases were both light and heavy chains. The inhibitor titer was considerably higher for Kogenate, a recombinant fVIII concentrate, than for Haemate P, a fVIII/vWf complex concentrate, in all inhibitor plasmas that had C2 domain specificity. In five inhibitor plasmas with A2 domain specificity and in five with both A2 and C2 domain specificities, Kogenate gave titers similar to or lower than those with Haemate P. The inhibitory effect of IgG of each inhibitor plasma was then compared with recombinant fVIII and its complex with vWf. When compared to the other 10 inhibitor IgGs, IgG concentration, which inhibited 50% of fVIII activity (IC50), was remarkably higher for the fVIII/vWf complex than for fVIII in all the inhibitor IgGs that had C2 domain reactivity. Competition of inhibitor IgG and vWf for fVIII binding was observed in an ELISA system. In 10 inhibitors that had C2 domain reactivity, the dose dependent inhibition of fVIII-vWf complex formation was observed, while, in the group of inhibitors with A2 domain specificity, there was no inhibition of the complex formation except one case. We conclude that a subset of fVIII inhibitors, those that bind to C2 domain determinants, are less inhibitory to fVIII when it is complexed with vWf that binds to overlapping region in the C2 domain.


1978 ◽  
Vol 40 (02) ◽  
pp. 245-251 ◽  
Author(s):  
D Meyer ◽  
P A Mc Kee ◽  
L W Hoyer ◽  
T S Zimmerman ◽  
H R Gralnick

1986 ◽  
Vol 55 (01) ◽  
pp. 108-111 ◽  
Author(s):  
M Köhler ◽  
P Hellstern ◽  
C Miyashita ◽  
G von Blohn ◽  
E Wenzel

SummaryThis study was performed to evaluate the influence of different routes of administration on the efficacy of DDAVP treatment. Ten healthy volunteers received DDAVP intranasally (i.n.), subcutaneously (s.c.) and intravenously (i.v.) in a randomized cross-over trial. Factor XII and high molecular weight (HMW)-kininogen levels increased only slightly after DDAVP administration. The mean increase of factor VIII: C was 3.1 (i. v.), 2.3 (s. c.), and 1.3 (i.n.) - fold over baseline. Ristocetin cofactor (von Willebrand factor antigen) increased 3.1 (2.5), 2.0 (2.3) and 1.2 (1.2) - fold over baseline mean values after i.v., s.c. and i.n. DDAVP, respectively. The half-disappearance time of factor VIII and von Willebrand factor (vWF) after DDAVP ranged from five (factor VIII: C) to eight hours (vWF). The mean increase of fibrinolytic activity was more pronounced after i.v. DDAVP. The antidiuretic effect was moderate with no apparent differences between the routes of application. This study provides further evidence that both i.v. and s.c. DDAVP administration result in an appropriate and reliable stimulation of haemostasis. An additional advantage of s. c. administration is its suitability for home treatment.


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