The Plasma Levels of ADAMTS-13, von Willebrand Factor, VWFpp, and Fibrin-Related Markers in Patients With Systemic Sclerosis Having Thrombosis

Abstract

This study aimed to examine the hemostatic abnormalities in patients with systemic sclerosis (SSc) and the relationship between these abnormalities and thrombotic events (THEs), focusing on the difference in diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc). The plasma levels of ADAMTS-13 (a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13), von Willebrand factor (VWF), VWF propeptide (VWFpp), d-dimer, and soluble fibrin (SF) were measured in 233 patients with SSc. The relationship between their levels and organ involvement, including THEs and interstitial lung disease (ILD), was evaluated. The plasma levels of VWF and VWFpp were significantly elevated and ADAMTS-13 activity was significantly decreased in patients with SSc compared to healthy participants. The VWFpp in dcSSc was significantly higher than in lcSSc. Twelve patients with SSc were complicated with acute THE, and 25 patients with SSc were complicated with past THE. The plasma levels of d-dimer and SF were significantly elevated in patients with SSc having THE. The plasma levels of VWF and VWFpp were significantly elevated in patients with SSc having ILD. The plasma levels of d-dimer were elevated in patients with SSc having other connective tissue diseases (CTDs). The plasma levels of ADAMTS-13 were significantly decreased and VWF, VWFpp, and SF were increased in patients with a d-dimer level of ≥1 μg/mL. Systemic sclerosis carries a high risk of THE, especially in patients with other CTDs. Plasma hemostasis-related markers are closely related to ILD and THE. These markers are important as markers of organ involvement as well as THE.

Grupos sanguíneos y su relación con los niveles plasmáticos del Factor de von Willebrand

“…El propósito de este artículo es describir las características y mecanismos por los cuales el tipo de grupo sanguíneo podría influir en la concentración plasmática del FvW, así como diversas investigaciones que soportan o evidencian dicha influencia (34,36,48) . Los resultados de las investigaciones presentadas en esta revisión evidencian como factor común que los niveles plasmáticos del FvW están más disminuidos en pacientes con grupo sanguíneo tipo O que en los pacientes tipo No-O (A,B,AB), debido a que la proteólisis del factor por la metaloproteasa es más rápida en los pacientes con grupo O; aunque otros estudios muestran que la velocidad de proteólisis es diferente a la concentración de la metaloproteasa, por cuanto se ha encontrado como algo incongruente concentraciones más altas de la metaloproteasa ADAMTS-13 en pacientes con grupo tipo No-O (48)(49)(50) , en la cual mencionan posiblemente se deba a una forma de regulación debido a que estos pacientes presentan mayores niveles de FvW. Lo anterior muestra la necesidad de hacer más estudios enfocados a respaldar los hallazgos descritos durante la revisión del artículo.…”

“…La proteólisis del FvW por ADAMTS13 parece ser más rápida en los portadores del grupo sanguíneo O que el observado en portadores de sangre no-O. De igual forma la relación del ADAMTS13, reveló que esta enzima era más alta en el grupo de sujetos de grupo sanguíneo no-O, en comparación con los del grupo O; una posible explicación para esto se debe a que el aumento de los niveles plasmáticos de FvW en los individuos de grupo sanguíneo no-O, provoca un mecanismo de compensación que conduciría al aumento en ADAMTS13 (48)(49)(50) , por cuanto su papel es escindir los multímeros de FvW que pasan a la circulación, previniendo un estado de hipercoagulabilidad (48) .…”

Mediators of systemic sclerosis-associated interstitial lung disease (SSc-ILD): systematic review and meta-analyses

“…In blood, 5 out of the 43 markers (11.6%) were reported to be significantly lower in patients with SSc-ILD compared with healthy controls (Von Willebrand factor-cleaving protease (Adams-TS), 26 insulin-like growth factor 1 (IGF-1), 27 cathelicidin antimicrobial peptide (LL-37, CAMP), 28 adhesion molecule L-selectin 13 ). All other mediators (online supplemental file 5) were significantly increased in peripheral blood of patients with SS-c-ILD.…”

Contemporary Concise Review 2018: Interstitial lung disease

“…Vitamin D deficiency has been found to be a risk factor for CTD‐ILD in a retrospective study. Concerning systemic sclerosis, some potential predictors were investigated such as the CX3CL1 that is linked to progression when PH is absent or plasma levels of ADAMTS‐13, von Willebrand factor and Von Willebrand propeptide (VWFpp) in systemic sclerosis with thrombosis . Similar to IPF, rheumatoid arthritis associated with ILD (RA‐ILD) can be associated with MUC5B, a minor allele, with an odds ratio of 3.8 and is linked explicitly to UIP pattern on HRCT.…”