Naslov
High levels of FVIII and von Willebrand factor in chronic Graft-versus-Host Disease

Autori
Pulanić, Dražen ; Samardžić, Antonela ; Desnica, Lana ; Zadro, Renata ; Milosević, Milan ; Serventi Seiwerth, Ranka ; Duraković, Nadira ; Perić, Zinaida ; Coen Herak, Desiree ; Miloš, Marija ; Kraljevic, Lucija ; Mravak Stipetić, Marinka ; Bilić, Ervina ; Čeović, Romana ; Klepac Pulanic, Tajana ; Petricek, Igor ; Saban, Nina ; Zelić Kerep, Ana ; Ljubas Kelecic, Dina ; Vukić, Tamara ; Mazic, Sanja ; Bojanić, Ines ; Bilić, Ernest ; Batinić, Drago ; Vrhovac, Radovan ; Pavletić, Steven Živko

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
45th Annual Meeting of the European Society U: Bone Marrow Transplantation 54, 144–619 (2019). / - , 2019, B087-B087

Skup
45th Annual Meeting of the European Society for Blood and Marrow Transplantation

Mjesto i datum
Frankfurt na Majni, Njemačka, 24.03.2019. - 27.03.2019

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
factor VIII ; von Willebrand factor ; biomarkers ; chronic Graft-versus-Host Disease

Sažetak
Background: Chronic Graft-versus-Host Disease (cGvHD) is a serious late complication after allogeneic hematopoietic stem cell transplantation (alloHSCT) with heterogeneous presentation and still poorly understood pathophysiology including inflammation and endothelial dysfunction. Factor VIII (FVIII) and von Willebrand Factor (VWF) are coagulation factors but also known indicators of endothelial dysfunction and inflammation in different settings, and therefore could serve as interesting candidate biomarkers of cGvHD. Methods: Since 2013 patients after alloHSCT were assessed by the Multidisciplinary cGvHD team at the University Hospital Center Zagreb, Croatia, using established NIH cGvHD-related measurements. An extensive history, physical and laboratory evaluations were performed, including FVIII, VWF:Ag and VWF:Ac analysis. Descriptive statistic and non-parametric analyses were performed. Variables that showed significant univariate correlations were used in multivariate logistic regression (MLR) to identify the most predictive for FVIII, VWF:Ag and VWF:Ac in cGvHD patients. Results: 70 cGvHD patients and 41 controls (subjects after alloHSCT without cGvHD) were analysed. Median age of cGvHD patients was 42 (9-65) years, 50% females, 91.5% underwent alloHSCT for hematologic malignancies, 55.7% had myeloablative conditioning and 52.9% matched related donor. Median time from HSCT to study was 450.5 days and from cGvHD diagnosis to study 82 days. There were no demographic neither transplant related significant differences between cGvHD patients and controls beside stem cell source (peripheral blood 71.4% vs 51.2%, p=0.041) and history of acute GvHD (70.0% vs 22.0%, p< 0.001). Majority of patients had moderate (52.9%) or severe (42.6%) NIH global cGvHD score, 57.2% active cGvHD by clinician´s impression. Median number of organs involved by cGvHD was 3 (1-6), and the most frequently involved organs were mouth, skin and eyes (52.0% each). cGvHD patients compared to controls had higher FVIII levels (median 206 (52-453)% vs 182 (51-406)%, p=0.044, reference range 50-149%) and higher VWF:Ag (median 261.6 (76.6-601)% vs 203.2 (51.9-600)%, p=0.030, reference range 50-160%), while VWF:Ac showed a trend toward higher levels among patients (median 253.4 (54-601)% vs 178 (48.6-601)%, p=0.084, reference range 50-150%). Patients had higher GGT (p=0.002), lower anticardiolipin IgG (p=0.001) and IgM (p=0.003), and lower albumin (p=0.018) than controls, without differences between other laboratory parameters. Univariate analysis showed that among cGvHD patients higher FVIII was associated with worse Karnofsky score (KS) (p=0.031) and performance score (PS) (p=0.030), higher leukocytes (p=0.031), cholesterol (p=0.003), triglycerides, AST, ALT, GGT, LDH, and lower albumin. Higher VWF:Ag and VWF:Ac in cGvHD patients were associated with worse KS and PS (p< 0.001), with more active cGvHD (p< 0.001), worse NIH cGvHD liver (p=0.042 ; p=0.039) and NIH cGvHD mouth (p=0.012 ; p=0.009), higher total NIH score (p=0.044 ; p=0.005), higher number organs involved (p=0.013 ; p=0.003), higher ESR, monocytes, D-dimers, AST, ALT, GGT, LDH, triglycerides, β-2-microglobulin, ferritin, total proteins, IgA and lower albumin. MLR analysis showed leukocytes (p=0.018) and cholesterol (p=0.010) as the strongest predictor of FVIII (r2=49.8% ; p< 0.001), while strongest predictor of VWF:Ac was number of organs involved by cGvHD (r2=71.7% ; p=0.031). Conclusions: Results of this study detected high FVIII and VWF levels in cGvHD patients with possible reflections to cGvHD manifestations, what needs to be further confirmed in larger longitudinal studies. Disclosure: This work was supported, in part, by the Unity Through Knowledge Fund project entitled “Clinical and biological factors determining severity and activity of chronic Graft-versus-Host disease after allogeneic hematopoietic stem cell transplantation”, and also, in part, by the Croatian Science Foundation project entitled “New biomarkers for chronic Graft-versus-Host disease”. Antonela Samardzic - Work financed by the Croatian Science Fondations` “Young researchers` career development project - training of doctoral students”

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti, Dentalna medicina

Napomena
Kongresno priopćenje u CC časopisu - u procesu objavljivanja

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