Title
The association of global hemostasis and endothelial injury markers with the risk of new digital ulcer onset in systemic sclerosis: prospective cohort study
Creator
Čolić, Jelena
CONOR:
87428361
Copyright date
2022
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Language
Serbian
Cobiss-ID
Theses Type
Doktorska disertacija
description
Datum odbrane: 10.02.2023.
Other responsibilities
Academic Expertise
Medicinske nauke
University
Univerzitet u Beogradu
Faculty
Medicinski fakultet
Alternative title
Ispitivanje povezanosti pokazatelja globalne hemostaze i oštećenja endotela sa rizikom za nastanak novih digitalnih ranica u sistemskoj sklerozi: prospektivna kohortna studija
Publisher
[J. Čolić]
Format
54 str.
description
Medicine - Epidemiology / Medicina - Epidemiologija
Abstract (en)
Background: Digital vasculopathy (DV) is common in patients with systemic sclerosis (SSc) and might
be connected with the coagulation/fibrinolysis imbalance.
Aims: To evaluate endothelial dysfunction (ED) and hemostasis status in patients with SSc with a focus
on the onset of digital ulcers (DUs) over the course of the disease, in relation to the quality of life in these
patients.
Methods: Haemostatic parameters were determined in 58 SSc patients and 46 matched healthy controls
(HCs) by Thrombin generation (TG), Overall haemostatic potential and Turbidity assays. ED markers
were assessed by ELISA. Clot structure was visualized by Scanning electron microscopy (SEM). Quality
of life was assessed by SHAQ and EQ5D. A cohort with a history of DUs (hDUs) was followed (1.5
years) in order to assess predictive markers for new DU.
Results: Increased TG, denser fibrin clot (Cmax) and longer clot lysis time (CLT) were found in SSc
patients (p<0.05, respectively) compared to HC. Active disease was predicted by Cmax (AUC= 0.688,
p<0.05). ICAM1 was associated with CLT within SSc cohort, hDU cases and patients with novel DUs
(p<0.05, respectively).CLT itself determined hDUs cases (AUC 0.706, p<0.05). Cases with novel DU
exhibited longer CLT (p<0.001), especially patients with recurrent ulcers (p<0.05). The VAS Raynaud
phenomenon and CLT were independent predictors of new DUs (OR 1.1, 95% CI 1.0–1.1; OR 1.2,
95% CI 1.1–1.3, respectively). SEM revealed denser clots in cases with new DUs.
Conclusion: Enhanced coagulation and impaired fibrinolysis may have a critical role in SSc
pathogenesis. ICAM1 might contribute to impaired fibrinolysis, which could be considered as a key event
in DV genesis and progression in patients with SSc.
Abstract (sr)
Uvod: Oštećenja na nivou krvnih sudova prstiju (digitalna vaskulopatija, DV) javljaju se kod skoro svih
pacijenata sa sistemskom sklerozom (SSc) i mogu biti povezana sa poremećajem koagulacije/fibrinolize.
Ciljevi: Ispitati oštećenje endotela (OE) i hemostaze kod pacijenata sa SSc sa posebnim fokusom na
pojavu ranica na prstima (DUs) tokom bolesti u odnosu na kvalitet života.
Metod: Parametri hemostaze su odredjivani kod 58 SSc pacijenata i 46 kontrola (K) uparenih po
godinama starosti i polu, uz pomoć Trombin generacije (TG); Sveukupnog hemostatskog potencijal i
Turbidimetrijskog eseja. Markeri OE su analizirani ELISA-om. Struktura fibrinskog ugruška je
vizualizavana skenirajućim elektronskim mikroskopom (SEM). Kvalitet života je procenjivan SHAQ i
EQ5D upitnicima. Pacijenata koji su ikada u toku bolesti imali DUs (iDUs) praćeni su (1.5 godinu) kako
bi se procenili prediktivni markeri za nastanak nove ranice.
Rezultati: Povišena TG, gušći fibrinski ugrušak (Cmax) i duže vreme lize ugruška (CLT) su imali SSc
pacijenti (p<0.05, redom) u poredjenju sa K. Cmax je pokazao sposobnost da detektuje aktivnu bolest
(AUC= 0.688, p<0.05). ICAM1 je bio povezan sa CLT na nivou cele SSc kohorte, grupe sa iDUs i medju
pacijentima sa novom DU (p<0.05, redom). Pacijenti sa novom DU karakterisali su se produženim CLT-
om (p<0.001), posebno oni sa rekurentnim ranicama (p<0.05). Nezavisnim prediktorima za nove ranice
izdvojili su se težina Rejnovog fenomena i CLT (OR 1.1, 95% CI 1.0–1.1 and OR 1.2, 95% CI 1.1–1.3,
redom). SEM je potvrdio postojanje gusto pakovanog ugruška kod onih sa novom DU.
Zaključak: Hiperkoagulacija i oštećena fibrinoliza bi mogli imati kritičnu ulogu u patogenezi SSc.
ICAM1 može doprineti oštećenoj fibrinolizi, koja bi se mogla smatrati ključnom za nastanak DV i njenu
progresiju u SSc.
Authors Key words
systemic sclerosis, endothelial dysfunction, biomarkers, thrombin generation, clot lysis time,
clot density, fibrin clot structure, digital ulcers, quality of life
Authors Key words
sistemska skleroza, oštećenje endotelne funkcije, biomarkeri, stvaranje trombina, struktura
fibrinskog ugruška, vreme razgradnje ugruška, gustina ugruška, ranice na prstima, kvalitet života
Classification
616-002.77-036.22:612.115(043.3)
Type
Tekst
Abstract (en)
Background: Digital vasculopathy (DV) is common in patients with systemic sclerosis (SSc) and might
be connected with the coagulation/fibrinolysis imbalance.
Aims: To evaluate endothelial dysfunction (ED) and hemostasis status in patients with SSc with a focus
on the onset of digital ulcers (DUs) over the course of the disease, in relation to the quality of life in these
patients.
Methods: Haemostatic parameters were determined in 58 SSc patients and 46 matched healthy controls
(HCs) by Thrombin generation (TG), Overall haemostatic potential and Turbidity assays. ED markers
were assessed by ELISA. Clot structure was visualized by Scanning electron microscopy (SEM). Quality
of life was assessed by SHAQ and EQ5D. A cohort with a history of DUs (hDUs) was followed (1.5
years) in order to assess predictive markers for new DU.
Results: Increased TG, denser fibrin clot (Cmax) and longer clot lysis time (CLT) were found in SSc
patients (p<0.05, respectively) compared to HC. Active disease was predicted by Cmax (AUC= 0.688,
p<0.05). ICAM1 was associated with CLT within SSc cohort, hDU cases and patients with novel DUs
(p<0.05, respectively).CLT itself determined hDUs cases (AUC 0.706, p<0.05). Cases with novel DU
exhibited longer CLT (p<0.001), especially patients with recurrent ulcers (p<0.05). The VAS Raynaud
phenomenon and CLT were independent predictors of new DUs (OR 1.1, 95% CI 1.0–1.1; OR 1.2,
95% CI 1.1–1.3, respectively). SEM revealed denser clots in cases with new DUs.
Conclusion: Enhanced coagulation and impaired fibrinolysis may have a critical role in SSc
pathogenesis. ICAM1 might contribute to impaired fibrinolysis, which could be considered as a key event
in DV genesis and progression in patients with SSc.
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