Hemofilna artropatija,, sa karakterističnim oštećenjima zglobova, vodeći je uzrok
morbiditeta kod bolesnika sa teškom hemofilijom. Kontinuirana profilaksa intravenskom
primenom primenom faktora (F) VIII i IX je glavna klinička strategija u lečenju ovih
bolesnika. Nedavno je pokazano da se biomarkeri razgradnje zglobne hrskavice mogu
detektovati u serumu iili urinu i odražavaju stepen ukupnog oštećenja zglobova kod
bolesnika sa hemofilijom.
Ciljevi ove studije bili su: a) uporediti validnost dva laboratorijska testa –
rotaciona tromboelastometrija (ROTEM) i potencijal endogenog trombina (ETP) u
praćenju efikasnosti dva različita profilaktička režima lečenja bolesnika sa teškom
hemofilijom; b) odrediti korelaciju između koncentracije biomarkera degradacije zglobne
hrskavice u serumu i urinu i radiološkog skora za hemofilnu artropatiju; c) proceniti da li
određivannje koncentracije ovih biomarkera može biti korisna u praćenju efikasnosti
različitih režima profilakse teške hemofilije.
Ova studija obuhvatila je 20 odraslih bolesnika sa teškom hemofilijom. Pet
bolesnika sa hemofilijom A primalo je profilaksu koncentratom FVIII u standardnoj dozi
od 20 i.j./kg tri puta nedeljno, pet bolesnika sa hemofilijom A primalo je kao profilaksu
intermedijarne doze koncentrata FVIII, 10-15 i.j./kg tri puta nedeljno. Sedam bolesnika
sa hemofilijom A i tri bolesnika sa hemofilijom B primalo je koncentrat FVIII/IX samo
po potrebi (“on demand).
Kod bolesnika na profilaktičkoj terapiji, ROTEM i ETP određivani su inicijalno
pre početka profilakse, zatim, 20 minuta nakon primene prve doze profilakse i posle tri
meseca, pre primene sledeće profilaktičke doze. Kod bolesnika na “on demand” terapiji,
ROTEM i ETP rađeni su dva puta u intervalu od tri meseca. U ROTEM testu određivano
je vreme koagulacije (CT) unutrašnjeg puta (INTEM), dok je kod ETP određivana
kalkulisana vrednost površine ispod krive generacije trombina (ETP.AUC.cal) i
kalkulisane vrednosti maksimalne koagulacije (ETP.Cmax.cal)...Haemophilic arthropathy, with characteristic joint damage, is the main cause of
morbidity in individuals with severe haemophilia. The most important clinical strategy
for management of these patients is treatment by continous prophylaxis with
intravenously applied factor (F) VIII/IX. Recently, it was shown that serum and/or urine
biomarkers of cartilage turnover in joints reflected the degree of total joint degradation in
haemophilia patients.
The aims of this study were: a) to compare validity of two laboratory assays –
rotating thromboelastometry (ROTEM) and endogenous thrombin potential (ETP) in
monitoring and evaluating different prophylactic treatment regimens in patients with
severe haemophilia; b) to detect correlations between serum and urine concentrations of
biomarkers of joint cartilage degradation and the radiological score for haemophilic
arthropathy and c) to estimate whether measurement of these biomarkers could be useful
in monitoring the efficacy of different prophylaxis regimens for severe haemophilia.
This study included 20 adults patients with severe haemophilia, without inhibitor.
Five patients with haemophilia A were received prophylaxis with factor VIII (FVIII)
concentrate in standard dose 20 IU/kg three times per week, five patients with
haemophilia A were received intermediate dose of FVIII concentrate as prophylaxis, 10-
15 IU/kg three times per week. Seven patients with haemophilia A and 3 with
haemophilia B, were received FVIII/IX concentrate only on-demand.
In patients on prophylactic therapy, ROTEM and ETP were done initially before
start of prophylaxis, in addition, 20 minutes after application of first prophylactic dose
and afterwards 3 months, before receiving next prophylactic dose. In patients treated only
on-demand, ROTEM and ETP were done twice per three-months period. In ROTEM,
clotting time (CT) in intrinsic system (INTEM) was measured, whereas in ETP,calculated values of area under the thrombin generation curve (ETP.AUC2.cal) and
calculated values of maximal clotting (ETP.Cmax.cal) were estimated..
