The correlation between overall haemostatic potential and thrombin activatable fibrinolysis inhibitor dependent fibrinolysis with bleeding severity and treatment response in haemophilia A

Uvod. Hemofilija A je uroñena koagulopatija koja se karateriše smanjenim stvaranjem trombina, poremećajem stvaranja i stabilnosti koaguluma i ubrzanom fibrinolizom. Opisana je varijabilnost u težini kliničke slike i odgovora na terapiju kod bolesnika sa hemofilijom A koji imaju isti nivo FVIII. Mehanizam koji je u osnovi ove varijabilnosti nije razjašnjen, ali se smatra da mogu uticati brojni faktori kompleksnog sistema hemostaze. Odreñivanje aktivnosti FVIII jednostepenim koagulacijskim testom ili hromogenom testom se standardno koristi za dijagnozu i klasifikaciju hemofilije A kao i za praćenje terapije koncentratom FVIII. Meñutim, ovi testovi nisu uvek i u potpunosti pozdani za procenu težine krvarenja i odgovora na terapiju. Zato se ispituje uloga testova globalne hemostaze za ovu namenu u cilju dobijanja dodatnih, klinički korisnih podataka. Trombinom aktivirani inhibitor fibrinolize (TAFI) je molekul koji direktno povezuje procese koagulacije i fibrinolize. Poznato je da ubrzana fibrinoliza doprinosti povećanoj tendenciji krvarenja kod hemofilije A što može biti posledica poremećaja aktivacije TAFI usled smanjenog stvaranja trombina. Cilj. Cilj studije je bio ispitivanje: a) značaja ukupnog hemostatskog potencijala (UHP) u proceni težine krvarenja i odgovora na terapiju kod bolesnika sa hemofilijom A, b) uticaja faktora trombofilije na ukupni hemostatski potencijal i kliničku težinu hemofilije A i c) nivoa i aktivnosti TAFI kod bolesnika sa hemofilijom A i d) uticaj fibrinolize zavisne od TAFI na težinu krvarenja i odgovor na terapiju. Materijal i metode. Ova studija je obuhvatila 76 bolesnika sa hemofilijom A i 30 zdravih muškaraca koji su činili kontrolnu grupu. U odnosu na stepen deficita FVIII:C bolesnici su podeljeni u grupe sa teškim (5-<40 IJ/dl) oblikom hemofilije A. Na osnovu učestalosti spontanih krvarenja u zglobove bolesnici su podeljeni na grupu sa klinički teškim (>3 hemartroze godišnje) i klinički blagim (≤3 hemartroze godišnje) oblikom bolesti...Introduciton. Haemophilia A is inherited coagulopathy characterized by impaired thrombin generation, disturbed clot formation and stability, and by increased fibrinolysis. It is observed that patients with similar FVIII levels show different bleeding severity response to treatmnt. The mechanism behind this variability is not completely clear, but it seems that other factors of the complex haemostatic system may have influence. Determination of factor FVIII activity by one-stage coagulation or chromogenic assay is usually used for diagnosis and classification of haemophilia A as well as for monitoring of treatment with FVIII concentrate. However, those assays do not always and fully accurately reflect bleeding severity and responses to treatments. For that reason the role of global haemostasis assays is investigated in order to obtain additional, clinically useful information.Thrombin activatable fibrinolysis inhibitor (TAFI) represents direct molecular connection between blood coagulation and fibrinolysis. It has been recognized that increased fibrinolysis influences the severity of bleeding in haemophilia A and altered TAFI activation due to decreased thrombin generation might also contribute. Aim. The aim of the study was to investigate: a) the importance of overall haemostatic potential (OHP) in evaluation of bleeding severity and response to treatment in patients with haemophilia A, b) the influence of thrombophlia on overall haemostatic potential and clinical severity in haemophlia A, c) TAFI level and activity in haemophilia A and d) the influence of TAFI dependent fibrinolysis on bleeding severity and treatment response. Matherial and methods. Seventy-six patients with haemophilia A and 30 healthy males representing a control group were included in the study. Depending on FVIII:C levels haemophilia A patients were grouped as severe (< 1 IJ/dl), moderate (1-5 IJ/dl) or mild (>1-<40 IJ/dl). According to the number of spontaneous haemarthrosis patients were grouped as clinically severe (>3 haemarthrosis the per year) or clinically mild (≤3 hemartroze godišnje)..