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Kazalci aktivirane koagulacije pri bolnikih z vensko trombozo in mutacijo v genu za protrombin in faktor V
Avtor: Katarina Plausteiner
Mentor: znan. svet. dr. Mojca stegnar
Somentor: doc. dr. Borut Peterlin
Mutacija v genu za protrombin (G20120A) in mutacija v genu za faktor V (G1691A), ki se odraža kot neodzivnost na aktivirani protein C (nAPC), sta pomembna dejavnika tveganja za tromboembolijsko bolezen, ker sta domnevno povezani z aktivirano koagulacijo. Prevalenci obeh mutacij kažeta geografsko znacilno razporeditev, prevalenca mutacije za protrombin pa med bolniki z vensko trombozo v Sloveniji še ni bila znana.
Namen naloge je bil dolociti prevalenco mutacije v genu za protrombin pri bolnikih z vensko trombozo ter preuciti možno povezavo med to mutacijo ter mutacijo v genu za faktor V s povišanimi koncentracijami kazalcev aktivirane koagulacije: peptidom, ki nastane ob aktivaciji protrombina v trombin (F1+2), kompleksom med trombinom in antitrombinom (TAT) ter razgradnimi produkti premreženega fibrina (D-dimeri). Preveriti smo želeli hipotezo, da je prevalenca mutacije v protrombinu podobna prevalenci pri populacijah sosednjih držav ter da sta mutaciji v protrombinu in faktorju V povezani z povišanimi koncentracijami kazalcev aktivirane koagulacije pri bolnikih z vensko trombozo.
V retrospektivno raziskavo smo vkljucili 88 bolnikov, ki so preboleli vensko trombozo. Iz vzorcev krvi smo izolirali DNK in analizirali gen za protrombin. Mutacijo za faktor V smo dolocili z nAPC. Bolnikom smo izmerili koncentracije kazalcev aktivirane koagulacije (F1+2, TAT in D-dimere) z encimsko imunskimi preiskavami.
Iz dobljenih rezultatov smo ugotovili, da je bila prevalenca mutacije za protrombin 6,8%, nAPC 23,3% in obeh hkrati 3,5%, kar je v skladu s prevalenco obeh mutacij pri bolnikih z vensko trombozo pri populacijah sosednjih držav. Razlike med koncentracijami kazalcev aktivirane koagulacije med bolniki z razlicnimi genotipi niso bile statisticno znacilne. Pri skupini bolnikov z mutacijo v genu za protrombin ali brez nje smo dolocili F1+2: 1,5 proti 1,0 nmol/L (p=0,21), TAT: 6,3 proti 2,2 mg/L (p=0,16) in D-dimeri: 45 proti 37 mg/L (p=0,88), med skupinama z nAPC in brez nje F1+2: 1,2 proti 1,0 nmol/L (p=0,95), TAT: 2,2 proti 2,2 mg/L (p=0,86), D-dimeri: 26 proti 82 mg/L (p=0,08) ter med skupinami z obema mutacijama ali brez mutacij F1+2: 1,4 proti 1,0 nmol/L (p=0,66), TAT: 2,4 proti 2,2 mg/L (p=0,83), D-dimeri: 21 proti 39 mg/L (p=0,28, vse vrednosti so mediane).
Zakljucili smo, da je prevalenca mutacije za protrombin med bolniki z vensko trombozo v Sloveniji 6,8%, nAPC 23,3% in obeh hkrati 3,5%. Niti posamezni mutaciji niti kombinacija obeh mutacij nista bili povezani s povišanimi koncentracijami kazalcev aktivirane koagulacije v krvi.
[Abstract / English version]
Markers of activated coagulation in patients with deep vein thrombosis and mutations in genes for protrombin and factor V
Author: Katarina Plausteiner
Mentor: znan. svet. dr. Mojca stegnar
Co-mentor: doc. dr. Borut Peterlin
Mutation in prothrombin gene (G20120A) and mutation in factor V gene (G1691A), which is reflected as the resistance to activated protein C (nAPC), are important risk factors for thromboembolic disease, because they are presumably connected with activated coagulation. The prevalence of both mutations shows significant geographical distribution. The prevalence of prothrombin mutation is not yet known among patients with deep vein thrombosis in Slovenia.
The aim of the assignment was to determine the prevalence of prothrombin gene mutation in patients with deep vein thrombosis and to study the possible connection between this mutation, mutation in factor V and higher concentrations of markers of activated coagulation: peptid, which is released from prothrombin during its activation to thrombin (F1+2), complex between thrombin and antithrombin (TAT) and degradation products of cross-linked fibrin (D-dimers). We wished to check the hypothesis that the prevalence of prothrombin mutation is similar to that of the neighbouring populations and that prothrombin mutation and mutation in factor V are connected to higher concentrations of markers of activated coagulation in patients with deep vein thrombosis.
88 patients with deep vein thrombosis were included in the retrospective study. DNA was isolated and DNA analysis was performed. Mutation in factor V gene was determined as nAPC. Concentrations of markers of activated coagulation were measured with enzyme immuno assays.
From gathered data we concluded that the prevalence of prothrombin gene mutation is 6.8%, of nAPC 23.3% and of both 3.5%, which is in concordance with the prevalences of both mutations in patients with deep vein thrombosis in the neighbouring populations. Differences in concentrations of F1+2, TAT and D-dimers among patients with different genotypes were not statistically significant. In patients with or without the prothrombin mutation we measured F1+2: 1.5 vs 1.0 nmol/L (p=0.21), TAT: 6.3 vs 2.2 mg/L (p=0.16) and D-dimers: 45 vs 37 mg/L (p=0.88), in patients with and without nAPC F1+2: 1.2 vs 1.0 nmol/L (p=0.95), TAT: 2.2 vs 2.2 mg/L (p=0.86), D-dimers: 26 vs 82 mg/L (p=0.08) and in patients with both or without any mutation F1+2: 1.4 vs 1.0 nmol/L (p=0.66), TAT: 2.4 vs 2.2 mg/L (p=0.83), D-dimers: 21 vs 39 mg/L (p=0.28, all values are medians).
We concluded that the prevalence of prothrombin mutation among patients with deep vein thrombosis in Slovenia is 6.8%, of nAPC 23.3% and of both 3.5%. Neither of the two mutations nor the combination of both influenced the concentrations of markers of activated coagulation.