| Abstract | Cilj rada: Odrediti klinički značaj mutacija u genima za FV, FII, MTHFR, PAI-1 i ACE za
odabir terapije trombotskih incidenata, te odgovoriti na pitanje utječu li različite kombinacije
ovih mutacija i sâm rizik tromboze koji one nose na odluku o antikoagulantnoj terapiji.
Pacijenti i metode: U laboratoriju za kliničku genetiku Zavoda za patologiju, citologiju i
sudsku medicinu KBC-a Split prikupljeni su nalazi panela pet gena za pacijente starije od 18
godina (n=178), hospitalizirane zbog trombotskog incidenta, u razdoblju 2008.-2012. godine
(isključene su samo pacijentice s ginekološkom dijagnozom). Uvidom u otpusna pisma
pacijenata dobivene su precizne dijagnoze i način provedbe terapije. Na temelju statusa pet
gena ili najmanje prvih triju gena, koristeći literaturu razvrstali smo 177 pacijenata prema
genskom riziku za trombozu, (od nikakvog do vrlo visokog rizika).
Rezultati: Najučestalija dijagnoza bila je duboka venska tromboza (43,26%) i plućna
embolija (24,86%), dok je najučestaliji genski rizik tromboze bio niski rizik (44,07%).
Distribucija postavljenih dijagnoza bila je značajno različita s obzirom na modalitet terapije.
Najzastupljenija dijagnoza bila je venska tromboza (43,26%, 77/178), a najzastupljenija
terapija LMWH i varfarin (38,2%, 68/178). Nismo pronašli značajnu razliku u distribuciji
postavljenih dijagnoza u odnosu na distribuciju statusa svakog pojedinačnog od pet
istraživanih gena. Distribucija postavljenih dijagnoza bila je statistički značajno različita s
obzirom na kombinirani genski rizik tromboze (n=177, p<0,0001). Distribucija odabranih
terapijskih modaliteta bila je statistički značajno različita s obzirom na prisutni genski rizik u
cjelokupnoj našoj populaciji (n=177) i u podskupini pacijenata s nikakvim do niskim genskim
rizikom (n=136), p<0,0001. Najučestalija terapija u obje skupine bila je LMWH i varfarin
(37,85%, 67/177 i 33,09%, 45/136). Pronašli smo statistički značajnu razliku u izboru terapije
u odnosu na genski rizik za skupinu pacijenata s dijagnozom plućne embolije (n=44) i za
skupinu sa dijagnozom CVI (n=35). U prvoj skupini (n=44), najučestalija terapija je UFH i
varfarin (13/44), a sljedeća LMWH i varfarin (12/44). U skupini s dijagnozom CVI (n=35),
najučestalija terapija je acetilsalicilna kiselina (25/35). Najučestali genski rizik tromboze za
obje skupine je niski (18/44 i 19/35).
Zaključak: Genski status vjerojatno je bitan za odabir terapije malog broja pacijenata s
kompleksnim uplitanjem više različitih rizičnih čimbenika za trombozu, te za odluku o
trajanju terapije, prvenstveno u pacijenata s recidivnim trombozama. |
| Abstract (english) | Objectives: To determine the clinical significance of specific mutations in FV, FII, MTHFR,
PAI-1 and ACE genes in terms of therapeutical choices for thrombotic incidents. We
intended to find out if different combinations of these mutations will affect the decision on
thrombosis therapy.
Patients and methods: Thrombophilia panel test results were collected in the Laboratory for
Molecular Genetics in Split, for patients hospitalized due to thrombotic events, in the period
between 2008 and 2012. Patients younger than 18 years of age and women with
gynaecological diagnoses were excluded. By revisioning medical records, we retrieved
precise diagnoses and therapies for a total of 178 patients. Based on a gene status of all five or
at least three genes (FV, FII, MTHFR), we assigned a value of combined genetic risk for each
of the 177 patients.
Results: The most frequent diagnoses were deep vein thrombosis (43,26%) and pulmonary
embolism (24,86%), while the most frequent genetic risk of thrombosis was low risk
(44,07%). Distribution of diagnoses was significantly different conserning therapy modes.
The most frequent diagnosis was venous thrombosis (43,26%, 77/178), and the most
frequently used therapy was LMWH and warfarin (38,2%, 68/178). We found no statistically
significant difference in diagnoses distribution considering gene status of every of the five
genes. There was a statistically significant difference in diagnoses distribution conserning
genetic risk of thrombosis (n=177, p<0,0001). The distribution of therapy modes was
significantly different conserning genetic risk in the overall population (n=177) and also in
the subgroup of patients with none to low genetic risk (n=136), p<0,0001. The most
frequently used therapy in both groups was LMWH and warfarin (37,85%, 67/177 and
33,09%, 45/136). We found a statistically significant difference in a therapy choice
considering genetic risk for the subgroups of patients with pulmonary embolism (n=44) and
stroke (n=35). In the first subgroup, the most frequently used therapy was UFH and warfarin
(13/44), and LMWH and warfarin followed (12/44). In the stroke subgroup (n=35), acetylsalicylic acid was the mostly used therapy (25/35). The most frequent genetic risk of
thrombosis was low for both subgroups (18/44 and 19/35).
Conclusion: Gene status is probably relevant only in a small number of patients who have
multiple risk factors present, as well as in patients with recidivant thombotic events. |
