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Do početka 90-ih godina prevladavalo je uvriježeno mišljenje da su bolesnici s uznapredovalom jetrenom bolesti prirodno autoantikoagulirani i time zaštićeni od tromboembolijskih zbivanja. Međutim, novim saznanjima dugogodišnja je paradigma srušena. U bolesnika s cirozom jetre paralelno je reducirana sinteza prokoagulansa i endogenih antikoagulansa, dok je produkcija ekstrahepatalno sintetiziranih faktora, važnih za proces zgrušavanja i fibrinolize, očuvana. U stabilnoj jetrenoj bolesti sustav je „rebalansiran”, ali funkcionira u uskom rasponu homeostaze, što ga čini izuzetno fragilnim te ga i minimalni stres može uvesti u neželjeni ekstrem, trombozu ili krvarenje. Uz navedeno niz je drugih čimbenika koji prate jetrenu bolest, kao što su hemodinamske promjene, oštećenja drugih organa, ponajprije bubrega, te sklonost infekcijama, a koji pomiču ravnotežu prema sklonosti krvarenju ili pojačanom zgrušavanju. Konvencionalni laboratorijski testovi nisu prikladni za procjenu rizika od krvarenja u cirozi, rizični čimbenici za razvoj tromboze nisu nedvojbeno dokazani, a sigurnosni profil antitrombotskih lijekova u cirozi nije precizno utvrđen jer su ti bolesnici uglavnom isključeni iz velikih kliničkih studija. Zbog svega navedenoga dijagnostički i terapijski pristup u ovom je kontekstu kompleksan te nalaže timski rad hematologa, hepatologa i u fazi operativnog liječenja anesteziologa. U ovome preglednom radu osvrnut ćemo se na mehanizme poremećaja hemostaze i fibrinolize u bolesnika s cirozom jetre, incidenciju tromboembolijskih zbivanja, laboratorijsku dijagnostiku te profilaktičke i terapijske opcije u okviru internističke skrbi., Until the beginning of the 90ies, it was believed that patients with liver cirrhosis were auto-anticoagulated and thus protected from thromboembolic events. However, new discoveries have broken the longstanding paradigm. In deranged hepatic function there is a reduced synthesis of procoagulants and endogenous anticoagulants, however, extrahepatally synthesized hemostatic and fibrinolytic factors are disproportionately affected. In stable disease hemostatic system is ”rebalanced’’ but fragile, therefore, even a minimal stress can promote bleeding or thrombosis. Also, there are many concomitant factors, such as hemodynamic changes, other organ affection, namely kidney, and predisposition to infection, that shift the balance towards either bleeding or thrombosis. Conventional laboratory tests are not sufficient for evaluation of the bleeding risk, prothrombotic risk factors are not clearly identified, and safety profile of antithrombotic drugs is not precisely evaluated since cirrhotic patients are mainly excluded from big clinical trials. For all that is said, the diagnostic and therapeutic approach in this context is complex and requires teamwork of a hepatologist, hematologist and in a phase of operative treatment, the anesthesiologist. In this review article, we will discuss mechanisms of hemostatic and fibrinolytic abnormalities of liver cirrhosis, the incidence of thromboembolic events as well as prophylactic and therapeutic options in the setting of conservative treatment.

Thiopurine S-methyltransferase (TPMT) is an enzyme that converts thiopurine drugs into inactive metabolites. Over 20 variant TPMT-encoding alleles, which cause reduced enzymatic activity, have been discovered so far. Our aim was to investigate the frequencies of variant alleles, i.e. genotypes in inflammatory bowel disease (IBD) patients and healthy individuals and to compare these frequencies with selected world populations. The most common variant alleles TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C were analyzed with polymerase chain reactionbased assays and allele-specific polymerase chain reaction-based assays in 685 participants including 459 IBD patients and 226 healthy volunteers. Study results revealed 434/459 (94.55%) IBD patients and 213/226 (94.25%) healthy subjects to be homozygous for the wild-type allele (TPMT*1/*1). TPMT*1/*2 and TPMT *1/*3C genotypes were found in 4/459 (0.87%) and 7/459 (1.53%) IBD patients, respectively; in healthy volunteers they were not found. TPMT*1/*3A genotype was found in 14/459 (3.05%) IBD patients and 13/226 (5.75%) healthy subjects. Variant genotypes were statistically significantly more common in Crohn’s disease subgroup than in ulcerative colitis subgroup. The prevalence of variant genotypes was 23/338 (6.80%) in Crohn’s disease subgroup as compared with 2/121 (1.65%) in ulcerative colitis subgroup (χ2=4.59; p=0.032). In conclusion, the most frequently occurring nonfunctional TPMT allele in Croatian population is TPMT*3A. The overall frequency of mutant alleles in our population is statistically nonsignificantly lower when compared with other populations of Caucasian origin. The Crohn’s disease group had more mutant alleles than the ulcerative colitis group., Tiopurin S-metiltransferaza (TPMT) je enzim koji sudjeluje u konverziji tiopurinskih lijekova u inaktivne metabolite. Dosad je otkriveno više od 20 varijanti TPMT-kodirajućih alela. Ovi aleli uzrokoju smanjenu enzimatsku aktivnost. Naš cilj je bio istražiti frekvenciju varijantnih alela odnosno genotipova u bolesnika oboljelih od upalnih bolesti crijeva i u zdravih osoba te usporediti dobivene frekvencije s frekvencijama odabranih svjetskih populacija. Najčešći varijantni aleli TPMT*2, TPMT*3A, TPMT*3B i TPMT*3C analizirani su metodama lančane reakcije polimeraze, odnosno alelspecifičnim metodama lančane reakcije polimeraze. U istraživanje je bilo uključeno 685 ispitanika; 459 ispitanika bili su bolesnici s upalnom bolesti crijeva, a 226 bili su zdravi dobrovoljci. Rezultati su pokazali da su 434/459 (94,55%) pacijenata s upalnom bolesti crijeva i 213/226 (94,25%) zdravih osoba homozigoti za divlji tip alela (TPMT*1/*1). Genotipovi TPMT*1/*2 i TPMT*1/*3C nađeni su u 4/459 (0,87%) odnosno 7/459 (1,53%) bolesnika; u zdravih dobrovoljaca nisu nađeni. Genotip TPMT*1/*3A nađen je u 14/459 (3,05%) bolesnika i 13/226 (5,75%) zdravih dobrovoljaca. Varijantni genotipovi bili su statistički značajno češći u podskupini bolesnika s Crohnovom bolešću, s učestalošću od 23/338 (6,80%) u odnosu na podskupinu bolesnika s ulceroznim kolitisom, gdje je učestalost varijantnih genotipova bila 2/121 (1,65%) (χ2=4,46; p=0,035). U zaključku, najčešći nefunkcionalni TPMT alel u Hrvatskoj populaciji je TPMT*3A. Ukupna frekvencija varijantnih alela u našoj je populaciji statistički neznačajno niža u odnosu na druge populacije bjelačkog podrijetla. Bolesnici s Crohnovom bolešću imaju više varijantnih alela u odnosu na podskupinu bolesnika s ulceroznim kolitisom.

Do početka 90-ih godina prevladavalo je uvriježeno mišljenje da su bolesnici s uznapredovalom jetrenom bolesti prirodno autoantikoagulirani i time zaštićeni od tromboembolijskih zbivanja. Međutim, novim saznanjima dugogodišnja je paradigma srušena. U bolesnika s cirozom jetre paralelno je reducirana sinteza prokoagulansa i endogenih antikoagulansa, dok je produkcija ekstrahepatalno sintetiziranih faktora, važnih za proces zgrušavanja i fi brinolize, očuvana. U stabilnoj jetrenoj bolesti sustav je „rebalansiran”, ali funkcionira u uskom rasponu homeostaze, što ga čini izuzetno fragilnim te ga i minimalni stres može uvesti u neželjeni ekstrem, trombozu ili krvarenje. Uz navedeno niz je drugih čimbenika koji prate jetrenu bolest, kao što su hemodinamske promjene, oštećenja drugih organa, ponajprije bubrega, te sklonost infekcijama, a koji pomiču ravnotežu prema sklonosti krvarenju ili pojačanom zgrušavanju. Konvencionalni laboratorijski testovi nisu prikladni za procjenu rizika od krvarenja u cirozi, rizični čimbenici za razvoj tromboze nisu nedvojbeno dokazani, a sigurnosni profi l antitrombotskih lijekova u cirozi nije precizno utvrđen jer su ti bolesnici uglavnom isključeni iz velikih kliničkih studija. Zbog svega navedenoga dijagnostički i terapijski pristup u ovom je kontekstu kompleksan te nalaže timski rad hematologa, hepatologa i u fazi operativnog liječenja anesteziologa. U ovome preglednom radu osvrnut ćemo se na mehanizme poremećaja hemostaze i fi brinolize u bolesnika s cirozom jetre, incidenciju tromboembolijskih zbivanja, laboratorijsku dijagnostiku te profi laktičke i terapijske opcije u okviru internističke skrbi.

Waist circumference is a good predictor of the risk of heart diseases, but data on the relationship between waist circumference and pulmonary diseases are sparse. The aim of this study was to investigate its influence on pulmonary function regarding exercise capacity in moderate and severe chronic obstructive pulmonary disease (COPD), according to Global Initiative for Lung Diseases (GOLD) stages. During 2009, a total of 70 COPD patients aged 33 to 80 years were stratified into GOLD 2 and GOLD 3 stages. Diagnostic separation between COPD severity groups was made upon percentage of predicted forced expiratory volume in 1 second. Anthropometric measures, lung function testing and prognostic scoring systems were assessed. Logistic regression analysis was used to make comparisons while taking into account the possible confounding factors. Waist circumference did not show substantial variations between GOLD 2 and GOLD 3 stages (p0.5). There was a weak positive correlation between waist circumference and percent of predicted 6-minute walking distance (r = 0.237; p = 0.001). Another parameter, suprailiac skinfold, was significantly different between GOLD 2 and GOLD 3 stages (19.41 vs. 15.32 mm; p = 0.047). Although waist circumference is a meaningful marker of abdominal obesity, which influences pulmonary function, we failed to prove its importance in correlation with functional lung capacity in a selected COPD population. However, suprailiac skinfold deserves greater attention and further evaluation.