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ID naloge: 65 Letnik: 1999 Predmet: interna medicina
Zdravljenje akutne venske tromboze z nizkomolekularnim heparinom
Avtor: Martina Terbižan, Gregor Tratar
Mentor: prof. dr. Polona Peternel, dr. med. in znan. svet. dr. Mojca Stegnar, dipl. biol.
Nizkomolekularni heparin je novo zdravilo za zdravljenje venske tromboze (VT), ki je glede na klinicne rezultate vsaj enako ucinkovito in varno kot standardni heparin. Antikoagulacijski ucinek nizkomolekularnega heparina se odraža predvsem z inhibicijo aktivnosti faktorja Xa, vpliv na druge teste hemostaze pa se redko proucuje.
V raziskavo smo vkljucili 59 zaporednih bolnikov z objektivno potrjeno VT spodnjih udov. Bolnike smo nakljucno razdelili v skupino, zdravljeno s standarnim heparinom (28 bolnikov, 15 M, 13 Ž, starih 45-93, `x = 67.6 let), in v skupino, zdravljeno z nizkomolekularnim heparinom-dalteparinom (31 bolnikov; 17 M, 14 Ž, starih 30-90, `x = 68.6 let). Standardni heparin smo predpisovali v 2-3 podkožnih injekcijah dnevno in ga odmerjali glede na vrednosti aktiviranega parcialnega tromboplastinskega casa (APTC). Nizkomolekularni heparin smo predpisovali v odmerku 200 IE/kg telesne teže v 1 podkožni injekciji dnevno. Od drugega dne zdravljenja z nizkomolekularnim in standardnim heparinom so bolniki dobivali tudi varfarin. Pred zacetkom zdravljenja in vsak dan med njim smo odvzeli vensko kri za dolocitev APTC in aktivnosti anti Xa. Pred zacetkom zdravljenja in vsak drugi dan zdravljenja smo merili še komplekse trombin-antitrombin, fibrinopeptide 1+2, D-dimere in trombotest.
Pri obeh skupinah bolnikov smo izmerili pomemben porast anti Xa aktivnosti že prvi dan in nato vse dni zdravljenja (vsi p<0.001). Pri bolnikih, zdravljenih z nizkomolekularnim heparinom, je bil porast vecji kot pri bolnikih, zdravljenih s standardnim heparinom (p<0.001). Podaljšanje APTC smo izmerili pri obeh skupinah vse dni zdravljenja (vsi p<0.001). V skupini, zdravljeni s standardnim heparinom, je bilo podaljšanje APTC vecje kot pri bolnikih, zdravljenih z nizkomolekularnim heparinom (p<0.001). Pri bolnikih iz obeh skupin smo izmerili povecano koncentracijo D-dimerov, fibrinopeptidov 1+2 ter kompleksov trombin-antitrombin pred zacetkom zdravljenja, med zdravljenjem so vrednosti upadale. Razlik med skupinama ni bilo.
Rezultati naše raziskave kažejo, da nizkomolekularni heparin ne inhibira samo faktorja Xa, temvec vpliva tudi na APTC.
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[Abstract / English version]
Treatment of acute vein thrombosis with low molecular weight heparin
Author: Martina Terbižan, Gregor Tratar
Mentor: prof. dr. Polona Peternel, dr. med. in znan. svet. dr. Mojca Stegnar, dipl. biol.
Low molecular weight heparin is a new drug for treatment of deep vein thrombosis. According to clinical results it is at least as effective and safe as the conventional heparin. The main anticoagulant effect of low molecular weight heparin is inhibition of factor Xa. Effects on other tests of haemostasis are rarely studied.
Fifty-nine consecutive patients with objectively confirmed deep vein thrombosis of the leg were randomized into group treated with conventional heparin (28 patients, 15 M, 13 F, age 45-93, mean= 67.6 years) and group treated with low molecular weight heparin- dalteparin (31 patients, 17 M, 14 F, age 30-90, mean= 68.6 years). Conventional heparin was given in 2-3 subcutaneus injections daily and its dose adjusted according to activated partial thromboplastin time (APTT). Low molecular weight heparin was administred in a fixed dose of 200 IU/kg body weight in one subcutaneus injection. On the second day of treatment the therapy with warfarin was introduced. Before treatment and every day of treatment blood for measuring APTT and anti Xa activity was collected. Before treatment and every second day blood for measuring thrombin-antithrombin complexes, fibrinopeptides 1+2, D-dimers and thrombotest was also collected.
In both groups there was an increase of anti Xa activity during the first day of treatment The increase persisted till the end of the treatment (all p<0.001). In patients treated with low molecular heparin, the activity of anti Xa was greater than in patients treated with conventional heparin (p<0.001). In both groups prolongation of APTT (all p<0.001) was determined. In the group of patients treated with conventional heparin, the prolongation of APTT was greater than in patients treated with low molecular weight heparin (p<0.001). Increased concentration of D-dimers, fibrinopeptides 1+2 and thrombin-antithrombin complexes were measured in both groups of patients before the treatment. During treatment concentration of all markers decreased similary in both groups. There were no differences between the two groups.
Our results show, that low molecular weight heparin not only inhibits factor Xa, but influences also APTT.
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