Koncentracija inhibitora faktora tkivnog puta u bolesnika s dubokom venskom trombozom liječenih nefrakcioniranim i niskomolekularnim heparinom

Gaćina, Petar (2009) Koncentracija inhibitora faktora tkivnog puta u bolesnika s dubokom venskom trombozom liječenih nefrakcioniranim i niskomolekularnim heparinom. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Although there are numerous causes of deep vein thrombosis (DVT), the exact cause of DVT may frequently be difficult to identify with certainty in daily routine. A decreased concentration of tissue factor pathway inhibitor (TFPI) as the only known inhibitor of the extrinsic pathway of coagulation has been implicated as a potential risk factor for DVT. The administration of heparin results in its increased plasma concentration. The mechanism of heparin antithrombotic action and differences in the action of unfractionated and low-molecular heparin (nadroparin) have not yet been fully clarified. Considering the issues stated above, the main objective was to assess the possible differences in the concentration of total and free TFPI between DVT patients treated with unfractionated heparin and those administered nadroparin. The aim was also to determine the possible correlation of TFPI (total and free) concentration with activated partial thromboplastin time (APTT) and differences in the concentration of total and unbound TFPI according to DVT patient age before and during the treatment with unfractionated heparin and nadroparin. The study included 100 patients with DVT diagnosed by two-dimensional color Doppler, divided into two groups of 50 patients: one group treated with unfractionated heparin and the other treated with nadroparin. Study parameters were determined before, and at 4 h and 48 h of therapy administration. Statistically significantly higher levels of free TFPI were recorded in DVT patients administered unfractionated heparin in comparison with those treated with nadroparin at 4 h and 48 h. At 4 h of therapy administration, the levels of free TFPI were statistically significantly higher as compared with the levels measured before and 48 h of therapy administration in both patient groups. There was no statistically significant difference between the levels of free TFPI measured before and 48 h of either unfractionated heparin or nadroparin administration. Between-group differences in total TFPI did not reach statistical significance. Total TFPI showed a statistically significant positive correlation with APTT before therapy in the group of patients treated with unfractionated heparin. In the group of patients treated with nadroparin, a significant positive correlation was found between freeTFPI and APTT at 4 h and 48 h, and between total TFPI and APTT at 48 h of therapy administration. In the group of DVT patients aged ≤50 administered unfractionated heparin, significantly higher levels of free TFPI were recorded at 48 h of therapy administration as compared with the age-matched group administered nadroparin. In the group of DVT patients aged >50 treated with unfractionated heparin, the levels of free TFPI were significantly higher at both 4 h and 48 h as compared with the patients age ≤ 50 and the age-matched group administered nadroparin. In comparison with nadroparin, study results showed the use of unfractionated heparin in the treatment of DVT patients to cause a statistically significantly greater increase in the level of free TFPI, which has an anticoagulant action, whereas differences in total TFPI were not statistically significant. At 48 h, the levels of free TFPI returned to pretherapeutic values in both therapy groups, possibly suggesting reduction of the factor reserve in DVT patients.

Abstract in Croatian

Brojni su uzroci nastanka duboke venske tromboze (DVT). Unatoč tome u svakodnevnoj praksi često nismo u mogućnosti razjasniti siguran razlog nastanka DVT. Kao mogući rizični čimbenik za DVT navodi se smanjena koncentracija inhibitora faktora tkivnog puta (IFTP) koji je jedini poznati inhibitor vanjskog puta zgrušavanja. Nakon primjene heparina njegova se plazmatska koncentracija povećava. Nije u potpunosti poznat ni antitrombotski mehanizam djelovanja heparina, a naročito razlike u djelovanju nefrakcioniranog i niskomolekularnog heparina (nadroparina). S obzirom na navedenu problematiku osnovni zadatak je bio ispitati postoje li razlike u koncentraciji ukupnog i slobodnog IFTP u bolesnika s DVT liječenih nefrakcioniranim i nadroparinom. Također je bio cilj ispitati postoji li povezanost koncentracije IFTP (ukupnog i slobodnog) s aktiviranim parcijalnim tromboplastinskim vremenom (APTV) , te postoje li razlike u koncentraciji ukupnog i slobodnog IFTP ovisno o dobi bolesnika s DVT prije i za vrijeme liječenja nefrakcioniranim heparinom i nadroparinom. Ispitivanja su provedena u 100 bolesnika kod kojih smo dvodimenzionalnim obojenim doplerom dijagnosticirali DVT. Jedna skupina (50 bolesnika) je liječena nefrakcioniranim heparinom, a druga (također 50 bolesnika) nadroparinom. Sve navedene parametre smo mjerili prije, te 4 i 48 h nakon terapije. U bolesnika s DVT liječenih nefrakcioniranim heparinom nakon 4 i 48 h nađene su statistički značajno veće vrijednosti slobodnog IFTP u odnosu na skupinu bolesnika liječenih nadroparinom. Statistički značajno veće bile su vrijednosti slobodnog IFTP nakon 4 h u skupinama bolesnika liječenih nefrakcioniranim heparinom i nadroparinom u odnosu na vrijednosti prije i 48 h nakon terapije. Nije bilo statistički značajne razlike između vrijednosti slobodnog IFTP mjerenih prije i 48h poslije terapije nefrakcioniranim heparinom i nadroparinom. Razlike ukupnog IFTP između terapijskih skupina nisu bile značajne. Nađene su statistički značajne pozitivne korelacije između vrijednosti ukupnog IFTP i APTV prije terapije u skupini bolesnika liječenih nefrakcioniranim heparinom, dok su u skupini bolesnika liječenih nadroparinom bile značajne pozitivne korelacije između vrijednosti slobodnog IFTP i APTV 4 i 48 h poslije terapije, te ukupnog IFTP i APTV 48 h poslije terapije. Skupina bolesnika ≤50 godina liječena nefrakcioniranim heparinom imala je značajno veće vrijednosti slobodnog IFTP 48 h nakon terapije u odnosu na skupinu liječenu nadroparinom. Vrijednosti slobodnog IFTP 4 i 48 h poslije terapije nefrakcioniranim heparinom u bolesnika s DVT >50 godina bilo su značajno veće u odnosu na bolesnike ≤50 godina i na dobnu skupinu >50 godina liječenu nadroparinom. Rezultati ispitivanja ukazuju na to da primjena nefrakcioniranog heparina u odnosu na nadroparin u bolesnika s DVT uzrokuje statistički značajno veći porast slobodnog IFTP koji ima protuzgrušavajuće djelovanje, dok razlike ukupnog IFTP nisu značajne. Nakon 48 h u objema terapijskim skupinama vrijednosti slobodnog IFTP su se izjednačile s vrijednostima prije terapije, što bi moglo ukazivati na smanjene rezerve navedenog čimbenika u bolesnika s DVT.

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