Author/Editor		Stecher, Adela; Kremžar, Boriana
Title		Mehanizem delovanja rekombinantnega faktorja VIIa in uporaba pri stanjih, ki jih spremlja huda krvavitev
Translated title		Mode of action of recombinant factor VIIa and the use in severe haemorrhage states
Type		članek
Source		Zdrav Vestn
Vol. and No.		Letnik 75, št. 4
Publication year		2006
Volume		str. 241-6
Language		slo
Abstract		Background Diffuse non-surgical life threatening haemorrhages are common cause of death in surgical patients. They are usually caused by a disorder of haemostasis of different aetiologies. When the haemorrhage can not be stopped with standard measures, we can resort to the rFVIIa preparation. Numerous studies have proven the effectiveness of rFVII in treating of untractable haemorrhages as well as in preventing the haemorrhages in patients with known blood coagulation disorders. When high dosages of rFVIIa, which binds to tissue factor (TF), are administered, huge quantity of thrombin forms. Thrombin affects fibrinogen and at the same time activates huge quantity of factor XIII and of Thrombin Activatable Fibrinolysis Inhibitor (TAFI). The created fibrin clot is more resistant to fibrinolysis than a normal one. It is also important to know that rFVIIa in high concentrations can activate factors IX and X on the surface of thrombocytes, independently of TF. The effect of rFVIia is limited to the location of injury but despite this there is a possibility of thrombosis. Because rFVIIa binds not only to the TF containing cells, but also to injured cells containing phospatidyl serine, caution is needed where septic patients, patients with extensive tissue necrosis or with atherosclerotic changes are concerned. The following facts must hold true in order for rFVIIa to be administered: the haemorrhage is non-surgical and does not stop after application of standard measures; the patient does not suffer from hypothermia; the platelets value is higher than 50 x 10/l (except when thrombocytopenia is the indication for use); the fibrinogen value is higher than 50 mg/l; blood pH is higher than 7.2. (Abstract truncated at 2000 characters)
Summary		Izhodišča Difuzne nekirurške krvavitve povečujejo umrljivost kirurških bolnikov. Vzrok zanje so motnje hemostaze različne etiologije. Če krvavitve navkljub standardnim ukrepom ne moremo ustaviti, lahko uporabimo rekombinantni faktor VIIa (rFVIIa). Kompleks rFVIIa-tkivni faktor (TF) aktivira faktorje koagulacije, zato se tvorijo velike količine trombina. Ta deluje na fibrinogen in hkrati aktivira velike količine faktorja XIII in trombin-aktivirajoči inhibitor fibrinolize (TAFI). Nastali fibrinski strdek je močnejši in odpornejši na fibrinolizo od običajnega. rFVIIa v visokih plazemskih koncentracijah lahko neodvisno od TF aktivira faktor IX in X na površini trombocitov. Čeprav se delovanje rFVIIa omejuje na mesto poškodbe, je možen zaplet tromboza. Previdnost je potrebna pri bolnikih s sepso, z obsežnimi nekrozami tkiv in aterosklerotičnimi spremembami. Pred uporabo rFVIIa morajo biti izpolnjeni naslednji pogoji: krvavitev je nekirurška in se ne ustavlja kljub standardnim ukrepom: bolnik ne sme biti podhlajen; število trombocitov naj bo višje od 50 x 10/l (razen takrat, ko je indikacija za njegovo uporabo trombocitopenija); koncentracija fibrinogena naj bo višja od 50 mg/l; pH krvi naj bo višji od 7,2. Začetni odmerek rFVIIa je 90-120 mig/kg intravensko. Če se krvavitev ne ustavi, damo drugi odmerek 90-100 mig/kg najkasneje v dveh urah. Specifične laboratorijske preiskave za določanje učinka rFVIIa ni na voljo. Znano je, da se ob uporabi rFVIIa vrednost protrombinskega časa (PČ/INR) normalizira. Zaključki rFVIIa je učinkovito zdravilo za zaustavitev neobvladljivih krvavitev. Potrebno je opravitidodatne študije, s pomočjo katerih bo mogoče potrditi morebitne, še nepoznane stranske učinke in določiti optimalne pogoje za uporabo.
Descriptors		FACTOR VIIA RECOMBINANT PROTEINS HEMORRHAGE INTRAOPERATIVE COMPLICATIONS WOUNDS AND INJURIES THROMBOCYTOPENIA ANTICOAGULANTS