ZDRAVLJENJE BOLNICE S VON WILLEBRANDOVO BOLEZNIJO TIPA 3 IN INHIBITORJI
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1 ZDRAVLJENJE BOLNICE S VON WILLEBRANDOVO BOLEZNIJO TIPA 3 IN INHIBITORJI B. Faganel Kotnik, L. Kitanovski, J. Jazbec, K. Strandberg, M. Debeljak, Bakija, M. Benedik Dolničar A. Trampuš Laško, 9. april 2016
2 Von Willebrandova bolezen tip 3 - nacionalni register 2016 MOTNJA STRJEVANJA SKUPNO TEŽKA HEMOFILIJA A HEMOFILIJA B 23 8 PRENAŠALKE HEMOFILIJE A/B ( F) 23/7 TROMBOCITOPATIJE 21 3 POMANJKANJE FAKTORJA V 12 2 POMANJKANJE FAKTORJA VII 14 2 POMANJKANJE FAKTORJA XI 19 3 POMANJKANJE FAKTORJA X 2 1 POMANJKANJE FIBRINOGENA 3 0 VON WILLEBRANDOVA BOLEZEN POMANJKANJE FAKTORJEV F V + F VIII 2
3 Von Willebrandov faktor
4 Von Willebrandov faktor
5 Von Willebrandov faktor
6 Von Willebrandov faktor
7 Von Willebrandova bolezen tip 3 Odsotnost von Willebrandovega faktorja (VWF) in znižana aktivnost FVIII Krvavitve: iz sluznic po operaciji krvavitve v sklepe in mišice Willebrand EA Von. Haemophilia 1999; 5:
8 Von Willebrandova bolezen tip 3 Odsotnost von Willebrandovega faktorja (VWF) in znižana aktivnost FVIII Krvavitve: iz sluznic po operaciji krvavitve v sklepe in mišice Willebrand EA Von. Haemophilia 1999; 5:
9 Nastanek protiteles proti VWF Nastanek protiteles proti VWF je redek zaplet zdravljenja VWB tipa 3. Zdravljenje s koncentratom VWF neučinkovito.
10 Nastanek protiteles proti VWF Nastanek protiteles proti VWF je redek zaplet zdravljenja VWB tipa 3. Zdravljenje s koncentratom VWF neučinkovito povzroči lahko anafilaktično reakcijo. Bergamaschini L et al. J Lab Clin 1995; 125:
11 Prikaz primera Šestletni deklici smo v starosti 14 mesecev opredelili VWB tipa 3. Do 3. leta starosti je prejela IU (509 IU/kg/leto) plazemskega koncentrata VWF/FVIII Haemate P v 33-tih ED. Ob zadnji aplikaciji je utrpela blago alergijsko reakcijo. Dve leti kasneje je deklica brez zapletov prejela Wilate. Čez tri mesece je bila operirana zaradi vnete ciste ostanka škržnih lokov. Prejemala je Wilate, traneksamično kislino in antibiotik.
12 Prikaz primera Dan po operaciji: - VWF: RCo 0 - FVIII:C 4,5 % inhibitorji proti VWF? Terapija: rfviia (NovoSeven ) µg kg -1 na 2-3 ure traneksamična kislina rfviii (Advate ) bolus 80 IU kg -1, nato kontinuirana infuzijo c:fviii 10 dni vzdrževali med 30-39%
13 Prikaz primera protitelesa proti VWF(ELISA): pozitivna protitlesa proti FVIII: negativna
14 Protitelesa proti VWF Se razvijejo po več ED koncentratu pri 10% bolnikov s tipom 3 VWD. Pogosteje se razvijejo pri bolnikih s VWB, ki: - so utrpeli alergijsko reakcijo po vbrizganju koncentrata FVIII/VWF - pri katerih je vzročna mutacija za VWB delna ali popolna delecija gena za VWF. Mannucci PM, Federici AB. Antibodies to von Willebrand factor in von Willebrand disease. Adv Exp Med Biol 1995; 386:
15 Zdravljenje krvavitev rfviii: Ker je razpolovni čas vbrizganega FVIII:C pri teh bolnikih kratek, je potrebno FVIII predpisati v CI v 10- do 20-krat višjih odmerkih, kot pri bolnikih s hemofilijo brez inhibitorjev. Poročil o uporabi rfviia je malo.
16 Dejavniki tveganja Tip mutacije - delna ali popolna delecija, redkeje napačnosmiselna mutacija, ali mutacija, ki spremeni bralni okvir - homozigotna delecija nukleotida C, ekson 19 VWF(NM_ :c.2435delC; p.pro812argfster31). James PD et al. Blood 2013; 122:
17 Dejavniki tveganja Tip mutacije - delna ali popolna delecija, redko napačnosmiselna mutacija, ali mutacija, ki spremeni bralni okvir - homozigotna delecija nukleotida C, ekson 19 VWF(NM_ :c.2435delC). Nevarni signali vnetje operacija James PD et al. Blood 2013; 122:
18 Dejavniki tveganja Tip mutacije - delna ali popolna delecija, redko napačnosmiselna mutacija, ali mutacija, ki spremeni bralni okvir - homozigotna delecija nukleotida C, ekson 19 VWF(NM_ :c.2435delC). Nevarni signali vnetje operacija Imunski odziv James PD et al. Blood 2013; 122:
19 Izzivi Zdravljenje krvavitev Indukcija imunske tolerance? Pergantou s sod*. The challenging management of a child with type 3 von Willebrand disease and antibodies to von Willebrand factor. Haemophilia 2012, 18(3):e66 7.
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