XXI st Congress of the International Society on Thrombosis and Haemostasis

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1 2 XXI st Congress of the International Society on Thrombosis and Haemostasis Congress aemostasis hrombosis news 2(2 st ISTH),,7 6 ( )2 ( )74 78,, ISTH 2,9742,,,,,,,, Report FVIII-specific memory B-cells in patients with hemophilia A S.D. van Haren ( ) Report 2 Thrombin generation in severe hemophiliacs with different clinical phenotype E. Santagostino ( ) Report 3 Biochemical and functional characterization of chemically modified recombinant von Willebrand factor (rvwf) as a carrier prolonging survival of rfviii in hemophilia A knock-out mice P.L. Turecek () Report 4 A Fluorogenic Thrombin Generation Test (FTGT) for factor VIII activity demonstrated success of cell therapy with liver sinusoidal endothelial cells (LSEC) in haemophilia A mice S. Raut ( ) Report Breakthrough bleeding in severe haemophilia A. Does the FVIII trough level matter? P. Collins ( )

2 Report FVIII-specific memory B-cells in patients with hemophilia A S. D. van Haren Sanquin Research, Sanquin Blood Supply Foundation (, ) A 2%, VIIIFVIII FVIII FVIII B IgG, IgG IgG 4, A - B 96-9~ B, IgG, FVIII ELISAIgG FVIII-IgG, ELISPOT IgG (ASC), FVIII- B 2 BU/mL, FVIII-IgG, ELISA ELISPOT, (ITI) B Sanquin Blood Supply Foundation S.D. van Haren A FVIII- B, B, FVIII ITI6 (PBMC)CD9+B sortingcd4 EL4.BT (A~A), ELISPOT FVIII-ASC, 244/ 6 CD9+( ) FVIII-ASC FVIII-IgG, ITI A6, FVIII- IgGFVIII-ASC van Haren ASC ( ), B ITI,,,, B A, ITIFVIII- B (N=6) ELISAFVIII- B - B B FVIII CD P<. A A2 A3 A4 A.... ITI FVIII/() Tuaillon, 26 Fondere, 24 Bernasconi,22 Crotty,23 B HIV A B ~83 HBASC/ 6 CD9+ ~9 HIV-ASC/ 6 CD9+ 67~2 TTASC/ 6 IgG ASC ~ VVASC/ 6 IgG ASC ~244 FVIII/ 6 CD9+

3 Report 2 Thrombin generation in severe hemophiliacs with different clinical phenotype E. Santagostino Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Maggiore Hospital Foundation, University of Milan (, ) VIII FVIII IX%,,, A FVIII ETP, A Maggiore Hospital Foundation E. Santagostino, A TGA FVIII A severe bleeders SB : 2 /, 2 IU/kg/, 22mild bleeders MB : 2 /, IU/kg/ 28intermediate bleeders IB :SBMB SB MB 3, SB, MB 3 MBSB MBSBFVIII/IX, MBSB IB PTG22A MB %, IB 7%, FV Leiden IB 7%, SB % ETPMB8nM IB 47nM P<., SB44nM P<. MB, Santagostino,, (MB),(IB)(SB) PRP ETP ( ) ( ) / (IU/kg/ ) SB(22) IB(28) MB(22) P 38 (2-76) (-4) 36 (2-6) 227 ( ) 38 (23-62) 2 (-6) (3-2) 68 (27-24) 32 (22-73) 3 (-) (-2) 6 (2-487) NS <.* <.* <.* (%) <.* PTG22A(%) 7 NS FV Leiden(%) 7 NS * P for trend<. PRP *P<. P for trend<.

4 Report 3 Biochemical and functional characterization of chemically modified recombinant von Willebrand factor (rvwf) as a carrier prolonging survival of rfviii in hemophilia A knock-out mice P. L. Turecek Research and Development, Baxter BioScience, Baxter BioScience P.L.Turecek, 2 PEG PEGrVWF in vitro, FVIII FVIII/VWF PEG-rVWFrFVIII in vivo 2 PEG- rvwf PEG-rVWF k-ss, PEG-rVWF 2k-SGSDS- SDS-PAGE, PEG, VWF 86s - 2.IU/mL rvwf, PEG-rVWF k-ss, 2k-SG VIII, rvwf PEG, rvwfrvwfpeg PEG-rVWF k-ss, 2k-SG, VWF, rvwf,peg-rvwf k-ss, 2k-SG, FVIII, A FVIII:N=,rFVIII 3 IU/kg PEG-rVWF k-ss rvwf2 U/kg N=, rfviii 2 IU/kg PEG-rVWF 2k-SG FVIIIrVWF, 3, 9, 24 32VWF FVIII/VWF, rfviii IU/kgPEG-rVWF k-ssrvwf U/kgrVWF FVIII3, 924 FVIII, PEG-rVWF k-ss PEG-rVWF 2k-SGrFVIII FVIII/VWF, rfviiirfviii rvwf, rfviii, rfviii PEG-rVWF k-ss, rvwf rfviii2 Turecek, PEG-rVWFFVIII rfviii FVIII rvwf PEG-rVWFk-SS rfviii rfviii 2 FVIII/VWFrFVIII rfviii+rvwf rfviii+peg-rvwf rfviii rfviii( %). AUC=2* PEG-rVWF+rFVIII AUC=8* rvwf+rfviii AUC=-6* AUC=* AUC=89* N= N= (h) *[AUC](-32):(mLU/mLh)/(IU/kg) *[AUC](-24):(mLU/mLh)/(IU/kg) rfviii( %) PEG-rVWF+rFVIII rvwf+rfviii rfviii (h)

5 Report 4 A Fluorogenic Thrombin Generation Test (FTGT) for factor VIII activity demonstrated success of cell therapy with liver sinusoidal endothelial cells (LSEC) in haemophilia A mice S. Raut Haemostasis Section, Biotherapeutics Group, National Institute for Biological Standards and Control (, ) National Institute for Biological Standards and Control Raut, A FVIII LSEC FVIII, FTGT; <. IU/mL, ETP, FVIII,, FTGT, LSEC FVB/N-tie-2-GFP LSEC 2 6,, FVB/N-tie-2-GFP LSEC, in vitro FVIII FVB/N-tie-2-GFP LSECNOD/ SCIDA, GFP Dil-Ac- LDL, LSEC 2% FVB/N-tie-2-GFP LSECA2, RT-PCRFVIII mrna, 29RT-PCRFVIII, 2, mrna FVB/N-tie-2-GFP LSECA, FTGTFVIII3 %FVIII 2, FVIII, FVIII 2% Raut, ALSEC, FVIII 3%, FTGTFTGT, FVIII, NOD/SCID A FTGT VIIIFTGT: 2 FVB/N-tie-2-GFP LSECA VIII : Tie-2-GFP LSEC NOD/SCIDA FVIII (RFU) (NP) % NP % NP.% NP.% NP FVIII FVIII () ( ) LSECA

6 Report Breakthrough bleeding in severe haemophilia A. Does the FVIII trough level matter? P. Collins Haematology, University Hospital of Wales (, ), FVIII < IU/dL ( ) ( ) FVIII< IU/dL () : N= (.7-.7) 396 (94-68) 29 ( ) (~9 ) ~6 N= 3.2 (2.-.7) 364 (6-4) 2.3 ( ) P P. Collins, VIII FVIII A, ADAPT Analysis of Data from ADVATE Prospective Trials FVIII~6N=48~6 N=2ADVATE, ~62~4 IU/kg 3~4, 7, ~6, 3.FVIII < IU/ dl, ~62, ~67, ~6~6, FVIII < IU/dL, ~6 N=84 NS 7 (-43) ~6 N=6 23 (2-) NS (28-24) ( ). 7.7 (2.-4.) P NS NS 8. (.46-3.).4,, FVIII< IU/dL, FVIII< IU/dL, FVIII < IU/dL, ~6 -A ~6 -B ADVATE, FVIII FVIII< IU/dL ~62.%, ~6.3%, ADVATE Collins, FVIII A,, ~6 8%, ~68%,,, QOL FVIII< IU/dL A. FVIII< IU/dL : ~ FVIII< IU/dL(/ ) B. FVIII< IU/dL : ~ FVIII< IU/dL(/ )