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診断 治療 技術講座 2018; 29 4 : 413-420 APTT 波形解析 APTT waveform Hideo WADA Key words: APTT, waveform, hemophilia, anticoagulant therapy 1978 1982 1982 1983 1985 NIH 1985 2000 / 2008 1 activated partial thromboplastin time: APTT APTT f 1a APTT 1 st derivative 2 2 nd derivative 2 APTT APTT 1 st derivative velocity: v 1b 2 nd derivative acceleration: a 1c APTT 2 biphasic pattern: bp 514-8507 2-174 Tel: 059-232-1111 Fax: 0592-31-5204 E-mail: wadahide@clin.medic.mie-u.ac.jp 1 1 2 3 2, 3 a v 1/2 1/2f 3 1a 1v 1-1/2f 1 2a 1 2 2a 2 2v 1/2 2-1/2f 4 1 3a 1 2 3a 2 3v 3 10 1d 1 st derivative 2 nd derivative VIII FVIII lupus anticoagulant: LA APTT Instrumentation Laboratory IL IL ACL-TOP 29 4

414 1 APTT a f 1 b First derivative v 2 c Second derivative a 3 3 APTT 2a c A B LA APTT APTT bp APTT 4 APTT 3 bp APTT 1a 1v 1-1/2f 3 2a 2v LA LA APTT FVIII APTT r= 0.541 1 2 2a 1 2a 2 r=0.760 1 APTT 2a 1 2a 2 APTT FVIII APTT FVIII 5

415 2 a b c d APTT 4 4 APTT 2d 2a 2v 1a 1v 1/2 1-1/2f 2 3v 3a 2 direct oral anticoagulant DOAC 2a 2v 1a 1v 1/2 1-1/2f DOAC 3 DOAC APTT DOAC APTT APTT Xa 6 Xa APTT r<0.2 deep vein thrombosis: DVT DVT APTT 29 4

416 1 FVIII APTT APTT P 0.587 P=0.0001 Y=27.9 0.308X 1 0.760 P<0.0001 Y= 1.68+0.038X 2 0.760 P<0.0001 Y= 0.314+0.069X 1 0.407 P=0.0124 Y=14.8 0.219X 2 0.353 P=0.0320 Y=13.6 0.039X 0.508 P=0.013 Y=20.2 0.136X 0.547 P=0.0005 Y= 1.19+0.058X 0.372 P=0.0235 Y=14.0 0.048X 1/2 0.527 P=0.0008 Y=20.6 0.131X 1/2 0.301 P=0.0699 Y=17.4 0.020X APTT 0.541 P=0.0006 Y=23.9 0.227X 0.021 P=0.9027 Y=7.76+0.003X APTT: activated partial thromboplastin time 6 3 APTT a DVT b DVT cd 5

417 4 APTT a b 1 c MB: **P<0.001 *P<0.05 5 APTT DVT major bleeding: MB MB 1v 1 3a 1 2v 1v 3a 1 2v 4 2 5 APTT 5 APTT 1 1a 1 1v A B LA Xa disseminated intravascular coagulation: DIC 5a b 1 2a 1 A B DIC Xa 5c 2v Xa 5d 1 3a 1 A B LA Xa DIC 5e 3v A B LA Xa DIC 29 4

418 2 APTT s 1 35.5 32.6 37.4 38.9 34.5 42.5 HH 43.8 39.0 51.0 HHH BBB mabs/ 2 457 411 535 362 255 571 H 400 290 604 7.45 6.80 8.00 9.8 8.8 10.6 HHH 11.2 9.8 13.3 HHH BBB 2 mabs/ 2 224 170 255 240 204 307 H 259 203 325 HH 17.7 16.7 18.7 31.8 29.2 35.6 HHH 37.3 33.4 41.9 HHH BBB 38.7 36.2 40.8 38.7 35.3 42.9 43.6 39.2 50.5 HHH BBB mabs/ 183 144 200 385 262 562 HHH 401 314 619 HHH 19.5 18.0 20.3 38.9 36.2 42.7 45.5 42.0 52.4 1/2 1/2 mabs 328 286 431 280 236 323 HHH 343 305 407 BBB 1/2 40.9 37.8 42.7 42.9 40.5 47.0 HH 49.0 43.4 54.8 HHH BBB 30 99 99 mabs: m-absorbance H p<0.05 HH p<00.1 HHH p<00.1 B p<0.05 BB p<00.1 BBB p<00.1 5 5f 2a 1 2v 1 6 thromboelastgram: TEG thrombin generation test: TGT TEG TGT VIII APTT FVIII APTT 7 APTT APTT 7 1 APTT 2 APTT APTT VIII 3 APTT DOAC 4 APTT LA 5 APTT 6 COI

419 5 APTT HV HA A HB B Inhibitor FVIII apl + warfarin Anti-Xa Xa PW TP DIC *p<0.05 **p<0.01 ***p<0.001 3 29 4

420 1 Toh CH, Giles AR: Waveform analysis of clotting test optical profiles in the diagnosis and management of disseminated intravascular coagulation (DIC). Clin Lab Haematol 24: 321 327, 2002. 2 Matsumoto T, Nogami K, Shima M: A combined approach using global coagulation assays quickly differentiates coagulation disorders with prolonged aptt and low levels of FVIII activity. Int J Hematol 105: 174 183, 2017. 3 Matsumoto T, Wada H, Fujimoto N, Toyoda J, Abe Y MR, Ohishi K, Yamashita Y, Ikejiri M, Hasegawa K, Suzuki K, Imai H, Nakatani K, Katayama N: An evaluation of the activated partial thromboplastin time waveform. Clin Appl Thromb Hemost 24: 764 770, 2018. 4 Katayama H, Matsumoto T, Wada H, Fujimoto N, Toyoda J, Abe Y, Ohishi K, Yamashita Y, Ikejiri M, Habe K, Katayama N: An evaluation of hemostatic abnormalities in patients with hemophilia according to the activated partial thromboplastin time waveform. Clin Appl Thromb Hemost 2018. 5 Matsumoto T, Nogami K, Tabuchi Y, Yada K, Ogiwara K, Kurono H, Arai N, Shima M: Clot waveform analysis using CS-2000i distinguishes between very low and absent levels of factor VIII activity in patients with severe haemophilia A. Haemophilia 23: e427 e435, 2017. 6 Hasegawa M, Wada H, Tone S, Yamaguchi T, Wakabayashi H, Ikejiri M, Watanabe M, Fujimoto N, Matsumoto T, Ohishi K, Yamashita Y, Katayama N, Sudo A: Monitoring of hemostatic abnormalities in major orthopedic surgery patients treated with edoxaban by APTT waveform. Int J Lab Hematol 40: 49 55, 2018. 7 Nogami K, Matsumoto T, Tabuchi Y, Soeda T, Arai N, Kitazawa T, Shima M: Modified clot waveform analysis to measure plasma coagulation potential in the presence of the anti-factor IXa/factor X bispecific antibody emicizumab. J Thromb Haemost 16: 1077 1088, 2018.