JP6526717B2 - 線維素溶解及び線溶亢進を検出するための方法及び試薬 - Google Patents
線維素溶解及び線溶亢進を検出するための方法及び試薬 Download PDFInfo
- Publication number
- JP6526717B2 JP6526717B2 JP2016565692A JP2016565692A JP6526717B2 JP 6526717 B2 JP6526717 B2 JP 6526717B2 JP 2016565692 A JP2016565692 A JP 2016565692A JP 2016565692 A JP2016565692 A JP 2016565692A JP 6526717 B2 JP6526717 B2 JP 6526717B2
- Authority
- JP
- Japan
- Prior art keywords
- inhibitor
- fibrinolysis
- blood sample
- container
- blood
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 230000020764 fibrinolysis Effects 0.000 title claims description 111
- 238000000034 method Methods 0.000 title claims description 80
- 239000003153 chemical reaction reagent Substances 0.000 title description 7
- 210000004369 blood Anatomy 0.000 claims description 222
- 239000008280 blood Substances 0.000 claims description 222
- 239000003112 inhibitor Substances 0.000 claims description 135
- 229960000401 tranexamic acid Drugs 0.000 claims description 76
- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical group NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 claims description 76
- 230000035602 clotting Effects 0.000 claims description 70
- 238000004458 analytical method Methods 0.000 claims description 65
- 230000002829 reductive effect Effects 0.000 claims description 48
- 230000015271 coagulation Effects 0.000 claims description 39
- 238000005345 coagulation Methods 0.000 claims description 39
- 230000023597 hemostasis Effects 0.000 claims description 31
- SDZRWUKZFQQKKV-JHADDHBZSA-N cytochalasin D Chemical compound C([C@H]1[C@@H]2[C@@H](C([C@@H](O)[C@H]\3[C@]2([C@@H](/C=C/[C@@](C)(O)C(=O)[C@@H](C)C/C=C/3)OC(C)=O)C(=O)N1)=C)C)C1=CC=CC=C1 SDZRWUKZFQQKKV-JHADDHBZSA-N 0.000 claims description 26
- 230000003480 fibrinolytic effect Effects 0.000 claims description 26
- 206010053567 Coagulopathies Diseases 0.000 claims description 24
- 239000003527 fibrinolytic agent Substances 0.000 claims description 24
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims description 18
- 229940049370 fibrinolysis inhibitor Drugs 0.000 claims description 17
- 239000002874 hemostatic agent Substances 0.000 claims description 17
- 239000011248 coating agent Substances 0.000 claims description 16
- 238000000576 coating method Methods 0.000 claims description 16
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 claims description 15
- 229960002684 aminocaproic acid Drugs 0.000 claims description 15
- 108010039627 Aprotinin Proteins 0.000 claims description 12
- 229960000446 abciximab Drugs 0.000 claims description 12
- 229960004405 aprotinin Drugs 0.000 claims description 12
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 claims description 12
- 238000007711 solidification Methods 0.000 claims description 11
- 230000008023 solidification Effects 0.000 claims description 11
- 102000003886 Glycoproteins Human genes 0.000 claims description 10
- 108090000288 Glycoproteins Proteins 0.000 claims description 10
- 239000002126 C01EB10 - Adenosine Substances 0.000 claims description 9
- 108010056764 Eptifibatide Proteins 0.000 claims description 9
- 229960005305 adenosine Drugs 0.000 claims description 9
- 229940125669 adenosine diphosphate receptor inhibitor Drugs 0.000 claims description 9
- 229960004468 eptifibatide Drugs 0.000 claims description 9
- GLGOPUHVAZCPRB-LROMGURASA-N eptifibatide Chemical compound N1C(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCCNC(=N)N)NC(=O)CCSSC[C@@H](C(N)=O)NC(=O)[C@@H]2CCCN2C(=O)[C@@H]1CC1=CN=C2[C]1C=CC=C2 GLGOPUHVAZCPRB-LROMGURASA-N 0.000 claims description 9
- 229960003425 tirofiban Drugs 0.000 claims description 9
- COKMIXFXJJXBQG-NRFANRHFSA-N tirofiban Chemical compound C1=CC(C[C@H](NS(=O)(=O)CCCC)C(O)=O)=CC=C1OCCCCC1CCNCC1 COKMIXFXJJXBQG-NRFANRHFSA-N 0.000 claims description 9
- 108091006082 receptor inhibitors Proteins 0.000 claims description 7
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 claims description 7
- 230000009286 beneficial effect Effects 0.000 claims description 5
- 230000008901 benefit Effects 0.000 claims description 4
- 230000004044 response Effects 0.000 claims description 3
- YHFLGNYPQYCDGP-UHFFFAOYSA-N 2-aminohexanoic acid;6-aminohexanoic acid Chemical compound CCCCC(N)C(O)=O.NCCCCCC(O)=O YHFLGNYPQYCDGP-UHFFFAOYSA-N 0.000 claims description 2
- 210000001772 blood platelet Anatomy 0.000 description 116
- 230000006870 function Effects 0.000 description 79
- 238000003556 assay Methods 0.000 description 39
- 108010073385 Fibrin Proteins 0.000 description 33
- 102000009123 Fibrin Human genes 0.000 description 33
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 32
- 229950003499 fibrin Drugs 0.000 description 32
- 239000000504 antifibrinolytic agent Substances 0.000 description 31
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 21
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 21
- 229960000187 tissue plasminogen activator Drugs 0.000 description 21
- 108010049003 Fibrinogen Proteins 0.000 description 18
- 102000008946 Fibrinogen Human genes 0.000 description 18
- 229940012952 fibrinogen Drugs 0.000 description 18
- 208000007536 Thrombosis Diseases 0.000 description 15
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 14
- 208000014674 injury Diseases 0.000 description 14
- 230000008733 trauma Effects 0.000 description 13
- 108010088842 Fibrinolysin Proteins 0.000 description 12
- 230000033001 locomotion Effects 0.000 description 12
- 229940012957 plasmin Drugs 0.000 description 12
- 238000013169 thromboelastometry Methods 0.000 description 12
- 208000032843 Hemorrhage Diseases 0.000 description 11
- 230000002439 hemostatic effect Effects 0.000 description 11
- 230000000670 limiting effect Effects 0.000 description 11
- 230000008569 process Effects 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- 238000004090 dissolution Methods 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 8
- 238000001514 detection method Methods 0.000 description 8
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 8
- 238000001356 surgical procedure Methods 0.000 description 8
- 102000013566 Plasminogen Human genes 0.000 description 7
- 108010051456 Plasminogen Proteins 0.000 description 7
- 230000009089 cytolysis Effects 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 239000005995 Aluminium silicate Substances 0.000 description 6
- 206010020973 Hypocoagulable state Diseases 0.000 description 6
- 239000012190 activator Substances 0.000 description 6
- 235000012211 aluminium silicate Nutrition 0.000 description 6
- 230000000740 bleeding effect Effects 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 230000035945 sensitivity Effects 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 102000003801 alpha-2-Antiplasmin Human genes 0.000 description 5
- 108090000183 alpha-2-Antiplasmin Proteins 0.000 description 5
- 238000002825 functional assay Methods 0.000 description 5
- 230000000977 initiatory effect Effects 0.000 description 5
- 229940044551 receptor antagonist Drugs 0.000 description 5
- 239000002464 receptor antagonist Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 4
- 206010010356 Congenital anomaly Diseases 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108010058861 Fibrin Fibrinogen Degradation Products Proteins 0.000 description 4
- 108090000190 Thrombin Proteins 0.000 description 4
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 4
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 4
- 230000001567 anti-fibrinolytic effect Effects 0.000 description 4
- 229940082620 antifibrinolytics Drugs 0.000 description 4
- 230000007812 deficiency Effects 0.000 description 4
- 239000000208 fibrin degradation product Substances 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000002797 plasminogen activator inhibitor Substances 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 4
- 229960004072 thrombin Drugs 0.000 description 4
- 230000000007 visual effect Effects 0.000 description 4
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 3
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 3
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 3
- 102100025306 Integrin alpha-IIb Human genes 0.000 description 3
- 101710149643 Integrin alpha-IIb Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 108010000499 Thromboplastin Proteins 0.000 description 3
- 102000002262 Thromboplastin Human genes 0.000 description 3
- -1 abciximab Proteins 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 230000023555 blood coagulation Effects 0.000 description 3
- 239000003114 blood coagulation factor Substances 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 239000001110 calcium chloride Substances 0.000 description 3
- 229910001628 calcium chloride Inorganic materials 0.000 description 3
- 238000004364 calculation method Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 230000002008 hemorrhagic effect Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000012886 linear function Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000003068 static effect Effects 0.000 description 3
- 230000004936 stimulating effect Effects 0.000 description 3
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 239000003154 D dimer Substances 0.000 description 2
- 208000031220 Hemophilia Diseases 0.000 description 2
- 208000009292 Hemophilia A Diseases 0.000 description 2
- 208000026350 Inborn Genetic disease Diseases 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- 208000015294 blood coagulation disease Diseases 0.000 description 2
- 239000012503 blood component Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 2
- 230000009852 coagulant defect Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000005670 electromagnetic radiation Effects 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 239000000282 fibrinogen degradation product Substances 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 208000016361 genetic disease Diseases 0.000 description 2
- 208000031169 hemorrhagic disease Diseases 0.000 description 2
- 230000000988 hyperfibrinolytic effect Effects 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 230000002934 lysing effect Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000003805 procoagulant Substances 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000000954 titration curve Methods 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- 208000031104 Arterial Occlusive disease Diseases 0.000 description 1
- 208000037157 Azotemia Diseases 0.000 description 1
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 1
- 239000005528 B01AC05 - Ticlopidine Substances 0.000 description 1
- 239000005465 B01AC22 - Prasugrel Substances 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102100022641 Coagulation factor IX Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 206010051055 Deep vein thrombosis Diseases 0.000 description 1
- 108010076282 Factor IX Proteins 0.000 description 1
- 108010080865 Factor XII Proteins 0.000 description 1
- 102000000429 Factor XII Human genes 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102000010752 Plasminogen Inactivators Human genes 0.000 description 1
- 108010077971 Plasminogen Inactivators Proteins 0.000 description 1
- 206010073391 Platelet dysfunction Diseases 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 208000010378 Pulmonary Embolism Diseases 0.000 description 1
- 102000003938 Thromboxane Receptors Human genes 0.000 description 1
- 108090000300 Thromboxane Receptors Proteins 0.000 description 1
- 108010069102 Thromboxane-A synthase Proteins 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 206010047249 Venous thrombosis Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 230000010100 anticoagulation Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 208000021328 arterial occlusion Diseases 0.000 description 1
- 238000013096 assay test Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229960004588 cilostazol Drugs 0.000 description 1
- RRGUKTPIGVIEKM-UHFFFAOYSA-N cilostazol Chemical compound C=1C=C2NC(=O)CCC2=CC=1OCCCCC1=NN=NN1C1CCCCC1 RRGUKTPIGVIEKM-UHFFFAOYSA-N 0.000 description 1
- 229960003009 clopidogrel Drugs 0.000 description 1
- 230000001112 coagulating effect Effects 0.000 description 1
- 229960005188 collagen Drugs 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000000306 component Substances 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 208000027744 congestion Diseases 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 210000003674 cytoplasmic vesicle Anatomy 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 229960002768 dipyridamole Drugs 0.000 description 1
- IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 229960004222 factor ix Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 108010052295 fibrin fragment D Proteins 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000005389 magnetism Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000003593 megakaryocyte Anatomy 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 108010022749 platelet inhibitory factor Proteins 0.000 description 1
- 210000004623 platelet-rich plasma Anatomy 0.000 description 1
- 229960004197 prasugrel Drugs 0.000 description 1
- DTGLZDAWLRGWQN-UHFFFAOYSA-N prasugrel Chemical compound C1CC=2SC(OC(=O)C)=CC=2CN1C(C=1C(=CC=CC=1)F)C(=O)C1CC1 DTGLZDAWLRGWQN-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 208000037974 severe injury Diseases 0.000 description 1
- 230000009528 severe injury Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 150000003595 thromboxanes Chemical class 0.000 description 1
- 229960005001 ticlopidine Drugs 0.000 description 1
- PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 208000009852 uremia Diseases 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/86—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood coagulating time or factors, or their receptors
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/56—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving blood clotting factors, e.g. involving thrombin, thromboplastin, fibrinogen
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
- G01N33/49—Blood
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Physics & Mathematics (AREA)
- Urology & Nephrology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- Organic Chemistry (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Cell Biology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Ecology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
Description
本発明は、国立保健研究所から贈与された助成金第NIH−T32−GM008315号を利用して、政府支援の下で行われた。
本発明は、止血に関する。
本発明は、血液サンプルにおける線維素溶解及び線溶亢進を迅速かつ正確に検出する方法及び試薬を提供する。
一部の実施形態において、本発明は、線維素溶解及び線溶亢進を検出するための方法及び試薬(例えば、カップ)を提供する。本発明は、血餅における血小板の関与は、線維素溶解の発症及び範囲を部分的に認識不能にすることがあるという予想外の発見に由来している。したがって、止血状態についての検査の対象である血液サンプルの血小板機能を低下させることによって、血液サンプル(及び、その血液サンプルを採取した元の患者)における線維素溶解及び線溶亢進の検出を高速化することができる。
− 検出しきい値[tPA]: ΔLY30の場合、25〜50ng/mL;CK−LY30の場合、75〜100ng/mL
− 分析感度(70〜100ng/mLからの傾斜): ΔLY30の場合、19.67;CK−LY30の場合、8.01
− 傾斜のRSD(n=15): ΔLY30の場合、0.57; CK−LY30の場合、0.77
− 直線的相関(0〜200ng/mlからのR2): ΔLY30の場合、0.87; CK−LY30の場合、0.72。
− ベースライン信号(検出しきい値より下の平均レベル): ΔLY30の場合、−0.12; CK−LY30の場合、7.38
− ベースラインノイズ(ベースライン信号におけるSD): ΔLY30の場合、0.95; CK−LY30の場合、4.18。
Claims (31)
- 血液サンプルにおける線維素溶解または線溶亢進を検出するための方法であって、
a)線維素溶解の抑制因子が存在しない状況において、第1の容器において、低下した血小板機能を有する血液サンプルの第1の部分を対象として粘弾性解析を実施し、ある時点における前記第1の部分の凝固特性を取得し;
b)線維素溶解の抑制因子が存在する状況において、第2の容器において、前記低下した血小板機能を有する血液サンプルの第2の部分を対象として粘弾性解析を実施し、前記時点における前記第2の部分の凝固特性を取得し;
c)前記第1の部分の凝固特性を前記第2の部分の凝固特性と比較し、差を検出すること
を含み、前記第1の部分の凝固特性と前記第2の部分の凝固特性との間の前記差によって、前記血液サンプルにおける線維素溶解または線溶亢進が示される方法。 - 前記凝固特性は、前記粘弾性解析の出力の振幅である、請求項1に記載の方法。
- 前記凝固特性は、前記粘弾性解析の出力の振幅の一次導関数である、請求項1に記載の方法。
- 前記時点は、前記第1の部分の最大血餅強度の時である、請求項1に記載の方法。
- 前記時点は、前記粘弾性解析が開始された後、15分から35分までの間である、請求項1に記載の方法。
- 前記時点は、前記粘弾性解析が開始された後、20分未満である、請求項1に記載の方法。
- 前記時点は、前記線維素溶解の抑制因子により処理されていない前記血液サンプルにおいて、血餅硬度が20mmに達した時に得られる、請求項1に記載の方法。
- 前記第1の部分の凝固特性と前記第2の部分の凝固特性との間の前記差が少なくとも1%であることは、前記血液サンプルにおける線維素溶解または線溶亢進を示している、請求項1に記載の方法。
- 前記第1の部分の凝固特性と前記第2の部分の凝固特性との間の前記差が少なくとも2%であることは、前記血液サンプルにおける線維素溶解または線溶亢進を示している、請求項1に記載の方法。
- 前記低下した血小板機能を有する血液サンプルは、血小板機能の抑制因子を含む、請求項1に記載の方法。
- 前記血小板機能の抑制因子は、糖タンパク質IIb/IIIa受容体抑制因子である、請求項10に記載の方法。
- 前記糖タンパク質IIb/IIIa受容体抑制因子は、アブシキシマブ、エプチフィバチド、及びチロフィバンからなる群の中から選択される、請求項11に記載の方法。
- 前記血小板機能の抑制因子は、アデノシン二リン酸(ADP)受容体抑制因子、アデノシン再摂取抑制因子、またはトロンボキサン抑制因子である、請求項10に記載の方法。
- 前記血小板機能の抑制因子は、サイトカラシンDである、請求項10に記載の方法。
- 前記低下した血小板機能を有する血液サンプルは、血小板が減少した血液サンプルである、請求項1に記載の方法。
- 前記血小板が減少した血液サンプルは、血液サンプルから血小板を物理的に除去することによって得られる、請求項15に記載の方法。
- 前記線維素溶解の抑制因子は、トラネキサム酸である、請求項1に記載の方法。
- 前記線維素溶解の抑制因子は、アミノカプロン酸(ε−アミノカプロン酸)、及びアプロチニンからなる群から選択される、請求項1に記載の方法。
- 前記粘弾性解析は、止血分析器を使用して実施される、請求項1に記載の方法。
- 前記粘弾性解析は、前記第1の容器及び前記第2の容器、並びに第1のピン及び第2のピンを使用して実施され、前記第1のピンは前記第1の容器に対して移動し、前記第2のピンは前記第2の容器に対して移動する、請求項1に記載の方法。
- 前記粘弾性解析は、前記第1の容器及び前記第2の容器、並びに第1のピン及び第2のピンを使用して実施され、前記第1の容器は前記第1のピンに対して移動し、前記第2の容器は前記第2のピンに対して移動する、請求項1に記載の方法。
- 前記線維素溶解の抑制因子は、前記第2の容器の内面上のコーティングに含まれる、請求項1に記載の方法。
- 前記第1の容器及び前記第2の容器は、単一のカセット上に配置される、請求項1に記載の方法。
- 血小板機能の抑制因子は、前記第1の容器及び前記第2の容器の内面上のコーティングに含まれる、請求項10に記載の方法。
- 血小板機能の抑制因子は、前記サンプルに加えられる、請求項10に記載の方法。
- 前記血液サンプルは、患者から採取される、請求項1に記載の方法。
- 線維素溶解または線溶亢進が検出された場合、前記患者は、前記線維素溶解の抑制因子に反応する、請求項26に記載の方法。
- 線維素溶解または線溶亢進が起きている、またはそれらが起きる可能性がある患者における有益な反応を実現する線維素溶解の抑制因子を識別する方法であって、
a)線維素溶解の抑制因子が存在しない状況において、前記患者からの低下した血小板機能を有する血液サンプルの第1の部分を対象として粘弾性解析を実施し、ある時点における前記第1の部分の凝固特性を取得し;
b)線維素溶解の第1の抑制因子が存在する状況において、前記患者からの前記低下した血小板機能を有する血液サンプルの第2の部分を対象として粘弾性解析を実施し、前記時点における前記第2の部分の凝固特性を取得し;
c)線維素溶解の第2の抑制因子が存在する状況において、前記患者からの前記低下した血小板機能を有する血液サンプルの第3の部分を対象として粘弾性解析を実施し、前記時点における前記第3の部分の凝固特性を取得し;
d)前記第1の部分の凝固特性と前記第1の抑制因子が存在する状況における前記第2の部分の凝固特性との間の第1の差を、前記第1の部分の凝固特性と前記第2の抑制因子が存在する状況における前記第3の部分の凝固特性との間の第2の差と比較すること
を含み、前記第1の差が前記第2の差よりも大きい場合、前記患者は、前記第1の抑制因子による治療から有益な結果が得られ、前記第2の差が前記第1の差よりも大きい場合、前記患者は、前記第2の抑制因子による治療から有益な結果が得られるであろう方法。 - 前記患者は、人である、請求項28に記載の方法。
- 前記線維素溶解の第1の抑制因子は、トラネキサム酸である、請求項28に記載の方法。
- 前記線維素溶解の第1の抑制因子、及び前記線維素溶解の第2の抑制因子はそれぞれ、アミノカプロン酸、トラネキサム酸、及びアプロチニンからなる群の中から選択され、前記第1の抑制因子と前記第2の抑制因子は、同じではない、請求項28に記載の方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US14/270,269 US9354243B2 (en) | 2014-05-05 | 2014-05-05 | Methodologies and reagents for detecting fibrinolysis and hyperfibrinolysis in a blood sample using viscoelastic analysis |
PCT/US2014/036860 WO2015171116A1 (en) | 2014-05-05 | 2014-05-05 | Methodologies and reagents for detecting fibrinolysis and hyperfibrinolysis |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2017520757A JP2017520757A (ja) | 2017-07-27 |
JP6526717B2 true JP6526717B2 (ja) | 2019-06-05 |
Family
ID=56798204
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016565692A Active JP6526717B2 (ja) | 2014-05-05 | 2014-05-05 | 線維素溶解及び線溶亢進を検出するための方法及び試薬 |
Country Status (5)
Country | Link |
---|---|
US (2) | US9354243B2 (ja) |
EP (1) | EP3140650B1 (ja) |
JP (1) | JP6526717B2 (ja) |
CN (1) | CN106574922B (ja) |
WO (1) | WO2015171116A1 (ja) |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8448499B2 (en) | 2008-12-23 | 2013-05-28 | C A Casyso Ag | Cartridge device for a measuring system for measuring viscoelastic characteristics of a sample liquid, a corresponding measuring system, and a corresponding method |
US10539579B2 (en) | 2014-09-29 | 2020-01-21 | C A Casyso Gmbh | Blood testing system and method |
WO2016073668A1 (en) | 2014-11-06 | 2016-05-12 | The Regents Of The University Of Colorado | Identification of novel disease states using viscoelastic analysis in the presence of a thrombolytic agent |
US11187710B2 (en) | 2015-06-08 | 2021-11-30 | The Regents Of The University Of Colorado, A Body Corporate | Time independent viscoelastic analysis parameter for prediction of patient outcome |
CN105652022B (zh) * | 2015-12-31 | 2017-10-10 | 浙江盛域医疗技术有限公司 | 血栓弹力图仪质控品及其制备方法 |
JP7101351B2 (ja) * | 2016-04-28 | 2022-07-15 | シスメックス株式会社 | 血液検体の分析方法、血液検体分析用試薬及び試薬キット、並びに血液検体分析装置 |
EP3455366A4 (en) | 2016-05-11 | 2020-02-26 | Michael P. Chapman | VISCOELASTIC ANALYSIS OF PATIENTS WITH DISEASES RELATED TO THE CARDIOVASCULAR SYSTEM |
JP7002718B2 (ja) * | 2017-04-24 | 2022-02-10 | シスメックス株式会社 | 血液検体の分析方法、分析装置及びコンピュータプログラム |
WO2020051761A1 (zh) * | 2018-09-11 | 2020-03-19 | 深圳迈瑞生物医疗电子股份有限公司 | 凝血分析仪及其检测样本的方法、存储介质 |
CN110619938B (zh) * | 2019-10-22 | 2023-05-30 | 常熟常江生物技术有限公司 | 基于血栓弹力图的血小板抑制率计算方法 |
CN118010469B (zh) * | 2024-04-08 | 2024-07-02 | 中国人民解放军军事科学院军事医学研究院 | 一种纤维蛋白原浓度定量检测稀释液及其制备方法与应用 |
Family Cites Families (44)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5223227A (en) | 1989-06-19 | 1993-06-29 | Haemoscope Corporation | Disposable pin and cup with reuseable stem and collar for blood coagulation analyzer |
US5290764A (en) * | 1992-01-14 | 1994-03-01 | The Dupont Merck Pharmaceutical Company | Stabilization of active plasminogen activator inhibitor-1 |
US5232828A (en) * | 1992-03-09 | 1993-08-03 | Becton, Dickinson And Company | Coating agents for cell recovery |
US5447440A (en) * | 1993-10-28 | 1995-09-05 | I-Stat Corporation | Apparatus for assaying viscosity changes in fluid samples and method of conducting same |
US6979307B2 (en) * | 1997-06-24 | 2005-12-27 | Cascade Medical Enterprises Llc | Systems and methods for preparing autologous fibrin glue |
US6787363B2 (en) | 1999-02-22 | 2004-09-07 | Haemoscope Corporation | Method and apparatus for hemostasis and blood management |
US7179652B2 (en) | 1999-02-22 | 2007-02-20 | Haemoscope Corporation | Protocol for monitoring platelet inhibition |
US6225126B1 (en) | 1999-02-22 | 2001-05-01 | Haemoscope Corporation | Method and apparatus for measuring hemostasis |
US8008086B2 (en) * | 1999-02-22 | 2011-08-30 | Cora Healthcare, Inc. | Protocol for monitoring direct thrombin inhibition |
US8076144B2 (en) | 1999-02-22 | 2011-12-13 | Cora Healthcare, Inc. | Protocol for risk stratification of ischemic events and optimized individualized treatment |
US7732213B2 (en) * | 1999-02-22 | 2010-06-08 | Coramed Healthcare, Inc. | Method of evaluating patient hemostasis |
US6613573B1 (en) * | 1999-02-22 | 2003-09-02 | Haemoscope Corporation | Method and apparatus for monitoring anti-platelet agents |
KR100435783B1 (ko) * | 2000-07-31 | 2004-06-12 | 엘지전자 주식회사 | 운영 체계에서 사용자 메모리 유효성 검증 방법 |
JP5200312B2 (ja) | 2001-09-03 | 2013-06-05 | 富士通株式会社 | 電子機器 |
US7105198B2 (en) * | 2002-01-14 | 2006-09-12 | Medtronic Vascular, Inc. | Method for coating stent |
US20040131500A1 (en) * | 2002-01-18 | 2004-07-08 | Chow Herbert S. | Device and method for evaluating platelets |
GB0229837D0 (en) * | 2002-12-20 | 2003-01-29 | Axis Shield Diagnostics Ltd | Variants of activated factor XII |
US6890299B2 (en) | 2003-04-08 | 2005-05-10 | Haemoscope Corporation | Method and apparatus for monitoring hemostasis in connection with artificial surface devices |
US7261861B2 (en) | 2003-04-24 | 2007-08-28 | Haemoscope Corporation | Hemostasis analyzer and method |
US7524670B2 (en) | 2003-08-05 | 2009-04-28 | Haemoscope Corporation | Protocol and apparatus for determining heparin-induced thrombocytopenia |
US7422905B2 (en) * | 2004-02-27 | 2008-09-09 | Medtronic, Inc. | Blood coagulation test cartridge, system, and method |
GB0406819D0 (en) * | 2004-03-26 | 2004-04-28 | Dow Corning | Controlled release compositions |
US7399637B2 (en) | 2004-04-19 | 2008-07-15 | Medtronic, Inc. | Blood coagulation test cartridge, system, and method |
DE102005005824A1 (de) * | 2005-02-08 | 2006-08-17 | Zlb Behring Gmbh | Methode zur Differenzierung von Faktor XIII-gegenüber Fibrinogen-Mangelzuständen unter Einsatz thrombelastographischer Techniken |
US7381536B2 (en) * | 2005-03-01 | 2008-06-03 | Gurbel Paul A | Assessment of cardiac health and thrombotic risk in a patient |
WO2006125057A1 (en) | 2005-05-16 | 2006-11-23 | Haemoscope Corporation | Hemostasis analysis device and method |
CN101292161B (zh) * | 2005-10-18 | 2012-11-28 | 藤森工业株式会社 | 监测血栓形成的装置和监测血栓形成的方法 |
US7879615B2 (en) | 2005-10-20 | 2011-02-01 | Coramed Technologies, Llc | Hemostasis analyzer and method |
US20130002903A1 (en) * | 2006-04-13 | 2013-01-03 | Manico Joseph A | Camera user input based image value index |
FR2900734B1 (fr) * | 2006-05-05 | 2009-03-06 | Diagnostica Stago Soc Par Acti | Detection des maladies veineuses thromboemboliques par le dosage des d-dimeres et de la fibrine soluble |
FR2909180B1 (fr) * | 2006-11-29 | 2009-02-20 | Diagnostica Stago Soc Par Acti | Methode de mesure fonctionnelle de l'activite de la thrombomoduline plasmatique. |
GB0701821D0 (en) * | 2007-02-01 | 2007-03-14 | Pentapharm Ag | Diagnostic composition and its use in the determination of coagulation characteristics of a test liquid |
JP2010540929A (ja) | 2007-09-28 | 2010-12-24 | ティツー・バイオシステムズ・インコーポレーテッド | プラスチック製サンプル容器を用いるnmr装置による診断 |
JP5145426B2 (ja) * | 2007-11-02 | 2013-02-20 | メドプラスト ソシエテ アノニム | 空間的な線維素凝塊形成を監視するための方法及び装置 |
EP2063273A1 (en) * | 2007-11-21 | 2009-05-27 | Pentapharm GmbH | Method for assessing the fibrinogen contribution in coagulation |
FR2934052B1 (fr) * | 2008-07-17 | 2011-11-25 | Stago Diagnostica | Dosage de l'activite du facteur tissulaire circulant |
US8517979B2 (en) * | 2008-12-22 | 2013-08-27 | Abbott Laboratories | Carriers for hemostatic tract treatment |
BR112012014421B8 (pt) * | 2009-12-18 | 2021-07-27 | Entegrion Inc | dispositivo para medir resposta de coagulação em uma amostra de sangue |
JP2013522246A (ja) * | 2010-03-15 | 2013-06-13 | フェロサン メディカル デバイシーズ エイ/エス | 止血および/または創傷治癒を促進するための方法 |
CN102834722B (zh) * | 2010-03-30 | 2016-09-07 | Ca卡西索股份公司 | 用于测定测试液体的凝固特性的组合物 |
ES2854873T3 (es) * | 2011-02-15 | 2021-09-23 | Hemosonics Llc | Dispositivos, sistemas y procedimientos para la evaluación de la hemostasia |
IS2809B (is) * | 2011-03-08 | 2012-10-15 | Haskoli Islands | Blóðstorkumæling |
WO2012159021A2 (en) * | 2011-05-19 | 2012-11-22 | Hemosonics, Llc | Portable hemostasis analyzer |
EP2713878B1 (en) | 2011-05-26 | 2021-07-07 | The General Hospital Corporation | Optical thromboelastography system and method for evaluation of blood coagulation metrics |
-
2014
- 2014-05-05 WO PCT/US2014/036860 patent/WO2015171116A1/en active Application Filing
- 2014-05-05 EP EP14734284.4A patent/EP3140650B1/en active Active
- 2014-05-05 JP JP2016565692A patent/JP6526717B2/ja active Active
- 2014-05-05 US US14/270,269 patent/US9354243B2/en active Active
- 2014-05-05 CN CN201480079666.9A patent/CN106574922B/zh active Active
-
2016
- 2016-05-09 US US15/149,868 patent/US10935559B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
US10935559B2 (en) | 2021-03-02 |
CN106574922A (zh) | 2017-04-19 |
US20150316565A1 (en) | 2015-11-05 |
US20160252534A1 (en) | 2016-09-01 |
US9354243B2 (en) | 2016-05-31 |
JP2017520757A (ja) | 2017-07-27 |
WO2015171116A1 (en) | 2015-11-12 |
EP3140650B1 (en) | 2022-07-20 |
CN106574922B (zh) | 2020-06-05 |
EP3140650A1 (en) | 2017-03-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6526717B2 (ja) | 線維素溶解及び線溶亢進を検出するための方法及び試薬 | |
JP7246559B2 (ja) | 凝固分析を使用した抗凝固剤の検出および分類 | |
Konstantinidi et al. | Clinical application of thromboelastography/thromboelastometry (TEG/TEM) in the neonatal population: a narrative review | |
JP5514101B2 (ja) | トロンビンレセプターアンタゴニストによる血小板凝集阻害を測定する方法 | |
JP6877340B2 (ja) | 血栓溶解剤の存在下における粘弾性解析を用いた新規病態の確認 | |
JP5662802B2 (ja) | フォン−ビルブランド病ならびにフォン−ビルブランド病および血小板機能の後天性または先天性障害に関連する出血リスクの増加を評価するためのインビトロ診断法 | |
US11187710B2 (en) | Time independent viscoelastic analysis parameter for prediction of patient outcome | |
Sanak et al. | Assessment of hemocompatibility of materials with arterial blood flow by platelet functional tests | |
Govil et al. | Point-of-care testing of coagulation in intensive care unit: role of thromboelastography | |
Gant et al. | Abnormal platelet activity in dogs and cats–impact and measurement | |
Holt et al. | Quasi‐static acoustic tweezing thromboelastometry | |
MacIvor et al. | 27 How do we integrate thromboelastography with perioperative transfusion management? _3728 1386.. 1392 | |
KR20200118428A (ko) | 활성탄을 사용하여 지혈 장애를 진단하는 방법 | |
Schlimp et al. | Fibrinogen assays | |
Undas | Laboratory Testing for Fibrinogen Disorders: From Routine Investigations to Research Studies | |
Spiess | Perioperative coagulation monitoring | |
OGWENO | THE EFFECTS OF CRYSTALLOID SOLUTIONS ON THE HUMAN BLOOD COAGULATION SYSTEM | |
Swathi et al. | A Review of Thromboelastography |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20170426 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20180126 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180206 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180507 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20181016 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190129 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20190312 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20190409 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190508 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6526717 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |