JP7214712B2 - 血漿および全血中の抗凝固薬の検出のための方法ならびにデバイス - Google Patents
血漿および全血中の抗凝固薬の検出のための方法ならびにデバイス Download PDFInfo
- Publication number
- JP7214712B2 JP7214712B2 JP2020504364A JP2020504364A JP7214712B2 JP 7214712 B2 JP7214712 B2 JP 7214712B2 JP 2020504364 A JP2020504364 A JP 2020504364A JP 2020504364 A JP2020504364 A JP 2020504364A JP 7214712 B2 JP7214712 B2 JP 7214712B2
- Authority
- JP
- Japan
- Prior art keywords
- factor
- blood sample
- clotting
- clot formation
- formation time
- 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
- 210000004369 blood Anatomy 0.000 title claims description 160
- 239000008280 blood Substances 0.000 title claims description 160
- 238000000034 method Methods 0.000 title claims description 143
- 238000001514 detection method Methods 0.000 title claims description 81
- 239000003146 anticoagulant agent Substances 0.000 title claims description 44
- 229940127219 anticoagulant drug Drugs 0.000 title claims description 44
- 230000035602 clotting Effects 0.000 claims description 305
- 102000015081 Blood Coagulation Factors Human genes 0.000 claims description 205
- 108010039209 Blood Coagulation Factors Proteins 0.000 claims description 205
- 239000003114 blood coagulation factor Substances 0.000 claims description 205
- 206010053567 Coagulopathies Diseases 0.000 claims description 140
- 108010074860 Factor Xa Proteins 0.000 claims description 115
- 230000015271 coagulation Effects 0.000 claims description 86
- 238000005345 coagulation Methods 0.000 claims description 86
- 108010029144 Factor IIa Proteins 0.000 claims description 69
- 239000003112 inhibitor Substances 0.000 claims description 60
- 230000005764 inhibitory process Effects 0.000 claims description 56
- 230000001965 increasing effect Effects 0.000 claims description 34
- 230000007812 deficiency Effects 0.000 claims description 28
- 230000001419 dependent effect Effects 0.000 claims description 26
- 230000037361 pathway Effects 0.000 claims description 22
- 108010049003 Fibrinogen Proteins 0.000 claims description 21
- 102000008946 Fibrinogen Human genes 0.000 claims description 21
- 230000002159 abnormal effect Effects 0.000 claims description 21
- 229940012952 fibrinogen Drugs 0.000 claims description 21
- 238000003384 imaging method Methods 0.000 claims description 17
- 238000011144 upstream manufacturing Methods 0.000 claims description 17
- 108010000487 High-Molecular-Weight Kininogen Proteins 0.000 claims description 15
- 102100035792 Kininogen-1 Human genes 0.000 claims description 15
- 102000004411 Antithrombin III Human genes 0.000 claims description 13
- 108090000935 Antithrombin III Proteins 0.000 claims description 13
- 229960005348 antithrombin iii Drugs 0.000 claims description 13
- 239000011324 bead Substances 0.000 claims description 13
- 238000011282 treatment Methods 0.000 claims description 13
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 claims description 12
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 claims description 12
- 229960000187 tissue plasminogen activator Drugs 0.000 claims description 12
- 102100030951 Tissue factor pathway inhibitor Human genes 0.000 claims description 11
- 230000007547 defect Effects 0.000 claims description 11
- 108010013555 lipoprotein-associated coagulation inhibitor Proteins 0.000 claims description 11
- 108090000113 Plasma Kallikrein Proteins 0.000 claims description 10
- 108010025221 plasma protein Z Proteins 0.000 claims description 10
- 102100039418 Plasminogen activator inhibitor 1 Human genes 0.000 claims description 9
- 230000007423 decrease Effects 0.000 claims description 9
- 238000000684 flow cytometry Methods 0.000 claims description 8
- 230000006624 extrinsic pathway Effects 0.000 claims description 7
- 238000001917 fluorescence detection Methods 0.000 claims description 7
- 230000006623 intrinsic pathway Effects 0.000 claims description 7
- 108010047303 von Willebrand Factor Proteins 0.000 claims description 7
- 102100036537 von Willebrand factor Human genes 0.000 claims description 7
- 229960001134 von willebrand factor Drugs 0.000 claims description 7
- 102000013566 Plasminogen Human genes 0.000 claims description 6
- 108010051456 Plasminogen Proteins 0.000 claims description 6
- 238000011002 quantification Methods 0.000 claims description 6
- 230000000007 visual effect Effects 0.000 claims description 6
- 102100037362 Fibronectin Human genes 0.000 claims description 5
- 108010067306 Fibronectins Proteins 0.000 claims description 5
- 108090000481 Heparin Cofactor II Proteins 0.000 claims description 5
- 102100030500 Heparin cofactor 2 Human genes 0.000 claims description 5
- 238000004566 IR spectroscopy Methods 0.000 claims description 5
- 102100034869 Plasma kallikrein Human genes 0.000 claims description 5
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims description 5
- 101800004937 Protein C Proteins 0.000 claims description 5
- 102000017975 Protein C Human genes 0.000 claims description 5
- 229940096437 Protein S Drugs 0.000 claims description 5
- 108010066124 Protein S Proteins 0.000 claims description 5
- 102000029301 Protein S Human genes 0.000 claims description 5
- 101800001700 Saposin-D Proteins 0.000 claims description 5
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 claims description 5
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 claims description 5
- 102000003801 alpha-2-Antiplasmin Human genes 0.000 claims description 5
- 108090000183 alpha-2-Antiplasmin Proteins 0.000 claims description 5
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 5
- 229960000856 protein c Drugs 0.000 claims description 5
- 229960005356 urokinase Drugs 0.000 claims description 5
- 108090001015 cancer procoagulant Proteins 0.000 claims description 4
- 239000000725 suspension Substances 0.000 claims description 4
- 102000004179 Plasminogen Activator Inhibitor 2 Human genes 0.000 claims description 3
- 108090000614 Plasminogen Activator Inhibitor 2 Proteins 0.000 claims description 3
- 230000002429 anti-coagulating effect Effects 0.000 claims description 2
- 108010079356 FIIa Proteins 0.000 claims 1
- 101000609255 Homo sapiens Plasminogen activator inhibitor 1 Proteins 0.000 claims 1
- 238000010521 absorption reaction Methods 0.000 claims 1
- 239000003550 marker Substances 0.000 claims 1
- 230000003287 optical effect Effects 0.000 claims 1
- 230000033885 plasminogen activation Effects 0.000 claims 1
- 239000000523 sample Substances 0.000 description 138
- 238000002347 injection Methods 0.000 description 48
- 239000007924 injection Substances 0.000 description 48
- 229940127066 new oral anticoagluant drug Drugs 0.000 description 38
- 239000000556 agonist Substances 0.000 description 36
- 238000012360 testing method Methods 0.000 description 31
- 230000005856 abnormality Effects 0.000 description 30
- 238000003556 assay Methods 0.000 description 27
- 239000003814 drug Substances 0.000 description 27
- 239000000758 substrate Substances 0.000 description 26
- 210000002381 plasma Anatomy 0.000 description 25
- 229940079593 drug Drugs 0.000 description 22
- KGFYHTZWPPHNLQ-AWEZNQCLSA-N rivaroxaban Chemical compound S1C(Cl)=CC=C1C(=O)NC[C@@H]1OC(=O)N(C=2C=CC(=CC=2)N2C(COCC2)=O)C1 KGFYHTZWPPHNLQ-AWEZNQCLSA-N 0.000 description 18
- QNZCBYKSOIHPEH-UHFFFAOYSA-N Apixaban Chemical compound C1=CC(OC)=CC=C1N1C(C(=O)N(CC2)C=3C=CC(=CC=3)N3C(CCCC3)=O)=C2C(C(N)=O)=N1 QNZCBYKSOIHPEH-UHFFFAOYSA-N 0.000 description 17
- 208000032843 Hemorrhage Diseases 0.000 description 17
- 230000006870 function Effects 0.000 description 17
- 208000034158 bleeding Diseases 0.000 description 16
- 230000000740 bleeding effect Effects 0.000 description 16
- 239000011575 calcium Substances 0.000 description 16
- 229910052791 calcium Inorganic materials 0.000 description 16
- 239000013610 patient sample Substances 0.000 description 16
- 229960001148 rivaroxaban Drugs 0.000 description 16
- 229960003886 apixaban Drugs 0.000 description 15
- 239000003153 chemical reaction reagent Substances 0.000 description 14
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 13
- YBSJFWOBGCMAKL-UHFFFAOYSA-N dabigatran Chemical compound N=1C2=CC(C(=O)N(CCC(O)=O)C=3N=CC=CC=3)=CC=C2N(C)C=1CNC1=CC=C(C(N)=N)C=C1 YBSJFWOBGCMAKL-UHFFFAOYSA-N 0.000 description 13
- 229920000669 heparin Polymers 0.000 description 13
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 12
- 108010094028 Prothrombin Proteins 0.000 description 12
- 230000004807 localization Effects 0.000 description 12
- 102100026735 Coagulation factor VIII Human genes 0.000 description 11
- HGVDHZBSSITLCT-JLJPHGGASA-N Edoxaban Chemical compound N([C@H]1CC[C@@H](C[C@H]1NC(=O)C=1SC=2CN(C)CCC=2N=1)C(=O)N(C)C)C(=O)C(=O)NC1=CC=C(Cl)C=N1 HGVDHZBSSITLCT-JLJPHGGASA-N 0.000 description 11
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 11
- 208000015294 blood coagulation disease Diseases 0.000 description 11
- 210000001772 blood platelet Anatomy 0.000 description 11
- 229960003850 dabigatran Drugs 0.000 description 11
- 238000005259 measurement Methods 0.000 description 11
- 208000009292 Hemophilia A Diseases 0.000 description 10
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 10
- 239000013642 negative control Substances 0.000 description 10
- 229960000622 edoxaban Drugs 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- 108010014173 Factor X Proteins 0.000 description 8
- 108010074864 Factor XI Proteins 0.000 description 8
- 108010080805 Factor XIa Proteins 0.000 description 8
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 8
- 229960002897 heparin Drugs 0.000 description 8
- 238000013169 thromboelastometry Methods 0.000 description 8
- 102100022641 Coagulation factor IX Human genes 0.000 description 7
- 206010010356 Congenital anomaly Diseases 0.000 description 7
- 108010080865 Factor XII Proteins 0.000 description 7
- 102000000429 Factor XII Human genes 0.000 description 7
- 108010071241 Factor XIIa Proteins 0.000 description 7
- 206010028980 Neoplasm Diseases 0.000 description 7
- 102100027378 Prothrombin Human genes 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 230000010100 anticoagulation Effects 0.000 description 7
- 201000011510 cancer Diseases 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 238000011156 evaluation Methods 0.000 description 7
- 229940039716 prothrombin Drugs 0.000 description 7
- 201000003542 Factor VIII deficiency Diseases 0.000 description 6
- 108010073385 Fibrin Proteins 0.000 description 6
- 102000009123 Fibrin Human genes 0.000 description 6
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 6
- 208000007536 Thrombosis Diseases 0.000 description 6
- 229950011103 betrixaban Drugs 0.000 description 6
- 229950003499 fibrin Drugs 0.000 description 6
- 208000009429 hemophilia B Diseases 0.000 description 6
- 208000014674 injury Diseases 0.000 description 6
- 239000012313 reversal agent Substances 0.000 description 6
- 230000008733 trauma Effects 0.000 description 6
- 108090000190 Thrombin Proteins 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 230000009852 coagulant defect Effects 0.000 description 5
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 5
- 230000004064 dysfunction Effects 0.000 description 5
- 201000007219 factor XI deficiency Diseases 0.000 description 5
- 230000003480 fibrinolytic effect Effects 0.000 description 5
- 239000012530 fluid Substances 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 238000001356 surgical procedure Methods 0.000 description 5
- 229960004072 thrombin Drugs 0.000 description 5
- 229940019333 vitamin k antagonists Drugs 0.000 description 5
- 229960005080 warfarin Drugs 0.000 description 5
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 5
- 208000031220 Hemophilia Diseases 0.000 description 4
- 101000609261 Homo sapiens Plasminogen activator inhibitor 2 Proteins 0.000 description 4
- 102100039419 Plasminogen activator inhibitor 2 Human genes 0.000 description 4
- 230000007488 abnormal function Effects 0.000 description 4
- XHOLNRLADUSQLD-UHFFFAOYSA-N betrixaban Chemical compound C=1C=C(Cl)C=NC=1NC(=O)C1=CC(OC)=CC=C1NC(=O)C1=CC=C(C(=N)N(C)C)C=C1 XHOLNRLADUSQLD-UHFFFAOYSA-N 0.000 description 4
- 230000009089 cytolysis Effects 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 239000004205 dimethyl polysiloxane Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 201000007382 factor V deficiency Diseases 0.000 description 4
- 230000020764 fibrinolysis Effects 0.000 description 4
- 238000002073 fluorescence micrograph Methods 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000012544 monitoring process Methods 0.000 description 4
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 4
- 230000002035 prolonged effect Effects 0.000 description 4
- 229940024790 prothrombin complex concentrate Drugs 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 238000012549 training Methods 0.000 description 4
- 208000002004 Afibrinogenemia Diseases 0.000 description 3
- 208000023275 Autoimmune disease Diseases 0.000 description 3
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 3
- 208000027205 Congenital disease Diseases 0.000 description 3
- 208000029767 Congenital, Hereditary, and Neonatal Diseases and Abnormalities Diseases 0.000 description 3
- 206010016075 Factor I deficiency Diseases 0.000 description 3
- 108010076282 Factor IX Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 206010040047 Sepsis Diseases 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 230000001858 anti-Xa Effects 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000004364 calculation method Methods 0.000 description 3
- 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 3
- 229960003009 clopidogrel Drugs 0.000 description 3
- 208000011664 congenital factor XI deficiency Diseases 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 229960004222 factor ix Drugs 0.000 description 3
- 208000027826 familial dysfibrinogenemia Diseases 0.000 description 3
- 239000003527 fibrinolytic agent Substances 0.000 description 3
- 230000004907 flux Effects 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 208000018592 inherited blood coagulation disease Diseases 0.000 description 3
- 230000031700 light absorption Effects 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 3
- 238000012123 point-of-care testing Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000011896 sensitive detection Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 229960000103 thrombolytic agent Drugs 0.000 description 3
- 230000002537 thrombolytic effect Effects 0.000 description 3
- 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 class 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 2
- DTSJEZCXVWQKCL-BTJKTKAUSA-N (z)-but-2-enedioic acid;n-(5-chloropyridin-2-yl)-2-[[4-(n,n-dimethylcarbamimidoyl)benzoyl]amino]-5-methoxybenzamide Chemical compound OC(=O)\C=C/C(O)=O.C=1C=C(Cl)C=NC=1NC(=O)C1=CC(OC)=CC=C1NC(=O)C1=CC=C(C(=N)N(C)C)C=C1 DTSJEZCXVWQKCL-BTJKTKAUSA-N 0.000 description 2
- 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
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 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
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 2
- 206010011878 Deafness Diseases 0.000 description 2
- 206010016077 Factor IX deficiency Diseases 0.000 description 2
- 108010048049 Factor IXa Proteins 0.000 description 2
- 201000007371 Factor XIII Deficiency Diseases 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 108010067882 alpha 1-antitrypsin Pittsburgh Proteins 0.000 description 2
- 108010018823 anti-inhibitor coagulant complex Proteins 0.000 description 2
- 239000003698 antivitamin K Substances 0.000 description 2
- 230000023555 blood coagulation Effects 0.000 description 2
- 230000036760 body temperature Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000002296 eclampsia Diseases 0.000 description 2
- 229940047562 eliquis Drugs 0.000 description 2
- 201000007386 factor VII deficiency Diseases 0.000 description 2
- 208000005376 factor X deficiency Diseases 0.000 description 2
- 229940105776 factor viii inhibitor bypassing activity Drugs 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 230000023597 hemostasis Effects 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 208000002551 irritable bowel syndrome Diseases 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 239000003055 low molecular weight heparin Substances 0.000 description 2
- 229940127215 low-molecular weight heparin Drugs 0.000 description 2
- 230000005389 magnetism Effects 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- 229940089787 novel oral anticoagluant drug Drugs 0.000 description 2
- 230000004768 organ dysfunction Effects 0.000 description 2
- 238000002732 pharmacokinetic assay Methods 0.000 description 2
- 210000004623 platelet-rich plasma Anatomy 0.000 description 2
- 201000011461 pre-eclampsia Diseases 0.000 description 2
- 239000003805 procoagulant Substances 0.000 description 2
- 108010012557 prothrombin complex concentrates Proteins 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 229940011622 savaysa Drugs 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- 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 2
- 239000000243 solution Substances 0.000 description 2
- 238000011895 specific detection Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000002753 trypsin inhibitor Substances 0.000 description 2
- 238000002604 ultrasonography Methods 0.000 description 2
- 229940055725 xarelto Drugs 0.000 description 2
- 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
- IJRKANNOPXMZSG-SSPAHAAFSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;(2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O.OC(=O)CC(O)(C(O)=O)CC(O)=O IJRKANNOPXMZSG-SSPAHAAFSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 241000239290 Araneae Species 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 208000001593 Bernard-Soulier syndrome Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 229940122295 Clotting factor inhibitor Drugs 0.000 description 1
- 102100023804 Coagulation factor VII Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 206010063563 Congenital coagulopathy Diseases 0.000 description 1
- 208000028702 Congenital thrombocyte disease Diseases 0.000 description 1
- 241000725619 Dengue virus Species 0.000 description 1
- 241001115402 Ebolavirus Species 0.000 description 1
- 208000017701 Endocrine disease Diseases 0.000 description 1
- 108010014172 Factor V Proteins 0.000 description 1
- 108010023321 Factor VII Proteins 0.000 description 1
- 108010054218 Factor VIII Proteins 0.000 description 1
- 102000001690 Factor VIII Human genes 0.000 description 1
- 108010061932 Factor VIIIa Proteins 0.000 description 1
- 108010054265 Factor VIIa Proteins 0.000 description 1
- 108010074105 Factor Va Proteins 0.000 description 1
- 108010071289 Factor XIII Proteins 0.000 description 1
- 229940123583 Factor Xa inhibitor Drugs 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000710831 Flavivirus Species 0.000 description 1
- 208000012671 Gastrointestinal haemorrhages Diseases 0.000 description 1
- 208000013607 Glanzmann thrombasthenia Diseases 0.000 description 1
- 201000000584 Gray platelet syndrome Diseases 0.000 description 1
- 208000032759 Hemolytic-Uremic Syndrome Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241000270322 Lepidosauria Species 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 206010034246 Pelvic fractures Diseases 0.000 description 1
- 241000270285 Pituophis Species 0.000 description 1
- 208000013544 Platelet disease Diseases 0.000 description 1
- 238000012356 Product development Methods 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010081391 Ristocetin Proteins 0.000 description 1
- 208000003443 Unconsciousness Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 229930003448 Vitamin K Natural products 0.000 description 1
- 201000000839 Vitamin K Deficiency Bleeding Diseases 0.000 description 1
- 206010047634 Vitamin K deficiency Diseases 0.000 description 1
- 208000027276 Von Willebrand disease Diseases 0.000 description 1
- 241000907316 Zika virus Species 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000007818 agglutination assay Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000004019 antithrombin Substances 0.000 description 1
- 229960003856 argatroban Drugs 0.000 description 1
- KXNPVXPOPUZYGB-XYVMCAHJSA-N argatroban Chemical compound OC(=O)[C@H]1C[C@H](C)CCN1C(=O)[C@H](CCCN=C(N)N)NS(=O)(=O)C1=CC=CC2=C1NC[C@H](C)C2 KXNPVXPOPUZYGB-XYVMCAHJSA-N 0.000 description 1
- 208000025870 aspirin resistance Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- OIRCOABEOLEUMC-GEJPAHFPSA-N bivalirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)CNC(=O)CNC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 OIRCOABEOLEUMC-GEJPAHFPSA-N 0.000 description 1
- 229960001500 bivalirudin Drugs 0.000 description 1
- 108010055460 bivalirudin Proteins 0.000 description 1
- 239000010836 blood and blood product Substances 0.000 description 1
- 239000003130 blood coagulation factor inhibitor Substances 0.000 description 1
- 208000014759 blood platelet disease Diseases 0.000 description 1
- 229940125691 blood product Drugs 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 230000005983 bone marrow dysfunction Effects 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 230000007211 cardiovascular event Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- BGTFCAQCKWKTRL-YDEUACAXSA-N chembl1095986 Chemical compound C1[C@@H](N)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]([C@H]1C(N[C@H](C2=CC(O)=CC(O[C@@H]3[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)=C2C=2C(O)=CC=C(C=2)[C@@H](NC(=O)[C@@H]2NC(=O)[C@@H]3C=4C=C(C(=C(O)C=4)C)OC=4C(O)=CC=C(C=4)[C@@H](N)C(=O)N[C@@H](C(=O)N3)[C@H](O)C=3C=CC(O4)=CC=3)C(=O)N1)C(O)=O)=O)C(C=C1)=CC=C1OC1=C(O[C@@H]3[C@H]([C@H](O)[C@@H](O)[C@H](CO[C@@H]5[C@H]([C@@H](O)[C@H](O)[C@@H](C)O5)O)O3)O[C@@H]3[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O[C@@H]3[C@H]([C@H](O)[C@@H](CO)O3)O)C4=CC2=C1 BGTFCAQCKWKTRL-YDEUACAXSA-N 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 229960005188 collagen Drugs 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 239000003145 cytotoxic factor Substances 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000009547 development abnormality Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 208000009190 disseminated intravascular coagulation Diseases 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 208000030172 endocrine system disease Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960000610 enoxaparin Drugs 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 108010091897 factor V Leiden Proteins 0.000 description 1
- 229940012413 factor vii Drugs 0.000 description 1
- 229940012414 factor viia Drugs 0.000 description 1
- 229960000301 factor viii Drugs 0.000 description 1
- 229940012444 factor xiii Drugs 0.000 description 1
- KANJSNBRCNMZMV-ABRZTLGGSA-N fondaparinux Chemical compound O[C@@H]1[C@@H](NS(O)(=O)=O)[C@@H](OC)O[C@H](COS(O)(=O)=O)[C@H]1O[C@H]1[C@H](OS(O)(=O)=O)[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O[C@@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O4)NS(O)(=O)=O)[C@H](O3)C(O)=O)O)[C@@H](COS(O)(=O)=O)O2)NS(O)(=O)=O)[C@H](C(O)=O)O1 KANJSNBRCNMZMV-ABRZTLGGSA-N 0.000 description 1
- 229960001318 fondaparinux Drugs 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 208000030304 gastrointestinal bleeding Diseases 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 208000031169 hemorrhagic disease Diseases 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 230000000642 iatrogenic effect Effects 0.000 description 1
- 229960002308 idarucizumab Drugs 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 230000001000 lipidemic effect Effects 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000014508 negative regulation of coagulation Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 208000028591 pheochromocytoma Diseases 0.000 description 1
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- -1 polydimethylsiloxane Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000003331 prothrombotic effect Effects 0.000 description 1
- 238000013102 re-test Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229950004257 ristocetin Drugs 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 239000002435 venom Substances 0.000 description 1
- 231100000611 venom Toxicity 0.000 description 1
- 210000001048 venom Anatomy 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 235000019168 vitamin K Nutrition 0.000 description 1
- 239000011712 vitamin K Substances 0.000 description 1
- 208000016794 vitamin K deficiency hemorrhagic disease Diseases 0.000 description 1
- 150000003721 vitamin K derivatives Chemical class 0.000 description 1
- 229940046010 vitamin k Drugs 0.000 description 1
- 208000012137 von Willebrand disease (hereditary or acquired) Diseases 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/482—Serine endopeptidases (3.4.21)
- A61K38/4846—Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38)
-
- 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
- G01N33/4905—Determining clotting time of blood
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502746—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means for controlling flow resistance, e.g. flow controllers, baffles
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502761—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
-
- 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/16—Surface properties and coatings
- B01L2300/161—Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
- B01L2300/165—Specific details about hydrophobic, oleophobic surfaces
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/08—Regulating or influencing the flow resistance
- B01L2400/084—Passive control of flow resistance
- B01L2400/088—Passive control of flow resistance by specific surface properties
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Medicinal Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Biochemistry (AREA)
- Pathology (AREA)
- Dispersion Chemistry (AREA)
- Clinical Laboratory Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Ecology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Fluid Mechanics (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Automatic Analysis And Handling Materials Therefor (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762538618P | 2017-07-28 | 2017-07-28 | |
| US62/538,618 | 2017-07-28 | ||
| US201862699665P | 2018-07-17 | 2018-07-17 | |
| US62/699,665 | 2018-07-17 | ||
| PCT/US2018/043973 WO2019023508A1 (en) | 2017-07-28 | 2018-07-26 | METHODS AND DEVICES FOR DETECTION OF ANTICOAGULANTS IN PLASMA AND WHOLE BLOOD |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2020529593A JP2020529593A (ja) | 2020-10-08 |
| JP2020529593A5 JP2020529593A5 (enExample) | 2021-08-26 |
| JP7214712B2 true JP7214712B2 (ja) | 2023-01-30 |
Family
ID=63405342
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020504364A Active JP7214712B2 (ja) | 2017-07-28 | 2018-07-26 | 血漿および全血中の抗凝固薬の検出のための方法ならびにデバイス |
Country Status (10)
| Country | Link |
|---|---|
| US (4) | US20190111431A1 (enExample) |
| EP (1) | EP3658920A1 (enExample) |
| JP (1) | JP7214712B2 (enExample) |
| KR (1) | KR20200034749A (enExample) |
| CN (1) | CN111094990A (enExample) |
| AU (1) | AU2018307799A1 (enExample) |
| CA (1) | CA3071295A1 (enExample) |
| IL (1) | IL272320A (enExample) |
| SG (1) | SG11202000688UA (enExample) |
| WO (1) | WO2019023508A1 (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2750839C1 (ru) * | 2020-05-18 | 2021-07-05 | Общество с ограниченной ответственностью "Меднорд-Техника" (ООО "Меднорд-Т") | Устройство и способ экспресс-оценки агрегационной активности форменных элементов крови |
| US20220283190A1 (en) * | 2021-03-08 | 2022-09-08 | Galit H. Frydman | Methods and devices for detection of coagulation impairment |
| CN113945551A (zh) * | 2021-10-19 | 2022-01-18 | 重庆医科大学附属永川医院 | 一种血小板功能的微流控分析检测模型 |
| CN114558629B (zh) * | 2022-03-03 | 2024-06-04 | 四川微康朴澜医疗科技有限责任公司 | 一种微流控式血栓弹力分析检测试剂盒 |
| IL319816A (en) | 2022-09-30 | 2025-05-01 | Coagulo Medical Tech Inc | Modular microfluidic cartridge testing device, useful for point-of-care medical diagnostics and other applications |
| WO2025132678A1 (en) * | 2023-12-19 | 2025-06-26 | F. Hoffmann-La Roche Ag | Qualitative test for direct oral anticoagulants (doacs) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140038204A1 (en) | 2012-07-31 | 2014-02-06 | Baxter Healthcare S.A. | Selective measurement of active human protease coagulation factors |
| US20140038214A1 (en) | 2012-06-27 | 2014-02-06 | Colorado School Of Mines | Microfluidic flow assay and methods of use |
| JP2014038109A (ja) | 2007-09-20 | 2014-02-27 | Iline Microsystems Sl | マイクロ流体デバイスおよび流体の凝固時間測定方法 |
| US20140236494A1 (en) | 2011-11-04 | 2014-08-21 | Massachusetts Institute Of Technology | Multi-parameter thrombotic assay apparatus, systems, and methods |
| US20160069913A1 (en) | 2014-09-09 | 2016-03-10 | Perosphere Inc. | Microfluidic chip-based, universal coagulation assay |
| JP2016534714A (ja) | 2013-10-16 | 2016-11-10 | プレジデント アンド フェローズ オブ ハーバード カレッジ | 全血凝固のリアルタイムの臨床モニタリングおよび定量的評価 |
-
2018
- 2018-07-26 CN CN201880059719.9A patent/CN111094990A/zh active Pending
- 2018-07-26 JP JP2020504364A patent/JP7214712B2/ja active Active
- 2018-07-26 EP EP18760075.4A patent/EP3658920A1/en not_active Withdrawn
- 2018-07-26 CA CA3071295A patent/CA3071295A1/en active Pending
- 2018-07-26 WO PCT/US2018/043973 patent/WO2019023508A1/en not_active Ceased
- 2018-07-26 US US16/046,816 patent/US20190111431A1/en not_active Abandoned
- 2018-07-26 SG SG11202000688UA patent/SG11202000688UA/en unknown
- 2018-07-26 KR KR1020207004767A patent/KR20200034749A/ko not_active Abandoned
- 2018-07-26 AU AU2018307799A patent/AU2018307799A1/en not_active Abandoned
-
2020
- 2020-01-28 IL IL272320A patent/IL272320A/en unknown
-
2023
- 2023-01-25 US US18/159,281 patent/US20230166255A1/en not_active Abandoned
- 2023-01-25 US US18/159,276 patent/US20230158498A1/en not_active Abandoned
- 2023-01-25 US US18/159,283 patent/US20230158499A1/en not_active Abandoned
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014038109A (ja) | 2007-09-20 | 2014-02-27 | Iline Microsystems Sl | マイクロ流体デバイスおよび流体の凝固時間測定方法 |
| US20140236494A1 (en) | 2011-11-04 | 2014-08-21 | Massachusetts Institute Of Technology | Multi-parameter thrombotic assay apparatus, systems, and methods |
| US20140038214A1 (en) | 2012-06-27 | 2014-02-06 | Colorado School Of Mines | Microfluidic flow assay and methods of use |
| US20140038204A1 (en) | 2012-07-31 | 2014-02-06 | Baxter Healthcare S.A. | Selective measurement of active human protease coagulation factors |
| JP2016534714A (ja) | 2013-10-16 | 2016-11-10 | プレジデント アンド フェローズ オブ ハーバード カレッジ | 全血凝固のリアルタイムの臨床モニタリングおよび定量的評価 |
| US20160069913A1 (en) | 2014-09-09 | 2016-03-10 | Perosphere Inc. | Microfluidic chip-based, universal coagulation assay |
Non-Patent Citations (4)
| Title |
|---|
| Abhishek Jain,A shear gradient-activated microfluidic device for automated monitoring of whole blood haemostasis and platelet function,Nat. Commun.,2016年01月06日,Vol.7,Page.10176 |
| Jerome Duchemin,Influence of coagulation factors and tissue factor concentration on the thrombin generation test in plasma,Thromb Haemost,2008年03月12日,Vol.99,Page.767-773 |
| S Nayak,Using a Systems Pharmacology Model of the Blood Coagulation Network to Predict the Effects of Various Therapies on Biomarkers,CPT Pharmacometrics Syst. Pharmacol.,2015年06月19日,Vol.4,Page.396-405 |
| Shannon M. Bates,Coagulation Assays,Circulation,2005年,Vol.112,Page.e53-e60 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2019023508A1 (en) | 2019-01-31 |
| KR20200034749A (ko) | 2020-03-31 |
| US20190111431A1 (en) | 2019-04-18 |
| IL272320A (en) | 2020-03-31 |
| JP2020529593A (ja) | 2020-10-08 |
| AU2018307799A1 (en) | 2020-02-13 |
| SG11202000688UA (en) | 2020-02-27 |
| US20230166255A1 (en) | 2023-06-01 |
| CA3071295A1 (en) | 2019-01-31 |
| EP3658920A1 (en) | 2020-06-03 |
| US20230158499A1 (en) | 2023-05-25 |
| US20230158498A1 (en) | 2023-05-25 |
| CN111094990A (zh) | 2020-05-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7214712B2 (ja) | 血漿および全血中の抗凝固薬の検出のための方法ならびにデバイス | |
| Yang et al. | Prothrombin time | |
| JP7250744B2 (ja) | 凝固分析を使用した抗凝固剤の検出および分類 | |
| Schmidt et al. | The utility of thromboelastography to guide blood product transfusion: an ACLPS critical review | |
| Bliden et al. | Determination of non-Vitamin K oral anticoagulant (NOAC) effects using a new-generation thrombelastography TEG 6s system | |
| Levi et al. | A critical appraisal of point‐of‐care coagulation testing in critically ill patients | |
| Chee | Coagulation | |
| US20180185839A1 (en) | Microfluidic Device For Real-Time Clinical Monitoring And Quantitative Assessment Of Whole Blood Coagulation | |
| Van Veen et al. | Routine preoperative coagulation tests: an outdated practice? | |
| CN106574922A (zh) | 用于检测纤维蛋白溶解和纤溶亢进的方法学和试剂 | |
| WO2011057143A1 (en) | Compositions, methods and uses for simultaneous assay of thrombin and plasmin generation | |
| Dengate et al. | Differentiation between dogs with thrombosis and normal dogs using the overall hemostasis potential assay | |
| Brooks | Equine coagulopathies | |
| Zehnder et al. | Clinical use of coagulation tests | |
| US20220283190A1 (en) | Methods and devices for detection of coagulation impairment | |
| Vollmer et al. | A review of thromboelastography for nurses | |
| Thonon et al. | Hemostasis testing in the emergency department: a narrative review | |
| Caruso et al. | Point-of-care diagnostic assays and novel preclinical technologies for hemostasis and thrombosis | |
| Jardim et al. | Hypocoagulability in severe yellow fever infection is associated with bleeding: results from a cohort study | |
| Arpaci et al. | Does glycemic regulation affect hypercoagulable states in diabetic patients? | |
| Enifeni et al. | Relationships between transcranial Doppler velocity, Von Willebrand Factor, Factor VIII, and hematological parameters in children with sickle cell anemia: a comparative cross-sectional study | |
| Giansante et al. | Monitoring of hemostasis | |
| Pourang et al. | Comparison of Whole Blood Coagulation Profiles in COVID-19 and Sepsis Patients Using a Handheld Dielectric Coagulometer | |
| Spannagl et al. | Laboratory coagulation tests | |
| US11630101B2 (en) | Method for diagnosing anomalies in the coagulation of blood |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210714 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20210714 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20220524 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220530 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20220809 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20221026 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20221122 |
|
| 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: 20221222 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20230118 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 7214712 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |