Abstract: A method of monitoring thrombus formation is described, which comprises flowing anticoagulated blood into a thrombus formation chamber, in at least a part of which a thrombus formation inducer inducing thrombus formation is provided, while releasing the anticoagulant treatment or promoting blood coagulation to thereby monitor thrombus formation in the thrombus formation chamber.

Abstract: An apparatus for monitoring thrombus formation wherein anticoagulated blood is flown through a channel simulating a blood vessel while releasing the anticoagulant treatment or promoting blood coagulation to thereby monitor thrombus formation. This apparatus for monitoring thrombus formation comprises: a thrombus formation chamber in at least a part of which a thrombus formation inducer inducing thrombus formation is provided; an inlet tube which is connected to the thrombus formation chamber and through which blood is flown into the thrombus formation chamber; and a drug tube which is connected to the inlet tube and through which a drug releasing the anticoagulant treatment or a drug promoting blood coagulation is supplied.

Abstract: A microchip for measuring platelet function by allowing blood to flow through a channel to induce platelet aggregation, wherein the microchip has a channel provided inside thereof, wherein at least a part of the channel is coated with collagen for allowing adhesion of platelets; a plurality of walls extend along the direction of the flow of blood in the channel and divide the width of the channel to form a channel dividing section; and the walls are treated to have a surface roughness (Ra) of 10 to 200 nm.

Abstract: A microchip comprising therein a first channel which allows inflow of a first liquid selected from whole blood, platelet-rich plasma and a drug-treated liquid thereof, a second channel connected to the first channel, which allows inflow of a second liquid containing an agent that is reactive with the first liquid, and a merged channel extended from the connection portion of the first channel with the second channel, wherein, in the merged channel, a stirring section having a stirring bar for mixing the first liquid with the second liquid is provided; and a blood monitoring device using the same.

Abstract: An apparatus for monitoring thrombus formation wherein anticoagulated blood is flown through a channel simulating a blood vessel while releasing the anticoagulant treatment or promoting blood coagulation to thereby monitor thrombus formation. This apparatus for monitoring thrombus formation comprises: a thrombus formation chamber in at least a part of which a thrombus formation inducer inducing thrombus formation is provided; an inlet tube which is connected to the thrombus formation chamber and through which blood is flown into the thrombus formation chamber; and a drug tube which is connected to the inlet tube and through which a drug releasing the anticoagulant treatment or a drug promoting blood coagulation is supplied.

Abstract: A microchip for measuring platelet function by allowing blood to flow through a channel to induce platelet aggregation, wherein the microchip comprises a channel provided inside thereof, wherein at least a part of the channel is coated with collagen for allowing adhesion of platelets; a plurality of walls extend along the direction of the flow of blood in the channel and divide the width of the channel to form a channel dividing section; and the walls are treated to have a surface roughness (Ra) of 10 to 200 nm.

Abstract: A thrombin mutant in which at least serine at position 205 among amino acids in the active center of the thrombin B chain has been replaced with another amino acid, and further at least one of the following replacements have been introduced: (I) replacement of arginine at position 89 in the B-chain with another amino acid; (II) replacement of threonine at position 69 or serine at position 22 in the B-chain with another amino acid; (III) replacement of alanine at position 200 in the B-chain with another amino acid; and (IV) replacement of lysine at position 65 in the B-chain with threonine.

Abstract: A method for testing platelet function, wherein platelet function is tested by allowing anticoagulated blood, to which a weak platelet-activating reagent has been mixed, to pass through a capillary having a platelet-adhesive surface on at least a part of its inner surface, and observing or measuring the behavior of the blood in the capillary.

Abstract: A microchip comprising therein a first channel which allows inflow of a first liquid selected from whole blood, platelet-rich plasma and a drug-treated liquid thereof, a second channel connected to the first channel, which allows inflow of a second liquid containing an agent that is reactive with the first liquid, and a merged channel extended from the connection portion of the first channel with the second channel, wherein, in the merged channel, a stirring section having a stirring bar for mixing the first liquid with the second liquid is provided; and a blood monitoring device using the same.

Abstract: An apparatus for monitoring thrombus formation wherein anticoagulated blood is flown through a channel simulating a blood vessel while releasing the anticoagulant treatment or promoting blood coagulation to thereby monitor thrombus formation. This apparatus for monitoring thrombus formation comprises: a thrombus formation chamber in at least a part of which a thrombus formation inducer inducing thrombus formation is provided; an inlet tube which is connected to the thrombus formation chamber and through which blood is flown into the thrombus formation chamber; and a drug tube which is connected to the inlet tube and through which a drug releasing the anticoagulant treatment or a drug promoting blood coagulation is supplied.

Abstract: The present invention provides a thrombin derivative, comprising an A chain and a B chain, the B chain having an amino acid sequence in which one or more kinds of active center amino acids selected from the group consisting of serine at position 205, glycine at position 203, aspartic acid at position 99, and histidine at position 43 in an amino acid sequence of a thrombin B chain are substituted, having the properties: (1) cleaving a thrombin substrate at the ratio of 10% or less when it is reacted with the thrombin substrate in 50 mM Tris-HCl (pH 7.4) containing 0.1 M NaCl at 37° C. for 3 hours, and (2) maintaining a structure of exosite I.

Abstract: A thrombin derivative having a lowered fibrinogen activity, a process for producing thereof, an anhydrothrombin derivative having a lowered fibrinogen activity, and a process for producing thereof are provided. This invention is to provide a thrombin derivative formed by modifying carboxyl group(s) of the thrombin and an anhydrothrombin derivative formed by modifying carboxyl group(s) of the anhydrothrombin. The thrombin derivative can be utilized as a composition for inducing platelet aggregation and further as a reagent of specific aggregation for clinical testing and the like. By affinity chromatography using carboxyl group(s) bound with anhydrothrombin as a ligand, it is made possible to carry out necessary purification with high selectivity relative to the blood coagulation factor VIII.

Abstract: A thrombin derivative having a lowered fibrinogen activity, a process for producing thereof, an anhydrothrombin derivative having a lowered fibrinogen activity, and a process for producing thereof are provided. This invention is to provide a thrombin derivative formed by modifying carboxyl group(s) of the thrombin and an anhydrothrombin derivative formed by modifying carboxyl group(s) of the anhydrothrombin. The thrombin derivative can be utilized as a composition for inducing platelet aggregation and further as a reagent of specific aggregation for clinical testing and the like. By the affinity chromatography having carboxyl group(s) bound with anhydrothrombin as a ligand, it is made possible to carry out necessary purification with high selectivity relative to the blood coagulation factor VIII.

Abstract: A method for the refinement of a thrombin substrate, characterized by comprising therein a step of affinity chromatography formed by using an affinity adsorbent having as a ligand a thrombin or thrombin analogue deprived of nucleophilicity (activity) without causing stereostructure to the linkage with a substrate is disclosed.

Abstract: A method for a synthesis of anhydrothrombin is provided which features a short process, an easy procedure, and high yields.The method comprises(A) a step of causing an active serine residue site of thrombin to react with an inhibitor,(B) a step of performing an alkali treatment at a pH of not less than 11, and(C) a step of performing an operation of recovery, and carries out these steps sequentially in the order mentioned, and is characterized by causing at least the step of performing the operation of recovery to proceed in the presence of at least one compound selected from the group consisting of polyhydric alcohols and saccharides, and a salt or an amphoteric electrolyte.