Page last updated: 2024-10-24

positive regulation of coagulation

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of coagulation. [GOC:ai]

Positive regulation of coagulation is a complex biological process that involves a series of enzymatic reactions leading to the formation of a stable fibrin clot. This process is tightly regulated to ensure that clotting occurs only when necessary to prevent excessive bleeding, while avoiding inappropriate clot formation that can lead to thrombosis.

The coagulation cascade can be divided into three main phases:

1. **Initiation:** This phase is triggered by tissue injury, exposing tissue factor (TF) to the bloodstream. TF binds to Factor VIIa, activating it. The activated complex of TF and Factor VIIa then activates Factor X, marking the beginning of the coagulation cascade.

2. **Amplification:** Once Factor X is activated, it initiates the amplification phase by converting prothrombin to thrombin. This is a crucial step as thrombin is a key enzyme in the coagulation process. Thrombin has multiple roles, including:

* Cleaving fibrinogen to fibrin, forming the meshwork of the clot
* Activating Factor V and Factor VIII, further amplifying the cascade
* Activating platelets, contributing to clot stability
* Stimulating the release of more TF, initiating a positive feedback loop

3. **Propagation:** This phase involves the formation of a stable fibrin clot. Thrombin cleaves fibrinogen, generating fibrin monomers that self-assemble into a fibrin mesh. This mesh traps platelets and red blood cells, forming a stable clot that stops bleeding.

Positive regulation of coagulation involves mechanisms that enhance or accelerate the coagulation cascade. These include:

* **Increased production of clotting factors:** Various stimuli, including tissue injury and inflammation, can trigger the liver to produce more clotting factors, leading to a faster and more robust coagulation response.
* **Increased expression of TF:** The expression of TF, a key initiator of the coagulation cascade, can be upregulated by various factors, including inflammatory cytokines and tissue injury.
* **Activation of platelets:** Platelets play a crucial role in the coagulation process, adhering to the site of injury and releasing factors that promote clot formation.
* **Positive feedback loops:** The coagulation cascade itself is subject to positive feedback loops, where the products of the cascade further amplify the process. For example, thrombin activates Factor VIII, which in turn further activates Factor X, amplifying the cascade.

**Regulation of coagulation is crucial to maintain homeostasis and prevent both bleeding and thrombosis. While positive regulation is essential to ensure proper clotting, it must be tightly controlled to prevent excessive clotting that can lead to dangerous complications.**'
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Proteins (2)

ProteinDefinitionTaxonomy
Vitamin K epoxide reductase complex subunit 1 A vitamin K epoxide reductase complex subunit 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9BQB6]Homo sapiens (human)
Presenilin-1A presenilin-1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P49768]Homo sapiens (human)

Compounds (23)

CompoundDefinitionClassesRoles
tocopheroxy radicaltocopheroxy radical: RN given refers to radical ion (1+), (2R-(2R*(4R*,8R*)))-isomer; RN for cpd without isomeric designation not available 12/90tocopherol
7-amino-4-chloro-3-methoxy-2-benzopyran-1-oneisocoumarins
tarenflurbiltarenflurbil: R-enantiomer of flurbiprofen but not a COX inhibitor; modulates NF-kB, gamma-secretase, amyloid beta-protein;flurbiprofen
cholanic acid5beta-cholanic acids;
cholanic acid
t0901317T0901317: an LXRalpha and LXRbeta agonist
n-(n-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl esterDAPT : A dipeptide consisting of alanylphenylglycine derivatised as a 3,5-difluorophenylacetamide at the amino terminal and a tert-butyl ester at the carboxy terminal. A gamma-secretase inhibitor.carboxylic ester;
difluorobenzene;
dipeptide;
tert-butyl ester
EC 3.4.23.46 (memapsin 2) inhibitor
sulindac sulfidesulindac sulfide : An aryl sulfide that is a metabolite of sulindac. A non-steroidal anti-inflammatory drug, which also has anticancer activity.

sulindac sulfide: sulfated analog of indomethacin & inhibitor of prostaglandin synthesis in vitro; RN given refers to cpd without isomeric designation; structure given in first source
aryl sulfide;
monocarboxylic acid;
organofluorine compound
antineoplastic agent;
apoptosis inducer;
non-steroidal anti-inflammatory drug
l 685458L 685458: a gamma-secretase inhibitor; structure in first source

L-685,458 : A peptide and carboxamide that is L-leucyl-L-phenylalaninamide, L-Leu-L-Phe-NH2, which has been acylated on the N-terminus by a Phe-Phe hydroxyethylene dipeptide isotere, 2R-benzyl-5S-tert-butoxycarbonylamino-4R-hydroxy-6-phenylhexanoic acid. Compounds based on the structure of L-685,458 are potent inhibitors of gamma-secretase, which mediates the final catalytic step that generates the amyloid beta-peptide (Abeta), which assembles into the neurotoxic aggregates in the brains of sufferers of Alzheimer's disease.
carbamate ester;
monocarboxylic acid amide;
peptide;
secondary alcohol
EC 3.4.23.46 (memapsin 2) inhibitor;
peptidomimetic
mk 0752
ly 450139peptide
chf 50741-(3',4'-dichloro-2-fluoro(1,1'-biphenyl)-4-yl)cyclopropanecarboxylic acid: a beta-amyloid(1-42) lowering agent; structure in first source
ly 411575dibenzoazepine;
difluorobenzene;
lactam;
secondary alcohol
EC 3.4.23.46 (memapsin 2) inhibitor
4-(2-((1r)-1-(((4-chlorophenyl)sulfonyl)-2,5-difluoroanilino)ethyl)-5-fluorophenyl)butanoic acidsulfonamide
begacestat
e 2012
mrk 560MRK 560: a gamma-secretase inhibitor; MRK-560 is the (cis)-isomer; structure in first source
1, 3-di-(n-carboxybenzoyl-leucyl-leucyl)amino acetone1, 3-di-(N-carboxybenzoyl-leucyl-leucyl)amino acetone: structure in first source
pf 3084014nirogacestat : A member of the class of imidazoles that is 1H-imidazole substituted by a 1-[(2,2-dimethylpropyl)amino]-2-methylpropan-2-yl group at position 1 and a {N-[(2S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl]-L-norvalyl}amino group at position 4. It is a gamma-secretase inhibitor whose hydrobromide salt is indicated for adult patients with progressing desmoid tumours who require systemic treatment.

nirogacestat: an antineoplastic agent
bms 708163BMS 708163: structure in first sourceoxadiazole;
ring assembly
ro 4929097dibenzoazepine;
dicarboxylic acid diamide;
lactam;
organofluorine compound
EC 3.4.23.46 (memapsin 2) inhibitor
jnj 40418677
(r)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1h-pyrazolo(4,3-c)quinoline(R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo(4,3-c)quinoline: gamma secretase inhibitor; structure in first source
warfarin4-hydroxy-3-(3-oxo-1-phenylbutyl)-1-benzopyran-2-one : A member of the class of coumarins that is 4-hydroxycoumarin which is substituted at position 3 by a 1-phenyl-3-oxo-1-butyl group.

warfarin : A racemate comprising equal amounts of (R)- and (S)-warfarin. Extensively used as both an anticoagulant drug and as a pesticide against rats and mice.

Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.
benzenes;
hydroxycoumarin;
methyl ketone