Pharmacology
Procoagulants
The use of adsorbent chemicals, such as
eolites, and
other
hemostatic agents is also being explored for use in sealing severe injuries
quickly. Thrombin and fibrin glue are used surgically to treat bleeding and to
thrombose aneurysms.
Desmopressin is used to improve platelet function by activating
arginine vasopressin receptor 1A.
Coagulation factor concentrates are used to treat
hemophilia, to reverse the effects of anticoagulants, and to treat bleeding
in patients with impaired coagulation factor synthesis or increased consumption.
Prothrombin complex concentrate,
cryoprecipitate and
fresh frozen plasma are commonly-used coagulation factor products.
ecombinant
activated human factor VII is are increasingly popular in the treatment of
major bleeding.
Tranexamic acid and
aminocaproic acid inhibit fibrinolysis, and lead to a de facto
reduced bleeding rate. Before its withdrawal,
protinin
was used in some forms of major surgery to decrease bleeding risk and need for
blood products.
Anticoagulants
-
Anticoagulants and anti-platelet agents are amongst the most commonly used
medicines.
Anti-platelet agents include
spirin,
clopidogrel,
dipyridamole and
ticlopidine; the parenteral
glycoprotein IIb/IIIa inhibitors are used during
angioplasty.
Of the anticoagulants,
arfarin
(and related
coumarins) and
eparin are
the most commonly used. Warfarin interacts with vitamin K, while heparin and
related compounds increase the action of antithrombin on thrombin and factor Xa.
A newer class of drugs, the
direct thrombin inhibitors, is under development; some members are already
in clinical use (such as
epirudin).
Also under development are other small molecular compounds that interfere
directly with the enzymatic action of particular coagulation factors (e.g.
rivaroxaban).
Coagulation factors
Coagulation factors and related substances
| Number and/or name |
Function |
| I (ibrinogen) |
Forms clot (fibrin) |
| II (rothrombin) |
Its active form (IIa) activates I, V, VIII, XI, XIII, protein C,
platelets |
|
Tissue factor |
Co-factor of VIIa (formerly known as factor III) |
|
Calcium |
Required for coagulation factors to bind to phospholipid (formerly
known as factor IV) |
|
(proaccelerin, labile factor) |
Co-factor of X with which it forms the
prothrombinase complex |
| VI |
Unassigned � old name of Factor Va |
|
II
(stable factor) |
Activates IX, X |
|
VIII (antihemophilic factor) |
Co-factor of IX with which it forms the
enase
complex |
|
IX (Christmas factor) |
Activates X: forms
enase
complex with factor VIII |
|
(Stuart-Prower factor) |
Activates II: forms
prothrombinase complex with factor V |
|
XI (plasma thromboplastin antecedent) |
Activates IX |
|
II
(Hageman factor) |
Activates factor XI and prekallikrein |
|
XIII (fibrin-stabilizing factor) |
Crosslinks fibrin |
|
von Willebrand factor |
Binds to VIII, mediates platelet adhesion |
|
prekallikrein |
Activates XII and prekallikrein; cleaves HMWK |
|
high molecular weight kininogen (HMWK) |
Supports reciprocal activation of XII, XI, and prekallikrein |
|
fibronectin |
Mediates cell adhesion |
|
antithrombin III |
Inhibits IIa, Xa, and other proteases; |
|
heparin cofactor II |
Inhibits IIa, cofactor for heparin and
dermatan sulfate ("minor antithrombin") |
|
protein C |
Inactivates Va and VIIIa |
|
protein S |
Cofactor for activated protein C (APC, inactive when bound to
C4b-binding protein) |
|
protein Z |
Mediates thrombin adhesion to phospholipids and stimulates
degradation of factor X by ZPI |
|
Protein Z-related protease inhibitor (ZPI) |
Degrades factors X (in presence of protein Z) and XI (independently) |
|
plasminogen |
Converts to plasmin, lyses fibrin and other proteins |
|
alpha 2-antiplasmin |
Inhibits plasmin |
|
tissue plasminogen activator (tPA) |
Activates plasminogen |
|
urokinase |
Activates plasminogen |
|
plasminogen activator inhibitor-1 (PAI1) |
Inactivates tPA & urokinase (endothelial PAI) |
|
plasminogen activator inhibitor-2 (PAI2) |
Inactivates tPA & urokinase (lacental
PAI) |
|
cancer procoagulant |
Pathological
actor
X activator linked to thrombosis in
ancer |
|
