Coagulation is "the process of the interaction of blood coagulation factors that results in an insoluble fibrin clot."
|Pathway||Diagnostic test||Blood coagulation factor||Half-life||Abnormalities|
|Intrinsic||Partial thromboplastin time
|Factor VIII (Antihemophilic factor)|
|Factor IX||24 hours||Liver failure, heparin, warfarin therapy, Vitamin K deficiency|
|Factor X||40 hours||Liver failure, heparin, warfarin therapy, Vitamin K deficiency|
|Factor XI||Liver failure|
|Factor XII||Liver failure|
|Factor VII (Proconvertin; Stable factor)||5-7 hours||Liver failure, warfarin therapy, Vitamin K deficiency|
|Factor X||40 hours||Liver failure|
|Final Common Pathway||PT & PTT||Factor I (fibrinogen)||Liver failure|
|Factor II (prothrombin)||3 days||Liver failure, warfarin therapy, Vitamin K deficiency|
Factor X is a member of both the intrinsic and extrinsic pathways and, as with abnormalities of the final common pathway, affects both the partial thromboplastin time and the prothrombin time
Details and figures depicting the coagulation pathways are available online at the National Library of Medicine.
Production of coagulation factors
The synthesis of coagulation factors II, VII, IX, and X and proteins C and S is dependent on vitamin K. The half-lives of the cofactors range from five to seven hours for factor VII to 3 days for factor II (prothrombin).
Disorders of coagulation
Blood coagulation disorders are "hemorrhagic and thrombotic disorders that occur as a consequence of abnormalities in blood coagulation due to a variety of factors such as coagulation protein disorders; blood platelet disorders; blood protein disorders or nutritional conditions."
Factor I deficiency
Deficiency of Factor I (fibrinogen) may be inherited (afibrinogenemia) or acquired.
Factor II deficiency
Factor V deficiency
Factor V deficiency is a "(known as proaccelerin or accelerator globulin or labile factor) leading to a rare hemorrhagic tendency known as Owren's disease or parahemophilia. It varies greatly in severity. Factor V deficiency is an autosomal recessive trait."
Factor VIII deficiency
- Hemophilia A (HA), the most common form, involving Factor VIII (FVIII) deficiency
- Hemophilia B (HB), also called Christmas disease, due to a deficiency of Factor IX (FIX)
- Acquired hemophilia, an autoimmune disease that targets Factor VIII
Factor X deficiency
Factor X deficiency is a "blood coagulation disorder usually inherited as an autosomal recessive trait, though it can be acquired. It is characterized by defective activity in both the intrinsic and extrinsic pathways, impaired thromboplastin time, and impaired prothrombin consumption."
Multiple factor deficiencies
Multiple factor deficiencies may be present in disease, or produced deliberately in treating diseases of the coagulation system.
Surprisingly, patients with liver failure are not at reduced risk of embolism and thrombosis. The risk of thrombosis and embolism among patients with liver failure correlates with the partial thromboplastin time and not the International Normalized Ratio. Fatal pulmonary embolism has been reported, and may be due to reduction in synthesis by the liver of protein C, protein S, and antithrombin III and compared to reduction in coagulation factors.
Disseminated intravascular coagulation
Disseminated intravascular coagulation (DIC) affects all coagulation factors.
Preventing inappropriate coagulation
Heparin therapy primarily affects Factors IX and X of the intrinsic pathway.
Warfarin therapy reduces the vitamin K dependent cofactors II, VII, IX, and X and the vitamin K dependent Protein C. The level of factor II is thought to most influence coagulation. The levels of factor VII and Protein C fall the fastest after warfarin is started. With the exception of Factor IX, these factors are from either the extrinsic pathway or the final common pathway.
The effect of warfarin is measured by the prothrombin time (or the International Normalized Ratio derived from the prothrombin time) although warfarin can also affect the partial thromboplastin time.
Reversing inappropriate coagulation
Thrombolytic drugs are used to dissolve harmful clots caused either by a disorder of coagulation, or of an internal traumatic event, such as a myocardial infarction, where a clot is blocking necessary blood flow. They are proteins, produced by recombinant DNA technologies, or extracted from bacterial or human cell cultures.
Most cause the proenzyme, plasminogen, presented in plasma, to the active enzyme plasmin. Plasmin then dissolves fibrin and inactivates other proteins involved in coagulation, principally fibrinogen. The main tbrombolytics used in clinical practice are urokinase, streptokinase, or one of several forms of tissue plasminogen activator (TPA). The TPA variants include alteplase, Reteplase, and tenecteplase.
While thrombolysis can be extremely effective, truly modifying and reversing the disease process, they are absolutely contraindicated in an actively bleeding patient, and have relative contraindications in patients at high risk of hemorrhage. Indications for thrombolyis include:
In stroke, for example, it is utterly essential that the cause is confirmed to be ischemia rather than hemorrhage. Making this distinction often requires cerebral angiography.
Treating inadequate coagulation
Synthetic FVIII and FIX are available, and can be used for prophylaxis and treatment of acute hemorrhage. Other drugs can counter the inhibition in acquired hemophilia, or help accelerate coagulation in acute hemorrhage.
von Willebrand's disease
Factor XI Deficiency
Immune Thrombocytopenic Purpura
- Anonymous. Blood coagulation. National Library of Medicine. Retrieved on 2008-01-10.
- Eckhoff CD, Didomenico RJ, Shapiro NL (2004). "Initiating warfarin therapy: 5 mg versus 10 mg". Ann Pharmacother 38 (12): 2115–21. DOI:10.1345/aph.1E083. PMID 15522981. Research Blogging.
- Tymoczko, John L.; Stryer Berg Tymoczko; Stryer, Lubert; Berg, Jeremy Mark (2002). Biochemistry. New York: W.H. Freeman and Company. ISBN 0-7167-4955-6. Figure of coagulation pathways
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