The coagulation cascade and its pathways

What it is

Hemostasis is composed of four major events: primary hemostasis, which is the blood vessel and the platelets; secondary hemostasis, which is the coagulation pathway; fibrin clot formation and stabilization; and inhibition of coagulation. Drawn out in order, vascular injury leads to vasoconstriction, and through collagen to platelet activation, which with vWF and fibrinogen forms the platelet plug, and that is primary hemostasis; tissue factor sets off the coagulation cascade, which is secondary hemostasis, and thrombin then makes fibrinogen into fibrin and a blood clot; antithrombotic mechanisms hold the cascade in check; and plasmin ends it with fibrinolysis and clot degradation. The cascade itself runs as two arms that meet in one final common pathway. The intrinsic pathway runs XII, XI, IX and VIII. The extrinsic pathway is factor VII with tissue factor. The two arms meet in the common pathway, X then V then II, which ends with fibrinogen made into the fibrin clot.

How it is diagnosed

The factors, with the older names still used for them, and the job of each:

• Fibrinogen, factor I: the adhesive protein that forms the fibrin clot.
• Prothrombin, factor II: a vitamin K-dependent serine protease whose activated form is the main enzyme of coagulation.
• Tissue factor, factor III, also known as thromboplastin: the lipoprotein initiator of the extrinsic pathway.
• Calcium ions, factor IV: the metal cation necessary for coagulation reactions.
• Factor V, the labile factor: cofactor for activation of prothrombin to thrombin.
• Factor VII, proconvertin: with tissue factor it initiates the extrinsic pathway, and it is vitamin K-dependent.
• Factor VIII, antihemophilic factor: cofactor for intrinsic activation of factor X.
• Factor IX, Christmas factor: its activated form is the enzyme for intrinsic activation of factor X.
• Factor X, Stuart-Prower factor: its activated form is the enzyme for final common pathway activation of prothrombin.
• Factor XI, plasma thromboplastin antecedent: its activated form is the intrinsic activator of factor IX.
• Factor XII, Hageman factor: the factor that nominally starts the intrinsic pathway.
• Factor XIII, fibrin stabilizing factor: the transamidase that crosslinks the fibrin clot.
• High-molecular-weight kininogen: a cofactor, and it circulates in a complex with factor XI.
• Prekallikrein, the Fletcher factor: a serine protease whose activated form participates at the beginning of the intrinsic pathway.

Factors II, VII, IX and X are the vitamin K-dependent serine proteases of the list. Two tests read the cascade. APTT covers the intrinsic pathway plus the common pathway; PT covers the extrinsic pathway plus the common pathway. The mnemonic offered for them is tennis: PT and INR, tennis is played outside, for the extrinsic pathway; PTT, table tennis is played inside, for the intrinsic pathway. The fourth event, inhibition of coagulation, has its own named parts: antithrombin III, protein C with its inhibitor, protein S, and TFPI. Then comes fibrinolysis, plasminogen made into plasmin.