Coagulation is a part of an integrated series of haemostatic reactions, involving plasma, platelet, and vascular components.

Activated platelets contract their internal actin and myosin fibrils in their cytoskeleton, which leads to shrinkage of the clot volume.

The granules' contents activate a Gq-linked protein receptor cascade, resulting in increased calcium concentration in the platelets' cytosol.

[27] The coagulation factors are generally enzymes called serine proteases, which act by cleaving downstream proteins.

The contact activation pathway begins with formation of the primary complex on collagen by high-molecular-weight kininogen (HMWK), prekallikrein, and FXII (Hageman factor).

The minor role that the contact activation pathway has in initiating blood clot formation (or more specifically, physiological hemostasis) can be illustrated by the fact that individuals with severe deficiencies of FXII, HMWK, and prekallikrein do not have a bleeding disorder.

[33] Thrombin functions not only to convert fibrinogen to fibrin, it also activates Factors VIII and V and their inhibitor protein C (in the presence of thrombomodulin).

[34] The coagulation cascade is maintained in a prothrombotic state by the continued activation of FVIII and FIX to form the tenase complex until it is down-regulated by the anticoagulant pathways.

The initiation phase, mediated by the tissue factor exposure, proceeds via the classic extrinsic pathway and contributes to about 5% of thrombin production.

For example, beta-lysine, an amino acid produced by platelets during coagulation, can cause lysis of many Gram-positive bacteria by acting as a cationic detergent.

Vitamin K epoxide reductase is pharmacologically important as a target of anticoagulant drugs warfarin and related coumarins such as acenocoumarol, phenprocoumon, and dicumarol.

These drugs create a deficiency of reduced vitamin K by blocking VKORC, thereby inhibiting maturation of clotting factors.

Deficiencies of common pathway factors prothrombin, fibrinogen, FX, and FV will prolong both aPTT and PT.

[citation needed] Decreased platelet numbers (thrombocytopenia) is due to insufficient production (e.g., myelodysplastic syndrome or other bone marrow disorders), destruction by the immune system (immune thrombocytopenic purpura), or consumption (e.g., thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, paroxysmal nocturnal hemoglobinuria, disseminated intravascular coagulation, heparin-induced thrombocytopenia).

In this disease, there is a defect in von Willebrand factor (vWF), which mediates the binding of glycoprotein Ib (GPIb) to collagen.

[medical citation needed] In acute or chronic liver failure, there is insufficient production of coagulation factors, possibly increasing risk of bleeding during surgery.

Most cases of venous thrombosis are due to acquired states (older age, surgery, cancer, immobility).

Unprovoked venous thrombosis may be related to inherited thrombophilias (e.g., factor V Leiden, antithrombin deficiency, and various other genetic deficiencies or variants), particularly in younger patients with family history of thrombosis; however, thrombotic events are more likely when acquired risk factors are superimposed on the inherited state.

The use of adsorbent chemicals, such as zeolites, and other hemostatic agents are also used for sealing severe injuries quickly (such as in traumatic bleeding secondary to gunshot wounds).

Before its withdrawal, aprotinin was used in some forms of major surgery to decrease bleeding risk and the need for blood products.

Anti-platelet agents include aspirin, dipyridamole, ticlopidine, clopidogrel, ticagrelor and prasugrel; the parenteral glycoprotein IIb/IIIa inhibitors are used during angioplasty.

A newer class of drugs, the direct thrombin inhibitors, is under development; some members are already in clinical use (such as lepirudin, argatroban, bivalirudin and dabigatran).

Its soluble precursor, fibrinogen, was thus named by Rudolf Virchow (1821–1902), and isolated chemically by Prosper Sylvain Denis (1799–1863).

Alexander Schmidt suggested that the conversion from fibrinogen to fibrin is the result of an enzymatic process, and labeled the hypothetical enzyme "thrombin" and its precursor "prothrombin".

[65] At this stage, it was known that thrombokinase/thromboplastin (factor III) is released by damaged tissues, reacting with prothrombin (II), which, together with calcium (IV), forms thrombin, which converts fibrinogen into fibrin (I).

[citation needed] A first clue as to the actual complexity of the system of coagulation was the discovery of proaccelerin (initially and later called Factor V) by Paul Owren [no] (1905–1990) in 1947.

[66] Factor VII (also known as serum prothrombin conversion accelerator or proconvertin, precipitated by barium sulfate) was discovered in a young female patient in 1949 and 1951 by different groups.

Christmas lived in Canada and campaigned for blood transfusion safety until succumbing to transfusion-related AIDS at age 46.

The usage of Roman numerals rather than eponyms or systematic names was agreed upon during annual conferences (starting in 1955) of hemostasis experts.

[70] Exemplifying the close links between coagulation and inflammation, the horseshoe crab has a primitive response to injury, carried out by cells known as amoebocytes (or hemocytes) which serve both hemostatic and immune functions.