From Code to Clinic

Outline of hemostasis physiology

Definitions and etymology

Bleeding or hemorrhage is loss of blood, either externally (i.e. a wound) or internally (e.g. intracranial-, gastrointestinal bleeding, aortic aneurysm). "Hemorrhage" comes from the Greek word for "(violent) bleeding", which is haimorrhagia, from haima- meaning "blood" and -rhage meaning "to break" or "to burst".
The physiological process that limits bleeding is termed hemostasis, from the Greek words hema- which has the same root as haima above and means blood, and -stasis, which means "to halt". Historically hemostasis was synonymous with "styptic", which comes from Greek stuphein, "to contract", and styptic is still used when describing hemostatic, antihemorrhagic, substances, i.e. a "styptic" pencil (aluminium sulfate).
Hemostasis is the normal, physiological response to vessel injury, which results in the formation of a hemorrage-limiting thrombus (the Greek thrombos literally means "blood clot", and the plural form is thrombi). The process of thrombus formation is called thrombogenesis. When hemostasis is activated in the absence of bleeding (i.e. "hemostasis in the wrong place"), the pathological thrombogenesis is termed thrombosis (Rasche, 2001).
Hemostasis can be divided into a primary and a secondary process. Primary hemostasis is the initial injury response, involving platelets and circulating fibrinogen, and it results in the formation of a platelet plug. Secondary hemostasis is the process by which platelets and proteins interact to form a network of fibrin, which creates a stable thrombus. Secondary hemostasis is the part of the hemostatic process that is referred to as coagulation, the word stemming from the Latin coagulatus meaning "to clot" or "to curdle", in the sense of "changing from liquid to thick mass".
The process by which a fibrin clot is removed is called fibrinolysis (McRae, 2011).

Hemostatic balance and homeostasis

An increased tendency of the hemostatic system to produce thrombi is referred to as hypercoagulability, a prothrombotic state, or thrombophilia. A prohemorrhagic state is sometimes - but not always - the result of a lessened thrombogenic capability of the hemostatic system, called hypocoagulability or a "antithrombotic state". The hemostatic system needs to maintain a tight physiological balance so that it does not veer into either pathological extreme: on the one hand, it must maintain blood's fluidity and avoid a prothrombotic hypercoagulable state, on the other hand, it cannot "overcompensate" and enter a hypocoagulable state, since this would lead to bleeding (Rasche, 2001). Hemostasis is built on a powerful cascading procoagulant system that involves positive feedback loops, but a counterbalance is necessary to counteract a runaway coagulant process that unchecked would quickly coagulate all blood in the circulation. Physiological anticoagulant systems normally regulate coagulation and prevent inappropriate thrombogenesis (McRae, 2011). The equilibrium between the two potential extremes of the hemostatic system is called eucoagulability (from the Greek eu-, meaning "normal" or "good").
Hemostasis can thus be conceptualized as a weight scale, where one side holds procoagulant activity and the other side anticoagulant activity. If pathology or pharmacology disturbs the neutrality of the scale, there is a risk of thrombosis or bleeding.

Primary hemostasis

Secondary hemostasis

New and old models of coagulation


Classification of hypercoagulable states

Hypercoagulable states can be partitioned in several ways:

Classification Subtypes Examples
Thrombus type Red and white thrombi -
Blood vessel type Arterial thrombi, venous thrombi Myocardial infarction, ischemic-thrombotic stroke, pulmonary embolism, deep vein thrombosis
Blood vessel depth Deep and superficial veins Deep vein thrombosis, superficial vein thrombosis
Etiology Coagulation factor disorder, platelet disorder, autoimmunity, iatrogenic Congenital thrombophilia, myeloproliferative disorders (e.g. essential thrombocytosis), disseminated intravascular coagulation, antiphospholipid syndrome, heparin-induced thrombocytopenia, hormone therapy (e.g. combined hormonal contraception), trauma, major surgery