Ecchymoses are larger (1 to 2 cm) subcutaneous hematomas (colloquially called bruises). Extravasated red cells are phagocytosed and degraded by macrophages; the characteristic color changes of a bruise result from the enzymatic conversion of hemoglobin (red-blue color) to bilirubin (blue-green color) and eventually hemosiderin (golden-brown).
The clinical significance of any particular hemorrhage depends on the volume of blood that is lost and the rate of bleeding. Rapid loss of up to 20% of the blood volume, or slow losses of even larger amounts, may have little impact in healthy adults; greater losses, however, can cause hemorrhagic (hypovolemic) shock (discussed later). The site of hemorrhage also is important; bleeding that would be trivial in the subcutaneous tissues can cause death if located in the brain (
Fig. 4.4B ). Finally, chronic or recurrent external blood loss (e.g., due to peptic ulcer or menstrual bleeding) frequently culminates in iron deficiency anemia as a consequence of a loss of iron in hemoglobin. By contrast, iron is efficiently recycled from phagocytosed red cells, so internal bleeding (e.g., a hematoma) does not lead to iron deficiency.
Normal hemostasis comprises a series of regulated processes that culminate in the formation of a blood clot that limits bleeding from an injured vessel. The pathologic counterpart of hemostasis is thrombosis, the formation of blood clot (thrombus) within non-traumatized, intact vessels. This discussion begins with normal hemostasis and its regulation, to be followed by causes and consequences of thrombosis.
Hemostasis is a precisely orchestrated process involving platelets, clotting factors, and endothelium that occurs at the site of vascular injury and culminates in the formation of a blood clot, which serves to prevent or limit the extent of bleeding. The general sequence of events leading to hemostasis at a site of vascular injury is shown in
Fig. 4.5
Arteriolar vasoconstriction occurs immediately and markedly reduces blood flow to the injured area (
Fig. 4.5A ). It is mediated by reflex neurogenic mechanisms and augmented by the local secretion of factors such as endothelin, a potent endothelium-derived vasoconstrictor. This effect is transient, however, and bleeding would resume if not for activation of platelets and coagulation factors.
Primary hemostasis: the formation of the platelet plug. Disruption of the endothelium exposes subendothelial von Willebrand factor (vWF) and collagen, which promote platelet adherence and activation. Activation of platelets results in a dramatic shape change (from small rounded discs to flat plates with spiky protrusions that markedly increased surface area), as well as the release of secretory granules. Within minutes the secreted products recruit additional platelets, which undergo aggregation to form a primary hemostatic plug (
Fig. 4.5B
Secondary hemostasis: deposition of fibrin. Vascular injury exposes tissue factor at the site of injury. Tissue factor is a membrane-bound procoagulant glycoprotein that is normally expressed by subendothelial cells in the vessel wall, such as smooth muscle cells and fibroblasts. Tissue factor binds and activates factor VII (see later), setting in motion a cascade of reactions that culiminates in thrombin generation. Thrombin cleaves circulating fibrinogen into insoluble fibrin, creating a fibrin meshwork, and also is a potent activator of platelets, leading to additional platelet aggregation at the site of injury. This sequence, referred to as secondary hemostasis, consolidates the initial platelet plug (
Fig. 4.5C