The formed elements of human blood include red blood cells, white blood cells, and platelets. The first two cell types arise individually from myeloid and lymphoid stem cells in the bone marrow. In contrast, the source of platelets is a distinct precursor cell called the megakaryocyte, which literally means giant bone cell. Megakaryocytes are among the largest cells in the human body. Unlike other cell types, megakaryocytes contain a polyploid nucleus, meaning their DNA has been replicated more than once; in this case, ten or more rounds of DNA replication occur during megakaryocyte development.
During its lifetime, each megakaryocyte gives rise to millions of platelets, which are cleaved from the parent cell as cytosolic fragments lacking DNA or organelles. Red blood cells also lack a nucleus at maturity but live approximately 120 days. Platelets last 7 to 10 days on average. As with red cells, the liver and spleen remove senescent or non-functional platelets from the circulation.
The major function of platelets is to help form blood clots, especially in the arterial blood vessels. When the wall of a blood vessel is damaged or endothelial cells are sheared off the basement membrane, the collagen rich extracellular matrix (ECM) is exposed. Circulating platelets bind to an ECM protein called Von Willebrand Factor via a surface receptor called GPIb. Platelets form a logjam to directly plug small tears and holes. When the damage is more extensive, however, a series of enzymes known as the coagulation cascade is activated. This enzymatic cascade culminates in the formation of insoluble fibrin strands that trap platelets and other blood cells inside a web-like mesh, ultimately forming a blood clot or thrombus.
Platelets are also recruited to areas of inflammation by a variety of soluble factors. These include PAF (platelet activating factor) released by basophils; TXA2 (Thromboxane A2), an arachidonic acid derivative released from a variety of inflammatory cells; serotonin, released from platelets themselves; and adenosine, which, along with TXA2 triggers platelet aggregation. Activated platelets become express higher levels of adhesion molecules on their surfaces. In addition to GPIb, platelets also express the surface glycoprotein GPIIb/IIIa, which allows platelets to stick to each other more readily.
Blood clot formation is necessary for survival, but can be life threatening when it happens inappropriately. Anticoagulants like coumadin target the clotting factors produced in the liver. In contrast, antiplatelet drugs like aspirin, dipyridamole, and clopidogrel (Plavix) work by blocking platelet aggregation. Newer antiplatelet drugs include monoclonal antibodies and other antagonists against the GPIIb/IIIa receptor. These agents, including abciximab (ReoPro) and eptifibatide (Integrilin) are mainly used in the hospital setting.
