Platelets, or thrombocytes, are small cytoplasmic bodies derived from cells. They circulate in the blood of mammals and are involved in hemostasis leading to the formation of blood clots. Like red blood cells, platelets have no nucleus.
If the number of platelets is too low, excessive bleeding can occur, however if the number of platelets is too high, blood clots can form (thrombosis) which block blood vessels, and may cause a stroke and/or a heart attack. An abnormality or disease of the platelets is called a thrombocytopathy which could be either a low number (thrombocytopenia), a decrease in function (thrombasthenia) or an increase in number (thrombocytosis).
Endothelial cells produce a protein called von Willebrand's factor, a cell adhesion ligand, which helps endothelial cells adhere to collagen in the basement membrane. Under physiological conditions, neither collagen nor vWF pass into the bloodstream.
When endothelial damage occurs, platelets come into contact with exposed collagen and vWF, and the inhibitors the endothelium normally secretes are reduced.
When the platelets contact collagen, they are activated. They are also activated by thrombin (primarily through PAR-1), ADP receptors (P2Y1 and P2Y12) expressed on platelets. They can also be activated by a negatively charged surface, such as glass.
Platelet activation further results in the scramblase-mediated transport of negatively charged phospholipids to the platelet surface. These phospholipids provide a catalytic surface (with the charge provided by phosphatidylserine and phosphatidylethanolamine) for the tenase and prothrombinase complexes.
The most abundant platelet aggregation receptor is glycoprotein (GP) IIb/IIIa; this is a calcium-dependent receptor for fibrinogen, fibronectin, vitronectin, thrombospondin and von Willebrand factor (vWF). Other receptors include GPIb-V-IX complex (vWF) and GPVI (collagen).
Activated platelets will adhere, via glycoprotien (GP) Ia, to the collagen that is exposed by endothelial damage
Aggregation and adhesion act together to form the platelet plug. The high concentration of myosin and actin filaments in platelets are stimulated to contract during aggregation, further reinforcing the plug.
It also secretes e.g. platelet-derived growth factor (PDGF).
Both thrombocytopenia (or thrombopenia) and thrombocytosis may present with coagulation problems. Generally, low platelet counts increase bleeding risks (although there are exceptions, e.g. immune heparin-induced thrombocytopenia) and thrombocytosis (high counts) may lead to thrombosis (although this is mainly when the elevated count is due to myeloproliferative disorder).
Low platelet counts are generally not corrected by transfusion unless the patient is bleeding or the count has fallen below 5 x 109/L; it is contraindicated in thrombotic thrombocytopenic purpura (TTP) as it fuels the coagulopathy. In patients having surgery, a level below 50 x 109/L) is associated with abnormal surgical bleeding, and regional anaesthetic procedures such as epidurals are avoided for levels below 80-100.
Normal platelet counts are not a guarantee of adequate function. In some states the platelets, while being adequate in number, are dysfunctional. For instance, aspirin irreversibly disrupts platelet function by inhibiting cyclooxygenase-1 (COX1), and hence normal hemostasis; Platelets have no DNA and are unable to produce new cyclooxygenase. Normal platelet function will not return until the aspirin has ceased and enough of the affected platelets have been replaced by new ones, which can take over a week. Ibuprofen, another NSAID, does not have such a long duration effect, with platelet function returning in 24 hours , and taking ibuprofen before aspirin will prevent the irreversible effects of aspirin. Uremia (a consequence of renal failure) leads to platelet dysfunction that may be ameliorated by the administration of desmopressin.
Intravenous agents, often used to alter/suppress platelet function:
Disorders leading to platelet dysfunction or reduced count:
Disorders featuring an elevated count:
Disorders of platelet adhesion or aggregation:
Disorders of platelet metabolism
Disorders that indirectly compromise platelet function:
Disorders in which platelets play a key role:
Giulio Bizzozero (1846-1901), building on Schultze's findings, used "living circulation" to study blood cells of amphibians microscopically in vivo. One of his findings was the fact that platelets clump at the site of blood vessel injury, which precedes the formation of a blood clot. This observation confirmed the role of platelets in coagulation.
Pooled whole blood platelets, sometimes called "random" platelets, are made by taking a unit of whole blood that has not been cooled and placing it into a large centrifuge in what is referred to as a "soft spin." This splits the blood into three layers: the plasma, a "buffy coat" layer which includes the platelets, and the red blood cells. These are expressed into different bags for storage. From four to six of these are typically pooled into a single bag for a therapeutic dose, though individual components can also be used.
Apheresis platelets are collected using a mechanical device which draws blood from the donor and centrifuges the collected blood to separate out the platelets and other components to be collected. The remaining blood is returned to the donor. The advantage to this method is that a single donation provides at least one therapeutic dose, as opposed to the multiple donations for whole blood platelets. This means that a recipient is not exposed to as many different donors and has less risk of transfusion transmitted disease and other complications. Sometimes a person such as a cancer patient who requires routine transfusions of platelets will receive repeated donations from a specific donor to further minimize the risk.
Platelets are not crossmatched unless they contain a significant amount of RBCs, which results in a reddish-orange color to the product. This is usually associated with whole blood platelets, as apheresis methods are more efficient than "soft spin" centrifugation at isolating the specific components of blood. An effort is usually made to issue type specific platelets, but this is not as critical as it is with red blood cells.
Platelets collected by either method have a very short shelf life, typically five or seven days depending on the system used. This results in frequent problems with short supply, as testing the donations often uses up a full day of this time. Since there are no effective preservative solutions for platelets, they lose potency quickly and are best when fresh.
Platelets, either apheresis or random donor platelets, can be processed through a volume reduction process. In this process, the platelets are spun in a centrifuge and the excess plasma is removed, leaving 10 to 100 ml of platelet concentrate. Volume reduced platelets are normally only transfused to neonatal and pediatric patients when a large volume of plasma could overload the child's small circulatory system. The lower volume of plasma also reduces the chances of an adverse transfusion reaction to plasma proteins. Volume reduced platelets have a shelf life of only four hours.