Human blood smear: platelets. This slide has been stained with MayGrunwald Giemsa, and observed with a 100x objective in oil immersion.

A 250 ml bag of newly collected platelets.

Thrombocytes

(Primary hemostasis is the immediate response to injury, which involves platelets. Secondary hemostasis is the next response to injury, which involves other components of the clotting system.)

If the number of platelets is too low, that can cause bleeding. If the numbers of platelets is too high, that can cause blood clots (thrombosis) which block blood vessels, and cause strokes and heart attacks. An abnormality or disease of the platelets is called a thrombocytopathy^[1] which could be either a low number (thrombocytopenia), a decrease in function (thrombasthenia) or an increase in number (thrombocytosis).

Production and degradation

Platelets are produced in blood cell formation (hematopoiesis) by budding off from megakaryocytes. This process is regulated by thrombopoietin, a hormone usually produce by liver and kidney. Each megakaryocyte produces between 5,000 and 10,000 platelets.

Platelets circulate for approximately one week, and are then destroyed by the spleen and by Kupffer cells in the liver.

Function

Functions of Platelets can be generalised into a number of categories:

• Adhesion
• Aggregation
• Clot retraction
• Pro-coagulation
• Cytokine signalling
• Phagocytosis^[2]

Activation

The inner surface of blood vessels is lined with a thin layer of endothelial cells. Under the endothelial layer is a layer of collagen. When the endothelial layer is injured, the collagen is exposed.

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.

Once activated, they release coagulation factors and platelet activating factors. These substances are normally stored in one of two cytoplasmic granules:

• either the dense granules (containing ADP or ATP, calcium and serotonin)
• or the ?-granules (containing platelet factor 4, PDGF, fibronectin, B-thromboglobulin, vWF, fibrinogen, and coagulation factors V and XIII).

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.

Adhesion and aggregation

Platelet aggregation is the clumping of platelets together, using fibrin as the connecting agent. Activated platelets have fibrin receptors on their surfaces. Platelet adhesion is the process of platelets sticking to the damaged inner surface of the vessel wall. Adhesion can occur because collagen in the vessel wall is exposed when the endothelial surface lining the vessel is breached, and activated platelets have collagen receptors on their surfaces. 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.

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).

Platelet aggregation is stimulated by ADP, thromboxane and ?2 receptor-activation, but inhibited by other inflammatory products like PGI2 and PGD2.

Cytokine signalling

Besides being the chief cellular effector of hemostasis, platelets are rapidly deployed to sites of injury or infection and potentially modulate inflammatory processes by interacting with leukocytes and by secreting cytokines, chemokines and other inflammatory mediators^{[3] [4] [5] [6]}.

It also secretes e.g. platelet-derived growth factor (PDGF).

Role in disease

High and low counts

A normal platelet count in a healthy person is between 150,000 and 400,000 per mmł (microlitre) of blood (150–400 x 10⁹/L).^[7] 95% of healthy people will have platelet counts in this range. Some will have statistically abnormal platelet counts while having no abnormality, although the likelihood increases if the platelet count is either very low or very high.

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 ^[8], and taking ibuprofen before aspirin will prevent the irreversible effects of aspirin^[9]. Uremia (a consequence of renal failure) leads to platelet dysfunction that may be ameliorated by the administration of desmopressin.

Medications

Oral agents, often used to alter/suppress platelet function:

• aspirin
• clopidogrel
• cilostazol
• ticlopidine

Intravenous agents, often used to alter/suppress platelet function:

• abciximab
• eptifibatide
• tirofiban

Diseases

Disorders leading to a reduced platelet count:

• Thrombocytopenia
  • Idiopathic thrombocytopenic purpura - also known as immune thrombocytopenic purpura (ITP)
  • Thrombotic thrombocytopenic purpura
  • Drug-induced thrombocytopenia, e.g. heparin-induced thrombocytopenia (HIT)
• Gaucher's disease
• Aplastic anemia

Alloimmune disorders

• Fetomaternal alloimmune thrombocytopenia
• Some transfusion reactions

Disorders leading to platelet dysfunction or reduced count:

• HELLP syndrome
• Hemolytic-uremic syndrome
• Chemotherapy
• Dengue
• Alpha?Delta platelet storage pool deficiency (??SPD) is a rare inherited bleeding disorder.^[10]

Disorders featuring an elevated count:

• Thrombocytosis, including benign essential thrombocytosis (elevated counts, either reactive or as an expression of myeloproliferative disease); may feature dysfunctional platelets

Disorders of platelet adhesion or aggregation:

• Bernard-Soulier syndrome
• Glanzmann's thrombasthenia
• Scott's syndrome
• von Willebrand disease
• Hermansky-Pudlak Syndrome

Disorders of platelet metabolism

• Decreased cyclooxygenase activity, induced or congenital
• Storage pool defects, acquired or congenital

Disorders that indirectly compromise platelet function:

• Haemophilia

Disorders in which platelets play a key role:

• Atherosclerosis
• Coronary artery disease, CAD and myocardial infarction, MI
• Cerebrovascular disease and Stroke, CVA (cerebrovascular accident)
• Peripheral artery occlusive disease (PAOD)
• Cancer ^[11]

Discovery

Brewer^[12] traced the history of the discovery of the platelet. Although red blood cells had been known since van Leeuwenhoek, it was the German anatomist Max Schultze (1825-1874) who first offered a description of the platelet in his newly founded journal Archiv für mikroscopische Anatomie^[13]. He describes "spherules" much smaller than red blood cells that are occasionally clumped and may participate in collections of fibrous material. He recommends further study of the findings.

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^[14].

Additional images

<gallery> Image:Illu blood cell lineage.jpg|Blood cell lineage </gallery>

In transfusion medicine

Platelets are either isolated from collected units of whole blood and pooled to make a therapeutic dose or collected by Apheresis, sometimes concurrently with plasma or red blood cells. The industry standard is for platelets to be tested for bacteria before transfusion to avoid septic reactions, which can be fatal.

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.^[15] Volume reduced platelets have a shelf life of only four hours.^[16]

References

See also

• Hemostasis
• Plateletpheresis

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