New Trends in Anesthetic Management with Platelet Disorders

Abstract

SUMMARY P latelets are the blood cells that are involved in the cellular mechanisms of primary hemostasis that lead to the formation of blood clots. Low levels or dysfunction predispose for bleeding, while high levels, although usually asymptomatic, may increase the risk of thrombosis. The body has a very limited reserve of platelets, so they can be rapidly depleted. They contain RNA and several different types of granules; lysosomes, dense bodies (containing ADP, ATP, serotonin and calcium) and alpha granules (containing fibrinogen, factor V, vitronectin, thrombospondin and von Willebrand factor), the contents of which are released upon activation of the platelet. These granule contents play an important role in both hemostasis and in the inflammatory response. Platelets are produced in the bone marrow; the progenitor cell for platelets is the megakaryocyte. This large, multinucleated cell sheds platelets into the circulation. Thrombopoietin is a hormone, mainly produced by the liver that stimulates platelet production. It is bound to circulating platelets; if platelet levels are adequate, serum levels remain low. If the platelet count is decreased, more thrombopoeitin circulates freely and increases marrow production. The circulating life of a platelet is 9–10 days. After this it is sequestered in the spleen. Decreased function (or absence) of the spleen may increase platelet counts, while hypersplenism (overactivity of the spleen, e.g. Leukemia and cirrhosis) may lead to increased elimination and hence low platelet counts. Platelets are activated when brought into contact with collagen (which is exposed when the endothelial blood vessel lining is damaged), thrombin, ADP, with receptors expressed on white blood cells or the endothelial cells of the blood vessels. Once activated, they release a number of different coagulation factors and platelet activating factors. The platelets adhere to each other via adhesion receptors or integrins, and to the endothelial cells in the wall of the blood vessel forming a haemostatic plug in conjunction with fibrin, the high concentration of myosin and actin filaments in platelets are stimulated to contract during aggregation, further reinforcing the plug. The most common platelet adhesion 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). A normal platelet count in a healthy person is between 150,000 and 400,000 per mm3 of blood. 95% of healthy people will have platelet counts in this range. Both thrombocytopenia 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. Low platelet counts are generally not corrected by transfusion unless the patient is bleeding or the count has fallen below 5,000/mm3; it is contraindicated in thrombotic thrombocytopenic purpura (TTP) as it fuels the coagulopathy. In patients having surgery, a level below 50,000/mm3 is associated with abnormal surgical bleeding, and regional anesthetic procedures such as epidurals are avoided for levels below 80-100,000/mm3. 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 (COX-1), and hence normal hemostasis; normal platelet function may not return until the aspirin has ceased and all the affected platelets have been replaced by new ones, which can take over a week. Similarly, uremia (a consequence of renal failure) leads to platelet dysfunction.