Primary hemostasis has three major stages involving platelet adhesion, platelet activation, and platelet aggregation. Platelet adhesion is initiated by exposure of the endothelium as a result of damage to blood vessels. Exposed tissue factor–bearing cells trigger the simultaneous binding of von Willebrand factor to exposed collagen and circulating platelets. Platelets are nonnucleated, cytoplasmic, round or oval disks formed by budding off of large, multinucleated cells (megakaryocytes). Platelets have an essential function in coagulation, hemostasis, and blood thrombus formation. Activated platelets release a number of procoagulant factors, including thromboxane, a very potent platelet activator, from storage granules. These factors enter the circulation and activate other platelets and the cycle continues. The activated platelets aggregate at the site of vessel injury, and at this stage of hemostasis the glycoprotein IIb/IIIa receptors on the activated platelets bind fibrinogen, causing the platelets to stick together and form a plug. Coagulation must be localized to the site of vessel wall injury, or the growing platelet plug would eventually occlude the affected vessel. The fibrinolytic system, under normal circumstances, begins to work, once fibrin begins to form, to ensure coagulation is limited to the appropriate site. Thrombocytosis is an increase in platelet count. In reactive thrombocytosis, the increase is transient and short-lived, and it usually does not pose a health risk. One exception may be reactive thrombocytosis occurring after coronary bypass surgery. This circumstance has been identified as an important risk factor for postoperative infarction and thrombosis. The term thrombocythemia describes platelet increases associated with chronic myeloproliferative disorders; thrombocytopenia describes platelet counts of less than 140 × 10³/microL. Decreased platelet counts occur whenever the body’s need for platelets exceeds the rate of platelet production; this circumstance will arise if production rate decreases or platelet loss increases. The severity of bleeding is related to platelet count as well as platelet function. Platelet counts can be within normal limits, but the patient may exhibit signs of internal bleeding; this circumstance usually indicates an anomaly in platelet function. Abnormal findings by automated cell counters may indicate the need to review a smear of peripheral blood for platelet estimate. Abnormally large or giant platelets may result in underestimation of automated counts by 30% to 50%. A large discrepancy between the automated count and the estimate requires that a manual count be performed. Platelet clumping may result in the underestimation of the platelet count. Clumping may be detected by the automated cell counter or upon microscopic review of a blood smear. A citrated platelet count, performed on a specimen collected in a blue-top tube, can be performed to obtain an accurate platelet count from patients who demonstrate platelet clumping in EDTA-preserved samples.

Thrombopoiesis or platelet production is reflected by the measurement of the immature platelet fraction (IPF). This parameter can be correlated to the total platelet count in the investigation of platelet disorders. A low platelet count with a low IPF can indicate a disorder of platelet production (e.g., drug toxicity, aplastic anemia or bone marrow failure of another cause), whereas a low platelet count with an increased IPF might indicate platelet destruction or abnormally high platelet consumption (e.g., mechanical destruction, disseminated intravascular coagulation [DIC], idiopathic thrombocytopenic purpura [ITP], thrombotic thrombocytopenic purpura [TTP]).

Platelet size, reflected by mean platelet volume (MPV), and cellular age are inversely related; that is, younger platelets tend to be larger. An increase in MPV indicates an increase in platelet turnover. Therefore, in a healthy patient, the platelet count and MPV have an inverse relationship. Abnormal platelet size may also indicate the presence of a disorder. MPV and platelet distribution width (PDW) are both increased in ITP. MPV is also increased in May-Hegglin anomaly, Bernard-Soulier syndrome, myeloproliferative disorders, hyperthyroidism, and pre-eclampsia. MPV is decreased in Wiskott-Aldrich syndrome, septic thrombocytopenia, and hypersplenism.

Platelets have receptor sites that are essential for normal platelet function and activation. Drugs such as clopidogrel, abciximab (Reopro), eptifibatide (Integrilin), and tirofiban block these receptor sites and inhibit platelet function. Aspirin also can affect platelet function by the irreversible inactivation of a crucial cyclooxygenase (COX) enzyme. Medications like clopidogrel (Plavix) and aspirin are prescribed to prevent heart attack, stroke, and blockage of coronary stents. Studies have confirmed that up to 30% of patients receiving these medications may be nonresponsive. There are several commercial test systems that can assess platelet function and provide information that confirms platelet response. Platelet response testing helps ensure alternative or additional platelet therapy is instituted, if necessary. The test results can also be used preoperatively to determine whether antiplatelet medications have been sufficiently cleared from the patient’s circulation such that surgery can safely be performed without risk of excessive bleeding. Thromboxane A2 is a potent stimulator of platelet activation. 11-dehydrothromboxane B2 is the stable, inactive product of thromboxane A2 metabolism, released by activated platelets. Urine levels of 11-dehydrothromboxane B2 can be used to monitor response to aspirin therapy.

The metabolism of many commonly prescribed medications is driven by the cytochrome P450 (CYP450) family of enzymes. Genetic variants can alter enzymatic activity that results in a spectrum of effects ranging from the total absence of drug metabolism to ultrafast metabolism. Impaired drug metabolism can prevent the intended therapeutic effect or even lead to serious adverse drug reactions. Poor metabolizers (PM) are at increased risk for drug-induced side effects due to accumulation of drug in the blood, while ultra-rapid metabolizers (UM) require a higher than normal dosage because the drug is metabolized over a shorter duration than intended. Other genetic phenotypes used to report CYP450 results are intermediate metabolizer (IM) and extensive metabolizer (EM). CYP2C19 is a gene in the CYP450 family that metabolizes drugs such as clopidogrel (Plavix). Genetic testing can be performed on blood samples submitted to a laboratory. Testing for the most common genetic variants of CYP2C19 is used to predict altered enzyme activity and anticipate the most effective therapeutic plan. The test method commonly used is polymerase chain reaction. Counseling and informed written consent are generally required for genetic testing.