ABSTRACT
Although not identified as such at the time, cell-derived EVs were observed experimentally as early as 1946. Chargaff and West9 found that the clotting time of plasma, obtained by centrifugation at 1,900 × g, is prolonged after further centrifugation at 31,000 × g and that the “clotting factor” removed by the high-speed centrifugation is found in the sedimented pellet. In 1967, Wolf10 published a study providing evidence for the occurrence, in normal plasma, of a coagulant material that was sedimented by high-speed centrifugation that had originated from platelets but was distinguishable from intact platelets. He first described these MVs as “platelet dust” as they were not only rich in phospholipid but demonstrated platelet factor 3 (PF3)-like procoagulant activity.11 During the last 20-30 years, extensive research has been performed on cell-derived EVs within the blood. We now know that they can be released not only from platelets but also from erythrocytes, leukocytes, endothelial cells, and other diverse cell types. Historically, most assays have been based on flow cytometry (see Chapter 8), and these are still regarded as the gold standard methods. More recently immunological capture assays or procoagulant assays have been developed. Present-day assays for procoagulant activity are based either on a clotting/chromogenic assay principle12 or on a thrombin generation principle.13 Measurement makes use of specific properties of the different types of vesicles. Their moni-toring is rapidly gaining importance in disease detection, disease progression monitoring, and treatment. All these assay types have advantages and disadvantages (Table 6.1). The user must choose the best assay to suit his or her requirements.
