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Coagulopathy
Published in Stephen M. Cohn, Alan Lisbon, Stephen Heard, 50 Landmark Papers, 2021
Conventional coagulation tests (CCTs) including PT, aPTT, INR, platelet count and fibrinogen level remain widely used; however, they have significant limitations. One major limitation with CCTs is the measurement of platelet dysfunction, which is a frequent occurrence in ICU populations. While several platelet function assays exist, only a limited number are in regular use clinically. Tests based on platelet aggregation (VerifyNow) or platelet adhesion under shear stress (platelet function analyzer [PFA]) are available as rapid, point of care tests that can both be helpful in determining the presence of an antiplatelet agents (aspirin, GPIIb/IIIa antagonists, or P2Y12 inhibition) and in determining level of clot forming ability. The PFA-100 in particular, can be used to rapidly determine the absence of aspirin or GPIIb/IIIa antagonists due to its high negative predictive value. However, this the result is limited as a positive result is non-specific [5]. Considerations such as rapidity of testing, characterization of complete coagulation pathway, cumbersome nature of numerous laboratory tests, and closer association with clinical outcomes led to the development of viscoelastic measurements of whole blood (TEG, ROTEM). Since the development of these viscoelastic tests, multiple studies have shown a superior improvement in testing turnaround times, prediction of massive transfusion and mortality as well as improvement in directed transfusion [6, 7].
Laboratory Instrumentation, Reagents, Methods, and Patient Sample as Variables in Coagulation
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
James W. Cook, William A. Rock
Dade International, Incorporated, has developed new Dade PFA Reagents to aid in the detection of platelet dysfunction in citrated human whole blood. The PFA-100 instrument and test cartridge system simulates the process of platelet adhesion and aggregation in vitro. The system determines the time from the start of the test until the platelet plug covers an aperture, hence automating and standardizing the bleeding time.
Haemostasis: Normal Physiology, Disorders of Haemostasis and Thrombosis
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
Elizabeth Jones, Russell David Keenan
Platelet function abnormalities generally present with post-surgical bleeding, mucocutaneous bleeding and/or menorrhagia. Platelet function abnormalities are most usually seen secondary to medication but there are very severe inherited disorders worth discussing here. Investigation of platelet function disorders will depend on a significant bleeding history usually with normal coagulation tests. A prolonged bleeding time is characteristic of platelet function disorders. A bleeding time is a very simple test where a cut of defined length, thickness and depth is made on the medial anterior aspect of the forearm and the time is measured in seconds until the bleeding stops. The bleeding time is rarely used as it is difficult to control and there is significant observer variability as well as the risk of scarring. Other platelet tests available include a screening test called the PFA-100 and more formal platelet aggregation studies. Platelet aggregation studies take a senior coagulation scientist a few hours and must be performed on fresh platelets. Therefore, this is an assay that must be booked with your laboratory in advance. In addition, intracellular platelet nucleotides can also be measured to aid diagnosis. Lastly, confirmation of some disorders may be sought by use of flow cytometry with monoclonal antibodies directed against absent receptors.
Thromboelastography versus bleeding time for risk of bleeding post native kidney biopsy
Published in Renal Failure, 2020
Amir Gal-Oz, Amitay Papushado, Ilya Kirgner, Shmuel Meirsdorf, Doron Schwartz, Idit Francesca Schwartz, Asia Zubkov, Ayelet Grupper
The risk of bleeding has led to standard screening of the primary hemostasis before a renal biopsy is performed [10], although no strong evidence exists to support this practice. While a bleeding time (BT) test is considered to be standard practice for the assessment of platelet function in uremic patients [11], it requires technical expertise, has questionable reproducibility and accuracy, and poorly predicts clinical bleeding risks [12–15]. Although there are no randomized prospective studies evaluating the use of a BT test in the setting of a percutaneous renal biopsy, observational studies have demonstrated a higher bleeding complication rate in those patients with abnormal test results [16–21]. Other series, however, report no increased risk [22,23], so the value of this practice remains to be debated [22,24]. Platelet function analyzer-100 (PFA-100) test measures activated platelets and is more sensitive in comparison with the bleeding time for bleeding disorders. However, it was not found to be useful in predicting bleeding post kidney biopsy [25,26].
Platelet aggregation measured by single-platelet counting and using PFA-100 devices
Published in Platelets, 2018
Natalia Dovlatova, Stan Heptinstall
PFA-100 was aimed to become a more standardised and non-invasive replacement of the bleeding time test and was evaluated as a screening tool to assess platelet dysfunction in suspected platelet function disorders. A significant reduction in platelet reactivity in severe platelet defects, such as Glanzmann thrombasthenia and Bernard-Soulier syndrome was demonstrated using the PFA-100 (8,9), and the approach also proved valuable in identifying patients with von Willebrand’s disease (10,11) making PFA-100 a useful tool to exclude these severe platelet defects. Another advantage over LTA is the ability to detect platelet abnormalities using relatively small volumes of blood, making it particularly useful in pediatric patients. However, beyond these observations the use of PFA-100 in detecting platelet dysfunction did not add much value to the traditional testing with light transmission aggregometry (LTA). It showed lack of sensitivity and specificity to mild platelet defects, such as dense granule secretion defects (11–13), which are among the most prevalent of platelet abnormalities (14). More recently, a new cartridge has been introduced with supposedly higher sensitivity in evaluating the function of P2Y12 receptor (INNOVANCE PFA P2Y*). Indeed, it was shown to detect abnormal platelet responses in patients with P2Y12 receptor defects (15), which, although rare, represent a distinct and well -characterised platelet defect (14).
Platelet biomechanics, platelet bioenergetics, and applications to clinical practice and translational research
Published in Platelets, 2018
Mitchell J. George, James Bynum, Prajeeda Nair, Andrew P. Cap, Charles E. Wade, Charles S. Cox, Brijesh S. Gill
The PFA-100 (Siemens Corp., Washington D.C.) simulates in vitro shear stress and measures platelet adhesion and aggregation. Blood is injected through a collagen coated capillary tube until occlusion which signifies the primary metric, closure time (CT). The device accepts whole blood and does not require elaborate sample preparation like optical aggregometry. The test is valuable clinically to aid in diagnosis of clotting disorders like von Willebrands disease, however due to its lack of specificity it is limited to screening purposes only. In addition, the assay provides limited information in that it only reports one metric of blood coagulation (40).