Update on diagnostic testing for platelet function disorders: What is practical and useful?

Abstract

Introduction Platelet function disorders (PFD) are an important group of bleeding disorders that require validated and practical laboratory strategies for diagnosis. Methods This review summarizes the authors’ experiences, current literature, and an international survey to evaluate the practices of diagnostic laboratories that offer tests for PFD. Results Blood counts, blood film review, and aggregation tests are the most commonly performed investigations for PFD and help determine whether there is thrombocytopenia and/or defective platelet function due to a variety of causes. The performance characteristics of tests for PFD, and the level of evidence that these tests detect bleeding problems, are important issues to determine where tests are useful for diagnostic or correlative purposes, or research only uses. Platelet aggregation assays, and quantitative analysis of platelet dense granule numbers, are tests with good performance characteristics that detect abnormalities associated with increased bleeding in a significant proportion of individuals referred for PFD investigations. Lumiaggregometry estimates of platelet adenosine triphosphate release show greater variability which limits the diagnostic usefulness. Diagnostic laboratories report that fiscal and other constraints, including a lack of high‐quality evidence, limit their ability to offer an expanded test menu for PFD. Conclusion PFD are clinically important bleeding disorders that remain challenging for diagnostic laboratories to investigate. While some PFD tests are well validated for diagnostic purposes, gaps in scientific evidence and resource limitations influence diagnostic laboratory decisions on which PFD tests to offer.

Laboratory Techniques Used to Diagnose Constitutional Platelet Dysfunction

“…It detects abnormalities associated with increased bleeding in a significant proportion of individuals referred for CPDF assessment. 8 This assay analyzes in vitro platelet aggregation in a GPIIb/IIIa-dependent manner by measuring the increased light transmission through dense PRP after addition of exogenous soluble activators except ristocetin. Ristocetin causes the binding of VWF to the GPIb complex leading to platelet agglutination.…”

Strengths and Weaknesses of Light Transmission Aggregometry in Diagnosing Hereditary Platelet Function Disorders

“…A recent survey of diagnostic laboratories on inherited platelet dysfunctions found that most laboratories perform LTA. This test has good performance characteristics and detects abnormalities associated with increased bleeding in a significant proportion of individuals referred for platelet function disorder (PFD) investigations [4]. LTA is typically used as a first-line test to guide diagnosis of PFD.…”

Highly oxidized low-density lipoprotein does not facilitate platelet aggregation

“… 4 , 5 However, platelet activation also induces initiation and progression of atherosclerosis by several mechanisms, including adhesion, subsequent monocyte recruitment to the endothelium, and induction of proinflammatory mediators. 6 – 10 Many studies have shown that oxLDL is a causative substance in development of cardiovascular disease (CVD) by promoting activation and aggregation of platelets. 2 , 11 – 13 However, low oxLDL levels attenuate platelet function and aggregation in vitro .…”

“…However, LTA is not ideal for diagnosing thrombosis and determining the effects of antiplatelet drugs because of the complicated test process, including many types of agonists, a low sensitivity, and a lack of standardization. 9 …”