Diagnosis of mild platelet function disorders. Reliability and usefulness of light transmission platelet aggregation and serotonin secretion assays

Abstract

Summary Light transmission platelet aggregation (PA), adapted to measure platelet secretion (PS), is the reference test for diagnosing platelet functional disorders (PFD). Problems with these assays include lack of standardisation, unknown reproducibility and lack of universally accepted diagnostic criteria. We addressed these issues in patients with inherited mucocutaneous bleeding (MCB). Normal and abnormal PA tests in 213 patients were reproducible in 93·3% and 90·4% of the cases, respectively. Mean intra‐subject coefficient of variation for PA with strong agonists were <9% and mean intra‐class correlation coefficient for weak agonists were >0·86 (P < 0·0001). Concomitant impaired PA with 10 μmol/l‐adrenaline and 4 μmol/l‐ADP was observed in 13·7% of the controls. This combination was not considered per se a criterion for PFD. PA with adrenaline ≥42% or irreversible aggregation with 4 μmol/l ADP had 93% and 95% Negative Predictive Value for diagnosing PFD, respectively. PA defects were consistently associated with abnormal PS. In contrast, 14·3% of patients with MCB had isolated PS. Thus, standardized PA/PS assays are highly reproducible and concordant in normal and patient populations. Normal PA with adrenaline and low ADP concentration robustly predict a normal PA. Simultaneous PA/PS assays enable the diagnosis of isolated PS defects. This study confirmed that hereditary PA–PS defects are highly prevalent.

A prospective cohort study of light transmission platelet aggregometry for bleeding disorders: Is testing native platelet-rich plasma non-inferior to testing platelet count adjusted samples?

“…Platelet function disorders are common bleeding disorders that often impair platelet function by light transmission aggregometry (LTA) (1)(2)(3)(4). Most laboratories perform LTA to evaluate bleeding disorders, as recommended (5)(6)(7)(8), but the procedures used vary, including whether native (N) or platelet count adjusted (A) platelet-rich plasma (PRP) samples are tested (4,5).…”

New developments in laboratory diagnosis and monitoring

“…Although some laboratories perform Ôscreening testsÕ [such as the bleeding time and Platelet Function Analyzer-100 Ò (Siemens/Dade-behing, Marburg, Germany) closure time] [19], neither the bleeding time nor the closure time has sufficient sensitivity to rule out common platelet function disorders [23,25]. LTA has considerable diagnostic utility when performed by rigorously standardized procedures [25,26] with validated reference intervals [27] on samples from individuals referred for bleeding problems. Laboratories need to consider the potential for false positives, as LTA abnormalities with two or more agonists are much …”

Novel loci involved in platelet function and platelet count identified by a genome-wide study performed in children

“…In contrast to previous approaches assessing only a few platelet traits, we evaluated a wide range of parameters, including platelet aggregation and secretion elicited by several agonists at different concentrations. Considering that the performance and analysis of a whole set of platelet assays is a complex and laborious process requiring a high degree of standardization, 28 we believe our study provides a unique source of genetic associations that can contribute to identify new loci relevant in platelet physiology. Statistically, the INGENIAHS revealed associations with P values in the 10 -8 -10 -5 range similar to those previously reported for GWAS.…”