The Role of Whole Blood Platelet Aggregation Studies in the Diagnosis of Unexplained Bleeding Tendencies
Authors: De Simone Nicole , Sarode Ravi , Yates Sean , Matevosyan Karen , Reddy Manasa , Gavva Chakri , Zia Ayesha , Shen Yu-Min 
Published: October 2019

Abstract
Introduction:
Platelet aggregation studies (PAS) are an important and underutilized diagnostic test (due to non-availability in most clinical laboratories and the requirement to be performed within 4 hours of sample collection) used in the evaluation of unexplained mucocutaneous type of bleeding after ruling out von Willebrand disease. Platelet aggregation studies are typically performed by one of two methods: impedance method using whole blood aggregometry (WBA) and light transmission aggregometry (LTA) using platelet rich plasma (PRP). WBA confers several advantages over LTA. First, it does not require centrifugation, which not only reduces testing time by half, but also avoids platelet activation and loss of giant thrombocytes. Second, in vivo conditions are better replicated reflecting the natural milieu including red and white blood cells, which are known to affect platelet function in vivo. In addition, WBA requires smaller blood volume making testing feasible for neonates and pediatric patients. Lastly, simultaneous assessment of platelet ATP release is performed to assess secretion defects. Despite these advantages, WBA is not commonly used.
Aims: To analyze our data to further support the diagnostic utility of WBA in identifying platelet dysfunction as the etiology of bleeding tendencies.
Methods: A retrospective chart review of patients on whom PAS were performed between June 2011 and September 2014.
Results: We performed 202 PAS on 162 patients. 82% of patients were females and the average age was 28 years (range 9 months-87 years). 24 (15%) patients were pediatric (range 9 months-18 years). 83 of 162 (51%) patients had abnormal results (52% of adults and 50% of the pediatric cases). 26 of the 162 (16%) patients had repeat studies performed. Of these patients, 77% (20/26) had reproducible findings that confirmed the previous results. 8% (2/26) had normalized platelet function after discontinuation of medications (e.g. statins, fish oil, selective serotonin reuptake inhibitor) known to induce platelet dysfunction. 15% (4/26) had different responses to agonists on repeat testing. Abnormal WBA studies revealed decreased to absent responses to various agonists described in table 1. In patients on selective serotonin release inhibitors (SSRIs), there was a spectrum of responses to agonists; the most common abnormality was global dysfunction. Abnormalities to single agonists, such as ADP and AA, were also seen in patients taking SSRIs. Non-steroidal anti-inflammatory drugs affected aggregation with arachidonic acid (AA) and AA+ADP. Statins affected aggregation with AA alone, AA+ADP and AA+ATP secretion. 3 patients had platelet dysfunction consistent with Acquired Glanzmann's Syndrome due possibly to autoantibodies in the setting of chronic lymphocytic leukemia.
Conclusion: Over 50% patients tested by WBA had abnormal platelet function giving high positive predictive value for this test in a selected group of patients who otherwise would have carried a non-specific bleeding diagnosis with non-specific treatment.
Table 1. Distribution of Agonists Eliciting Impaired Responses Agonists Eliciting Impaired Response Number of Studies with Abnormal Results AA+Collagen (Aspirin like defect) 27 (23%) AA+Collagen+ADP 22 (18%) AA+ADP 21 (17%) AA+Collagen+ADP+Ristocetin (Global dysfunction) 19 (15%) ADP 11 (9%) AA 7 (6%) ADP+Collagen 4 (3%) AA+ADP+Ristocetin 3 (2%) Decreased ATP Secretion 8 (7%) AA=Arachidonic Acid

Disclosures
No relevant conflicts of interest to declare.