Abstract Number: PB0903
Meeting: ISTH 2021 Congress
Background: Gi-coupled platelet P2Y12 receptor for ADP plays an important role in platelet function. Patients with inherited P2Y12 defect present with mild-moderate muco-cutaneous bleeding. Stepwise algorithmic approach using platelet function tests can help identify ADP P2Y12 receptor defect.
Aims: To report findings in patients with ADP P2Y12 receptor defect(n=7) diagnosed using algorithmic approach.
Methods: Patients presenting with bleeding symptoms from May 2017 to January 2021 were evaluated after informed consent using stepwise algorithm (Figure1). Patients diagnosed with P2Y12 receptor defect were included. ISTH-Bleeding Assessment tool(BAT) was used to score bleeding symptoms. Screening tests for Primary hemostasis were Complete blood counts, modified Ivy’s bleeding time and closure time(CT) on Platelet function analyzer-200 (PFA-200) using Collagen/ADP, Collagen/Epinephrine and P2Y cartridges. Light Transmission Aggregometry(LTA) and lumi-aggregometry were performed for patients with abnormal screening tests. P2Y12 defect was suspected when ADP, even at high concentrations(20µM) was unable to induce full, irreversible platelet aggregation. P2Y12 defect was confirmed using vasodilator-stimulated phosphoprotein-phosphorylation(VASP-P) flow-cytometric assay and VerifyNow-P2Y12 assay(VN-P2Y12).
Results: The median(IQR) age of patients was 11 years(4 – 38) with male:female ratio of 1:2.5. ISTH-BAT score ranged from 3-8(Median:6) with elevated ISTH-BAT score in 6/7 patients. All cases had normal platelet count(IQR 254-290 x 109/L). Bleeding time was prolonged in 6/7 patients. PFA-200 CT for Collagen/ADP and P2Y cartridges was prolonged in all cases, while Collagen/Epinephrine CT was prolonged in 6 patients. LTA showed markedly reduced, rapidly reversible aggregation in response to high concentration (20µM) ADP (figure 2) with normal ATP release in all cases. VN-P2Y12 platelet reactivity test showed markedly reduced P2Y12 Reaction Units. VASP-P flow-cytometric assay revealed 0% platelet reactivity index in all cases, confirming the diagnosis of P2Y12 defect.
Conclusions: ADP P2Y12 receptor defect can be identified using functional assays and should be suspected in patients with mild-moderate muco-cutaneous bleeding and markedly reduced response to high dose ADP(20µM).
To cite this abstract in AMA style:Dave R, Geevar T, Mammen J, Vijayan R, Samuel A, Singh S, Nair S. Identification of ADP P2y12 Receptor Defect by Functional Assays Using Algorithmic Approach – A Case Series [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/identification-of-adp-p2y12-receptor-defect-by-functional-assays-using-algorithmic-approach-a-case-series/. Accessed November 30, 2023.
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