Reevaluation of platelet function in chronic immune thrombocytopenia: impacts of platelet size, platelet‐associated anti‐αIIbβ3 antibodies and thrombopoietin receptor agonists

Abstract

Platelet function of immune thrombocytopenia (ITP) has been controversial because of methodological problems associated with low platelet counts. In this study, we evaluated platelet function in 21 patients with chronic ITP (cITP) using the recently developed flow cytometry (FCM)based platelet aggregation assay (FCA) along with a PAC1/CD62P assay. Since ITP platelets are larger than controls, whole platelets (whole gating method) and size-adjusted platelets (size-adjusted method) were analysed in the PAC1/CD62P via FCM. We found that: (i) aggregation was equivalent [phorbol myristate acetate (PMA) or adenosine diphosphate (ADP)-induced] or enhanced [protease-activated receptor 1-activating peptide (PAR1AP)-induced] in cITP compared with control by FCA; (ii) PAC1 or CD62P was also equivalent or enhanced in cITP in the whole gating method; and (iii) in sharp contrast, the size-adjusted method revealed that ADP-, PAR1AP-, and collagen synthetic liquid reactive peptide (SRP)-induced PAC1 and ADP-induced CD62P were impaired in cITP. These data suggested that an increase in the number of larger-sized platelets may compensate for the impaired platelet function of cITP, leading to non-inferiority of overall platelet function in cITP. Furthermore, we revealed that ADPinduced aggregation was impaired in the patients with thrombopoietin receptor agonists (TPO-RAs) or platelet-associated anti-aIIbb3 antibodies compared with the control, suggesting that the presence of anti-aIIbb3 autoantibodies and/or administration of TPO-RAs may have a negative impact on platelet function.

Serial platelet level index improves prediction of pulmonary hemorrhage in patients with Stenotrophomonas maltophilia respiratory infections and thrombocytopenia

“…The clinical consensus regarding the lowest platelet level needed to prevent bleeding in certain circumstances is that platelet counts must be above 20–50 × 10 3 /μl for bronchoscopy exams and 50 × 10 3 /μl for transbronchial lung biopsies ( 21 ). Statistical results from the present study show that platelet levels above 60–100 × 10 3 /μl may plausibly prevent PH in patients with sepsis, liver disease, and other causes, while lower platelet counts (above 17.5 × 10 3 /μl) may be tolerated in patients with hematological diseases.…”

Serial Platelet Level Index Improves Prediction of Pulmonary Hemorrhage in Stenotrophomonas maltophilia Respiratory Infections

“…Although thrombocytopenia is an independent determining factor for PH, patients experiencing long-term thrombocytopenia may develop a certain mechanism by which to compensate for the bleeding tendency. A previous study identi ed that an increased number of larger-sized platelets may compensate for the impaired platelet function in patients with chronic idiopathic thrombocytopenia [17]. In acute myeloid leukemia patients who have thrombocytopenia, platelet aggregation and platelet activation predicted bleeding better the platelet count alone [18].…”

Classic Light Transmission Platelet Aggregometry: Do We Still Need it?

“…Despite these challenges, flow cytometry is a promising technique for diagnosing well-characterized platelet disorders and may be performed before or complementary to LTA. [81][82][83][84][85] The mepacrine assay is another potentially useful flow cytometry assay that enables evaluation of the secretion and incorporation capacities of platelets. It works by quantifying platelet fluorescence before and after stimulation.…”