The effects of eltrombopag, a thrombopoietin-receptor agonist, on platelet function in immune thrombocytopenia (ITP) are not fully characterized. This study used whole blood flow cytometry to examine platelet function in 20 patients receiving eltrombopag treatment at days 0, 7, and 28. Platelet surface expression of activated GPIIb/IIIa, P-selectin, and GPIb was measured with and without low and high adenosine diphosphate (ADP) and thrombin receptor activating peptide (TRAP) concentrations. Before eltrombopag treatment with no ex vivo agonist, platelet activation was higher in ITP patients than controls. Platelet GPIb and activated GPIIb/IIIa expression without added agonist was unchanged following eltrombopag treatment, whereas a slight increase in P-selectin was observed. Expression of P-selectin and activated GPIIb/IIIa in response to high-dose ADP was lower during eltrombopag treatment than at baseline. Eltrombopag led to a slight increase in platelet reactivity to TRAP only in responders to eltrombopag but not to levels above those in controls; whole blood experiments demonstrated that this increase was probably because of higher platelet counts rather than higher platelet reactivity. In conclusion, although thrombocytopenic ITP patients have higher baseline platelet activation than controls, eltrombopag did not cause platelet activation or hyper-reactivity, irrespective of whether the platelet count increased. (Blood. 2012;119(17): 4066-4072) IntroductionImmune thrombocytopenia (ITP) is an autoimmune condition characterized by antibody-mediated accelerated platelet destruction and suboptimal platelet production, which leads to various degrees of thrombocytopenia and bleeding symptoms. 1,2 Thrombopoietin receptor (TPO-R) agonists have recently been developed for the treatment of patients with ITP, and can dramatically increase platelet counts and reduce bleeding symptoms in the majority of patients, including some with severe refractory thrombocytopenia. [3][4][5] Eltrombopag, is an oral, small-molecule TPO-R agonist that interacts with the transmembrane domain of the receptor in a noncompetitive manner with endogenous TPO, thereby activating intracellular signal transduction pathways and leading to enhanced megakaryocyte differentiation, proliferation, and platelet production. 6 Patients with ITP often have few bleeding symptoms despite very low platelet counts, suggesting that ITP platelets are highly functional. [7][8][9] The TPO-R is expressed on circulating platelets, 10 and although TPO stimulation in vitro does not directly activate platelets, it potentiates platelet reactivity to several agonists, including adenosine diphosphate (ADP), thrombin, and collagen. 11-13 Administration of eltrombopag to healthy volunteers does not increase platelet aggregation or platelet surface expression of P-selectin or activated GPIIb/IIIa. 14 However, the effect of eltrombopag on platelet function in vivo in thrombocytopenic patients is unknown and requires study because of the potential for thrombosis with higher (...

No abstract

No abstract

Objectives To assess the independent relationships of obesity and obstructive sleep apnea (OSA) with hypertension/elevated blood pressure (EBP) in adolescent patients. Study Design A retrospective cohort analysis was performed on 501 patients (age 13‐21 years) with three separate blood pressure measurements within 6 months of polysomnography. EBP was defined as average systolic blood pressure (SBP) ≤120 mm Hg; obesity as body mass index Z‐score ≤1.65; and OSA as obstructive apnea‐hypopnea index <1. Pearson correlations and multivariable analyses were performed to assess the independent effects of the apnea‐hypopnea index and body mass index Z‐score on SBP. Results Of 501 patients (mean age 16 ± 2 years), 246 (49%) were male. OSA was present in 329 (66%) patients, obesity in 337 (67%), and EBP in 262 (52%). EBP was present in 70% of obese adolescents and 60% of adolescents with OSA. Univariable correlation showed a significant relationship between SBP, body mass index Z‐score, and apnea‐hypopnea index. Multivariable linear regression analysis showed blood pressure was significantly associated with body mass index Z‐score (β = .46; P < .01), age (β = .25; P < .01), and height Z‐score (β = .14; P < .01), but not apnea‐hypopnea index (β = .01; P = .72). Conclusions The relationship between OSA and EBP in adolescents is most closely associated with the degree of obesity. Further studies are needed to assess the effect of the treatment of obesity and OSA on blood pressure in adolescents.

No abstract