Avatrombopag increases platelet count but not platelet activation in patients with thrombocytopenia resulting from liver disease.

Essentials Thrombopoietin (TPO) lowers the threshold for platelet activation. TPO receptor agonists (RAs) may therefore also lead to platelet activation. Patients with chronic liver disease and thrombocytopenia participated in a randomized trial. The TPO-RA avatrombopag did not increase platelet activation in vivo or reactivity in vitro. BACKGROUND: The thrombopoietin (TPO) receptor agonist (TPO-RA) avatrombopag has recently been Food and Drug Administration-approved for the treatment of thrombocytopenia in patients with chronic liver disease (CLD) scheduled for a procedure. The TPO receptor c-mpl is expressed on the platelet surface, and TPO lowers the threshold for platelet activation. TPO-RAs may therefore also lead to platelet activation. OBJECTIVES: To evaluate the effects of avatrombopag on platelet activation. PATIENTS/METHODS: CLD patients with thrombocytopenia participated in a randomized, double-blind, placebo-controlled, parallel-group study. No patient received a platelet transfusion within 10 days of study blood draws. Platelet activation was evaluated with whole blood flow cytometry (which, unlike other methods, is accurate in thrombocytopenic samples). RESULTS: Avatrombopag, but not placebo, increased platelet counts. As measured by platelet surface P-selectin and activated glycoprotein IIb-IIIa: (i) the numbers of circulating activated platelets were not increased in avatrombopag-treated patients as compared with placebo-treated patients; and (ii) platelet reactivity to low and high concentrations of ADP and thrombin receptor-activating peptide was not increased in avatrombopag-treated patients as compared with placebo-treated patients. CONCLUSIONS: In this randomized, double-blind, placebo-controlled, parallel-group study of CLD patients with thrombocytopenia, avatrombopag increased platelet counts but did not increase platelet activation in vivo or platelet reactivity in vitro.

Postcardiopulmonary bypass hypoxemia: a prospective study on incidence, risk factors, and clinical significance.

OBJECTIVE: To evaluate the clinical significance of low arterial oxygen tension-inspired oxygen concentration (PaO2-FIO2) ratio, as a measure of hypoxemia, in the early period after cardiac surgery with cardiopulmonary bypass (CPB); and to evaluate the preoperative, intraoperative, and postoperative factors contributing to the development of hypoxemia within the first 24 hours after cardiac surgery with CPB. DESIGN: Prospective observational study. SETTING: University hospital. PARTICIPANTS: Patients who underwent elective or emergency cardiac surgery with CPB (n = 466). INTERVENTIONS: Preoperative clinical and laboratory data were recorded, as were intraoperative and postoperative data regarding the PaO2-FIO2 ratio, fluid and drug therapy, and chest radiograph. Data analysis evaluated hypoxemia as depicted by the PaO2-FIO2 ratios at 1, 6, and 12 hours after surgery. Thereafter, the effect of the PaO2-FIO2 ratios on time to extubation, lung injury, and length of hospital stay was evaluated. The risk factors were analyzed in 3 separate periods: preoperative, intraoperative, and postoperative. Univariate and multivariate analyses were performed on each period separately. All data were analyzed in 2 consecutive steps: univariate analysis and multivariate analysis. MEASUREMENTS AND MAIN RESULTS: PaO2-FIO2 ratios after CPB were significantly lower compared with baseline values. Six patients (1.32%) met the clinical criteria compatible with acute lung injury. All 6 patients had prompt recovery. Significant risk factors for hypoxemia were age, obesity, reduced cardiac function, previous myocardial infarction, emergency surgery, baseline chest radiograph with alveolar edema, high creatinine level, prolonged CPB time, decreased baseline PaO2-FIO2, use of dopamine after discontinuation of CPB, coronary artery bypass grafting, use of left internal mammary artery, higher pump flow requirement during CPB, increased level of hemoglobin or total protein content, persistent hypothermia 2 and 6 hours after surgery, requirement for reexploration, event requiring reintubation, and chest radiograph with alveolar edema 1 hour after surgery. Six hours after surgery, a lower PaO2-FIO2 ratio correlated significantly with time to extubation and lung injury. CONCLUSIONS: This study shows that despite improvements in the technique of CPB, hypoxemia depicted by low PaO2-FIO2 ratios is common in patients after CPB. It is short lived, however, and has minimal effect on the postoperative clinical course of these patients.