Pharmacometrics Analysis of Rivaroxaban in Chinese Children Aged Over 2 Years

Opportunistic blood sampling will be performed at multiple predefined time points based on the principle of sparse sampling. It includes: 1. Day 1, 20 minutes -1 h after the first dose; 2. Day 1, 7±1 h after the first dose; 3. After at least three continuous doses (≥ Day 4): before the scheduled dose at that day, which is defined as the trough concentration; 4. After at least three continuous doses (≥ Day 4): 3±1 h the scheduled dose at that day, which is defined as the peak concentration. And peak and trough concentrations will be re-measured after each dose adjustment

Opportunistic blood sampling will be performed at multiple predefined time points based on the principle of sparse sampling. It includes: 1. Day 1, 20 minutes -1 h after the first dose; 2. Day 1, 7±1 h after the first dose; 3. After at least three continuous doses (≥ Day 4): before the scheduled dose at that day, which is defined as the trough concentration; 4. After at least three continuous doses (≥ Day 4): 3±1 h the scheduled dose at that day, which is defined as the peak concentration. And peak and trough concentrations will be re-measured after each dose adjustment

It is binary variable. Every echocardiography conducted during study period will be documented. Researcher will document whether new thrombosis occurs in coronary arteries, and record the number of involved coronary arteries.

It is a binary variable. Researcher will document major bleeding or clinically relevant non-major bleeding events. Major bleeding is defined as 1.Fatal bleeding; 2.Clinically overt bleeding associated with a decrease in Hemoglobin of ≥20 g/L in a 24-h period; 3.Critical site bleeding, such as retroperitoneal, pulmonary, pericardial, intracranial, or otherwise involves the central nervous system; 4.Bleeding that requires an intervention via an invasive procedure; 5.Overt bleeding for which a reversal agent is administered. Clinically relevant non-major bleeding event is defined as 1.Bleeding that results in a medical or procedural intervention not meeting major bleeding criteria, including a medication change (reducing, holding, or changing anticoagulation or addition of new medication) ; 2.Bleeding that results in hospitalization or increased level of care; 3.Overt bleeding for which a blood product is administered, and does not meet the criteria for major bleeding

Opportunistic sampling will be performed using the remaining blood specimens collected for rivaroxaban plasma concentration measurement. Genetic polymorphisms related to rivaroxaban metabolism and transport will be examined, including CYP3A4, ABCB1, ABCG2, and et.cl CYP3A4: Cytochrome P450 Family 3 Subfamily A Member 4, ABCB1: ATP Binding Cassette Subfamily B Member 1; ABCG2: ATP Binding Cassette Subfamily G Member 2