Characteristics and outcome of a territory-wide cohort study of patients with acquired hemophilia A in Hong Kong.

INTRODUCTION: Acquired hemophilia A (AHA) is a rare bleeding disorder with destruction of factor VIII by autoantibodies. Comprehensive data for Chinese patients are lacking. Predictors of hospital stay have not been investigated. METHODS: A territory-wide review of patients diagnosed with AHA from January 1, 2012, to December 31, 2021 was performed by retrieving patients' information from an electronic database system in Hong Kong. RESULTS: Overall, 165 patients were included in this 10-year study, and the estimated incidence was 2.4 per million/year, which was higher than those reported from Caucasian cohorts. The median age of diagnosis was 80 years old. Patients had a long hospital stay (median: 25 days) and high mortality (55.2 %). The majority of deaths were caused by immunosuppression-related sepsis (49.5 %). Age was an independent predictor of overall survival (Hazard ratio: 1.065, 95 % CI: 1.037-1.093, p < 0.001), complete remission (CR) status (odd ratios (OR): 0.948, 95 % CI: 0.921-0.976, p < 0.001) and time to achieve CR (OR: 1.043, 95 % CI: 1.019-1.067, p < 0.001). Higher hemoglobin level on presentation was associated with shorter time to achieve CR (OR: 0.888, 95 % CI: 0.795-0.993, p = 0.037). Factor VIII level < 1 % normal, high inhibitor titer and intensive immunosuppressive regimen predicted long hospital stay. CONCLUSION: We presented comprehensive data of Chinese patients with AHA which comprised predominantly frail elderly who required long hospital stay and had high sepsis-related mortality. This posed challenges in managing AHA in such patients. Individualized immunosuppressive therapy is needed to balance the benefits and risk of septic complications.

Plasma apixaban levels in Chinese patients with chronic kidney disease-Relationship with renal function and bleeding complications.

Introduction: Accumulation of apixaban in plasma is a major concern in patients with chronic kidney disease (CKD). Studies that investigated plasma apixaban level in CKD patients and its association with clinically significant events are scarce. Methods: Patients with CKD Stage 1-4 who were taking apixaban, either 2.5 mg BD or 5 mg BD were recruited. The peak and trough plasma apixaban level were measured after 2 h and 12 h of last dose respectively. The results were correlated with renal function and clinical events during the period of follow-up from 1 January 2018 to 31 October 2021. Results: 141 patients (CKD Stage 1, n = 12; Stage 2, n = 74; Stage 3, n = 48, stage 4, n = 7) were included for analysis. The plasma peak and trough apixaban were significantly higher in patients with CKD stage 3 when compared with those having CKD stage 2 and 1 (peak levels: 223.4 ± 107.8 ng/ml vs. 161.0 ± 55.2 ng/ml vs. 126.6 ± 30.2 ng/ml; trough levels: 118.3 ± 67.9 ng/ml vs. 81.2 ± 33.0 ng/ml vs. 51.9 ± 31.1 ng/ml, p < 0.05 or all) in patients taking 5 mg BD. Plasma trough apixaban level was negatively correlated with eGFR in patients taking 5 mg BD (r 2 = -0.174, p < 0.001) and 2.5 mg BD (r 2 = -0.215, p < 0.05). The plasma peak and trough apixaban level correlated with PT (r 2 = 0.065, p = 0.003 and r 2 = 0.096, p < 0.01 respectively). Multivariate analysis showed that plasma trough apixaban levels were associated with the risk of bleeding complications (Odd ratio: 1.011, 95% CI:1.002-1.021, p = 0.023). Conclusion: The plasma apixaban level shows a trend of increase with worsening renal function, and an increase in the plasma apixaban level is suggestive of an increased risk of bleeding complications in patients with CKD. Further large-scale prospective studies are needed to evaluate relationship between plasma apixaban level and renal function as well as safety outcome in CKD patients. Moreover, the role of drug level monitoring should be prospectively evaluated for dosage optimization and the minimization of bleeding risks in CKD patients.

Plasma Rivaroxaban Level in Patients With Early Stages of Chronic Kidney Disease-Relationships With Renal Function and Clinical Events.

Introduction Drug accumulation of rivaroxaban is a concern in patients with chronic kidney disease (CKD). Data regarding the plasma rivaroxaban levels in early CKD patients and its relationship with clinical events is lacking. Methods Early CKD patients (Stage 1-3) with atrial fibrillation who received rivaroxaban (15 or 20 mg daily) were recruited. Plasma rivaroxaban levels were measured at 2 hours (peak) and 24 hours (trough) after drug administration, and correlated with eGFR and clinically significant events during the follow-up period (1 January 2018 to 31 October 2021). Results Ninety-two patients were included (CKD stage 1 n=10, stage 2 n=53, stage 3 n=29). Plasma trough levels in patients with stage 3 CKD were significantly higher than those with stage 2 and 1 CKD (66.0±34.9 ng/ml vs. 35.7 ± 24.7 ng/ml vs. 34.7 ± 26.2 ng/ml, respectively, p=0.005), and showed inverse relationship with eGFR (r=0.391, p=0.001) in patients receiving 20 mg daily. The plasma trough rivaroxaban level correlated with PT and APTT (r = 0.650 and 0.44, respectively, p<0.001 for both). Plasma trough rivaroxaban level in those with bleeding were higher than those who did not (59.9 ± 35.6 ng/ml vs. 41.1 ± 29.2 ng/ml, p=0.011), and multivariate analysis suggested that plasma trough rivaroxaban level was associated with the rate of bleeding complications (OR: 1.020, 95% CI 1.002-1.038, p=0.028). Conclusion Plasma trough rivaroxaban levels correlated with renal function in early CKD patients, and its measurement may help dosage optimization in patients with renal impairment. Moreover, our data suggests that there may be an association between plasma trough rivaroxaban level and the rate of bleeding complication.