Perioperative continuous infusions of factor VIII versus factor IX for patients with hemophilia A or B undergoing major surgery.

Continuous factor VIII (FVIII) or factor IX (FIX) infusions are commonly used for patients with hemophilia A (HA) or B (HB) undergoing surgery to secure perioperative hemostasis. To describe differences between the initial recovery and subsequent FIX and FVIII levels, and describe clinical outcomes among HB and HA patients receiving perioperative continuous infusion (CI) of recombinant FVIII and FIX concentrates. Retrospective chart review was conducted on 8 consecutive patients with HB and 7 consecutive patients with HA who underwent major surgery between 2014 and 2018 and received continuous infusions of standard half-life factor concentrate. Median initial bolus dose per kilogram was higher for HB compared to HA patients [90.8 (IQR 78.0-98.7) vs. 52.1 (IQR 48.6-55.6) IU/kg], while initial CI dose-rates were similar [4.3 (IQR 3.8-4.6) vs. 4.2 (IQR 3.8-4.4) IU/kg/h]. Median post-bolus recovery was higher for FVIII compared to FIX [1.70 (IQR 1.23-1.75) vs. 0.88 (IQR 0.75-1.00) IU/mL]. Median factor levels also were higher for FVIII on post-operative days 1 to 3. HB patients had greater mean intraoperative estimated blood loss [285.7 (range 0-1000) vs. 142.8 (range 0-400) mL] and longer median length of hospital stay [9 (IQR 8-12) vs. 5 (IQR 4-6.5) days]. Our initial evidence suggests greater in vivo yield of rFVIII compared to rFIX in the perioperative setting. We identified poorer clinical outcomes in this small cohort of perioperative HB patients indicating that they may benefit from a higher CI rate for adequate surgical hemostatic coverage.

Reducing use of coagulation tests in a family medicine practice setting: An implementation study.

Introduction: Clinicians often order the international normalized ratio (INR) and activated partial thromboplastin time (APTT) to evaluate for the possibility of inherited bleeding disorders despite sensitivities and specificities of 1%-2%. The most accurate tool to evaluate for bleeding disorders is a validated bleeding assessment tool (BAT). Our aim was to reduce coagulation testing by >50% in a large family practice in Ontario, Canada. Methods: We conducted an implementation study from May 2016 to February 2020. Iterative interventions included introduction of a validated BAT into the electronic medical record (EMR); removal of the APTT as a prepopulated selection from the laboratory requisition; and education targeting family medicine teams and laboratory personnel. The primary outcome was the rate of pre- and post-APTT testing. Creatinine testing was the control. Data were analyzed via an interrupted time series analysis using Stata 13. Results: Immediately following education of the laboratory personnel on coagulation testing, the APTT rate level dropped by 1.26 tests per 100 patient visits per month (p < 0.001) and was sustained until the end of the study. Meanwhile, the PT/INR and creatinine testing rate levels did not change (rate level = -0.02 per 100 visits per month, p = 0.79 and 0.49, p = 0.22 respectively). There was good uptake of the BAT following integration and 18/88 (20%) obtained a referral to hematology after BAT completion. Conclusions: Multidisciplinary, iterative interventions reduced APTT testing and enabled the use of BATs to guide hematology referrals in a large family practice.

A prospective observational study of the incidence, natural history, and risk factors for intravenous immunoglobulin-mediated hemolysis.

BACKGROUND: Intravenous Immune Globulin (IVIG) is used to treat numerous immune-mediated and inflammatory conditions. There is growing awareness of hemolysis, occasionally severe, as a side-effect of this therapy. While most cases are associated with anti-A and/or anti-B isoagglutinins, the frequency and mechanism of hemolysis remain poorly characterized. STUDY DESIGN AND METHODS: A prospective observational study was conducted to determine incidence, natural history and risk factors for IVIG-mediated hemolysis. A total of 99 infusions of high-dose IVIG (2 g/kg or higher) administered to 78 non-group O patients were monitored and graded according to Canadian IVIG Hemolysis Pharmacovigilance Group. Serum ferritin and C3/C4 levels were monitored as indicators of macrophage activation and complement consumption, respectively. Supplementary investigations included assessment for ABO zygosity, Secretor status, FcR polymorphisms, eluate IgG subclass, monocyte monolayer assay, and a panel of cytokines. RESULTS: Hemolysis was observed in 32 of 99 (32%) of infusions, with 19 of 99 (19%) grade 2 or higher. Hemolysis was only apparent 5-10 days after a completed IVIG infusion in 84% of cases and was associated with increases in serum ferritin without complement-consumption. In univariate analysis, increased risk was observed in group AB patients, first-time IVIG recipients, those not taking immuosuppressive medications, or patients treated with a specific IVIG brand; however, in multivariate analysis, product association was no longer observed. No other patient- or practice-related risk factors were identified. CONCLUSION: IVIG-mediated hemolysis is common and frequently severe. Monitoring for 5-10 days following an infusion should be considered in non-O patients receiving high-dose IVIG with known risk factors.