Abstract Number: PB0939
Meeting: ISTH 2020 Congress
Background: Emicizumab, a bispecific monoclonal antibody, bridges activated factor (F) IX and FX replacing the function of missing activated FVIII.
Aims: To present the surgical experiences in the STASEY trial.
Methods: Following informed consent and ethics committee approval, PwHA aged ≥12 years with FVIII inhibitors received emicizumab 3 mg/kg/week for 4 weeks, then 1.5 mg/kg/week for the remaining 2-year treatment period (NCT03191799). Minor and unplanned major surgeries were managed per the investigator’s discretion. Additional peri-operative prophylaxis, if any, and frequency and management of post-operative bleeds, were analyzed.
Results: As at 20 May 2019, 31 minor and 9 major surgeries were performed in 22 and 8 participants, respectively, in the study treatment phase (one minor procedure [skin graft] was combined with a major procedure [arthrodesis] and is not included here). Two-thirds (20/31; 64.5%) of minor surgeries were managed without prophylactic coagulation factor; of these, only 3/20 (15%) required post-operative treatment for bleeds (Figure 1). One of 11 (9%) minor surgeries managed with prophylactic coagulation factor required post-operative treatment for a bleed. Dental interventions with antifibrinolytics were uncomplicated with the exception of one case where an additional dose of FVIIa 90 ug/kg was added; the combined use of antifibrinolytics and FVIIa led to hypertrophic clot formation at the extraction site, which required surgical removal. Overall, 8/9 (89%) major surgeries were managed with prophylactic coagulation factor, resulting in four treated post-operative bleeds, two untreated bleeds, and two resulting in no bleeds. Table 1 shows case details of arthroscopic knee and major hip replacement surgeries.
Conclusions: In PwHA with FVIII inhibitors on emicizumab, most minor procedures were performed without prophylactic coagulation factor and did not result in post-operative treated bleeds. Major surgeries were safely performed with additional coagulation prophylaxis.
|Surgery||Patient Characteristics||Emicizumab Dosing||Pre-operative Treatment||Peri- and Post-operative Treatment||Case Details and Outcomes|
|Semi-acute arthroscopic knee surgery due to infected knee prosthesis (minor)||47-year old male with hemophilia A and long-lasting high titer FVIII inhibitors (292 BU)||Emicizumab 1.5 mg/kg/week for 5 months prior to surgery; emicizumab dosing was continued post-operatively||Bolus rFVIIa 85 µg/kg was administered 1 hour pre-operation||rFVIIa 60 µg/kg every 4 hours for 5 days||The PwHA presented with an active infection of the knee; 2 punctures (intra-articular and in the surrounding tissue) were covered by 2 bolus injections of 60 µg/kg rFVIIa given 3 hours apart
Cultures were positive for Klebsiella Pneumoniae; PwHA was admitted and treated with antibiotics
The arthroscopic knee surgery was uneventful and there was no evidence of TMA
On Day 4 after surgery, the PwHA was discharged
|Total hip replacement (major)||51-year old male with hemophilia A with high-responding FVIII inhibitors||Emicizumab 1.5 mg/kg/week for 44 weeks prior to surgery; emicizumab dosing was continued post-operatively||Bolus rFVIIa 90 µg/kg was administered at the start of surgery||During surgery, rFVIIa 80 µg/kg was administered every 3 hours
Post-operatively, rFVIIa 80 µg/kg dosing was administered every 4 hours (Day 1-3); every 6 hours (Day 4-7); and every 8 hours (Day 8-11)
TA (3 g/24 hours) and prophylactic LMW heparin were administered for the entire post-operative period
|The surgeon rated hemostasis as ‘good to excellent’; the lowest hemoglobin (99 g/L) was recorded on Day 2
The patient had no signs of TMA and was discharged in good health on Day 11
|BU, Bethesda unit; LMW, low molecular weight; PwHA, person with hemophilia A; rFVIIa, activated recombinant activated factor VII; TA, tranexamic acid; TMA, thrombotic microangiopathy.
*These case details are from case narratives provided by two STASEY trial investigators; Patient was aged 50 years at enrollment on the STASEY trial.
[Table 1. Case Details of an Arthroscopic Knee Surgery and a Hip Replacement*]
To cite this abstract in AMA style:Castaman G, Santagostino E, Kremer Hovinga J, Schutgens R, Robson S, Meier O, Jiménez-Yuste V. Surgical Experience from the Phase III STASEY Trial of Emicizumab Prophylaxis in Persons with Hemophilia A (PwHA) with FVIII Inhibitors: Data from the Second Interim Analysis [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/surgical-experience-from-the-phase-iii-stasey-trial-of-emicizumab-prophylaxis-in-persons-with-hemophilia-a-pwha-with-fviii-inhibitors-data-from-the-second-interim-analysis/. Accessed May 17, 2021.
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