Invasive procedures in patients with haemophilia: Review of low‐dose protocols and experience with extended half‐life FVIII and FIX concentrates and non‐replacement therapies

Abstract

The performance of surgery and invasive procedures in patients with haemophilia is currently facing new challenges globally. The first is the appropriate application of low‐dose protocols of clotting factor concentrates (CFC) achieving adequate perioperative haemostasis in resource constraint environments. The increasing availability of CFC through humanitarian aid programmes allows more invasive surgeries to be performed for which efficacy and safety data should be more widely collected and reported. Second, extended half‐life CFC that are increasingly available in many countries represent valuable alternatives to standard half‐life products in surgical patients allowing reduced number of infusions and lower consumption, in particular for extended half‐life factor IX. Third, in the era of recently introduced non‐factor prophylaxis, some minor surgical procedures can now be performed without additional haemostatic treatment, others with few low‐dose administrations of CFC or bypassing agents. Additional factor VIII or bypassing treatment has proven to be safe and effective in association with emicizumab for major surgeries, and it was effectively given at low doses in association with fitusiran. No thrombotic complications have been reported in the surgical setting so far. A multidisciplinary team/facility remains crucial to manage major surgery in patients on prophylaxis with these new agents.

Adoption of emicizumab (Hemlibra®) for hemophilia A in Europe: Data from the 2020 European Association for Haemophilia and Allied Disorders survey

“…For example, data on management of inhibitor and non‐inhibitor patients on emicizumab undergoing surgery is currently scarce and no guidelines on a European or global level, only proposals and recommendations on a national level, are available so far 12,13,14 . Results of the EAHAD survey are mostly in line with these recommendations and with published data from the HAVEN studies and two HTCs in the US 15,16,17 . Regarding bypassing agents, rFVIIa is the treatment of choice for patients with inhibitors on emicizumab 10,11,13,14,16 .…”

Neurosurgery in a patient with severe hemophilia B: an experience using eftrenonacog alfa as perioperative management

“…Some patients required up to 2 doses of rFIXFc on the day of the surgery. 2,6,7 Before surgery, our patient received a single bolus of 93 IU/kg of rFIXFc. This dose was similar to that from the surgeries described in clinical trials.…”

“…These procedures require the intensified administration of concentrates of the deficient factor (FVIII in the case of hemophilia A and FIX in the case of hemophilia B) to reduce the bleeding risk associated with those procedures. 1,2 In recent years, new strategies have been developed for the prophylactic treatment of patients with hemophilia, such as extended half-life factor concentrates (EHL). These products have shown improved pharmacokinetic properties, achieving parameters of half-life (t 1/2 ) 3-to 5-fold longer in FIX EHL compared with standard FIX concentrates.…”

Management of a High-Risk Surgery with Emicizumab and Factor VIII in a Child with a Severe Hemophilia A and Inhibitor

“…This dual treatment could also be applicable without an inhibitor at the doses usually administered. 15 In our patient, the FVIII:C chromogenic assay appeared to be a reliable tool for peri-surgical monitoring in children despite concomitant treatment with emicizumab as it was proposed. 8 9 TGA with low TF concentration performed in parallel to FVIII:C measures could be helpful.…”