Spanish consensus guidelines on prophylaxis with bypassing agents for surgery in patients with haemophilia and inhibitors

Abstract

Introduction: Patients with severe haemophilia and inhibitors against factor VIII who require surgery need a prophylactic approach to prevent bleeding complications. Scientific evidence to decide the best prophylactic treatment is very limited and mainly based on retrospective or case series. Aims: To develop evidence-and expert opinion-based guidelines for prophylactic therapy for patients with haemophilia and inhibitors undergoing surgery. Methods: A panel of nine Spanish haematologists undertook a systematic review of the literature and selected publications providing relevant information regarding the prophylactic management of patients with haemophilia and inhibitors undergoing dental extraction, minor surgery or major surgery. Results: Although evidence is very limited, the panel considers that it seems advisable that prophylaxis should be given in most cases with a bypassing agent (aPCC or rFVIIa) and should start immediately before minor or major surgery. Patients should be closely monitored to enable dose/product modification as needed. Conclusion: It is necessary to communicate clinical experience in a detailed way in order to ensure optimal schemes of prophylaxis for patients with haemophilia and inhibitors. Development of objective outcomes to evaluate efficacy is crucial.

Major surgery management in patients with haemophilia A and inhibitors on emicizumab prophylaxis without global coagulation monitoring

“…When rFVIIa is used alone, different dosing regimens (35–220 µg/kg) have been recommended (Mingot‐Castellano et al , ). In the first prospective randomised study, the dose of 90 μg/kg every 2 h from skin incision/intubation and for the following 48 h and every 2–6 h for an additional 3 days resulted in successful haemostasis in all patients (60% of success with 35 µg/kg).…”

Recommendations on multidisciplinary management of elective surgery in people with haemophilia

“…Close collaboration and communication among the MDT members and the patient/family is vital throughout . Surgery in inhibitor patients remains the most challenging area and should only be conducted at an HTC by an experienced, specialized MDT …”

“…1 Surgery in inhibitor patients remains the most challenging area and should only be conducted at an HTC by an experienced, specialized MDT. [5][6][7][8][9][10][11][12][13][14][15] The importance and organization of the MDT has been discussed in depth elsewhere 6,8,15 ; however, a gap can exist between best practice perspectives and practical application. With this in mind, a multidisciplinary panel of specialists was convened to provide practical recommendations on the application of the established principles of multidisciplinary management of elective surgery and the comprehensive care model for PWH.…”

The socioeconomic burden of patients affected by hemophilia with inhibitors

“…In the last years, a growing number of studies reported a successful use of presurgical prophylaxis with rFVIIa and aPCC during major surgery in controlling bleeding with a hemostatic efficacy rated as good/excellent in 85%‐90% of all procedures . Doses and duration of treatment with bypassing agents are highly heterogeneous, being variable according to type of surgical procedure, thus as a consequence, the optimal approach to ensure adequate surgical bleeding control is not yet well established …”

“…[27][28][29] Doses and duration of treatment with bypassing agents are highly heterogeneous, being variable according to type of surgical procedure, 30 thus as a consequence, the optimal approach to ensure adequate surgical bleeding control is not yet well established. 31,32 In the recent years, novel approaches to the treatment of patients with hemophilia and inhibitors are under study or in late-stage F I G U R E 1 Treatment algorithm. aPCC, activated Prothrombin Complex Concentrate; BU, Bethesda Units; ITI, Immune Tolerance Induction (ITI); rFVIIa, recombinant activated Factor VII [Colour figure can be viewed at wileyonlinelibrary.com] pipeline and include a bispecific antibody recognizing activated Factor IX and Factor X, proteins required to activate the natural coagulation cascade, with a role partially similar to the cofactor FVIII, restoring the normal blood clotting process.…”