Antithrombotic Treatment in Patients With Hemophilia: an EHA-ISTH-EAHAD-ESO Clinical Practice Guidance

Abstract

Cardiovascular disease is an emerging medical issue in patients with hemophilia (PWH) and its prevalence is increasing up to 15% in PWH in the United States. Atrial fibrillation, acute and chronic coronary syndromes, venous thromboembolism, and cerebral thrombosis are frequent thrombotic or prothrombotic situations, which require a careful approach to fine-tune the delicate balance between thrombosis and hemostasis in PWH when using both procoagulant and anticoagulant treatments. Generally, PWH could be considered as being naturally anticoagulated when clotting factors are <20 IU/dL, but specific recommendations in patients with very low levels according to the different clinical situations are lacking and mainly based on the anecdotal series. For PWH with baseline clotting factor levels >20 IU/dL in need for any form of antithrombotic therapy, usually treatment without additional clotting factor prophylaxis could be used, but careful monitoring for bleeding is recommended. For antiplatelet treatment, this threshold could be lower with single-antiplatelet agent, but again factor level should be at least 20 IU/dL for dual antiplatelet treatment. In this complex growing scenario, the European Hematology Association in collaboration with the International Society on Thrombosis and Haemostasis, the European Association for Hemophilia and Allied Disorders, the European Stroke Organization, and a representative of the European Society of Cardiology Working Group on Thrombosis has produced this current guidance document to provide clinical practice recommendations for health care providers who care for PWH.

Guidance for the antithrombotic management of persons with haemophilia and cardiovascular disease

“…If the decision for oral anticoagulation in PWH has been made, is there a need for monitoring anticoagulation treatment and dose adjustment? The present commentary on the article by Schutgens et al 22 is written by a long-standing insider in haemophilia care, 12,19 who chose to enlist the input of a cardiologist and geriatrician with specific expertise on the aging PWH. Impressed by the clarity of the settings of the guidance blueprint (Table 1), we are convinced that it is a badly needed handbook to be widely consulted by those confronted with the clinical situations epitomised by the comprehensive and well-focussed clinical questions.…”

“…Furthermore, the European Society of Cardiology (ESC) and the European Stroke Organisation (ESO) contributed with input from cardiologists and neurologists. The ensuing publication 22 offers the most recent and comprehensive guidance that can be practically employed by those confronted with the painstaking scenario of handling at the same time thrombosis and bleeding in PWH. The clinical practice guidelines stem from the analysis of publications of non‐randomised studies, observational studies including case series and case reports, as well as consensus documents based upon the Delphi methodology 22 .…”

“…The ensuing publication 22 offers the most recent and comprehensive guidance that can be practically employed by those confronted with the painstaking scenario of handling at the same time thrombosis and bleeding in PWH. The clinical practice guidelines stem from the analysis of publications of non‐randomised studies, observational studies including case series and case reports, as well as consensus documents based upon the Delphi methodology 22 . Aware of the limitations inherent in these reports, the authors of the guidance document chose of not adopting the GRADE nomenclature but instead a simple, three‐level ranking system offering from strong to weak recommendations 22 .…”

“…22 Aware of the limitations inherent in these reports, the authors of the guidance document chose of not adopting the GRADE nomenclature but instead a simple, three-level ranking system offering from strong to weak recommendations. 22 The whole clinical practice guidance contains six sections with 24 clinically relevant questions (Table 1). The answers to the questions have been discussed and reviewed among panel members during virtual meetings and correspondence, so that unanimous consensus was ultimately reached.…”

“…The clinical practice guidelines stem from the analysis of publications of non‐randomised studies, observational studies including case series and case reports, as well as consensus documents based upon the Delphi methodology 22 . Aware of the limitations inherent in these reports, the authors of the guidance document chose of not adopting the GRADE nomenclature but instead a simple, three‐level ranking system offering from strong to weak recommendations 22 . The whole clinical practice guidance contains six sections with 24 clinically relevant questions (Table 1).…”