Management of rare inherited bleeding disorders: Proposals of the French Reference Centre on Haemophilia and Rare Coagulation Disorders

Abstract

Introduction: The rare coagulation disorders may present significant difficulties in diagnosis and management. In addition, considerable inter-individual variation in bleeding phenotype is observed amongst affected individuals, making the bleeding risk difficult to assess in affected individuals. The last international recommendations on rare inherited bleeding disorders (RIBDs) were published by the United Kingdom Haemophilia Centre Doctors' Organisation in 2014. Since then, new drugs have been marketed, news studies on surgery management in patients with RIBD have been published, and new orphan diseases have been described. Aim: Therefore, the two main objectives of this review, based on the recent recommendations published by the French Reference Centre on Haemophilia and Rare Bleeding Disorders, are: (i) to briefly describe RIBD (clinical presentation and diagnostic work-up) to help physicians in patient screening for the early detection of such disorders; and (ii) to focus on the current management of acute haemorrhages and long term prophylaxis, surgical interventions, and pregnancy/delivery in patients with RIBD.

Rare bleeding disorders: Advances in management

“…Bleeding symptoms can be relatively minor, (e.g., mild epistaxis), whereas some are life‐threatening, such as intracranial haemorrhage. Central nervous system (CNS), umbilical cord bleeding, hemarthroses and soft tissue hematomas are frequent with severe fibrinogen, FVII, FX and FXIII deficiencies; gastrointestinal tract bleeding occurs mainly in FX deficiency and spontaneous abortion is frequent in women with afibrinogenemia and FXIII deficiency 6 . Back in 2007, the European network of rare bleeding disorders (EN‐RBD) explored the association between residual clotting levels and clinical bleeding severity 7 .…”

“…Presently, evidence is lacking to optimize management of acute bleeding in HFDs. A few national guidelines and experts’ consensus have proposed a target fibrinogen level ≥ 1 g/L and ≥ 1.5 g/L in case of minor or major bleeding, respectively 6,44,54 . Similar targets have been proposed to prevent surgical bleeding 44,48 .…”

“…A few national guidelines and experts' consensus have proposed a target fibrinogen level ≥ 1 g/L and ≥ 1.5 g/L in case of minor or major bleeding, respectively. 6,44,54 Similar targets have been proposed to prevent surgical bleeding. 44,48 Tranexamic acid is usually added, even though precaution is needed when planning treatments for patients with thrombotic-related dysfibrinogenemia.…”

“…Central nervous system (CNS), umbilical cord bleeding, hemarthroses and soft tissue hematomas are frequent with severe fibrinogen, FVII, FX and FXIII deficiencies; gastrointestinal tract bleeding occurs mainly in FX deficiency and spontaneous abortion is frequent in women with afibrinogenemia and FXIII deficiency. 6 Back in 2007, the European network of rare bleeding disorders (EN-RBD) explored the association between residual clotting levels and clinical bleeding severity. 7 The results of this study showed that the association between coagulant activity and clinical bleeding severity was strong in fibrinogen, combined FV + VIII, FX, and FXIII deficiencies, whereas it was weak in FV and FVII deficiencies and not evident for FXI deficiency (Table 1).…”

“…Generally, experts suggest keeping a trough fibrinogen level ≥ 1 g/L throughout the pregnancy and ≥1.5 g/L at delivery and in early the post-partum. 6,44,54 The role of fibrinogen infusion in prevent and treat obstetrical complications in mild or moderate hypofibrinogenemia and dysfibrinogenemia has not been specifically investigated. Given the complexity of pregnancy management in HFDs, it is crucial to develop international collaborations and foster prospective studies in order to determine the impact of fibrinogen infusion on obstetrical complications, the minimal fibrinogen threshold to target to decrease the risk of bleeding and to allow a neuraxial anaesthesia, the efficacy and security of oral antifibrinolytics to prevent post-partum haemorrhage.…”