Efficacy and safety of a recombinant von Willebrand factor treatment in acquired von Willebrand syndrome in case of bleeding and surgical procedures.

INTRODUCTION: Acquired von Willebrand syndrome (AVWS) is a rare haemorrhagic disorder. The prophylaxis and treatment of bleeding before surgery are complex. Since 2018, a new recombinant VWF (rVWF) concentrate that contains no factor VIII (FVIII) but a high amount of high molecular weight VWF multimers has been available in France. AIM: To describe the real-world experience of using rVWF in non-surgical bleeding and surgical procedures in patients with AVWS. METHODS: Fifteen bleeding episodes in seven patients and 16 surgeries in 10 patients were retrospectively analysed in t French haemostasis centres. RESULTS: During bleeding, the median number of infusions was only 1 (range 1-27) with a median loading dose of 58 IU/kg (range 17-116) rVWF and a total median dose of 65 IU/kg (range 35-1488) rVWF. Bleeding control was rated markedly effective in 73% (11/15) of the cases and ineffective in 27% (4/15). During surgeries, the median number of infusions was 3 (range 1-8) with a preoperative loading dose of 60 IU/kg (range 23-118) rVWF and a total median dose of 123 IU/kg (range 31-542). The overall clinical efficacy was qualified as excellent, good and poor (ISTH criteria) in respectively 7 (43%), 6 (38%) and 3 (19%) procedures. There was no accumulation of VWF or FVIII during postoperative monitoring. No thromboembolic events nor adverse events were reported. CONCLUSION: This French 'real-world' experience shows that rVWF could be of interest in the treatment and prophylaxis of bleeding in patients with AVWS, with no clinically significant safety concern.

Efficacy and safety of a recombinant Von Willebrand Factor treatment in patients with inherited Von Willebrand Disease requiring surgical procedures.

INTRODUCTION: Von Willebrand Disease is a common inherited haemorrhagic disorder due to a deficiency of Von Willebrand Factor (VWF). In case of surgical procedures in patients who are not responsive or have contraindications to desmopressin, replacement therapy with VWF concentrates is indicated. Until recently, only plasma-derived VWF concentrates were available. A new recombinant VWF (rVWF) concentrate that contains no Factor VIII (FVIII) but a high amount of high molecular weight VWF multimers has been available in France since 2018. AIM: Describe real-world experience of using rVWF in surgical procedures. METHODS: Sixty-three surgeries for 55 patients were retrospectively analysed in 7 French haemostasis centres. RESULTS: During minor surgeries, the median (range) number of infusions was 1 (1-8) with a preoperative loading dose of 35 (19-56) rVWF IU/kg and a total median dose of 37.5 IU (12-288). During major surgeries, the median (range) number of infusions was only 3 (1-14) with a median preoperative loading dose of 36 IU (12-51) rVWF IU/kg, and a total median dose of 108 IU (22-340) rVWF IU/kg. The overall clinical efficacy was qualified as excellent/good in 61 of the procedures (97%), moderate in 1 (1.5%) and poor in 1 (1.5%). There was no accumulation of VWF or FVIII during postoperative monitoring. No thromboembolic events, anti-VWF antibodies or adverse events were reported. CONCLUSION: This French 'real-world' experience shows that a few infusions and low doses of rVWF provided effective prevention of bleeding in major and minor surgeries in inherited VWD, with no clinically significant safety concerns.

Apixaban for treatment of venous thromboembolism in an obese patient with Glanzmann thrombasthenia.

Background: Glanzmann thrombasthenia (GT) is a rare congenital platelet function disorder associated with a severe bleeding diathesis. Thrombotic manifestations remain a rare condition. We report here the first case of recurrent venous thromboembolism (VTE) successfully treated with apixaban in a patient with GT. Our patient's morbid obesity was an additional challenge. Key Clinical Question: The Key Clinical Question was to determine if direct oral anticoagulants are suitable for patients with both obesity and GT. Clinical Approach: In our patient, the first episode of VTE occurred after the use of a low dose of activated recombinant factor VII for a minor procedure, whereas the second was unprovoked. Administration of rivaroxaban very quickly led to the appearance of bleeding symptoms and subsequently led to poor compliance and extension of deep vein thrombosis. The patient was switched to apixaban, with very good efficacy and safety over the cumulative 18 months of use. Conclusion: The last updated guidelines now recommend the use of rivaroxaban and apixaban for management of VTE in patients with obesity. Regarding patients with GT, there is still insufficient data on the use of direct oral anticoagulants. Management of thrombotic manifestations in these patients remains a rare and complex condition and could be improved by the creation of a specific international registry.

[Placenta percreta management in a patient with a severe congenital hypofibrinogenemia]. / Gestion d'un placenta percreta chez une patiente atteinte d'une hypofibrinogénémie congénitale sévère.

The obstetrical follow-up of patients with a severe hypofibrinogenemia requires a multidisciplinary collaboration because of potential maternal-fetal complications (recurrent miscarriages, intrauterine fetal demise, post-partum hemorrhage, thrombosis). We report the obstetrical management of a multiparous patient with a severe congenital hypofibrinogenemia associated with a platelet disorder (abnormal phospholipid externalization). A therapeutic strategy based on a biweekly administration of fibrinogen concentrates associated with enoxaparin and aspirin allowed the maintenance of pregnancy. But this last one got complicated by a placenta percreta requiring a salvage hysterectomy with an appropriate hemorrhage prophylaxis.

[Switching toward the use of recombinant factor VIII Fc fusion protein Study among 30 patients with severe hemophilia A]. / Switch vers un facteur VIII recombinant fusionné avec un fragment Fc Expérience chez 30 patients hémophiles A.

Only a few studies on real-world clinical use of recombinant factor VIII -fusionned with Fc (rFVIIIFc, efmoroctocog alpha) have been performed to date, with data on the annual bleeding rate (ABR), the prophylaxis regimen, and FVIII consumption. The aim of our study was to report the real-world clinical application of rFVIIIFc with additional elements, both biological and clinical. A prospective monocentric study has been conducted in the Haemophilia treatment center (HTC) of the Strasbourg university hospital among the severe haemophilia A patients. Thirty male patients were enrolled in the study. After injection of rFVIIIFc, the average time spent above 5%, 2% and 1% of FVIII was respectively almost 3, 4 and 5 days. The average half-life was 15.8 hours. A strong linear correlation between incremental recovery of rFVIIIFc and weight and between rFVIIIFc half-life and basal VWF:Ag level was observed. FVIII activity measurement for rFVIIIFc showed similar results than those previously published. In the follow-up, residual FVIII activity was on average the one of a mild haemophilia patient, corroborated by the results of endogenous thrombin potential of the thrombin generation assay. In clinical practice, rFVIIIFc was well tolerated and patients were mostly satisfied or indifferent of the switch. A single failure was however noticed. No FVIII inhibitor has been detected. Decrease in FVIII consumption was observed, with reduced or unchanged ABR. The switch was an actual success for almost all of the 30 patients, corroborated by satisfactory clinical and biological results.