Safety of von Willebrand factor substitution for neuraxial anesthesia in women with persistent von Willebrand deficiency at delivery

Position du problème et objectif(s) de l’étude

Neuraxial anesthesia (NA) constitutes a risk for patients with bleeding disorders, the main hemorrhagic adverse effect being perimedullary hematoma. No clear recommendation has been issued concerning NA use for delivery in patients with von Willebrand disease (VWD) and with von Willebrand factor (VWF) levels not spontaneously corrected by the end of pregnancy. Our aim was to describe the use of von Willebrand factor to authorize NA during labor in French centers.

Matériel et méthodes

After approval from the Ethics committee of Saint-Etienne University Hospital, (registration no. IRBN052023), we performed a retrospective review among the 42 French hospitals of the MHEMO network. Inclusion criteria were: women with, 1) VWF deficiency not spontaneously corrected at the end of pregnancy, 2) who received VWF (± FVIII) infusions at delivery and 3) who benefited from NA. The main objective was to describe the experience of the French hospitals that used VWF before NA during delivery in these patients over the period 2008 to 2022. The main outcomes were: von Willebrand factor activity and antigen levels (VWF:Act and VWF:Ag), FVIII levels, the doses of VWF administered in this context and complications of the NA. A Wilcoxon test was used to compare values between the different periods evaluated.

Résultats & Discussion

Thirty-two patients participated in the study, accounting for 40 pregnancies in total. Out of the 42 eligible centers, patients were included from the 8 centers having allowed an NA with VWF substitution. All VWD types were represented, except type 3. VWF, FVIII, fibrinogen and platelet levels were recorded before and at the end of pregnancy. From baseline to the term of pregnancy (before VWF injection), VWF:Act median levels rose significantly from 12% [2.3-29] to 19% [8-49] and VWF:Ag from 21% [6-96] to 51.5% [8-100]. Median FVIII levels tended to increase from 39.75% [8-81.6] to 79.3% [11-184.3] (Figure 1). The majority of patients had very low VWF:Act levels at term, below 20% in 22 pregnancies. At term, median platelet count was 246.5 G/L [133-407] and median fibrinogen level was 4.66 g/L [3.05-6.2]. The monitoring of VWF levels, the type of VWF±FVIII substitution and the doses administered were also noted. The median dose of VWF concentrates used for the first infusion was 50 IU/kg [16-66]. The median number of VWF infusions was 4 [1-18]. Depending on the center, VWF:Act assays were performed mostly at peak or at residual levels. After substitution, the VWF:Act median value of 82.7% [44-229], with all but one patient achieving a level above 50% (Figure 2). No spinal subdural hematoma or ecchymosis related to NA were observed in any of the 32 patients during the 40 deliveries. We also performed a review of the literature concerning the use of NA at delivery in VWD patients. Among the 21 studies reviewed accounting for 190 deliveries, all neuraxial anesthesia were uneventful.

Conclusion

In conclusion, our results suggest that patients with VWD manifesting VWF levels not spontaneously corrected by the end of pregnancy could safely benefit from NA with VWF substitution. Based on these results, and considering national and international recommendations, we formulated proposals on how to manage these patients. Management could consist in injecting VWF concentrates prior to NA to maintain a VWF:Act level above 50% (that should be monitored) until 6 hours after catheter removal. We think that NA under an adequate substitution of VWF is safe and beneficial for these patients.

Auteurs

Yaquine MECHELFEKH (1) , Sarah GUÉRIN (2), Kenza KALI (3), Noyel PAULINE (4), Aurélie MONTMARTIN (5), Marie TUFFIGO (1), Benoit GUILLET (6), Maud COLINART THOMAS (7), Alexandre BUTELET (7), Céline FALAISE (8), Nicolas DRILLAUD (9), Miréla CHIRILA-HETSCH (10), Laurent MACCHI (11), Philippe BEURRIER (12), Brigitte TARDY (13) - (1)Laboratoire D’hématologie, Chu D'angers, Univ Angers, Nantes Université, Chu Angers, Inserm, Cnrs, Crci2na, F-49000 Angers, Angers, France, (2)Anesthesia And Intensive Care Department, University Hospital Center Of Angers, Angers, France, (3)Inserm Cic 1408 Laboratory Of Hematology, Saint-Étienne, France, (4)Laboratoire D'hématologie, Chu De Saint-Etienne, Saint-Étienne, France, (5)Inserm U1059, Sainbiose Dysfonction Vasculaire Et Hémostase, Université De Lyon, Saint-Etienne, Saint-Étienne, France, (6)Haemophilia Treatment Center, Rennes University Hospital, Rennes, France, (7)Centre For Constitutional Bleeding Disorders, Reims University Hospital, Reims, France, (8)Hemostasis Clinical Center, Marseille University Hospital, Assistance Publique-Hôpitaux De Marseille, Marseille, France, (9)Haemophilia Centre, Nantes University Hospital, Nantes, France, (10)Service D'hématologie, Hôpital De Valence, Valence, France, (11)University Of Poitiers, Inserm 1313, Irmetist, F-86000 Poitiers, France; Chu De Poitiers, Laboratory Of Hematology, F-86000, Poitiers, Poitiers, France, (12)Hemophilia Treatment Center, Vascular And Coagulation Clinic, University Hospital Angers, Angers, France, (13)Centre De Ressources Et De Compétence Maladies Hémorragiques, Chu Saint-Etienne, Hôpital Nord Sainbiose, Inserm, U1059, Université Lyon Inserm, Cic 1408, Chu Saint-Etienne, Hôpital Nord, Saint-Etienne, France, Saint-Étienne, France

Orateur(s)

Brigitte TARDY ()