Introduction: Von Willebrand disease (VWD) is the most common inherited bleeding disorder affecting as many as 1% of the population. Mucocutaneous symptoms predominate, and include ecchymosis, menorrhagia, and epistaxis. In addition, perioperative bleeding is common, and often prompts diagnosis; therefore, affected patients require perioperative VWD-specific therapy to prevent surgical related bleeding. VWF-specific therapy includes DDAVP, intravenous and nasal, and VWF concentrates, plasma derived, and more recently, recombinant. Unfortunately, few standard evidence-based guidelines are in place concerning the perioperative management of VWD, in part due to a limited number of high quality clinical research studies addressing the topic. Because of this, treatments vary widely, often based on local practice and physician experience. To evaluate the efficacy and safety of perioperative VWD-specific therapy, we aimed to describe our experience managing VWD patients undergoing surgery.
Methods: We performed a retrospective chart review of patients with VWD receiving care at the Hemophilia Center of Western Pennsylvania (HCWP) who underwent surgery at a University of Pittsburgh Medical Center (UPMC) affiliated hospital between January 1, 2015, and May 31, 2017. Surgery was defined as any invasive procedure, including childbirth. Data collected included demographics; VWD subtype; VWD-specific therapy, including type, dose, frequency, and duration; estimate blood loss during surgery; presence of postoperative bleeding; and whether or not thrombosis occurred.
Results: A total of64 patients with VWD receiving care at HCWP underwent surgery at an UPMC-affiliated hospital during the time period. The mean age of participants was 32.9 ± 17.5 years (median 33, range 2 to 89). Of these, 86% of patients were female. By type, 80% were type 1 VWD; 17% were type 2 VWD (2A, n=1; 2B, n=5; 2M, n=3; and 2N, n=2); and 2 were type 3 VWD (Table 1). The most common surgeries performed included vaginal delivery, n=7; cesarean section, n=6; dental extraction, n=4; colonoscopy with biopsy, n=3; and breast biopsy, n=3 (Table 1). 83% of patients received VWF concentrates, and the remaining patients received DDAVP (Table 1). Reasons for VWF concentrate use included DDAVP allergy, poor response to DDAVP, type of VWD, and type of surgery. Dosing, frequency, and duration of VWD-specific therapy differed considerably. Estimated blood loss (EBL), intraoperatively, was minimal (defined as less than 100 mL) in all but 12 surgeries, 11 of which involved childbirth with EBL 1000 mL or less in all. The other surgery was a dental extraction of 23 teeth with EBL 270 mL. Postoperative bleeding occurred in 3 patients, and included minor epistaxis following adenoidectomy and minor oral mucosa bleeding following a single dental extraction. 1 patient experienced a large breast hematoma following bilateral breast reduction requiring operative evacuation. No thromboses occurred.
Discussion: We describe the perioperative management of 64 patients with VWD at our institution. VWD-specific therapy was both safe and effective, evidenced by minimal bleeding and no adverse events. A large number of patients were pregnant. It is our practice to utilize VWF concentrates in most pregnant VWD patients during childbirth due to the risk of DDAVP induced fluid retention and hyponatremia in the peripartum period. Our findings are indicative of its efficacy and safety in this particular situation. Despite these findings, there were considerable differences in dosing, frequency, and duration of VWD-specific therapy. This parallels the known variation in treatment of VWD among practitioners, in large part, due to the lack of evidence-based guidelines available to help standardize therapy. In conclusion, we describe the safe and effective perioperative management of VWD while acknowledging differences in treatment, which further underscores the need for high quality clinical research studies and evidence-based guidelines to standardize the perioperative management of VWD.
Ragni: Alnylam, CSL Behring, Dimensions, Genetech/Roche,Pfizer, Shire, SPARK: Research Funding; A Anylam,Biomarin,Tecere, Benitec: Honoraria.
Asterisk with author names denotes non-ASH members.