DDAVP Prevents Post-Intervention Bleeding Complications in Patients With Low von Willebrand Factor Levels

A recent study suggests 1-desamino-8-D-arginine vasopressin (DDAVP) prevents bleeding in patients with low von Willebrand factor (VWF) levels undergoing major and minor elective procedures. The researchers, led by Dearbhla Doherty, MD, of the St. James’s Hospital in Dublin, Ireland, added that while DDAVP is effective for certain subgroups of patients with low VWF levels, a personalized approach to management may also be important for the prevention of bleeding complications.

“[Recent studies] have demonstrated that a significant number of patients with plasma VWF:Ag in the 30 to 50 IU/dL range have a bleeding phenotype [but the] reason why some of these patients with mild to moderate reductions in plasma VWF display a significant bleeding phenotype remains unclear,” Dr. Doherty and coauthors wrote. “Given all these unanswered questions, the management of patients with low VWF, particularly at times of hemostatic challenge, continues to pose significant challenges for physicians.”

The retrospective study evaluated the efficacy and safety of various peri-procedure management options among 60 patients with well characterized low VWF. Patients included in the retrospective cohort were enrolled in the Low Von Willebrand in Ireland Cohort (LoVIC) study. Overall, patients underwent a total of 160 invasive procedures, at a median of two procedures per patient. Procedures were classified as either minor (68.1%), major (6.9%), or dental (25%).

Approximately 87% of patients in LoVIC study who underwent a procedure were female, and 90% of patients were blood group O. The median age of the patients with low VWF who had undergone a procedure was significantly higher compared with the overall LoVIC cohort (45 vs. 41 years; p<0.01).

Dental procedures were mostly tooth extractions, while minor procedures largely included endoscopies as well as arthroscopies, joint injections, and skin lesion excision. Most of the major procedures included orthopedic, tonsillectomy, and abdominal surgery.

Bleeding complications were rare, occurring in only 3.8% of the reviewed procedures. The mean age of patients who developed bleeding complications was 53.8 years.

Clinicians developed periprocedural management plans for patients based on personal bleeding histories, DDAVP trial responses, basal VWF levels, and the nature of the procedure. Treatment options were:

  • observation only
  • tranexamic acid 1 g administered 3 times daily
  • DDAVP 0.3 μg/kg (at a maximum of 27 μg)
  • clotting factor concentrate

The DDAVP option was not considered for patients with low VWF who were older than 55 years, per the study’s institutional policy.

Seventeen procedures were not covered with any tranexamic acid or DDAVP prophylaxis. While patients in this cohort accounted for only 11% of the total cohort, they accounted for 33% of the total bleeding complications observed.

Among the 71 patients with low VWF who completed DDAVP trials, the researchers noted an “excellent and sustained” VWF response.

The median plasma VWF:Ag levels at one and four hours after DDAVP infusion were 167 IU/dL and 130 IU/dL, respectively. In addition, the median VWF:RCo levels were 160 IU/dL at one hour and 117 IU/dL at four hours following DDAVP. “These data confirm that DDAVP administration triggers significant secretion of endogenous VWF stores that effectively corrects plasma VWF antigen and activity levels in patients with low VWF,” they explained.

The use of DDAVP in these patients was effective for the prevention of bleeding in minor and major elective procedures, Dr. Doherty and coauthors concluded. In addition, treatment with DDAVP was associated with bleeding prevention among patients with significant bleeding histories.

Treatment with tranexamic acid monotherapy was also effective for the prevention of bleeding in patients with low VWF who underwent non-dental minor procedures. The authors noted that these patients often received tranexamic acid because they were considered too old to receive DDAVP. Bleeding complications were reported in three of the 40 elective procedures covered with tranexamic acid alone. All bleeding complications that occurred with tranexamic acid monotherapy occurred in patients who underwent the dental intervention, the authors added.

“Cumulatively, these findings highlight the fact that adult patients who satisfy clinicopathological criteria for a low VWF diagnosis may still have a bleeding risk even if basal VWF levels have risen above 50 IU/dL,” Dr. Doherty and coauthors concluded. However, limitations of this study included its retrospective nature, as well as the small sample size, which may limit the generalizability of the results. According to the investigators, the small sample size warrants future adequately powered studies that can offer more robust evidence to guide optimal treatment strategies for patients with low VWF levels.

Study authors report no relevant conflicts of interest.

Reference

Doherty D, Lavin M, O’Sullivan JM, et al. Management of elective procedures in low von Willebrand factor patients in the LoVIC study. J Thromb Haemost. 2020 December 21. [Epub ahead of print]