A Prospective Evaluation of Bleeding Tendency and Efficacy of Antihemorrhagic Treatments in Patients with Increased Von Willebrand Factor (VWF) Clearance (Von Willebrand Disease Vicenza AND C1130F Mutation).

Background. von Willebrand disease Vicenza (VWD-VI) is characterized by severely reduced FVIII and VWF levels, the presence of ultra-large multimers in plasma, heightened response to desmopressin and increased clearance of VWF after desmopressin. Increased clearance of VWF has been identified in other VWF mutations, such as C1130F with similarly low FVIII/VWF levels as in VWD-VI. So far, the bleeding risk of these patients has not been formally established and it is unclear whether they need a different treatment approach.

Aims, Design of the study, Patients and Methods. We prospectively evaluated the clinical history of 60 patients (32 M, 28 F) with VWD Vicenza (carrying R1205H mutation) and 23 patients (9 M, 14 F) with C1130F mutation, both characterized by increased VWF clearance. All in-hospital visits for bleeding symptoms, treatments and prophylaxis prior to invasive procedures were recorded together with home-treatments. All the remaining patients were contacted yearly to update their bleeding symptoms, if any. The study lasted from January 2002 to December 2007.

Results. During follow-up, 21/60 (35 %) and 9/23 (39 %) of patients with VWD-VI or C1130F respectively did not require treatment for bleeding or prior to invasive procedures. Ten patients with VWD-VI and 5 with C1130F had 1 to 3 tooth extraction instances treated with a single desmopressin infusion plus oral tranexamic acid for 5 days, without mishap. A single patient carrying out dental extraction without any prophylaxis had bleeding promptly stopped by a single desmopressin infusion. Four women with VWD-VI and 6 with C1130F had 1 or 2 pregnancies during follow-up, and successfully completed delivery by using two or three desmopressin infusions over 24-48 hours after vaginal delivery. Epistaxis requiring consultation or treatment was almost limited to pediatric age and a single adult patient only required treatment for an isolated episode. A single post-traumatic joint bleeding required a successful treatment with desmopressin. Only 3/15 (20 %) women in fertile age with VWD-VI required treatment for menorrhagia (iron suppletion, combined oral estroprogestinic pill, tranexamic acid) compared to 8/9 (89 %) with C1130F mutation. Most minor surgical interventions were successfully covered with desmopressin while major surgery required FVIII/VWF concentrates since prolonged hemostasis was required.

Conclusions. Spontaneous bleeding in patients with VWD-VI and C1130F appeared to be mainly limited to epistaxis in pediatric age and menorrhagia in females. Most of clinical situations are successfully manageable with desmopressin, as usually occurs for other type 1 VWD patients, and despite the short FVIII and VWF half-life post-infusion.