Tonsillectomy in a Patient with Type 3 Von Willebrand Disease

Introduction: Type 3 Von Willebrand Disease (VWD) is a rare autosomal recessive bleeding disorder characterized by a complete deficiency of von Willebrand factor (VWF) and markedly reduced levels of FVIII, which confers a severe bleeding phenotype. Conventional management is with plasma-derived von Willebrand factor / FVIII concentrates. These products do not fully correct the bleeding diathesis, for several possible reasons: (a) platelets remain deficient in VWF; (b) subendothelial matrix remains deficient in VWF; and (c) available products lack the highest molecular weight VWF multimers. Because of the low prevalence of type 3 VWD, reports on surgical procedures are scarce. We reviewed the literature and identified one case report of a patient with type 3 VWD who underwent tonsillectomy (Alusi et al. 1995). That case was complicated by major intra-operative bleeding as well as prolonged hemorrhage in the two weeks following surgery, despite factor replacement with concentrate, cryoprecipitate, platelet transfusion and tranexamic acid. We report on the management of a patient with type 3 VWD undergoing a tonsillectomy, which demonstrates the importance of local measures in hemostatic control.

Case: A 29 year old woman with Type 3 VWD (baseline VWF:Ag 4 IU/dL, VWF:RCoF <5 IU/dL, FVIII 1 IU/dL) had a 2 year history of recurrent tonsillar hemorrhage despite regular prophylaxis with plasma-derived VWF concentrate (Humate-P®). Each episode occurred in the absence of trauma or infection, and bleeding was difficult to control despite Humate-P and tranexamic acid. Lee et al. (2010) have previously reported that VWD is a cause of spontaneous tonsillar hemorrhage. Due to the recurrent nature of the bleeding episodes, a tonsillectomy was recommended.

In preparation for the surgical procedure, we performed pharmacokinetic studies, which revealed a yield of VWF activity of 2.35IU/dL per U/kg and a half-life of VWF activity of 8.8 hours. We administered an initial loading dose of 63IU/kg (RCoF) of Humate-P preoperatively, achieving a VWF activity level (by latex agglutination: HemosIL vWF activity, Instrumentation Laboratories) of 126%. The tonsillectomy was uneventful, and the estimated blood loss intra-operatively was <50 mL. Surgical hemostasis was augmented by administration of tranexamic acid 1000mg intravenously pre-operatively and by continuous infusion intra-operatively, as well as 5 mL of fibrin sealant (Tisseel) administered to each tonsillar bed. A dose of Humate-P of 22.6 IU/kg was given post-operatively, and subsequent doses of 11.3 IU/kg were given q 4 hourly to maintain trough VWF activity of approximately 100IU/dL. Post-operative doses of tranexamic acid were omitted due to a transcribing error until day #3. On day #4 the Humate P dosing was reduced to 11.5U/kg q6h, which maintained trough VWF activity levels of approximately 50%. No bleeding occurred until post-operative day #9, when the eschar at the wound side detached. Bleeding continued despite re-bolus of Humate-P (23IU/kg) followed by resumption of q4h dosing, administration of tranexamic acid topically in the form of a 5% solution in addition to systemic administration, and application of topical silver nitrate. Hypotension transiently developed and the hemoglobin fell from 106 to 66g/L, requiring a return to the operating room. Further application of fibrin sealant promptly secured hemostasis.

Conclusion: Surgery in a patient with type 3 VWD requires careful planning and collaboration between hematologists with expertise in bleeding disorders, the bleeding disorders nursing staff and surgical team. This case highlights the importance of monitoring for an extended period post-operatively, and demonstrates that bleeding can occur despite maintaining adequate VWF levels. Topical measures such as fibrin sealant play a key role in controlling bleeding in this context.