Atypical Variant of Acquired von Willebrand Syndrome in Wilms Tumor: Is Hyaluronic Acid Secreted by Nephroblastoma Cells the Cause?

Abstract

Acquired von Willebrand syndrome (AvWS) has been reported in eight children with Wilms tumor (nephroblastoma in four boys and four girls) at a mean age of 3.3 years (range, 0.33-9 years). Only three of eight patients with AvWS in Wilms tumor presented with mild mucocutaneous bleeding symptoms. The AVWS in seven children with Wilms tumor featured either undetectable or very low von Willebrand factor antigen (vWF.Ag) levels (mean, 3%) and decreased values for vWF ristoectin cofactor (RCF) activity (mean, 20%) and factor VIII coagulant (VIIIc) activity (mean, 16%). The response to 1-desamino-8-argi nine vasopressin (DDAVP) was good in two and poor in one patient. Multimeric analysis of the vWF showed a normal pattern of type I von Willebrand disease (vWD) in three patients and an absence of multimers consistent with type In v WD in two patients. The higher functional levels, as compared with antigen levels, with increased ratios for factor VIIIc/vWFAg (mean, 5.3) and vWF.RCF/vWF.Ag (mean, 6.6) in seven patients with Wilms tumor are unexplained physiologically and are not consistent with type I vWF deficiency. The absence of vWD in the patient's family, and the return of factor VIII-VWF parameters to normal after chemotherapy or surgical removal of the Wilms tumor, support the diagnosis of AvWS causally related to the Wilms tumor. The causative agent is thought to be hyaluronic acid secreted by nephroblastoma cells of the Wilms tumor. Prospective studies to determine the nature of AvWS in children with Wilms tumor are warranted.

Keywords

Acquired von Willebrand syndrome factor VIII Hyaluronic acid von Willebrand disease von Willebrand factor Wilms tumor.

References

Sadler JE A revised classification of von Willebrand disease. Thromb Haemost 1994;71:520.

Jakway JF Acquired von Willebrand's disease. Hematol Oncol Clin N Am 1992;6:1409.

Tefferi A. , Nichols WL Acquired von Willebrand disease: concise review of occurrence, diagnosis, pathogenesis and treatment. Am J Med 1997; 103:536.

Mohri H. , Motomura S. , Matsuzaki M. , et al. Clinical significance of inhibitors in acquired von Willebrand Syndrome. Blood 1998;91: 3623.

Van Genderen Pjj , Michiels JJ Acquired von Willebrand disease . Baillieres. Clin Haematol 1998;11:319.

Montgomery RR , Hays T. , Tubergen DG Spontaneous remission of acquired von Willebrand's disease following resection of Wilm's tumor. Pediatr Res 1978; 12:469.

Noronha PA , Gruby MA , Maurer HS Acquired von Willebrand disease in a patient with Wilms tumor. J Pediatr 1979;95:997.

Scott JP , Montgomery RR , Tubergen DG , et al. Acquired von Willebrand's disease in association with Wilm's tumor regression following treatment. Blood 1981;58:665.

Bracey AW , Wu Ahb , Aceves J. , et al. Platelet dysfunction associated with Wilms tumor and hyaluronic acid. Am J Hematol 1987;24:247.

10.

Han P. , Lou J. , Wong HB Wilms' tumor with acquired von Willebrand's disease, Aust Paediatr J 1987;23:253.

11.

Coppes MJ , Zandvoort SH , Sparling CR , et al. Acquired von Willebrand disease in Wilm's tumor patients. J Clin Invest 1992;10:422.

12.

Soff GA , Green D. Autoantibody to von Willebrand factor in systemic lupus erythematoses . J Lab Clin Med 1992; 121:424.

13.

Wu Ahb , Parker OS , Ford L. Hyperviscosity caused by hyaluronic acid in serum in a case of Wilm's tumor . Clin Chem 1984;30:914.

14.

Michiels JJ , van Vliet Hhdm. Acquired von Willebrand disease in monoclonal gammapathy: effectiveness of high-dose intravenous gamma globulin . Clin Appl Thromb Hemost 1999;5:152.

15.

Federici AB , Rand JH , Budde U. , et al. Diagnosis and management of acquired von WiHebrattd Syndrome: recommendations based on the results of the International Registry. Thromb Haemost 2000;84:345.