von Willebrand Disease in Children: Diagnosis and Management of a Pediatric Cohort in One Single Center in Argentina

ABSTRACT

Clinical and laboratory data of children with von Willebrand disease (VWD) types have been derived from retrospective studies and small case series. This article reports on the clinical and laboratory data of a large pediatric cohort in one single Argentinian center. The biological and clinical responses to desmopressin and replacement therapies are also described. Over a 15-year period, 194 of 1150 children (16.9%) were diagnosed as having type 1 VWD (80%), type 2 VWD (19%), and type 3 VWD (1%). The distribution of the different type 2 VWD subtypes was type 2A VWD, 43%; type 2B VWD, 32%; type 2M VWD, 19%; and type 2N VWD, 6%. Eighty patients with type 1 VWD and 12 patients with type 2 VWD were prospectively evaluated to desmopressin (DDAVP) response. A complete response was observed in all children with type 1 VWD, whereas 40% of the children with severe type 1 VWD and with type 2 VWD achieved a complete response. All the children who received DDAVP as prophylaxis or treatment for bleeding had good clinical evolution. Considering the restricted availability of specialized hemostasis centers, we believe our clinical and laboratory approach appropriate for the detection of patients with different types of VWD. Further studies are necessary to determine epidemiological aspects of VWD in Argentina to estimate the necessary facilities and trained personnel for the diagnosis and management of patients with VWD.

KEYWORDS

von Willebrand disease - children - desmopressin

REFERENCES

• 1 Sadler J E, Budde U, Eikenboom J C Working Party on von Willebrand Disease Classification et al. Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.  J Thromb Haemost. 2006;  4 (10) 2103-2114
• 2 Werner E J, Broxson E H, Tucker E L, Giroux D S, Shults J, Abshire T C. Prevalence of von Willebrand disease in children: a multiethnic study.  J Pediatr. 1993;  123 (6) 893-898
• 3 Biss T T, Blanchette V S, Clark D S et al.. Quantitation of bleeding symptoms in children with von Willebrand disease: use of a standardized pediatric bleeding questionnaire.  J Thromb Haemost. 2010;  8 (5) 950-956
• 4 Nichols W L, Hultin M B, James A H et al.. von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA).  Haemophilia. 2008;  14 (2) 171-232
• 5 Mannucci P M. How I treat patients with von Willebrand disease.  Blood. 2001;  97 (7) 1915-1919
• 6 Nolan B, White B, Smith J, O'Reily C, Fitzpatrick B, Smith O P. Desmopressin: therapeutic limitations in children and adults with inherited coagulation disorders.  Br J Haematol. 2000;  109 (4) 865-869
• 7 Allen G C, Armfield D R, Bontempo F A, Kingsley L A, Goldstein N A, Post J C. Adenotonsillectomy in children with von Willebrand disease.  Arch Otolaryngol Head Neck Surg. 1999;  125 (5) 547-551
• 8 Sutor A H. DDAVP is not a panacea for children with bleeding disorders.  Br J Haematol. 2000;  108 (2) 217-227
• 9 Jiménez-Yuste V, Prim M P, De Diego J I et al.. Otolaryngologic surgery in children with von Willebrand disease.  Arch Otolaryngol Head Neck Surg. 2002;  128 (12) 1365-1368
• 10 Revel-Vilk S, Schmugge M, Carcao M D, Blanchette P, Rand M L, Blanchette V S. Desmopressin (DDAVP) responsiveness in children with von Willebrand disease.  J Pediatr Hematol Oncol. 2003;  25 (11) 874-879
• 11 Sánchez-Luceros A, Meschengieser S S, Woods A I et al.. Biological and clinical response to desmopressin (DDAVP) in a retrospective cohort study of children with low von Willebrand factor levels and bleeding history.  Thromb Haemost. 2010;  104 (5) 984-989
• 12 Bowman M, Riddel J, Rand M L, Tosetto A, Silva M, James P D. Evaluation of the diagnostic utility for von Willebrand disease of a pediatric bleeding questionnaire.  J Thromb Haemost. 2009;  7 (8) 1418-1421
• 13 National Committee for Clinical Laboratory Standards (NCCLS) .Collection, Transport, and Processing of Blood Specimens for Testing Plasma-Based Coagulation Assays: Approved Guideline. Publication H21–A4.Wayne, PA: NCCLS; 2002
• 14 Frontroth J P, Hepner M, Sciuccati G, Feliú Torres A, Pieroni G, Bonduel M. Prospective study of low-dose ristocetin-induced platelet aggregation to identify type 2B von Willebrand disease (VWD) and platelet-type VWD in children.  Thromb Haemost. 2010;  104 (6) 1158-1165
• 15 Lahiri D K, Nurnberger Jr J I. A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies.  Nucleic Acids Res. 1991;  19 (19) 5444
• 16 Andrew M, Vegh P, Johnston M, Bowker J, Ofosu F, Mitchell L. Maturation of the hemostatic system during childhood.  Blood. 1992;  80 (8) 1998-2005
• 17 Srivastava A, Rodeghiero F. Epidemiology of von Willebrand disease in developing countries.  Semin Thromb Hemost. 2005;  31 (5) 569-576
• 18 Rodeghiero F, Ruiz-Sáez A, Bolton-Maggs P H, Hayward C P, Nair S C, Srivastava A. Laboratory issues in bleeding disorders.  Haemophilia. 2008;  14 (Suppl 3) 93-103
• 19 Bujnicki H L, Sidonio R F, Moore C G et al.. Predictors of von Willebrand disease in children: a case control study.  Blood. 2010;  116 712 (Abst)
• 20 Rodeghiero F, Tosetto A, Abshire T et al. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders.  J Thromb Haemost. 2010;  8 (9) 2063-2065
• 21 Favaloro E J, Thom J, Patterson D et al.. Desmopressin therapy to assist the functional identification and characterisation of von Willebrand disease: differential utility from combining two (VWF:CB and VWF:RCo) von Willebrand factor activity assays?.  Thromb Res. 2009;  123 (6) 862-868
• 22 Lee C A, Hubbard A, Sabin C A ISTH-SSC sub-committee on VWF et al. Laboratory diagnosis of von Willebrand disease: results from a prospective and blind study in 32 laboratories worldwide using lyophilized plasmas.  J Thromb Haemost. 2010;  9 220-222
• 23 Casais P, Carballo G A, Woods A I et al.. R924Q substitution encoded within exon 21 of the von Willebrand factor gene related to mild bleeding phenotype.  Thromb Haemost. 2006;  96 (2) 228-230
• 24 Federici A B, Mazurier C, Berntorp E et al.. Biologic response to desmopressin in patients with severe type 1 and type 2 von Willebrand disease: results of a multicenter European study.  Blood. 2004;  103 (6) 2032-2038
• 25 Castaman G, Lethagen S, Federici A B et al.. Response to desmopressin is influenced by the genotype and phenotype in type 1 von Willebrand disease (VWD): results from the European Study MCMDM-1VWD.  Blood. 2008;  111 (7) 3531-3539
• 26 Federici A B, Iorio A, Castaman G. Clinical efficacy and safety versus biological response to desmopressin (DDAVP) in inherited von Willebrand disease (VWD) types 1 and 2: Initial results from the International study group on DDAVP in VWD in a cohort of 229 patients.  Blood. 2010;  116 238 (Abst)