Korean J Hematol.  2008 Dec;43(4):232-237. 10.5045/kjh.2008.43.4.232.

von Willebrand Disease in Childhood Chronic ITP

• Park SM
• Lee JH
• Lee KS

• KMID: 1485081
• DOI: http://doi.org/10.5045/kjh.2008.43.4.232

Abstract

BACKGROUND
This study was performed to diagnose von Willebrand disease (vWD) in children with chronic immune thrombocytopenic purpura (ITP).
METHODS
Seventeen cases of chronic ITP were included in this study. Screening tests and specific tests were performed. These tests were also performed on their families when the patient was diagnosed vWD. Their past histories and family histories for bleeding tendencies were also reviewed.
RESULTS
Five cases were diagnosed with vWD: One had a low level of vWF:RCo and factor VIII with a normal level of vWF:Ag, and others had a low level of vWF:RCo and vWF:Ag with a normal level of factor VIII. Among these, two cases showed abnormal screening test results, with prolongation of the aPTT or BT. The vWF multimer test could be performed in three cases, and two cases had a normal pattern and one had a abnormal pattern. Among the five vWD children, the past histories and family histories of a bleeding tendency could be obtained for four vWD patients and three families showed a bleeding tendency. But all the families were found to be normal on the first screening and the specific tests.
CONCLUSION
von Willebrand disease was combined in 5 cases (29.4%) among the 17 chronic ITP children. More evaluations, such as the vWF multimer test and the ristocetin-induced platelet aggregation (RIPA) test are needed to confirm the subtype. A follow-up test of the same type should be repeated on family members who have a history of bleeding, but they have normal test results for the diagnosis or exclusion of vWD.

Keyword

Chronic immune thrombocytopenic purpura; von Willebrand disease; Children

MeSH Terms

Child
Factor VIII
Follow-Up Studies
Hemorrhage
Humans
Mass Screening
Platelet Aggregation
Purpura, Thrombocytopenic, Idiopathic
von Willebrand Diseases
Factor VIII

Reference

1). von Willebrand EA. Hereditary pseudohemophilia. Fins Lackarenracllsk Handl. 1926. 68:87–112.

2). Cox Gill J. Diagnosis and treatment of von Willebrand disease. Hematol Oncol Clin North Am. 2004. 18:1277–99.

3). Nicholas WC., Ginsburg D. von Willebrand disease. Medicine. 1997. 76:1–20.

4). Sadler JE. A revised classification of von Willebrand disease. For the subcommittee on von Willebrand factor of the scientific and standardization committee of the international society on thrombosis and haemostasis. Thromb Haemost. 1994. 71:520–5.

5). Sadler JE., Matsushita T., Dong Z., Tuley EA., Westfield LA. Molecular mechanism and classification of von Willlebrand disease. Thromb Haemost. 1995. 74:161–6.

6). Nichols WL., Hultin MB., James AH, 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. 14:171–232.

7). Katsanis E., Luke KH., Hsu E., Li M., Lilllicrap D. Prevalence and significance of mild bleeding disorders in children with recurrent epistaxis. J Pediatr. 1988. 113:73–6.

8). Bowie EJ. von Willebrand's disease. Clinical picture, diagnosis and treatment. Clin Lab Med. 1984. 4:303–17.

9). Zimmerman TS., Ruggeri ZM. von Willebrand's disease. Clin Haematol. 1983. 12:175–200.

10). Pottinger BE., Read RC., Paleolog EM., Higgins PG., Pearson JD. von Willebrand factor is an acute phase reactant in man. Thromb Res. 1989. 53:387–94.

11). Lee KS., Kim EJ. Clinical feature of von Willebrand disease. Korean J Pediatr Hematol-Oncol. 1998. 5:278–84.

12). Hepner DL., Tsen LC. Severe thrombocytopenia, type 2B von Willebrand disease and pregnancy. Anesthesiology. 2004. 101:1465–7.

13). Kaplan RN., Bussel JB. Differential diagnosis and management of thrombocytopenia in childhood. Pediatr Clin N Am. 2004. 51:1109–40.

14). Soliman DE., Broadman LM. Coagulation defects. Anesthesiol Clin. 2006. 24:549–78.

15). Ruggeri ZM., Pareti FI., Mannucci PM., Ciavarella N., Zimmerman TS. Heightened interaction between platelets and factor VIII/von Willebrand factor in a new subtype of von Willebrand's disease. N Engl J Med. 1980. 302:1047–51.

16). Kroner PA., Kluessendorf ML., Scott JP., Montgomery RR. Expressed full-length von Willebrand factor containing missense mutations linked to type IIB von Willebrand disease shows enhanced binding to platelets. Blood. 1992. 79:2048–55.

17). Weiss HJ., Sussman II. A new von Willebrand variant (type 1, New York): increased ristocetin induced platelet aggregation and plasma von Willebrand factor containing the full range of multimers. Blood. 1986. 68:149–56.

18). Holmberg L., Berntorp E., Donnér M., Nilsson IM. von Willebrand's disease characterized by increased ristocetin sensitivity and the presence of all von Willebrand factor multimers in plasma. Blood. 1986. 68:668–72.

19). Miller JL., Kupinski JM., Castella A., Ruggeri AM. von Willebrand factor binds to platelets and induces aggregation in platelet-type but not type IIB von Willebrand disease. J Clin Invest. 1983. 72:1532–42.

20). Miller JL., Castella A. Platelet-type von Willebrand's disease: characterization of a new bleeding disorder. Blood. 1982. 60:790–4.

21). Takafuta T., Fujimura K., Shimomura T, et al. Precise diagnosis by gene analysis and successful management of delivery in three patients with type II B von Willebrand disease. Int J Hematol. 1994. 60:163–72.

22). Meyer D., Fressinaud E., Gaucher C, et al. Gene defects in 150 unrelated French cases with type 2 von Willebrand disease: from the patient to the gene. INSERM Network on Molecular Abnormalities in von Willebrand Disease. Thromb Heamost. 1997. 78:451–6.

23). Zhang Z., Blombäck M., Anvret M. Understanding von Willebrand's disease from gene defects to the patients. J Intern Med Suppl. 1997. 740:115–9.

24). Song JW., Choi JR., Song KS. Investigation of von Willebrand factor gene mutations in Korean von Willebrand disease patients. Korean J Lab Med. 2007. 27:169–76.

25). Michiels JJ., Budde U., van der Planken M., van Vliet HH., Schroyens W., Berneman Z. Acquired von Willebrand syndromes: clinical features, aetiology, pathophysiology, classification and management. Best Pract Res Clin Haematol. 2001. 14:401–36.