title: Similarity in joint function limitation in Type 3 von Willebrand's disease and moderate haemophilia A.
abstract: Type 3 von Willebrand's disease (VWD) is a rare bleeding diathesis with complete or near complete deficiency of von Willebrand factor (VWF) and low factor VIII (FVIII) levels. In contrast, only FVIII is decreased in haemophilia A (HA). Both disorders are complicated by arthropathy. The purpose of this study was to further clarify the roles of FVIII and VWF: Antigen (VWF:Ag) in joint range of motion (ROM) loss over time. We compared joint ROM loss and other bleeding manifestations in 100 Type 3 VWD subjects (FVIII<5%) and 1814 moderate HA subjects (FVIII 1-5%) within the U.S. Universal Data Collection (UDC) database. High rates of bleeding were reported at baseline. During follow-up, moderate HA patients reported a joint (46% vs. 34%, P < 0.0001) or muscle bleed (27% vs. 16%, P < 0.0001) in a higher proportion of visits than VWD patients. Other bleeds, including mucosal, were reported in a greater proportion of visits among patients with Type 3 VWD than among those with HA (49% vs. 32%, P < 0.0001). Multivariate analysis revealed no difference in joint ROM loss over time in the Type 3 VWD vs. moderate HA populations. A higher FVIII level was protective in both VWD and HA (P < 0.001). Our findings support the hypothesis of primacy of the FVIII level in determining risk of joint haemorrhage, and may help target therapy in Type 3 VWD and moderate HA to prevent joint disability.
authors.affiliation: Hemophilia and Coagulation Disorders Program, Division of Hematology-Oncology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA. sumisood@med.umich.edu
authors.forename: S L
authors.initials: SL
authors.lastname: Sood
authors.forename: A
authors.initials: A
authors.lastname: Cuker
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.forename: A D
authors.initials: AD
authors.lastname: Metjian
authors.forename: E Y
authors.initials: EY
authors.lastname: Chiang
authors.forename: J M
authors.initials: JM
authors.lastname: Soucie
authors.forename: B A
authors.initials: BA
authors.lastname: Konkle
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003710:Demography; D005260:Female; D005500:Follow-Up Studies; D006467:Hemophilia A / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D006470:Hemorrhage / Q000150:complications / Q000503:physiopathology; D006801:Humans; D007596:Joints / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D016059:Range of Motion, Articular / Q000502:physiology*; D012307:Risk Factors; D013997:Time Factors; D055815:Young Adult; D056729:von Willebrand Disease, Type 3 / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*
references.citation: Haemophilia. 2009 Jul;15(4):918-25
references.pmid: 19473418
references.citation: Acta Orthop Scand. 1970;41(5):539-44
references.pmid: 5313525
references.citation: Semin Thromb Hemost. 2006 Sep;32(6):555-65
references.pmid: 16977566
references.citation: Blood. 2004 Apr 1;103(7):2467-73
references.pmid: 14615381
references.citation: Haemophilia. 2004 Jul;10(4):360-6
references.pmid: 15230950
references.citation: Thromb Haemost. 2000 Dec;84(6):977-80
references.pmid: 11154144
references.citation: Haemophilia. 2011 May;17(3):500-7
references.pmid: 21070485
references.citation: Blood Transfus. 2008 Sep;6 Suppl 2:s26-32
references.pmid: 19105507
references.citation: J Clin Invest. 1977 Aug;60(2):390-404
references.pmid: 17621
references.citation: Thromb Res. 2006;118 Suppl 1:S19-22
references.pmid: 16545435
references.citation: Haemophilia. 2008 Nov;14 Suppl 5:47-53
references.pmid: 18786010
references.citation: Blood Coagul Fibrinolysis. 2005 Apr;16 Suppl 1:S23-6
references.pmid: 15849523
references.citation: Br J Haematol. 2000 Dec;111(4):1236-9
references.pmid: 11167767
references.citation: J Thromb Haemost. 2006 Oct;4(10):2103-14
references.pmid: 16889557
references.citation: J Thromb Haemost. 2009 Jul;7 Suppl 1:65-70
references.pmid: 19630771
references.citation: Semin Hematol. 2008 Apr;45(2 Suppl 1):S50-7
references.pmid: 18544426
references.citation: Haemophilia. 2008 Mar;14(2):171-232
references.pmid: 18315614
references.citation: Thromb Haemost. 2011 Apr;105(4):597-604
references.pmid: 21301780
references.citation: Arthritis Rheum. 2002 Nov;46(11):2857-66
references.pmid: 12428225
references.citation: Thromb Res. 2006;118 Suppl 1:S3-7
references.pmid: 16580053
references.citation: Clin Lab Haematol. 1983;5(2):149-56
references.pmid: 6603956
references.citation: Eur J Clin Chem Clin Biochem. 1994 Apr;32(4):313-7
references.pmid: 7518699
references.citation: Haemophilia. 1999 May;5(3):223-31; discussion 222
references.pmid: 10444294
references.citation: Semin Thromb Hemost. 2006 Sep;32(6):621-5
references.pmid: 16977572
references.citation: Haemophilia. 2013 Jan;19(1):76-81
references.pmid: 22823000