Prevalence of Suspected Collagen Disorders In the Adult Bleeding Disorder Clinic.
Authors: Jackson Shannon , Odiaman Leah , Brown Morna , Spitzer Carol , Card Robert T. , Poon Man-Chiu 
Published: October 2019

Abstract
Abstract 1399

Background:
Disorders of collagen may be associated with a mild bleeding tendency because of the interaction of collagen with von Willebrand factor (VWF) and platelets required during primary hemostasis and generalized soft tissue fragility. Therefore, collagen disorders may be unrecognized contributors to existing disorders of primary hemostasis. Synergism between these entities could produce a more significant bleeding tendency than predicted based on laboratory abnormalities alone. Symptomatic joint hypermobility (SJH) is found in over 90% of collagen disorders and can be objectively measured as a surrogate marker of a potential collagen disorder.

Objective:
To determine the prevalence of suspected collagen disorders in a cohort of adult subjects with mucocutaneous inherited bleeding disorders in comparison to healthy controls using SJH as a marker for a potential collagen disorder.

Methods:
Fifty-five consecutive subjects, ≥ 16 years of age, attending the Adult Bleeding Disorders (BD) Clinic with a history of von Willebrand disease, platelet function disorder or undefined bleeding disorder and 60 controls (age and sex-matched) were enrolled between June 2008 and February 2010. All subjects were assessed for: i) Generalized joint hypermobility, defined using the Beighton score whereby a score of ≥ 4 out of 9 is considered positive; ii) SJH, defined using the major Brighton criteria which is a Beighton score of ≥ 4 AND arthralgia for longer than 3 months in 4 or more joints; and, iii) Bleeding score (BS), using the Condensed MCMDM1-VWD, with a positive score defined as ≥ 4 for both sexes. CBC, blood group, VWF:Ag, VWF:RCo, FVIII:C and closure times were collected prospectively in the control group and retrospectively in the clinic subjects in addition to bleeding time and platelet aggregation studies.

Results:
The prevalence of SJH with a positive bleeding score was 24% in the BD clinic and 1.6% in controls (see table).
Seventy-seven percent of SJH subjects (10/13) in the BD clinic had a prior personal or family history of Ehlers-Danlos Syndrome, other Joint Hypermobility Syndrome or Osteogenesis Imperfecta (OI). Only the OI subject had prior clinical documentation of a collagen disorder. There was no statistical difference in laboratory measures of hemostasis or bleeding score in the BD clinic subjects with or without SJH. Of interest, mean bleeding time in the BD clinic subjects (available in 38 subjects) was 10.5 minutes in the SJH group and 10 minutes in the non-SJH group suggesting that bleeding time is not a good screening test for the presence of abnormal collagen. Isolated joint hypermobility (Beighton score of ≥ 4) not associated with arthralgia was common in both groups (40% and 30% respectively) in this predominately female population of subjects with inherited mucocutaneous bleeding.

Conclusions:
SJH suggesting a collagen disorder is common and often unrecognized in the BD clinic as a potential contributor to the bleeding symptoms. Asymptomatic joint hypermobility is common in this predominately female population and not an adequate screening tool for a potential collagen disorder. A prolonged bleeding time did not predict the presence of SJH in this cohort. Further study is required to confirm the nature of collagen disorders in the BD clinic population and the relationship to bleeding manifestations.

Disclosures:
No relevant conflicts of interest to declare.