von Willebrand

[obophenotype-user]

Von: Miller, Clare E [clare.miller@imperial.ac.uk] Gesendet: Dienstag, 23. September 2014 09:03 An: Robinson, Peter Betreff: RE: von Willebrand Disease HPO terms

Peter

Great to meet you yesterday. Sorry to not find you yesterday pm - I had to escape early due to boiler issues in London. I also will not be around for much of today due to clinic commitments.

I have reviewed the initial list of HPO terms I sent you. I'm wondering if the ambiguity you mentioned lies in the somewhat overlapping terms in multimer analysis?

I have made slight changes to the suggestions I initially proposed and have added possible textual definitions:

• Abnormality of von Willebrand Factor
  • Reduced quantity of von Willebrand Factor
  • Reduced von Willebrand Factor activity
  • Impaired Ristocetin Cofactor assay activity* : Abnormal response to ristocetin as manifested by reduced or lacking aggregation of platelets upon addition of ristocetin to platelet-poor plasma.
  • Impaired collagen-binding activity: Abnormal response to collagen as manifested by reduced or lacking ability of plasma von WIllebrand Factor to bind collagen. [An ELISA-based assay is typically used; the test is sensitive to loss of von Willebrand Factor high molecular weight multimers.] [Type 1, Type 2A, Type 2B, Type 3]
  • Abnormal von Willebrand Factor multimer distribution: Deviation from the normal von Willebrand Factor multimer pattern
  • Absence of large forms only: Absence of large von Willebrand Factor multimers on gel electrophoresis, with preservation of an otherwise normal multimer pattern. [Type 2B VWD]
  • Absence of large and intermediate forms only: Absence of large and intermediate von Willebrand Factor multimers on gel electrophoresis, with preservation of an otherwise normal multimer pattern. [Type 2A VWD]
  • Absence of all forms: Absence of all von Willebrand Factor multimers [Type 3 VWD].
  • Abnormal presence of Ultra-large von Willebrand Factor multimers: Detection of abnormal ultra-large von Willebrand factor multimers [VWD Vicenza].
  • Enhanced response to low-concentration ristocetin: Abnormal response to ristocetin as manifested by increased aggregation of platelets upon addition of low-dose ristocetin to platelet-rich plasma. [Type 2B VWD, RIPA test].

I also wondered if there is any value in adding the following bleeding terms, which are captured in the International bleeding assessment tool. I need to double check that I haven't missed them

• Prolonged bleeding following circumcision
• Cephalhaematoma
• Oral cavity bleeding
• Excessive bleeding from superficial cuts
• Excessive bleeding post-venepuncture
• I'm not sure if this is a valid term; I had initially suggested "reduced ristocetin-induced platelet agglutination", but this is impossible to distinguish from the existing term HP:0011871: impaired ristocetin-induced platelet agglutination which already appears as a subclass of HP:0003540: impaired platelet aggregation. There is a subtle difference between the ristocetin-induced platelet aggregation test implied by HP:0003540 which uses patient's platelet-rich plasma to diagnose the platelet function defect Bernard-Soulier syndrome and the ristocetin cofactor assay, which also measures ristocetin-induced platelet aggregation but uses platelet-poor plasma and is used to diagnose VWD, where the defect lies in the plasma rather than platelets.

I look forward to hearing your thoughts, I will try and catch you at some point this pm or tomorrow, or otherwise we can discuss remotely at a later date.

Reported by: pnrobinson

Original Ticket: obo/human-phenotype-requests/337

[obophenotype-user]

• status: unread --> closed-accepted

Original comment by: pnrobinson

[obophenotype-user]

I have added these terms as requested with the following exception.

Absence of large and intermediate forms only => This is not good, because there is no way of expressing the phenotypic feature of lack of intermediate forms. The way to code this for a patient would be to use the terms for both absence of large forms and absence of intermediate forms.

I have also use slightly different term names to disambiguate these concepts.

Please let me know if this is OK.

Original comment by: pnrobinson