The present review provides a clearer picture of the effect of C1584 on the level and properties of von Willebrand factor (VWF). The C1584 variant is associated with decreased VWF levels (especially in combination with blood group O) and VWF function, and with slightly enhanced VWF proteolysis, and there is evidence to support its association with enhanced VWF clearance. These properties help explain the enrichment for C1584 in mild type 1 VWD and the observed marked association of the variant and blood group O in this mild bleeding disorder. It has been proposed that the mildly enhanced VWF proteolysis associated with C1584 (and also with blood group O) may compromise clot formation, offering a further rationale for the enrichment of the variant in type 1 VWD. C1584 shows variable penetrance and this is still not fully understood. It reflects the interaction of C1584 with other variables, one of which is clearly blood group O. Genome-wide association studies aimed at identifying loci involved in the control of the VWF level may provide further insights into C1584 penetrance and, more generally, into mechanisms underlying type 1 VWD and also cardiovascular disease.

Keywords:
ADAMTS13, Blood group O, C1584, Proteolysis, Y/C1584
© 2009 S. Karger AG, Basel
2009
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.