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Pediatric Von Willebrand Disease Workup

  • Author: Suchitra S Acharya, MBBS, MD; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
 
Updated: Dec 16, 2014
 

Laboratory Studies

Screening tests for von Willebrand disease (VWD) include the following:

  • CBC count: Assess platelet number and morphology, which should be normal in most patients with von Willebrand disease, except those with type 2B von Willebrand disease who may have thrombocytopenia.
  • Template bleeding time: Because it is reasonably well standardized, the template bleeding time is used as a screening test for primary hemostasis. The reference range for the bleeding time in children is longer than that of adults. Results of the bleeding time are affected by many technical factors, such as the direction of the incision and the skill of the technician. Although a bleeding time outside of the reference range may suggest a defect in hemostasis, it is not diagnostic. Similarly, a bleeding time within the reference range does not exclude the presence of such a defect. Although neither sensitive nor specific for von Willebrand disease, template-bleeding time is outside of the reference range in about 50% of patients with type 1 von Willebrand disease. Patients with von Willebrand disease types 2A, 2B, 2M, and 3 often have prolonged bleeding times. The template bleeding time has largely been replaced by automatic platelet function analyzers (PFAs) such as the PFA-100.
  • Prothrombin time (PT) is within reference range in von Willebrand disease.
  • Activated partial thromboplastin time (aPTT): Approximately 25% of patients with type 1 von Willebrand disease have aPTT results outside of the reference range. These results may be caused by concurrent deficiencies of other clotting factors in addition to, or rather than, factor VIII (FVIII). The aPTT should be outside of the reference range in patients with severe von Willebrand disease or type 2N von Willebrand disease in whom circulating FVIII levels are very low. Because aPTT and the template bleeding time are insensitive tests for von Willebrand disease, add von Willebrand factor (VWF) activity to the screening tests performed for patients with suspected bleeding disorders (see below).

Specific assays include the following:

  • von Willebrand factor levels: von Willebrand factor levels vary and can be influenced by numerous factors including blood type. Individuals with type O blood have lower values of von Willebrand factor levels on average, whereas those with type AB blood have higher values of von Willebrand factor. Day-to-day variation in von Willebrand factor levels is a normal occurrence in the same individual; therefore, a single level within reference range does not exclude the diagnosis of von Willebrand disease. Also, estrogen levels increase von Willebrand factor and may affect results in adolescent females and women with menorrhagia.
  • FVIII activity: FVIII activity is variably decreased.
  • von Willebrand factor activity (ristocetin cofactor): Ristocetin is an antibiotic that causes von Willebrand factor to bind to and, subsequently, to activate platelets. In the ristocetin cofactor assay, platelets from individuals who are healthy, standard concentrations of ristocetin, and varying quantities of patient or control plasma are used. In individuals who are healthy, platelets rapidly agglutinate in response to ristocetin; however, the presence of plasma von Willebrand factor is necessary for the reaction to occur. The degree of platelet agglutination is proportional to the concentration of von Willebrand factor in the plasma. Several variations of this assay have been developed. Because the result of this assay reflects the functional activity of von Willebrand factor, it is usually called the von Willebrand factor activity. It is variably decreased in von Willebrand disease.
  • von Willebrand factor antigen: The total plasma concentration of von Willebrand factor protein is measured by one of several assays. The Laurell rocket immunoelectrophoresis technique measures the amount of von Willebrand factor protein in the plasma, whereas radioimmunoassays and enzyme-linked immunoabsorbent assays reflect the number of von Willebrand factor–binding sites. These tests determine the total amount of von Willebrand factor antigen in the plasma but do not reflect its molecular structure and, hence, may be normal in von Willebrand disease variants with abnormal multimers. Therefore, von Willebrand factor antigen is variably decreased.

In multimer analysis to determine the physical structure of von Willebrand factor (ie, whether high molecular weight multimers are present), plasma is electrophoresed through agarose gel. The presence or absence of high molecular weight von Willebrand factor is used to classify von Willebrand disease. Absence or decreased levels of high molecular weight von Willebrand factor multimers is consistent with type 2 von Willebrand disease. Further analysis of von Willebrand factor subunits has been performed with sophisticated electrophoretic techniques, resulting in the description of many type 2 variants.

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Other Tests

In some laboratories, platelet von Willebrand factor analysis is performed. Gene analysis can also be performed for diagnosis.

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Contributor Information and Disclosures
Author

Suchitra S Acharya, MBBS, MD Program Head, Bleeding Disorders and Thrombosis Program, Cohen Children's Medical Center of New York; Associate Professor of Pediatrics and Pediatrics in Medicine, Hofstra North Shore-LIJ School of Medicine at Hofstra University

Suchitra S Acharya, MBBS, MD is a member of the following medical societies: American Society of Hematology, International Society on Thrombosis and Haemostasis, Hemophilia and Thrombosis Research Society, World Federation of Hemophilia

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Associate Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology, American Federation for Clinical Research, Council on Medical Student Education in Pediatrics, Hemophilia and Thrombosis Research Society, American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA Executive Vice President, Chief Medical and Academic Officer, Renown Heath

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American College of Healthcare Executives, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

J Martin Johnston, MD Associate Professor of Pediatrics, Mercer University School of Medicine; Director of Hematology/Oncology, The Children's Hospital at Memorial University Medical Center; Consulting Oncologist/Hematologist, St Damien's Pediatric Hospital

J Martin Johnston, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, International Society of Paediatric Oncology

Disclosure: Nothing to disclose.

Acknowledgements

John D Geil, MD Associate Professor of Pediatrics, Division of Hematology/Oncology, University of Kentucky College of Medicine; Consulting Staff, Department of Pediatric Hematology/Oncology, University of Kentucky Children's Hospital

John D Geil, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, and Society for Neuro-Oncology

Disclosure: Nothing to disclose.

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Structure and domains of von Willebrand factor.
 
 
 
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