Von Willebrand disease laboratory findings
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Laboratory Findings
- The diagnosis of von Willebrand’s disease (VWD) begins with a relevant personal or family history of mucocutaneous bleeding.
- When VWD is suspected, the first level of testing comprises measurements of the the following three tests:[1][2][3][4]
Initial tests:
1. VWF antigen (VWF:Ag) level
2. VWF–ristocetin cofactor activity [VWF:RCo] as a measure of platelet-binding activity of VWF.
- The VWF:RCo assay may be replaced by newer assays that measure the binding of VWF to a recombinant wild-type GPIb fragment with the use of ristocetin or the spontaneous binding of VWF to a gain-of-function recombinant mutant GPIb fragment.
3. Factor VIII activity (FVIII:C).
- When the results of all first-level tests are normal, VWD is ruled out; because of biologic variability, however, the tests should be repeated if values are at the low end of the normal range or if VWD is strongly suspected.[3]
- If these first-level tests reveal definitive abnormalities, a diagnosis of VWD can be made; if the results are not conclusive, second-level tests are required.
- VWD can be subtyped on the basis of these second-level tests to enable appropriate choice of therapy.
Second-level tests include the following:
- VWF multimer distribution using gel electrophoresis
- Ristocetin-induced platelet aggregation (RIPA)
- A rare platelet defect due to a gain-of-function mutation in the GPIbα receptor, known as platelet-type VWD, has a phenotype similar to that of type 2B VWD; the two disorders can be distinguished with the use of genetic testing.
- Persons with a bleeding tendency who have VWF levels between 30 and 50 IU per deciliter (the lower limit of the normal range) are classified as having “low VWF” or “possible type 1 disease” but are not classified as having definitive VWD.[3]
- When von Willebrand factor antigen is undetectable (or the level is <5 IU per deciliter, according to the latest disease classification), type 3 von Willebrand’s disease is diagnosed[5][3]
- A proportional decrease in von Willebrand factor antigen and von Willebrand factor–ristocetin cofactor activity fits the diagnosis of type 1 von Willebrand’s disease.
- A disproportional reduction in von Willebrand factor–ristocetin cofactor activity as compared with von Willebrand factor antigen (ratio of von Willebrand factor–ristocetin cofactor activity to von Willebrand factor antigen, ≤0.6) indicates type 2 disease.
- Further subtyping tests, such as assays of von Willebrand factor multimers and ristocetin-induced platelet aggregation, are then required to determine the phenotypic characteristics that define types 2A, 2B, and 2M.
- A platelet aggregation assay will show an abnormal response to ristocetin with normal responses to the other agonists used. A platelet function assay (PFA) will give an abnormal collagen/adrenaline closure time and in most cases (but not all) a normal collagen/ADP time. Type 2N can only be diagnosed by performing a "factor VIII binding" assay. Detection of vWD is complicated by vWF being an acute phase reactant with levels rising in infection, pregnancy and stress.
Other tests performed in any patient with bleeding problems are:
- complete blood count (especially platelet counts),
- APTT (activated partial thromboplastin time),
- prothrombin time,
- thrombin time
- fibrinogen level.
- Testing for factor IX may also be performed if hemophilia B is suspected.
Other coagulation factor assays may be performed depending on the results of a coagulation screen.
- Patients with Von Willebrand disease will typically display a normal prothrombin time and a variable prolongation of partial thromboplastin time.
References
- ↑ Bodó I, Eikenboom J, Montgomery R, Patzke J, Schneppenheim R, Di Paola J (2015). "Platelet-dependent von Willebrand factor activity. Nomenclature and methodology: communication from the SSC of the ISTH". J. Thromb. Haemost. 13 (7): 1345–50. doi:10.1111/jth.12964. PMID 25858564.
- ↑ Flood VH, Gill JC, Morateck PA, Christopherson PA, Friedman KD, Haberichter SL, Hoffmann RG, Montgomery RR (2011). "Gain-of-function GPIb ELISA assay for VWF activity in the Zimmerman Program for the Molecular and Clinical Biology of VWD". Blood. 117 (6): e67–74. doi:10.1182/blood-2010-08-299016. PMC 3056647. PMID 21148813.
- ↑ 3.0 3.1 3.2 3.3 Sanders YV, Groeneveld D, Meijer K, Fijnvandraat K, Cnossen MH, van der Bom JG, Coppens M, de Meris J, Laros-van Gorkom BA, Mauser-Bunschoten EP, Leebeek FW, Eikenboom J (2015). "von Willebrand factor propeptide and the phenotypic classification of von Willebrand disease". Blood. 125 (19): 3006–13. doi:10.1182/blood-2014-09-603241. PMID 25673639.
- ↑ F. Stufano, A. S. Lawrie, S. La Marca, C. Berbenni, L. Baronciani & F. Peyvandi (2014). "A two-centre comparative evaluation of new automated assays for von Willebrand factor ristocetin cofactor activity and antigen". Haemophilia : the official journal of the World Federation of Hemophilia. 20 (1): 147–153. doi:10.1111/hae.12264. PMID 24028703. Unknown parameter
|month=ignored (help) - ↑ Sadler JE, Budde U, Eikenboom JC, Favaloro EJ, Hill FG, Holmberg L, Ingerslev J, Lee CA, Lillicrap D, Mannucci PM, Mazurier C, Meyer D, Nichols WL, Nishino M, Peake IR, Rodeghiero F, Schneppenheim R, Ruggeri ZM, Srivastava A, Montgomery RR, Federici AB (2006). "Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor". J. Thromb. Haemost. 4 (10): 2103–14. doi:10.1111/j.1538-7836.2006.02146.x. PMID 16889557.