Advertisement

Current approaches to diagnostic testing in von Willebrand Disease

      Abstract

      Von Willebrand Disease (VWD) is considered the most common inherited bleeding disorder. It has multiple subtypes and a primary symptom of mucocutaneous bleeding. Some researchers in this field speculate that inherited disorders of platelet function may be as common but underdiagnosed due to the difficulty of accessing testing. The diagnostic approach for this disease has evolved as new instruments and diagnostic testing have become available. The ISTH-Bleeding Assessment Tool is a validated instrument that is used to screen patients referred for bleeding symptoms for further laboratory testing. The three main screening tests used in the diagnosis of VWD include von Willebrand Factor (VWF) antigen, platelet-dependent VWF activity, and factor VIII activity. Improvements in laboratory assays discussed include changes in how traditional assays are performed as well as the addition of new laboratory assays. The role of genetic testing and management of patients with borderline low von Willebrand factor are also discussed.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Transfusion and Apheresis Science
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Leebeek F.W.
        • Eikenboom J.C.
        Von Willebrand’s Disease.
        N Engl J Med. 2016; 375: 2067-2080
        • Nichols W.L.
        • Hultin M.B.
        • James A.H.
        • Manco-Johnson M.J.
        • Montgomery R.R.
        • Ortel T.L.
        • et al.
        von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA).
        Haemophilia. 2008; 14: 171-232
        • Sharma R.
        • Flood V.H.
        Advances in the diagnosis and treatment of Von Willebrand disease.
        Blood. 2017; 130: 2386-2391
        • Rodeghiero F.
        • Tosetto A.
        • Abshire T.
        • Arnold D.
        • Coller B.
        • James P.
        • et al.
        ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders.
        J Thromb Haemost. 2010; 8: 2063-2065
        • Laffan M.A.
        • Lester W.
        • O'Donnell J.S.
        • Will A.
        • Tait R.C.
        • Goodeve A.
        • et al.
        The diagnosis and management of von Willebrand disease: a United Kingdom Haemophilia Centre doctors organization guideline approved by the British Committee for standards in haematology.
        Br J Haematol. 2014; 167: 453-465
        • Pathare A.
        • Al Omrani S.
        • Al Hajri F.
        • Al Obaidani N.
        • Al Balushi B.
        • Al Falahi K.
        Bleeding score in type 1 von Willebrand disease patients using the ISTH-BAT questionnaire.
        Int J Lab Hematol. 2018; 40: 175-180
        • Elbatarny M.
        • Mollah S.
        • Grabell J.
        • Bae S.
        • Deforest M.
        • Tuttle A.
        • et al.
        Normal range of bleeding scores for the ISTH-BAT: adult and pediatric data from the merging project.
        Haemophilia. 2014; 20: 831-835
        • Casey L.J.
        • Tuttle A.
        • Grabell J.
        • Hopman W.
        • Moorehead P.C.
        • Blanchette V.S.
        • et al.
        Generation and optimization of the self-administered pediatric bleeding questionnaire and its validation as a screening tool for von Willebrand disease.
        Pediatr Blood Cancer. 2017; 64
        • Deforest M.
        • Grabell J.
        • Albert S.
        • Young J.
        • Tuttle A.
        • Hopman W.M.
        • et al.
        Generation and optimization of the self-administered bleeding assessment tool and its validation as a screening test for von Willebrand disease.
        Haemophilia. 2015; 21: e384-8
        • Magnette A.
        • Chatelain M.
        • Chatelain B.
        • Ten Cate H.
        • Mullier F.
        Pre-analytical issues in the haemostasis laboratory: guidance for the clinical laboratories.
        Thromb J. 2016; 14: 49
        • Ghadimi K.
        • Levy J.H.
        • Welsby I.J.
        Perioperative management of the bleeding patient.
        Br J Anaesth. 2016; 117: iii18-iii30
        • Flood V.H.
        • Christopherson P.A.
        • Gill J.C.
        • Friedman K.D.
        • Haberichter S.L.
        • Bellissimo D.B.
        • et al.
        Clinical and laboratory variability in a cohort of patients diagnosed with type 1 VWD in the United States.
        Blood. 2016; 127: 2481-2488
        • Chen J.
        • Hinckley J.D.
        • Haberichter S.
        • Jacobi P.
        • Montgomery R.
        • Flood V.H.
        • et al.
        Variable content of von Willebrand factor mutant monomer drives the phenotypic variability in a family with von Willebrand disease.
        Blood. 2015; 126: 262-269
        • Lotta L.A.
        • Maino A.
        • Tuana G.
        • Rossio R.
        • Lecchi A.
        • Artoni A.
        • et al.
        Prevalence of disease and relationships between laboratory phenotype and bleeding severity in platelet primary secretion defects.
        PLoS One. 2013; 8: e60396
        • Fasulo M.R.
        • Biguzzi E.
        • Abbattista M.
        • Stufano F.
        • Pagliari M.T.
        • Mancini I.
        • et al.
        The ISTH bleeding assessment tool and the risk of future bleeding.
        J Thromb Haemost. 2018; 16: 125-130
        • Sukhu K.
        • Martin P.G.
        • Cross L.
        • Keeling D.M.
        • Giangrande P.L.
        Evaluation of the von Willebrand factor antigen (vWF-Ag) assay using an immuno-turbidimetric method (STA Liatest vWF) automated on the MDA 180 coagulometer.
        Clin Lab Haematol. 2000; 22: 29-32
        • Favaloro E.J.
        • Thom J.
        • Baker R.
        Assessment of current diagnostic practice and efficacy in testing for von Willebrand’s disorder: results from the second Australasian multi-laboratory survey.
        Blood Coagul Fibrinolysis. 2000; 11: 729-7377
        • Villa P.
        • Iborra J.
        • Serra J.
        • Gilsanz A.
        • Casana P.
        • Aznar J.A.
        • et al.
        Evaluation of an automated method for the quantification of von Willebrand factor antigen. Its application in the study of vascular dysfunction.
        Haematologica. 2001; 86: 1180-1185
        • Favaloro E.J.
        • Aboud M.
        • Arthur C.
        Possibility of potential VWD misdiagnosis or misclassification using LIA technology and due to presence of rheumatoid factor.
        Am J Hematol. 2001; 66: 53-56
        • Patzke J.
        • Budde U.
        • Huber A.
        • Mendez A.
        • Muth H.
        • Obser T.
        • et al.
        Performance evaluation and multicentre study of a von Willebrand factor activity assay based on GPIb binding in the absence of ristocetin.
        Blood Coagul Fibrinolysis. 2014; 25: 860-870
        • Lawrie A.S.
        • Stufano F.
        • Canciani M.T.
        • Mackie I.J.
        • Machin S.J.
        • Peyvandi F.
        A comparative evaluation of a new automated assay for von Willebrand factor activity.
        Haemophilia. 2013; 19: 338-342
        • Favaloro E.J.
        • Bonar R.
        • Marsden K.
        Lower limit of assay sensitivity: an under-recognised and significant problem in von Willebrand disease identification and classification.
        Clin Lab Sci. 2008; 21: 178-183
        • Chandler W.L.
        • Peerschke E.I.
        • Castellone D.D.
        • Meijer P.
        Von Willebrand factor assay proficiency testing. The North American Specialized Coagulation Laboratory Association experience.
        Am J Clin Pathol. 2011; 135: 862-869
        • Flood V.H.
        • Gill J.C.
        • Morateck P.A.
        • Christopherson P.A.
        • Friedman K.D.
        • Haberichter S.L.
        • et al.
        Common VWF exon 28 polymorphisms in African Americans affecting the VWF activity assay by ristocetin cofactor.
        Blood. 2010; 116: 280-286
        • Flood V.H.
        • Gill J.C.
        • Morateck P.A.
        • Christopherson P.A.
        • Friedman K.D.
        • Haberichter S.L.
        • et al.
        Gain-of-function GPIb ELISA assay for VWF activity in the Zimmerman Program for the molecular and clinical biology of VWD.
        Blood. 2011; 117: e67-e74
        • Bodo I.
        • Eikenboom J.
        • Montgomery R.
        • Patzke J.
        • Schneppenheim R.
        • Di Paola J.
        Platelet-dependent von Willebrand factor activity. Nomenclature and methodology: communication from the SSC of the ISTH.
        J Thromb Haemost. 2015; 13: 1345-1350
        • de Maistre E.
        • Volot F.
        • Mourey G.
        • Aho L.S.
        • Ternisien C.
        • Briquel M.E.
        • et al.
        Performance of two new automated assays for measuring von Willebrand activity: HemosIL AcuStar and innovance.
        Thromb Haemost. 2014; 112: 825-830
        • Brown J.E.
        • Bosak J.O.
        An ELISA test for the binding of von Willebrand antigen to collagen.
        Thromb Res. 1986; 43: 303-311
        • Ni Y.
        • Nesrallah J.
        • Agnew M.
        • Geske F.J.
        • Favaloro E.J.
        Establishment and characterization of a new and stable collagen-binding assay for the assessment of von Willebrand factor activity.
        Int J Lab Hematol. 2013; 35: 170-176
        • Popov J.
        • Zhukov O.
        • Ruden S.
        • Zeschmann T.
        • Sferruzza A.
        • Sahud M.
        Performance and clinical utility of a commercial von Willebrand factor collagen binding assay for laboratory diagnosis of von Willebrand disease.
        Clin Chem. 2006; 52: 1965-1967
        • Flood V.H.
        New insights into genotype and phenotype of VWD.
        Hematology Am Soc Hematol Educ Progr. 2014; 2014: 531-535
        • James P.D.
        • Notley C.
        • Hegadorn C.
        • Leggo J.
        • Tuttle A.
        • Tinlin S.
        The mutational spectrum of type 1 von Willebrand disease: results from a Canadian cohort study.
        Blood. 2007; 109: 145-154
        • Goodeve A.
        • Eikenboom J.
        • Castaman G.
        • Rodeghiero F.
        • Federici A.B.
        • Batlle J.
        • et al.
        Phenotype and genotype of a cohort of families historically diagnosed with type 1 von Willebrand disease in the European study, molecular and clinical markers for the diagnosis and management of type 1 von Willebrand Disease (MCMDM-1VWD).
        Blood. 2007; 109: 112-121
        • Cumming A.
        • Grundy P.
        • Keeney S.
        • Lester W.
        • Enayat S.
        • Guilliatt A.
        • et al.
        An investigation of the von Willebrand factor genotype in UK patients diagnosed to have type 1 von Willebrand disease.
        Thromb Haemost. 2006; 96: 630-641
        • Swystun L.L.
        • James P.D.
        Genetic diagnosis in hemophilia and von Willebrand disease.
        Blood Rev. 2017; 31: 47-56
        • Jacobi P.M.
        • Gill J.C.
        • Flood V.H.
        • Jakab D.A.
        • Friedman K.D.
        • Haberichter S.L.
        Intersection of mechanisms of type 2A VWD through defects in VWF multimerization, secretion, ADAMTS-13 susceptibility, and regulated storage.
        Blood. 2012; 119: 4543-4553
        • Schneppenheim R.
        • Michiels J.J.
        • Obser T.
        • Oyen F.
        • Pieconka A.
        • Schneppenheim S.
        • et al.
        A cluster of mutations in the D3 domain of von Willebrand factor correlates with a distinct subgroup of von Willebrand disease: type 2A/IIE.
        Blood. 2010; 115: 4894-4901
        • Lynch C.J.
        • Cawte A.D.
        • Millar C.M.
        • Rueda D.
        • Lane D.A.
        A common mechanism by which type 2A von Willebrand disease mutations enhance ADAMTS13 proteolysis revealed with a von Willebrand factor A2 domain FRET construct.
        PLoS One. 2017; 12: e0188405
        • James P.
        • Lillicrap D.
        The role of molecular genetics in diagnosing von Willebrand disease.
        Semin Thromb Hemost. 2008; 34: 502-508
        • James P.D.
        • Goodeve A.C.
        von Willebrand disease.
        Genet Med. 2011; 13: 365-376
        • Goodeve A.
        • James P.
        • et al.
        Adam M.P. von Willebrand Disease, in GeneReviews ((R)). University of Washington, Seattle, Seattle (WA)1993
        • Sutherland M.S.
        • Keeney S.
        • Bolton-Maggs P.H.
        • Hay C.R.
        • Will A.
        • Cumming A.M.
        The mutation spectrum associated with type 3 von Willebrand disease in a cohort of patients from the north west of England.
        Haemophilia. 2009; 15: 1048-1057
        • James P.D.
        • Lillicrap D.
        • Mannucci P.M.
        Alloantibodies in von Willebrand disease.
        Blood. 2013; 122: 636-640
        • Shelton-Inloes B.B.
        • Chehab F.F.
        • Mannucci P.M.
        • Federici A.B.
        • Sadler J.E.
        Gene deletions correlate with the development of alloantibodies in von Willebrand disease.
        J Clin Invest. 1987; 79: 1459-1465
        • Gill J.C.
        • Endres-Brooks J.
        • Bauer P.J.
        • Marks Jr., W.J.
        • Montgomery R.R.
        The effect of ABO blood group on the diagnosis of von Willebrand disease.
        Blood. 1987; 69: 1691-1695