Perils, Problems, and Progress in Laboratory Diagnosis of von Willebrand Disease

Veronica H. Flood

doi:10.1055/s-0033-1363166

Seminars in Thrombosis and Hemostasis, Inhaltsverzeichnis

Semin Thromb Hemost 2014; 40(01): 041-048
DOI: 10.1055/s-0033-1363166

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Perils, Problems, and Progress in Laboratory Diagnosis of von Willebrand Disease

Veronica H. Flood

¹Division of Pediatric Hematology/Oncology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin

› Institutsangaben

Abstract

Diagnosis of von Willebrand disease (VWD) merits consideration of personal and family history of bleeding symptoms along with confirmatory laboratory testing. As the latter yields quantifiable results, overreliance on a laboratory diagnosis may occur. However, existing tests for VWD contain potential sources for error. Both intrinsic and extrinsic factors affecting these assays can contribute to either falsely normal or falsely abnormal results. This article will discuss the present available assays as well as new developments in diagnostic testing. A clear understanding of the limitations of VWD testing is helpful for ensuring the correct diagnosis of affected patients.

Keywords

von Willebrand factor - von Willebrand disease - bleeding - collagen - platelets

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Referenzen

References
1 Weiss HJ, Sussman II, Hoyer LW. Stabilization of factor VIII in plasma by the von Willebrand factor. Studies on posttransfusion and dissociated factor VIII and in patients with von Willebrand's disease. J Clin Invest 1977; 60 (2) 390-404
2 Mohri H, Fujimura Y, Shima M , et al. Structure of the von Willebrand factor domain interacting with glycoprotein Ib. J Biol Chem 1988; 263 (34) 17901-17904
3 Pareti FI, Niiya K, McPherson JM, Ruggeri ZM. Isolation and characterization of two domains of human von Willebrand factor that interact with fibrillar collagen types I and III. J Biol Chem 1987; 262 (28) 13835-13841
4 Sadler JE, Budde U, Eikenboom JC , et al; Working Party on von Willebrand Disease Classification. Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor. J Thromb Haemost 2006; 4 (10) 2103-2114
5 Goodeve AC. The genetic basis of von Willebrand disease. Blood Rev 2010; 24 (3) 123-134
6 Zimmerman TS, Dent JA, Ruggeri ZM, Nannini LH. Subunit composition of plasma von Willebrand factor. Cleavage is present in normal individuals, increased in IIA and IIB von Willebrand disease, but minimal in variants with aberrant structure of individual oligomers (types IIC, IID, and IIE). J Clin Invest 1986; 77 (3) 947-951
7 Ruggeri ZM, Lombardi R, Gatti L, Bader R, Valsecchi C, Zimmerman TS. Type IIB von Willebrand's disease: differential clearance of endogenous versus transfused large multimer von willebrand factor. Blood 1982; 60 (6) 1453-1456
8 Mancuso DJ, Kroner PA, Christopherson PA, Vokac EA, Gill JC, Montgomery RR. Type 2M:Milwaukee-1 von Willebrand disease: an in-frame deletion in the Cys509-Cys695 loop of the von Willebrand factor A1 domain causes deficient binding of von Willebrand factor to platelets. Blood 1996; 88 (7) 2559-2568
9 Mazurier C, Dieval J, Jorieux S, Delobel J, Goudemand M. A new von Willebrand factor (vWF) defect in a patient with factor VIII (FVIII) deficiency but with normal levels and multimeric patterns of both plasma and platelet vWF. Characterization of abnormal vWF/FVIII interaction. Blood 1990; 75 (1) 20-26
10 Favaloro EJ. Diagnosis and classification of von Willebrand disease: a review of the differential utility of various functional von Willebrand factor assays. Blood Coagul Fibrinolysis 2011; 22 (7) 553-564
11 Ingerslev J. A sensitive ELISA for von Willebrand factor (vWf:Ag). Scand J Clin Lab Invest 1987; 47 (2) 143-149
12 Castaman G, Tosetto A, Cappelletti A , et al. Validation of a rapid test (VWF-LIA) for the quantitative determination of von Willebrand factor antigen in type 1 von Willebrand disease diagnosis within the European multicenter study MCMDM-1VWD. Thromb Res 2010; 126 (3) 227-231
13 Kempfer AC, Silaf MR, Farias CE, Carballo GA, Woods AI, Lazzari MA. Binding of von Willebrand factor to collagen by flow cytometry. Am J Clin Pathol 1999; 111 (3) 418-423
14 Mina A, Favaloro EJ, Koutts J. A novel flow cytometry single tube bead assay for quantitation of von Willebrand factor antigen and collagen-binding. Thromb Haemost 2012; 108 (5) 999-1005
15 Gill JC, Endres-Brooks J, Bauer PJ, Marks Jr WJ, Montgomery RR. The effect of ABO blood group on the diagnosis of von Willebrand disease. Blood 1987; 69 (6) 1691-1695
16 Miller CH, Haff E, Platt SJ , et al. Measurement of von Willebrand factor activity: relative effects of ABO blood type and race. J Thromb Haemost 2003; 1 (10) 2191-2197
17 Hellgren M, Blombäck M. Studies on blood coagulation and fibrinolysis in pregnancy, during delivery and in the puerperium. I. Normal condition. Gynecol Obstet Invest 1981; 12 (3) 141-154
18 Stakiw J, Bowman M, Hegadorn C , et al. The effect of exercise on von Willebrand factor and ADAMTS-13 in individuals with type 1 and type 2B von Willebrand disease. J Thromb Haemost 2008; 6 (1) 90-96
19 Sadler JE. Von Willebrand disease type 1: a diagnosis in search of a disease. Blood 2003; 101 (6) 2089-2093
20 Howard MA, Sawers RJ, Firkin BG. Ristocetin: a means of differentiating von Willebrand's disease into two groups. Blood 1973; 41 (5) 687-690
21 Sakariassen KS, Bolhuis PA, Sixma JJ. Human blood platelet adhesion to artery subendothelium is mediated by factor VIII-Von Willebrand factor bound to the subendothelium. Nature 1979; 279 (5714) 636-638
22 Federici AB, Canciani MT, Forza I, Cozzi G. Ristocetin cofactor and collagen binding activities normalized to antigen levels for a rapid diagnosis of type 2 von Willebrand disease—single center comparison of four different assays. Thromb Haemost 2000; 84 (6) 1127-1128
23 Favaloro EJ, Lillicrap D, Lazzari MA , et al. von Willebrand disease: laboratory aspects of diagnosis and treatment. Haemophilia 2004; 10 (Suppl. 04) 164-168
24 Nichols WL, Hultin MB, James AH , 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 (2) 171-232
25 Kitchen S, Jennings I, Woods TA, Kitchen DP, Walker ID, Preston FE. Laboratory tests for measurement of von Willebrand factor show poor agreement among different centers: results from the United Kingdom National External Quality Assessment Scheme for Blood Coagulation. Semin Thromb Hemost 2006; 32 (5) 492-498
26 Meijer P, Haverkate F. An external quality assessment program for von Willebrand factor laboratory analysis: an overview from the European concerted action on thrombosis and disabilities foundation. Semin Thromb Hemost 2006; 32 (5) 485-491
27 Flood VH, Gill JC, Morateck PA , et al. Common VWF exon 28 polymorphisms in African Americans affecting the VWF activity assay by ristocetin cofactor. Blood 2010; 116 (2) 280-286
28 Flood VH, Friedman KD, Gill JC , et al. No increase in bleeding identified in type 1 VWD subjects with D1472H sequence variation. Blood 2013; 121 (18) 3742-3744
29 Murdock PJ, Woodhams BJ, Matthews KB, Pasi KJ, Goodall AH. von Willebrand factor activity detected in a monoclonal antibody-based ELISA: an alternative to the ristocetin cofactor platelet agglutination assay for diagnostic use. Thromb Haemost 1997; 78 (4) 1272-1277
30 Hulstein JJ, de Groot PG, Silence K, Veyradier A, Fijnheer R, Lenting PJ. A novel nanobody that detects the gain-of-function phenotype of von Willebrand factor in ADAMTS13 deficiency and von Willebrand disease type 2B. Blood 2005; 106 (9) 3035-3042
31 Vanhoorelbeke K, Cauwenberghs N, Vauterin S, Schlammadinger A, Mazurier C, Deckmyn H. A reliable and reproducible ELISA method to measure ristocetin cofactor activity of von Willebrand factor. Thromb Haemost 2000; 83 (1) 107-113
32 Federici AB, Canciani MT, Forza I , et al. A sensitive ristocetin co-factor activity assay with recombinant glycoprotein Ibalpha for the diagnosis of patients with low von Willebrand factor levels. Haematologica 2004; 89 (1) 77-85
33 Patzke J, Schneppenheim R. Laboratory diagnosis of von Willebrand disease. Hamostaseologie 2010; 30 (4) 203-206
34 Flood VH, Gill JC, Morateck PA , 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 (6) e67-e74
35 Chen D, Daigh CA, Hendricksen JI , et al. A highly-sensitive plasma von Willebrand factor ristocetin cofactor (VWF:RCo) activity assay by flow cytometry. J Thromb Haemost 2008; 6 (2) 323-330
36 Chen D, Tange JI, Meyers BJ, Pruthi RK, Nichols WL, Heit JA. Validation of an automated latex particle-enhanced immunoturbidimetric von Willebrand factor activity assay. J Thromb Haemost 2011; 9 (10) 1993-2002
37 Langdell RD, Wagner RH, Brinkhous KM. Effect of antihemophilic factor on one-stage clotting tests; a presumptive test for hemophilia and a simple one-stage antihemophilic factor assy procedure. J Lab Clin Med 1953; 41 (4) 637-647
38 Verbruggen B, Meijer P, Novákova I, Van Heerde W. Diagnosis of factor VIII deficiency. Haemophilia 2008; 14 (Suppl. 03) 76-82
39 Mazurier C, Meyer D. Factor VIII binding assay of von Willebrand factor and the diagnosis of type 2N von Willebrand disease—results of an international survey. On behalf of the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the ISTH. Thromb Haemost 1996; 76 (2) 270-274
40 Federici AB. Diagnosis of inherited von Willebrand disease: a clinical perspective. Semin Thromb Hemost 2006; 32 (6) 555-565
41 Ruggeri ZM, Zimmerman TS. Variant von Willebrand's disease: characterization of two subtypes by analysis of multimeric composition of factor VIII/von Willebrand factor in plasma and platelets. J Clin Invest 1980; 65 (6) 1318-1325
42 Budde U, Pieconka A, Will K, Schneppenheim R. Laboratory testing for von Willebrand disease: contribution of multimer analysis to diagnosis and classification. Semin Thromb Hemost 2006; 32 (5) 514-521
43 Budde U, Schneppenheim R, Eikenboom J , et al. Detailed von Willebrand factor multimer analysis in patients with von Willebrand disease in the European study, molecular and clinical markers for the diagnosis and management of type 1 von Willebrand disease (MCMDM-1VWD). J Thromb Haemost 2008; 6 (5) 762-771
44 Heyde E. Gastrointestinal bleeding in aortic stenosis. N Engl J Med 1958; 259: 196
45 Gill JC, Wilson AD, Endres-Brooks J, Montgomery RR. Loss of the largest von Willebrand factor multimers from the plasma of patients with congenital cardiac defects. Blood 1986; 67 (3) 758-761
46 Favaloro EJ, Facey D, Grispo L. Laboratory assessment of von Willebrand factor. Use of different assays can influence the diagnosis of von Willebrand's disease, dependent on differing sensitivity to sample preparation and differential recognition of high molecular weight VWF forms. Am J Clin Pathol 1995; 104 (3) 264-271
47 Flood VH, Gill JC, Friedman KD , et al; Zimmerman Program Investigators. Collagen binding provides a sensitive screen for variant von Willebrand disease. Clin Chem 2013; 59 (4) 684-691
48 Nyman D. Interaction of collagen with the factor VIII antigen-activity - von Willebrand factor complex. Thromb Res 1977; 11 (3) 433-438
49 Hoylaerts MF, Yamamoto H, Nuyts K, Vreys I, Deckmyn H, Vermylen J. von Willebrand factor binds to native collagen VI primarily via its A1 domain. Biochem J 1997; 324 (Pt 1) 185-191
50 Ribba AS, Loisel I, Lavergne JM , et al. Ser968Thr mutation within the A3 domain of von Willebrand factor (VWF) in two related patients leads to a defective binding of VWF to collagen. Thromb Haemost 2001; 86 (3) 848-854
51 Riddell AF, Gomez K, Millar CM , et al. Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor. Blood 2009; 114 (16) 3489-3496
52 Flood VH, Lederman CA, Wren JS , et al. Absent collagen binding in a VWF A3 domain mutant: utility of the VWF:CB in diagnosis of VWD. J Thromb Haemost 2010; 8 (6) 1431-1433
53 Brown JE, Bosak JO. An ELISA test for the binding of von Willebrand antigen to collagen. Thromb Res 1986; 43 (3) 303-311
54 Favaloro EJ. Collagen binding assay for von Willebrand factor (VWF:CBA): detection of von Willebrands Disease (VWD), and discrimination of VWD subtypes, depends on collagen source. Thromb Haemost 2000; 83 (1) 127-135
55 Favaloro EJ. Evaluation of commercial von Willebrand factor collagen binding assays to assist the discrimination of types 1 and 2 von Willebrand disease. Thromb Haemost 2010; 104 (5) 1009-1021
56 Favaloro EJ. An update on the von Willebrand factor collagen binding assay: 21 years of age and beyond adolescence but not yet a mature adult. Semin Thromb Hemost 2007; 33 (8) 727-744
57 Favaloro EJ. Toward a new paradigm for the identification and functional characterization of von Willebrand disease. Semin Thromb Hemost 2009; 35 (1) 60-75
58 Adcock DM, Bethel M, Valcour A. Diagnosing von Willebrand disease: a large reference laboratory's perspective. Semin Thromb Hemost 2006; 32 (5) 472-479
59 Flood VH, Gill JC, Christopherson PA , et al. Comparison of type I, type III and type VI collagen binding assays in diagnosis of von Willebrand disease. J Thromb Haemost 2012; 10 (7) 1425-1432
60 Flood VH, Gill JC, Christopherson PA , et al. Critical von Willebrand factor A1 domain residues influence type VI collagen binding. J Thromb Haemost 2012; 10 (7) 1417-1424
61 Larsen DM, Haberichter SL, Gill JC, Shapiro AD, Flood VH. Variability in platelet- and collagen-binding defects in type 2M von Willebrand disease. Haemophilia 2013; 19 (4) 590-594
62 Haberichter SL, Balistreri M, Christopherson P , et al. Assay of the von Willebrand factor (VWF) propeptide to identify patients with type 1 von Willebrand disease with decreased VWF survival. Blood 2006; 108 (10) 3344-3351
63 Haberichter SL, Castaman G, Budde U , et al. Identification of type 1 von Willebrand disease patients with reduced von Willebrand factor survival by assay of the VWF propeptide in the European study: molecular and clinical markers for the diagnosis and management of type 1 VWD (MCMDM-1VWD). Blood 2008; 111 (10) 4979-4985
64 Castaman G, Lethagen S, Federici AB , et al. Response to desmopressin is influenced by the genotype and phenotype in type 1 von Willebrand disease (VWD): results from the European Study MCMDM-1VWD. Blood 2008; 111 (7) 3531-3539
65 Mancuso DJ, Tuley EA, Westfield LA , et al. Structure of the gene for human von Willebrand factor. J Biol Chem 1989; 264 (33) 19514-19527
66 Goodeve A, Eikenboom J, Castaman G , 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 (1) 112-121
67 James PD, Notley C, Hegadorn C , et al. The mutational spectrum of type 1 von Willebrand disease: Results from a Canadian cohort study. Blood 2007; 109 (1) 145-154
68 Sutherland MS, Cumming AM, Bowman M , et al. A novel deletion mutation is recurrent in von Willebrand disease types 1 and 3. Blood 2009; 114 (5) 1091-1098
69 Gallinaro L, Cattini MG, Sztukowska M , et al. A shorter von Willebrand factor survival in O blood group subjects explains how ABO determinants influence plasma von Willebrand factor. Blood 2008; 111 (7) 3540-3545
70 Rydz N, Swystun LL, Notley C , et al. The C-type lectin receptor CLEC4M binds, internalizes, and clears von Willebrand factor and contributes to the variation in plasma von Willebrand factor levels. Blood 2013; 121 (26) 5228-5237
71 Bellissimo DB, Christopherson PA, Flood VH , et al. VWF mutations and new sequence variations identified in healthy controls are more frequent in the African-American population. Blood 2012; 119 (9) 2135-2140
72 Ruggeri ZM, Pareti FI, Mannucci PM, Ciavarella N, Zimmerman TS. Heightened interaction between platelets and factor VIII/von Willebrand factor in a new subtype of von Willebrand's disease. N Engl J Med 1980; 302 (19) 1047-1051
73 Scott JP, Montgomery RR. The rapid differentiation of type IIb von Willebrand's disease from platelet-type (pseudo-) von Willebrand's disease by the “neutral” monoclonal antibody binding assay. Am J Clin Pathol 1991; 96 (6) 723-728
74 Favaloro EJ. Phenotypic identification of platelet-type von Willebrand disease and its discrimination from type 2B von Willebrand disease: a question of 2B or not 2B? A story of nonidentical twins? Or two sides of a multidenominational or multifaceted primary-hemostasis coin?. Semin Thromb Hemost 2008; 34 (1) 113-127
75 Montgomery RR, Hathaway WE, Johnson J, Jacobson L, Muntean W. A variant of von Willebrand's disease with abnormal expression of factor VIII procoagulant activity. Blood 1982; 60 (1) 201-207
76 Gupta M, Lillicrap D, Stain AM, Friedman KD, Carcao MD. Therapeutic consequences for misdiagnosis of type 2N von Willebrand disease. Pediatr Blood Cancer 2011; 57 (6) 1081-1083
77 Lawrie AS, Stufano F, Canciani MT, Mackie IJ, Machin SJ, Peyvandi F. A comparative evaluation of a new automated assay for von Willebrand factor activity. Haemophilia 2013; 19 (2) 338-342
78 Verfaillie CJ, De Witte E, Devreese KM. Validation of a new panel of automated chemiluminescence assays for von Willebrand factor antigen and activity in the screening for von Willebrand disease. Int J Lab Hematol 2013; 35 (5) 555-565
79 Favaloro EJ, Bonar R, Chapman K, Meiring M, Funk Adcock D. Differential sensitivity of von Willebrand factor (VWF) 'activity' assays to large and small VWF molecular weight forms: a cross-laboratory study comparing ristocetin cofactor, collagen-binding and mAb-based assays. J Thromb Haemost 2012; 10 (6) 1043-1054
80 Favaloro EJ, Thom J, Patterson D , et al. Desmopressin therapy to assist the functional identification and characterisation of von Willebrand disease: differential utility from combining two (VWF:CB and VWF:RCo) von Willebrand factor activity assays?. Thromb Res 2009; 123 (6) 862-868