Laboratory Monitoring of Therapy in von Willebrand Disease: Efficacy of the PFA-100 and von Willebrand Factor:Collagen-Binding Activity as Coupled Strategies

ABSTRACT

Clinical management of von Willebrand disease (or von Willebrand disorder [vWD]) often involves factor replacement or desmopressin acetate (DDAVP) therapy to control (potential) bleeding. Laboratory monitoring involves testing patient samples prior to therapy and at discreet time points after therapy. Classical testing generally comprises assays for factor VIII:coagulant activity, von Willebrand factor (vWF):antigen and vWF:ristocetin cofactor activity. The PFA-100 (platelet function analyser) is a relatively new tool for the investigation of primary hemostasis, and studies have shown its potential utility in identifying both vWD and platelet disorders, and in monitoring DDAVP therapy in these patients. However, the PFA-100 has limited utility in monitoring factor replacement therapy. The collagen-binding activity (vWF:CB) assay is a relatively new functional vWF assay and studies have also shown its utility in identifying vWD, and in monitoring both DDAVP and factor replacement therapy in these patients. This review assesses the laboratory monitoring of therapy for vWD with a special focus on the combined potential utility of the PFA-100 and a vWF:CB assay sensitive for the presence or absence of large vWF multimers. This review should be of value to both hemostasis scientists and clinical specialists.

KEYWORDS

PFA-100 - von Willebrand factor (vWF) - von Willebrand disease - von Willebrand disorder (vWD) - laboratory monitoring - therapy - desmopressin (DDAVP) - review

REFERENCES

• 1 Sadler J E, Mannucci P M, Berntorp E et al.. Impact, diagnosis and treatment of von Willebrand Disease.  Thromb Haemost. 2000;  84 160-174
• 2 Federici A B. Management of inherited von Willebrand disease.  Semin Thromb Hemost. 2006;  32 616-620
• 3 Federici A B, Mazurier C, Berntorp E et al.. Biologic response to desmopressin in patients with severe type 1 and type 2 von Willebrand disease: results of a multicenter European study.  Blood. 2004;  103 2032-2038
• 4 United Kingdom Haemophilia Centre Doctors' Organisation (UKHCDO) . Guidelines on the selection and use of therapeutic products to treat haemophilia and other hereditary bleeding disorders.  Haemophilia. 2003;  9 1-23
• 5 Federici A B. Management of von Willebrand disease with factor VIII/von Willebrand factor concentrates: Results from current studies and surveys.  Blood Coagul Fibrinolysis. 2005;  16(suppl 1) S17-S21
• 6 Michiels J J, Gadisseur A, Budde U et al.. Characterization, classification, and treatment of von Willebrand disease: a critical appraisal of the literature and personal experiences.  Semin Thromb Hemost. 2005;  31 577-601
• 7 Kundu S K, Heilmann E J, Sio R, Garcia C, Davidson R M, Ostgaard R A. Description of an in-vitro platelet function analyser: PFA-100™.  Semin Thromb Hemost. 1995;  21(suppl 2) 106-112
• 8 Kundu S K, Heilmann E J, Sio R, Garcia C, Ostgaard R A. Characterisation of an in-vitro Platelet Function Analyser, PFA-100™.  Clin Appl Thromb Hemost. 1996;  2 241-249
• 9 Mammen E F, Alshameeri R S, Comp P C. Preliminary data from a field trial of the PFA-100™ system.  Semin Thromb Hemost. 1995;  21(suppl 2) 113-120
• 10 Mammen E F, Comp P C, Gosselin R et al.. PFA-100 system: a new method for assessment of platelet dysfunction.  Semin Thromb Hemost. 1998;  24 195-202
• 11 Carcao M D, Blanchette V S, Dean J A et al.. The Platelet Function Analyzer (PFA-100): a novel in-vitro system for evaluation of primary haemostasis in children.  Br J Haematol. 1998;  101 70-73
• 12 Ortel T L, James A H, Thames E H, Moore K D, Greenberg C S. Assessment of primary hemostasis by PFA-100 analysis in a tertiary care center.  Thromb Haemost. 2000;  84 93-97
• 13 Harrison P, Robinson M S, Mackie I J et al.. Performance of the platelet function analyser PFA-100 in testing abnormalities of primary haemostasis.  Blood Coagul Fibrinolysis. 1999;  10 25-31
• 14 Kerenyi A, Schlammadinger A, Ajzner E et al.. Comparison of PFA-100 closure time and template bleeding time of patients with inherited disorders causing defective platelet function.  Thromb Res. 1999;  96 487-492
• 15 Cattaneo M, Lecchi A, Agati B, Lombardi R, Zighetti M L. Evaluation of platelet function with the PFA-100 system in patients with congenital defects of platelet secretion.  Thromb Res. 1999;  96 213-217
• 16 Fressinaud E, Veyradier A, Truchaud F et al.. Screening for von Willebrand disease with a new analyzer using high shear stress: a study of 60 cases.  Blood. 1998;  91 1325-1331
• 17 Favaloro E J, Facey D, Henniker A. Use of a novel platelet function analyzer (PFA-100) with high sensitivity to disturbances in von Willebrand factor to screen for von Willebrand's disease and other disorders.  Am J Hematol. 1999;  62 165-174
• 18 Di Paola J, Federici A B, Mannucci P M et al.. Low platelet alpha2beta1 levels in type I von Willebrand disease correlate with impaired platelet function in a high shear stress system.  Blood. 1999;  93 3578-3582
• 19 Schlammadinger A, Kerenyi A, Muszbek L, Boda Z. Comparison of the O'Brien filter test and the PFA-100 platelet analyser in the laboratory diagnosis of von Willebrand's disease.  Thromb Haemost. 2000;  84 88-92
• 20 Favaloro E J. Template bleeding time and PFA-100® have low sensitivity to screen patients with hereditary mucocutaneous hemorrhages: comparative study of 148 patients - a rebuttal.  J Thromb Haemost. 2004;  2 2280-2282
• 21 Favaloro E J, Kershaw G, Bukuya M, Hertzberg M, Koutts J. Laboratory diagnosis of von Willebrand Disorder (VWD) and monitoring of DDAVP therapy: efficacy of the PFA-100® and VWF:CBA as combined diagnostic strategies.  Haemophilia. 2001;  7 180-189
• 22 Favaloro E J. Utility of the PFA-100® for assessing bleeding disorders and monitoring therapy: a review of analytical variables, benefits and limitations.  Haemophilia. 2001;  7 170-179
• 23 Favaloro E J. Clinical application of the PFA-100®.  Curr Opin Hematol. 2002;  9 407-415
• 24 Favaloro E J. The utility of the PFA-100 in identification of von Willebrand Disease: a concise review.  Semin Thromb Hemost. 2006;  32 537-545
• 25 Cattaneo M, Federici A B, Lecchi A et al.. Evaluation of the PFA-100 system in the diagnosis and therapeutic monitoring of patients with von Willebrand disease.  Thromb Haemost. 1999;  82 35-39
• 26 Fressinaud E, Veyradier A, Sigaud M, Boyer-Neumann C, Le Boterff C, Meyer D. Therapeutic monitoring of von Willebrand disease: interest and limits of a platelet function analyser at high shear rates.  Br J Haematol. 1999;  106 777-783
• 27 Meskal A, Vertessen F, Van der Planken M, Berneman Z N. The platelet function analyzer (PFA-100) may not be suitable for monitoring the therapeutic efficiency of von Willebrand concentrate in type III von Willebrand disease.  Ann Hematol. 1999;  78 426-430
• 28 Brown J E, Bosak J O. An ELISA test for the binding of von Willebrand antigen to collagen.  Thromb Res. 1986;  43 303-311
• 29 Favaloro E J, Grispo L, Exner T, Koutts J. Development of a simple collagen binding assay aids in the diagnosis of, and permits sensitive discrimination between, Type I and Type II von Willebrand's disease.  Blood Coagul Fibrinolysis. 1991;  2 285-291
• 30 Favaloro E J, Dean M, Grispo L, Exner T, Koutts J. Von Willebrand's disease: use of collagen binding assay provides potential improvement to laboratory monitoring of desmopressin (DDAVP) therapy.  Am J Hematol. 1994;  45 205-211
• 31 Favaloro E J. Von Willebrand factor (VWF) collagen binding (activity) assay (VWF:CBA) in the diagnosis of von Willebrand's disorder (VWD): a 15-year journey.  Semin Thromb Hemost. 2002;  28 191-202
• 32 Favaloro E J. Laboratory identification of von Willebrand disease: technical and scientific perspectives.  Semin Thromb Hemost. 2006;  32 456-471
• 33 Casonato A, Steffan A, Pontara E et al.. Post-DDAVP thrombocytopenia in Type 2B von Willebrand disease is not associated with platelet consumption: Failure to demonstrate glycocalicin increase or platelet activation.  Thromb Haemost. 1999;  81 224-228
• 34 Favaloro E J. Laboratory assessment as a critical component of the appropriate diagnosis and sub-classification of von Willebrand's disease.  Blood Rev. 1999;  13 185-204
• 35 Favaloro E J. Appropriate laboratory assessment as a critical facet in the proper diagnosis and sub-classification of von Willebrand's disorder.  Baillieres Best Pract Res Clin Haematol. 2001;  14 299-319
• 36 Michiels J J, van de Velde A, van Vliet H HDM, van der Planken M, Schroyens W, Berneman Z. Response of von Willebrand factor parameters to desmopressin in patients with Type 1 and Type 2 congenital von Willebrand disease: diagnostic and therapeutic implications.  Semin Thromb Hemost. 2002;  28 111-131
• 37 Eikenboom J C, Castaman G, Kamphuisen P W, Rosendaal F R, Bertina R M. The factor VIII/von Willebrand factor ratio discriminates between reduced synthesis and increased clearance of von Willebrand factor.  Thromb Haemost. 2002;  87 252-257
• 38 Mannucci P M, Lombardi R, Castaman G et al.. Von Willebrand disease “Vicenza” with larger-than-normal (supranormal) von Willebrand factor multimers.  Blood. 1988;  71 65-70
• 39 Casonato A, Pontara E, Sartorello F et al.. Reduced von Willebrand factor survival in type Vicenza von Willebrand disease.  Blood. 2002;  99 180-184
• 40 Mazurier C. Composition, quality controls and labeling of plasma-derived products for the treatment of von Willebrand disease.  Semin Thromb Hemost. 2006;  32 529-536
• 41 Favaloro E J, Bukuya M, Martinelli T et al.. A comparative multi-laboratory assessment of factor concentrate and implications for clinical efficacy as potential replacement therapy in von Willebrand's Disease (VWD).  Thromb Haemost. 2002;  87 466-476
• 42 Favaloro E J. Collagen binding assay for von Willebrand Factor (VWF:CBA): detection of von Willebrand's Disease (VWD), and discrimination of VWD subtypes, depends on collagen source.  Thromb Haemost. 2000;  83 127-135
• 43 Neugebauer B M, Goy C, Seitz R. A collagen binding assay: an additional method for von Willebrand factor activity in therapeutic concentrates.  Thromb Haemost. 2002;  88 871-872
• 44 Neugebauer B M, Goy C, Budek I, Seitz R. Comparison of two von Willebrand factor collagen-binding assays with different binding affinities for low, medium and high multimers of von Willebrand factor.  Semin Thromb Hemost. 2002;  28 139-147
• 45 Neugebauer B M, Volkers P, Seitz R. Von Willebrand factor potency determination by collagen binding assay. A collaborative study for the establishment of a European Pharmacopoeia method.  Pharmeuropeia. 2002;  14 315-327
• 46 Hubbard A R, Sands D, Chang A C, Mazurier C. Standardisation of von Willebrand factor in therapeutic concentrates: calibration of the 1st International Standard for von Willebrand Factor Concentrate (00/514).  Thromb Haemost. 2002;  88 380-386
• 47 Hubbard A R. von Willebrand factor standards for plasma and concentrate testing.  Semin Thromb Hemost. 2006;  32 522-528
• 48 Favaloro E J, Facey D, Grispo L. Laboratory assessment of von Willebrand factor: use of different assays can influence the diagnosis of von Willebrand's disease, depending on differing sensitivity to sample preparation and differential recognition of high molecular weight VWF forms.  Am J Clin Pathol. 1995;  104 264-271
• 49 Favaloro E J, Bonar B, Kershaw G et al.. (on behalf of the RCPA QAP in Haematology). Reducing errors in VWD identification: the experience of the RCPA Quality Assurance Program.  Semin Thromb Hemost. 2006;  32 505-513
• 50 Kallas A, Talpsep T. The von Willebrand factor collagen-binding activity assay: clinical application.  Ann Hematol. 2001;  80 466-471
• 51 Ver Elst K MM, van Vliet H DM, Kappers-Klunne M C, Leebeek F WG. In vitro studies, pharmacokinetic studies and clinical use of a high purity double virus inactivated FVIII/VWF concentrate (Immunate) in the treatment of von Willebrand disease.  Thromb Haemost. 2004;  92 67-74
• 52 Favaloro E J, Soltani S, McDonald J, Grezchnik E, Easton L, Favaloro J WC. Reassessment of ABO-blood group, gender and age on laboratory parameters used to diagnose von Willebrand Disorder (VWD): potential influence on the diagnosis versus the potential association with risk of thrombosis.  Am J Clin Pathol. 2005;  124 910-917