Evaluation of the PFA-100® System in the Diagnosis and Therapeutic Monitoring of Patients with von Willebrand Disease

Marco Cattaneo; Augusto B. Federici; Anna Lecchi; Barbara Agati; Rossana Lombardi; Federica Stabile; Paolo Bucciarelli

doi:10.1055/s-0037-1614626

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1999; 82(01): 35-39
DOI: 10.1055/s-0037-1614626

Rapid Communication

Schattauer GmbH

Evaluation of the PFA-100^® System in the Diagnosis and Therapeutic Monitoring of Patients with von Willebrand Disease

Authors

Marco Cattaneo

¹From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine, IRCCS Ospedale Maggiore, University of Milano, Italy
Augusto B. Federici

¹From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine, IRCCS Ospedale Maggiore, University of Milano, Italy
Anna Lecchi

¹From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine, IRCCS Ospedale Maggiore, University of Milano, Italy
Barbara Agati

¹From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine, IRCCS Ospedale Maggiore, University of Milano, Italy
Rossana Lombardi

¹From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine, IRCCS Ospedale Maggiore, University of Milano, Italy
Federica Stabile

¹From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine, IRCCS Ospedale Maggiore, University of Milano, Italy
Paolo Bucciarelli

¹From the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine, IRCCS Ospedale Maggiore, University of Milano, Italy

Abstract

Summary

We have evaluated platelet function at high shear with the PFA-100^® system in different subtypes of von Willebrand disease (vWD), before and after the intravenous infusions of desmopressin or a factor-VIII/von Willebrand factor (vWF) concentrate. Closure times with the PFA-100^® system were determined for both the collagen/ADP and the collagen/epinephrine cartridges in 52 patients with vWD (9 type 1 “platelet normal”, 5 type 1 “platelet-discordant”, 8 type 1 “platelet-low”, 6 type 2A, 9 type 2B, 6 type 2M Vicenza, 6 type 3 and 3 acquired vWD) and 40 controls. Measurements were repeated 1 and 4 h after the i.v. infusion of desmopressin (0.3 μg/Kg) in 26 patients with types 1, type 2M Vicenza or type 2A vWD, or of a factorVIII/vWF concentrate (Alphanate HT, 60 U/Kg) in 4 patients with type 3 vWD. At all time points, vWF plasma levels and the bleeding time (Symplate II) were also determined. Baseline closure times were longer in vWD patients than in controls with both the collagen/ADP and the collagen/ epinephrine cartridges. The sensitivity of the PFA-100^® system (88% and 87% with the two cartridges) was higher than that of the bleeding time (65%). Treatment with desmopressin normalized the closure times in patients with type 1 “platelet-normal” or type 2M Vicenza vWD, had no significant effects in patients with type 1 “platelet-low”, type 1 “platelet-discordant” or type 2A vWD. Infusion of a factorVIII/vWF concentrate in patients with type 3 vWD slightly shortened their prolonged closure times. In general, changes in PFA-100^® were paralleled by shortenings of the bleeding times and increases in plasma vWF levels. The PFA-100^® test reflects vWF-dependent platelet function under high shear stress and could be useful in the diagnosis and therapeutic monitoring of patients with vWD.

Full Text

References

References
1 Rodeghiero F, Castaman G, Dini E. Epidemiological investigation of the prevalence of von Willebrand's disease. Blood 1987; 69: 454-9.
2 Miller CH, Lenzi R, Breen C. Prevalence of von Willebrand's disease among US adults. Blood 1987; 70: 377-83.
3 Cattaneo M, Federici AB, Mannucci PM. Diagnosis and treatment of von Willebrand's disease. Int J Ped Hematol/Oncol 1994; 1: 499-508.
4 Wagner DD. The Weibel-Palade Body: the storage granule for von Wille-brand factor and P-selectin. Thromb Haemost 1993; 70: 105-10.
5 Meyer D, Girma JP. von Willebrand factor: Structure and function. Thromb Haemost 1993; 70: 99-104.
6 Ruggeri ZM. von Willebrand factor. J Clin Invest 1997; 99: 559-64.
7 Savage B, Shattil SJ, Ruggeri Z. Modulation of platelet function through adhesion receptors: A dual role for glycoprotein IIb-IIIa (integrin α_IIbβ₃) mediated by fibrinogen and glycoprotein Ib-von Willebrand factor. J Biol Chem 1992; 267: 11300-6.
8 Goto S, Salomon DR, Ikeda Y, Ruggeri ZM. Characterization of the unique mechanism mediating the shear-dependent binding of soluble von Wille-brand factor to platelets. J Biol Chem 1995; 270: 23352-61.
9 Sadler JE. A revised classification of von Willebrand disease. For the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost 1994; 71: 520-5.
10 Mannucci PM, Lombardi R, Castaman G, Dent JA, Lattuada A, Rode-ghiero F, Zimmerman TS. von Willebrand disease “"Vicenza” with larger-than-normal (supranormal) von Willebrand factor multimers. Blood 1988; 71: 65-70.
11 O'Brien JR, Salmon GP. Shear stress activation of platelet glycoprotein IIb/IIIa plus von Willebrand factor causes aggregation: filter blockage and the long bleeding time in von Willebrand's Disease. Blood 1987; 70: 1354-61.
12 Pareti I F, Cattaneo M, Carpinelli L, Zighetti ML, Bressi C, Mannucci PM, Ruggeri ZM. Evaluation of the abnormal platelet function in von Wille-brand disease by the blood filtration test. Thromb Haemost 1996; 75: 460-8.
13 Kundu SK, Heilmann E, Sio R, Garcia C, Ostgaart R. Characterization of an in vitro platelet function analyzer, PFA-100™. Clin Appl Thromb Hemost 1996; 2: 2419
14 Fressinaud E, Veyradiers A, Truchaud F, Martin I, Boyer-Neumann C, Trossaert M, Meyer D. Screening for von Willebrand disease with a new analyzer using high shear stress: a study of 60 cases. Blood 1998; 91: 1325-31.
15 Federici AB, Stabile F, Castaman G, Canciani MT, Mannucci PM. Treatment of acquired von Willebrand syndrome in patients with monoclonal gammopathy of uncertain significance: comparison of three different therapeutic approaches. Blood 1998; 92: 2707-11.
16 Kundu SK, Heilmann EJ, Sio R, Garcia C, Davidson RM, Ostgaard RA. Description of an “in vitro” platelet function analyzer- PFA-100™. Sem Thromb Hemost 1995; 21: 106-12.
17 Mammen EF, Alshameeri RS, Comp PC. Preliminary data from a field trial of the PFA-100™ system. Sem Thromb Hemost 1995; 21: 113-21.
18 Italian Working Group. Spectrum of von Willebrand's disease: A study of 100 cases. Br J Haematol 1977; 35: 101-12.
19 Gralnick HR, Rick ME, McKeown LP, Williams SB, Parker RI, Maisonneuve P, Jenneau C, Sultan Y. Platelet von Willebrand factor: an important determinant of the bleeding time in type I von Willebrand disease. Blood 1986; 68: 58-61.