Utility of the PFA-100® for assessing bleeding disorders and monitoring therapy: a review of analytical variables, benefits and limitations
E. J. Favaloro,
E. J. Favaloro
Diagnostic Haemostasis Laboratory, Department of Haematology, ICPMR, Westmead Hospital, NSW, Australia
Search for more papers by this authorE. J. Favaloro,
E. J. Favaloro
Diagnostic Haemostasis Laboratory, Department of Haematology, ICPMR, Westmead Hospital, NSW, Australia
Search for more papers by this author
Dr Emmanuel J. Favaloro
Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, WSAHS, Westmead, NSW, 2145, Australia. Tel.: + 61 2 9845 6211; fax: + 61 2 9689 2331; e-mail: [email protected]
Abstract
The PFA-100® (platelet function analyser) is a relatively new tool for the investigation of primary haemostasis. Recent studies have shown its utility in monitoring antiplatelet therapy (including aspirin) and as a screening tool for investigating possible von Willebrand disease (vWD) and various platelet disorders. More recently, the PFA-100® has been shown to be of value in monitoring DDAVP therapy in both vWD and platelet disorders. This paper reviews current findings, details the utility of the PFA-100® for some of these purposes, as well as reviewing analytical variables that may complicate the interpretation of results. The author highlights the benefits, as well as noting the limitations, of its use. Ultimately, the greatest strengths of the PFA-100® are its simplicity in use and excellent sensitivity to particular haemostatic disturbances such as vWD, platelet disorders and platelet-affecting medication. However, because it is thus a ‘global’ test system, this also creates a significant limitation, as the PFA-100® is not specific for, nor predictive of, any particular disorder. However, utilized appropriately, the PFA-100® can be considered a worthwhile addition to any haemostasis laboratory involved in the diagnosis or therapeutic-monitoring of bleeding disorders including vWD and platelet-dysfunctions. This review should be of value to both haemostasis scientists and clinical specialists.
Bibliography
- 1 Hutton RA & Ludlam CA. Platelet function testing. Association of Clinical Pathologists Broadsheet No. 122, 1989.
- 2 Frojmovic M. Biorheology. Report of the 1999 ISTH SSC Biorheology meeting URL: http://www.med.unc.edu/isth/99biorheology.html/
- 3 Kundu SK, Heilmann EJ, Sio R, Garcia C, Davidson RM & Ostgaard RA. Description of an in vitro platelet function analyser: PFA-100®. Semin Thromb Hemost 1995; 21 (Suppl. 2): 106–12.
- 4 Mammen EF, Alshameeri RS & Comp PC. Preliminary data from a field trial of the PFA-100® system. Semin Thromb Hemost 1995; 21 (Suppl. 2): 113–20.
- 5 Bock M, De Haan J & Beck KH et al. Standardization of the PFA-100® platelet function test in 105 mmol/L buffered citrate: effect of gender, smoking, and oral contraceptives. Br J Haematol 1999; 106: 898–904.
- 6 Sestito A, Sciahbasi A, Landolfi R, Maseri A, Lanza GA & Andreotti F. A simple assay for platelet-mediated hemostasis in flowing whole blood (PFA-100): reproducibility and effects of sex and age. Cardiologia 1999; 44: 661–5.
- 7 Carcao MD, Blanchette VS & Dean JA 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: 70–3.DOI: 10.1046/j.1365-2141.1998.00656.x
- 8 Knofler R, Weissbach G & Kuhlisch E. Platelet function tests in childhood. Measuring aggregation and release reaction in whole blood. Semin Thromb Hemost 1998; 24: 513–21.
- 9 Rand ML, Carcao MD & Blanchette VS. Use of the PFA-100 in the assessment of primary, platelet-related hemostasis in a pediatric setting. Semin Thromb Hemost 1998; 24: 523–9.
- 10 Suzuki S & Morishita S. Platelet hemostatic capacity (PHC) and fibrinolytic inhibitors during pregnancy. Semin Thromb Hemost 1998; 24: 449–51.
- 11 Suzuki S & Morishita S. The relationship between the onset of labor mechanisms and the hemostatic system. Immunopharmacology 1999; 43: 133–40.DOI: 10.1016/s0162-3109(99)00147-2
- 12 Heilmann EJ, Kundu SK, Sio R, Garcia C, Gomez R & Christie DJ. Comparison of four commercial citrate blood collection systems for platelet function analysis by the PFA-100 system. Thromb Res 1997; 87: 159–64.DOI: 10.1016/s0049-3848(97)00115-1
- 13 Von Pape K, Aland E & Bohner J . Platelet function analysis with PFA-100® in patients medicated with acetylsalicylic acid strongly depends on concentration of sodium citrate used for anticoagulation of blood sample. Thromb Res 2000; 98: 295–9.DOI: 10.1016/s0049-3848(99)00236-4
- 14 Nimmerfall K & Mischke R. Effect of unfractionated and low-molecular-weight heparin on platelet aggregation and in vitro bleeding time in dogs. DTW Dtsch Tierarztl Wochenschr 1999; 106: 439–44.
- 15 Kottke-Marchant K, Powers JB, Brooks L, Kundu S & Christie DJ. The effect of antiplatelet drugs, heparin, and preanalytical variables on platelet function detected by the platelet function analyzer (PFA-100). Clin Appl Thromb Hemost 1999; 5: 122–30.
- 16 Homoncik M, Jilma B, Hergovich N, Stohlawetz P, Panzer S & Speiser W. Monitoring of aspirin (ASA) pharmacodynamics with the platelet function analyzer PFA-100. Thromb Haemost 2000; 83: 316–21.
- 17 Ortel TL, James AH, Thames EH, Moore KD & Greenberg CS. Assessment of primary hemostasis by PFA-100 analysis in a tertiary care center. Thromb Haemost 2000; 84: 93–7.
- 18 Marshall PW, Williams AJ & Dixon RM et al. A comparison of the effects of aspirin on bleeding time measured using the Simplate method and closure time measured using the PFA-100, in healthy volunteers. Br J Clin Pharmacol 1997; 44: 151–5.
- 19 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: 1325–31.
- 20 Mammen EF, Comp PC & Gosselin R et al. PFA-100 system: a new method for assessment of platelet dysfunction. Semin Thromb Hemost 1998; 24: 195–202.
- 21 Keidel A & Mischke R. Clinical evaluation of platelet function analyzer PFA-100 in dogs. Berl Munch Tierarztl Wochenschr 1998; 111: 452–6.
- 22 Harrison P, Robinson MS & Mackie IJ et al. Performance of the platelet function analyser PFA-100 in testing abnormalities of primary haemostasis. Blood Coagul Fibrinolysis 1999; 10: 25–31.
- 23
Favaloro EJ,
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: 165–74.
10.1002/(SICI)1096-8652(199911)62:3<165::AID-AJH6>3.0.CO;2-C CAS PubMed Web of Science® Google Scholar
- 24 Feuring M, Haseroth K, Janson CP, Falkenstein E, Schmidt BM & Wehling M . Inhibition of platelet aggregation after intake of acetylsalicylic acid detected by a platelet function analyzer (PFA-100). Int J Clin Pharmacol Ther 1999; 37: 584–8.
- 25 Hezard N, Metz D & Nazeyrollas P et al. Use of the PFA-100 apparatus to assess platelet function in patients undergoing PTCA during and after infusion of cE3 Fab in the presence of other antiplatelet agents. Thromb Haemost 2000; 83: 540–4.
- 26 De Meijer A, Vollaard H, De Metz M, Verbruggen B, Thomas C & Novakova I. Meloxicam 15 mg/day, spares platelet function in healthy volunteers. Clin Pharmacol Ther 1999; 66: 425–30.
- 27 Escolar G, Cases A & Vinas M et al. Evaluation of acquired platelet dysfunctions in uremic and cirrhotic patients using the platelet function analyzer (PFA-100): influence of hematocrit elevation. Haematologica 1999; 84: 614–9.
- 28 Wahba A, Sander S & Birnbaum DE. Are in vitro platelet function tests useful in predicting blood loss following open heart surgery? Thorac Cardiovasc Surg 1998; 46: 228–31.
- 29 Kundu SK, Heilmann EJ, Sio R, Garcia C & Ostgaard RA. Characterisation of an in vitro Platelet Function Analyser, PFA-100®. Clin Appl Thromb Hemost 1996; 2: 241–9.
- 30 Favaloro EJ, 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: 180–89.
- 31 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: 487–92.DOI: 10.1016/s0049-3848(99)00152-8
- 32 Cattaneo M, Lecchi A, Agati B, Lombardi R & Zighetti ML. Evaluation of platelet function with the PFA-100 system in patients with congenital defects of platelet secretion. Thromb Res 1999; 96: 213–7.DOI: 10.1016/s0049-3848(99)00102-4
- 33 Cattaneo M, Federici AB & 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: 35–9.
- 34 Di Paola J, Federici AB & Mannucci PM et al. Low platelet alpha2, beta1 levels in type I von Willebrand disease correlate with impaired platelet function in a high shear stress system. Blood 1999; 93: 3578–82.
- 35 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.
- 36 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: 777–83.
- 37
Facey DA,
Favaloro EJ,
Maxwell E,
Baker R &
Hertzberg MS.
Type 2B von Willebrand’s disease in thirteen individuals from five unrelated Australian families: Phenotype and genotype correlations.
Am J Hematol
2000; 63: 197–9.DOI: 10.1002/(sici)1096-8652(200004)63:4<197::aid-ajh6>3.3.co;2-u
10.1002/(SICI)1096-8652(200004)63:4<197::AID-AJH6>3.0.CO;2-2 CAS PubMed Web of Science® Google Scholar
- 38 Favaloro EJ. Laboratory assessment as a critical component of the appropriate diagnosis and sub-classification of von Willebrand’s disease. Blood Rev 1999; 13: 185–204.DOI: 10.1054/blre.1999.0116
- 39 von Willebrand Working Party of the United Kingdom Haemophilia Centre Directors’ Organisation. Guidelines for the diagnosis and management of von Willebrand Disease. Haemophilia 1995; 3 (Suppl. 2): 1–8.
- 40 Dean JA, Blanchette VS & Carcao MD et al. von Willebrand Disease in a paediatric-based population – Comparison of Type 1 diagnostic criteria and use of the PFA-100® and a von Willebrand factor/collagen-bindiing assay. Thromb Haemost 2000; 84: 401–9.
- 41 Veyradier A, Fressinaud E, Boyer-Neumann C, Trossaert M & Meyer D. von Willebrand factor ristocetin cofactor activity correlates with platelet function in a high shear stress system. Thromb Haemost 2000; 84: 727–8.
- 42 Favaloro EJ, Smith J, Petinos P, Collecutt M, Street A & Hertzberg M on behalf of the RCPA Quality Assurance Program (QAP) in Haematology Scientific Haemostasis Advisory Panel. Laboratory testing, diagnosis and management of von Willebrand’s disease: Current practice in Australasia. Am J Clin Pathol 1999; 112: 712–9.
- 43 Meskal A, Vertessen F, Van der Planken M & Berneman ZN. 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: 426–30.DOI: 10.1007/s002770050542
Citing Literature
