Clinical Utility of the PFA-100

ABSTRACT

The PFA-100 (platelet function analyzer) is a relatively new tool for the investigation of primary hemostasis. This article reviews the history of the PFA-100 and details its clinical utility in several settings. The PFA-100 was first introduced to us in 1995 in an issue of Seminars in Thrombosis and Hemostasis, which included data from a field trial headed by Dr. Eberhard Mammen. Since that time, the PFA-100 has featured in nearly 500 publications and some 35 reviews. The PFA-100 has potential utility in monitoring antiplatelet therapy (including aspirin) and as a screening tool for investigating possible von Willebrand disease (VWD) and various platelet disorders. The PFA-100 also has potential value for monitoring DDAVP (desmopressin) therapy in both VWD and functional platelet disorders. Most recent attention has focused on sensitivity to antiplatelet medication, where a new language has also emerged, with researchers talking about “aspirin resistance,” “aspirin responsiveness,” and “aspirin nonresponsiveness.” Ultimately, the greatest strengths of the PFA-100 are its simplicity in use and excellent sensitivity to various hemostatic disturbances. However, because it is a “global” test system for primary hemostasis, this also creates a significant limitation because the PFA-100 is not specific for, nor predictive of, any particular disorder. However, used appropriately, the PFA-100 can be considered a worthwhile addition to hemostasis laboratories involved in the identification or therapeutic monitoring of primary hemostatic disorders. The potential future applications for this simple instrument are also briefly assessed.

KEYWORDS

PFA-100 - primary hemostasis - aspirin - VWD - von Willebrand disease

REFERENCES

• 1 Alshameeri R S, Mammen E F. Clinical experience with the Thrombostat 4000.  Semin Thromb Hemost. 1995;  21(Suppl 2) 1-10
• 2 Kundu S K, Heilmann E J, Sio R, Garcia C, Davidson R M, Ostgaard R A. Description of an in vitro platelet function analyzer—PFA-100.  Semin Thromb Hemost. 1995;  21(Suppl 2) 106-112
• 3 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) 113-121
• 4 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
• 5 Heilmann E J, Kundu S K, Sio R, Garcia C, Gomez R, Christie D J. Comparison of four commercial citrate blood collection systems for platelet function analysis by the PFA-100 system.  Thromb Res. 1997;  87 159-164
• 6 Marshall P W, Williams A J, Dixon R M 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;  44 151-155
• 7 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
• 8 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
• 9 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
• 10 Knöfler R, Weissbach G, Kuhlisch E. Platelet function tests in childhood. Measuring aggregation and release reaction in whole blood.  Semin Thromb Hemost. 1998;  24 513-521
• 11 Rand M L, Carcao M D, Blanchette V S. Use of the PFA-100 in the assessment of primary, platelet-related hemostasis in a pediatric setting.  Semin Thromb Hemost. 1998;  24 523-529
• 12 Suzuki S, Morishita S. Platelet hemostatic capacity (PHC) and fibrinolytic inhibitors during pregnancy.  Semin Thromb Hemost. 1998;  24 449-451
• 13 Keidel A, Mischke R. Clinical evaluation of platelet function analyzer PFA-100 in dogs.  Berl Munch Tierarztl Wochenschr. 1998;  111 452-456
• 14 Nicholson N S, Panzer-Knodle S G, Haas N F et al.. Assessment of platelet function assays.  Am Heart J. 1998;  135 S170-S178
• 15 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
• 16 Favaloro E J. Clinical application of the PFA-100^® .  Curr Opin Hematol. 2002;  9 407-415
• 17 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
• 18 Favaloro E J. Laboratory monitoring of therapy in von Willebrand disease: efficacy of the PFA-100^® and VWF:CB as coupled strategies.  Semin Thromb Hemost. 2006;  32 566-576
• 19 Favaloro E J, Bonar R, Duncan E, Rodgers S, Marsden K (on behalf of the RCPA QAP in Haematology). The utility of the PFA-100^® as a screening test of platelet function: an audit of haemostasis laboratories in Australia and New Zealand.  Blood Coagul Fibrinolysis. 2007;  18 441-448
• 20 Duncan E M, Bonar R, Rodgers S E, Favaloro E J, Marsden K. Methodology and outcomes of platelet aggregation testing in Australia, New Zealand and the Asia-Pacific region: results of a survey from the Royal College of Pathologists of Australasia Haematology Quality Assurance Program.  Int J Lab Hematol. 2009;  , in press
• 21 Favaloro E J, Lippi G, Adcock D M. Preanalytical and postanalytical variables: the leading causes of diagnostic error in haemostasis?.  Semin Thromb Hemost. 2008;  34 612-634
• 22 Jilma B. Platelet function analyzer (PFA-100): a tool to quantify congenital or acquired platelet dysfunction.  J Lab Clin Med. 2001;  138 152-163
• 23 Crescente M, Di Castelnuovo A, Iacoviello L, Vermylen J, Cerletti C, de Gaetano G. Response variability to aspirin as assessed by the platelet function analyzer (PFA)-100. A systematic review.  Thromb Haemost. 2008;  99 14-26
• 24 Dyszkiewicz-Korpanty A, Quinton R, Yassine J, Sarode R. The effect of a pneumatic tube transport system on PFA-100 closure time and whole blood platelet aggregation.  J Thromb Haemost. 2004;  2 354-356
• 25 Bock M, De Haan J, Beck K H et al.. Standardization of the PFA-100(R) platelet function test in 105 mmol/l buffered citrate: effect of gender, smoking, and oral contraceptives.  Br J Haematol. 1999;  106 898-904
• 26 Sestito A, Sciahbasi A, Landolfi R, Maseri A, Lanza G A, Andreotti F. A simple assay for platelet-mediated hemostasis in flowing whole blood (PFA-100): reproducibility and effects of sex and age.  Cardiologia. 1999;  44 661-665
• 27 Cho Y U, Chi H S, Jang S, Park C J. Reconfirmation of preanalytical variables and establishment of reference intervals of platelet function analyzer-100 closure times in Korean adults.  Korean J Lab Med. 2007;  27 318-323
• 28 Brockmann M A, Beythien C, Magens M M, Wilckens V, Kuehnl P, Gutensohn K. Platelet hemostasis capacity in smokers. In vitro function analyses with 3.2% citrated whole blood.  Thromb Res. 2001;  104 333-342
• 29 Lippi G, Manzato F, Franchini M, Brocco G, Florenziani G, Guidi G. Establishment of reference values for the PFA-100 platelet function analyzer in pediatrics.  Clin Exp Med. 2001;  1 69-70
• 30 Suzuki S, Morishita S. The relationship between the onset of labor mechanisms and the hemostatic system.  Immunopharmacology. 1999;  43 133-140
• 31 Davies J R, Fernando R, Hallworth S P. Hemostatic function in healthy pregnant and preeclamptic women: an assessment using the platelet function analyzer (PFA-100) and thromboelastography.  Anesth Analg. 2007;  104 416-420
• 32 Vincelot A, Nathan N, Collet D, Mehaddi Y, Grandchamp P, Julia A. Platelet function during pregnancy: an evaluation using the PFA-100 analyser.  Br J Anaesth. 2001;  87 890-893
• 33 Marietta M, Castelli I, Piccinini F et al.. The PFA-100 system for the assessment of platelet function in normotensive and hypertensive pregnancies.  Clin Lab Haematol. 2001;  23 131-134
• 34 Feuring M, Christ M, Roell A et al.. Alterations in platelet function during the ovarian cycle.  Blood Coagul Fibrinolysis. 2002;  13 443-447
• 35 Lippi G, Franchini M, Brocco G, Manzato F. Influence of the ABO blood type on the platelet function analyzer PFA-100.  Thromb Haemost. 2001;  85 369-370
• 36 Jilma-Stohlawetz P, Hergovich N, Homoncik M et al.. Impaired platelet function among platelet donors.  Thromb Haemost. 2001;  86 880-886
• 37 Moeller A, Weippert-Kretschmer M, Prinz H, Kretschmer V. Influence of ABO blood groups on primary hemostasis.  Transfusion. 2001;  41 56-60
• 38 Feuring M, Harenberg J, Peiter A et al.. Impact of ABO blood groups on tirofiban mediated inhibition of platelet function.  Platelets. 2005;  16 430-434
• 39 Welsby I J, Jones R, Pylman J et al.. Cardiothoracic Anesthesiology Research Endeavours . (C.A.R.E.). Blood ABO blood group and bleeding after coronary artery bypass graft surgery.  Blood Coagul Fibrinolysis. 2007;  18 781-785
• 40 Dalby M C, Davidson S J, Burman J F, Davies S W. Diurnal variation in platelet aggregation with the PFA-100 platelet function analyser.  Platelets. 2000;  11 320-324
• 41 Pamukcu B, Oflaz H, Acar R D et al.. The role of exercise on platelet aggregation in patients with stable coronary artery disease: exercise induces aspirin resistant platelet activation.  J Thromb Thrombolysis. 2005;  20 17-22
• 42 Lippi G, Montagnana M, Salvagno G L, Franchini M, Guidi G C. Comparison of platelet function between sedentary individuals and competitive athletes at rest.  Thromb J. 2006;  4 10
• 43 Aurigemma C, Fattorossi A, Sestito A et al.. Relationship between changes in platelet reactivity and changes in platelet receptor expression induced by physical exercise.  Thromb Res. 2007;  120 901-909
• 44 Nimmerfall K, Mischke R. Effect of unfractionated and low-molecular-weight heparin on platelet aggregation and in vitro bleeding time in dogs.  Dtsch Tierarztl Wochenschr. 1999;  106 439-444
• 45 Kottke-Marchant K, Powers J B, Brooks L, Kundu S, Christie D J. 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;  5 122-130
• 46 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;  83 316-321
• 47 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
• 48 Rudnicka A R, Rumley A, Lowe G D, Strachan D P. Diurnal, seasonal, and blood-processing patterns in levels of circulating fibrinogen, fibrin D-dimer, C-reactive protein, tissue plasminogen activator, and von Willebrand factor in a 45-year-old population.  Circulation. 2007;  115 996-1003
• 49 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
• 50 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
• 51 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
• 52 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
• 53 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
• 54 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
• 55 Dean J A, Blanchette V S, Carcao M D 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;  84 401-409
• 56 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 Willebrands disease.  Thromb Haemost. 2000;  84 88-92
• 57 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
• 58 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
• 59 Harrison P, Robinson M, Liesner R et al.. The PFA-100: a potential rapid screening tool for the assessment of platelet dysfunction.  Clin Lab Haematol. 2002;  24 225-232
• 60 Buyukasik Y, Karakus S, Goker H et al.. Rational use of the PFA-100 device for screening of platelet function disorders and von Willebrand disease.  Blood Coagul Fibrinolysis. 2002;  13 349-353
• 61 Wuillemin W A, Gasser K M, Zeerleder S S, Lämmle B. Evaluation of a Platelet Function Analyser (PFA-100) in patients with a bleeding tendency.  Swiss Med Wkly. 2002;  132 443-448
• 62 Nitu-Whalley I C, Lee C A, Brown S A, Riddell A, Hermans C. The role of the platelet function analyser (PFA-100) in the characterization of patients with von Willebrand's disease and its relationships with von Willebrand factor and the ABO blood group.  Haemophilia. 2003;  9 298-302
• 63 Cariappa R, Wilhite T R, Parvin C A, Luchtman-Jones L. Comparison of PFA-100 and bleeding time testing in pediatric patients with suspected hemorrhagic problems.  J Pediatr Hematol Oncol. 2003;  25 474-479
• 64 Posan E, McBane R D, Grill D E, Motsko C L, Nichols W L. Comparison of PFA-100 testing and bleeding time for detecting platelet hypofunction and von Willebrand disease in clinical practice.  Thromb Haemost. 2003;  90 483-490
• 65 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
• 66 Quiroga T, Goycoolea M, Muñoz B et al.. Template bleeding time and PFA-100 have low sensitivity to screen patients with hereditary mucocutaneous hemorrhages: comparative study in 148 patients.  Thromb Haemost. 2004;  2 892-898
• 67 Koscielny J, Ziemer S, Radtke H et al.. A practical concept for preoperative identification of patients with impaired primary hemostasis.  Clin Appl Thromb Hemost. 2004;  10 195-204
• 68 Philipp C S, Miller C H, Faiz A et al.. Screening women with menorrhagia for underlying bleeding disorders: the utility of the platelet function analyser and bleeding time.  Haemophilia. 2005;  11 497-503
• 69 Penas N, Pérez-Rodríguez A, Torea J H et al.. Willebrand disease R1374C: type 2A or 2M? A challenge to the revised classification. High frequency in the northwest of Spain (Galicia).  Am J Hematol. 2005;  80 188-196
• 70 Favaloro E J, Lloyd J, Rowell J et al.. Comparison of the pharmacokinetics of two von Willebrand factor concentrates [Biostate and AHF (High Purity)] in people with von Willebrand disorder. A randomised cross-over, multi-centre study.  Thromb Haemost. 2007;  97 922-930
• 71 Perel J M, Just S, Rowell J, Williams B, Kennedy G A. Utility of the PFA-100 analyser in the evaluation of primary haemostasis in a paediatric population.  Int J Lab Hematol. 2007;  29 480-481
• 72 Podda G M, Bucciarelli P, Lussana F, Lecchi A, Cattaneo M. Usefulness of PFA-100 testing in the diagnostic screening of patients with suspected abnormalities of hemostasis: comparison with the bleeding time.  J Thromb Haemost. 2007;  5 2393-2398
• 73 Favaloro E J, Patterson D, Denholm A et al.. Differential identification of a rare form of platelet-type (pseudo-) von Willebrand disease from type 2B VWD using a simplified ristocetin-induced-platelet-agglutination (RIPA) mixing assay and confirmed by genetic analysis.  Br J Haematol. 2007;  139 623-626
• 74 Karger R, Donner-Banzhoff N, Müller H H, Kretschmer V, Hunink M. Diagnostic performance of the platelet function analyzer (PFA-100) for the detection of disorders of primary haemostasis in patients with a bleeding history-a systematic review and meta-analysis.  Platelets. 2007;  18 249-260
• 75 Giannini S, Mezzasoma A M, Leone M, Gresele P. Laboratory diagnosis and monitoring of desmopressin treatment of von Willebrand's disease by flow cytometry.  Haematologica. 2007;  92 1647-1654
• 76 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
• 77 Franchini M, Gandini G, Manzato F, Lippi G. Evaluation of the PFA-100 system for monitoring desmopressin therapy in patients with type 1 von Willebrand's disease.  Haematologica. 2002;  87 670
• 78 Koscielny J, von Tempelhoff G F, Ziemer S et al.. A practical concept for preoperative management of patients with impaired primary hemostasis.  Clin Appl Thromb Hemost. 2004;  10 155-166
• 79 Franchini M, Zugni C, Veneri D et al.. High prevalence of acquired von Willebrand's syndrome in patients with thyroid diseases undergoing thyroid surgery.  Haematologica. 2004;  89 1341-1346
• 80 Michiels J J, Gadisseur A, van der Planken M, Schroyens W, van de Velden A, Berneman Z. Guidelines for the evaluation of intravenous desmopressin and von Willebrand factor/factor VIII concentrate in the treatment and prophylaxis of bleedings in von Willebrand disease types 1, 2, and 3.  Semin Thromb Hemost. 2006;  32 636-645
• 81 Hanebutt F L, Rolf N, Loesel A, Kuhlisch E, Siegert G, Knoefler R. Evaluation of desmopressin effects on haemostasis in children with congenital bleeding disorders.  Haemophilia. 2008;  14 524-530
• 82 Rose S S, Faiz A, Miller C H, Saidi P, Philipp C S. Laboratory response to intranasal desmopressin in women with menorrhagia and platelet dysfunction.  Haemophilia. 2008;  14 571-578
• 83 van Vliet H HDM, Kappers-Klunne M C, Leebeek F WG et al.. PFA-100 monitoring of von Willebrand factor (VWF) responses to DDAVP and FVIII/VWF concentrate substitution in von Willebrand disease type 1 and 2.  Thromb Haemost. 2008;  100 462-468
• 84 Favaloro E J. A better approach to monitoring of therapy in von Willebrand disease?.  Thromb Haemost. 2008;  100 371-373
• 85 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
• 86 Harrison C, Khair K, Baxter B, Russell-Eggitt I, Hann I, Liesner R. Hermansky-Pudlak syndrome: infrequent bleeding and first report of Turkish and Pakistani kindreds.  Arch Dis Child. 2002;  86 297-301
• 87 Liang H P, Morel-Kopp M C, Curtin J et al.. Heterozygous loss of platelet glycoprotein (GP) Ib-V-IX variably affects platelet function in velocardiofacial syndrome (VCFS) patients.  Thromb Haemost. 2007;  98 1298-1308
• 88 Giannini S, Mezzasoma A M, Guglielmini G, Rossi R, Falcinelli E, Gresele P. A new case of acquired Glanzmann's thrombasthenia: diagnostic value of flow cytometry.  Cytometry B Clin Cytom. 2008;  74 194-199
• 89 Francis J, Francis D, Larson L, Helms E, Garcia M. Can the Platelet Function Analyzer (PFA)-100 test substitute for the template bleeding time in routine clinical practice?.  Platelets. 1999;  10 132-136
• 90 Wahba A, Sander S, Birnbaum D E. Are in-vitro platelet function tests useful in predicting blood loss following open heart surgery?.  Thorac Cardiovasc Surg. 1998;  46 228-231
• 91 Lasne D, Fiemeyer A, Chatellier G, Chammas C, Baron J F, Aiach M. A study of platelet functions with a new analyzer using high shear stress (PFA 100) in patients undergoing coronary artery bypass graft.  Thromb Haemost. 2000;  84 794-799
• 92 Forestier F, Coiffic A, Mouton C, Ekouevi D, Chêne G, Janvier G. Platelet function point-of-care tests in post-bypass cardiac surgery: are they relevant?.  Br J Anaesth. 2002;  89 715-721
• 93 Fattorutto M, Pradier O, Schmartz D, Ickx B, Barvais L. Does the platelet function analyser (PFA-100) predict blood loss after cardiopulmonary bypass?.  Br J Anaesth. 2003;  90 692-693
• 94 Cammerer U, Dietrich W, Rampf T, Braun S L, Richter J A. The predictive value of modified computerized thromboelastography and platelet function analysis for postoperative blood loss in routine cardiac surgery.  Anesth Analg. 2003;  96 51-57
• 95 Avidan M S, Alcock E L, Da Fonseca J et al.. Comparison of structured use of routine laboratory tests or near-patient assessment with clinical judgement in the management of bleeding after cardiac surgery.  Br J Anaesth. 2004;  92 178-186
• 96 Hertfelder H J, Bös M, Weber D, Winkler K, Hanfland P, Preusse C J. Perioperative monitoring of primary and secondary hemostasis in coronary artery bypass grafting.  Semin Thromb Hemost. 2005;  31 426-440
• 97 Madan M, Berkowitz S D, Christie D J et al.. Rapid assessment of glycoprotein IIb/IIIa blockade with the platelet function analyzer (PFA-100) during percutaneous coronary intervention.  Am Heart J. 2001;  141 226-233
• 98 Madan M, Berkowitz S D, Christie D J, Smit A C, Sigmon K N, Tcheng J E. Determination of platelet aggregation inhibition during percutaneous coronary intervention with the platelet function analyzer PFA-100.  Am Heart J. 2002;  144 151-158
• 99 Van der Planken M G, Claeys M J, Vertessen F J et al.. Comparison of turbidimetric aggregation and in vitro bleeding time (PFA-100) for monitoring the platelet inhibitory profile of antiplatelet agents in patients undergoing stent implantation.  Thromb Res. 2003;  111 159-164
• 100 Konopka A, Spychalska J, Sitkiewicz D et al.. Expression of platelet surface receptors and early changes in platelet function in patients with STEMI treated with abciximab and clopidogrel versus clopidogrel alone.  Am J Cardiovasc Drugs. 2007;  7 433-439
• 101 van Werkum J W, Gerritsen W B, Kelder J C et al.. Inhibition of platelet function by abciximab or high-dose tirofiban in patients with STEMI undergoing primary PCI: a randomised trial.  Neth Heart J. 2007;  15 375-381
• 102 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;  66 425-430
• 103 van Kraaij D J, Hovestad-Witterland A H, de Metz M, Vollaard E J. A comparison of the effects of nabumetone vs meloxicam on serum thromboxane B2 and platelet function in healthy volunteers.  Br J Clin Pharmacol. 2002;  53 644-647
• 104 Fischetti D, Sciahbasi A, Leone A M et al.. Ticlopidine and aspirin fail to suppress the increased platelet aggregability that follows percutaneous coronary interventions.  J Thromb Thrombolysis. 2000;  10 265-269
• 105 Fattorutto M. Measurement of the effect of ticlopidine with the platelet function analyser (PFA-100) during coronary stent implantation.  Am Heart J. 2003;  146 E8
• 106 Hayward C P, Harrison P, Cattaneo M, Ortel T L, Rao A K. The Platelet Physiology Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis . Platelet function analyzer (PFA)-100 closure time in the evaluation of platelet disorders and platelet function.  J Thromb Haemost. 2006;  4 312-329
• 107 Reny J L, De Moerloose P, Dauzat M, Fontana P. Use of the PFA-100 closure time to predict cardiovascular events in aspirin-treated cardiovascular patients: a systematic review and meta-analysis.  J Thromb Haemost. 2008;  6 444-450
• 108 Snoep J D, Hovens M M, Eikenboom J C et al.. Association of laboratory-defined aspirin resistance with a higher risk of recurrent cardiovascular events: a systematic review and meta-analysis.  Arch Intern Med. 2007;  167 1593-1599
• 109 Krasopoulos G, Brister S J, Beattie W S et al.. Aspirin “resistance” and risk of cardiovascular morbidity: systematic review and meta-analysis.  BMJ. 2008;  336 195-198
• 110 Reny J L, Quéré I, de Moerloose P, Fontana P. Aspirin response variability assessed with the PFA-100 device.  Thromb Haemost. 2008;  99 968-969
• 111 Crescente M, Di Castelnuovo A, Iacoviello L, de Gaetano G, Cerletti C. Rebuttal to “Aspirin response variability assessed with the PFA-100 device” by Reny et al.  Thromb Haemost. 2008;  99 969
• 112 Crescente M, Di Castelnuovo A, Iacoviello L, de Gaetano G, Cerletti C. PFA-100 closure time to predict cardiovascular events in aspirin-treated cardiovascular patients: a meta-analysis of 19 studies comprising 3,003 patients.  Thromb Haemost. 2008;  99 1129-1131
• 113 Ziegler S, Maca T, Alt E, Speiser W, Schneider B, Minar E. Monitoring of antiplatelet therapy with the PFA-100 in peripheral angioplasty patients.  Platelets. 2002;  13 493-497
• 114 Grau A J, Reiners S, Lichy C, Buggle F, Ruf A. Platelet function under aspirin, clopidogrel, and both after ischemic stroke: a case-crossover study.  Stroke. 2003;  34 849-854
• 115 Mueller T, Haltmayer M, Poelz W, Haidinger D. Monitoring aspirin 100 mg and clopidogrel 75 mg therapy with the PFA-100 device in patients with peripheral arterial disease.  Vasc Endovascular Surg. 2003;  37 117-123
• 116 Jilma B. Synergistic antiplatelet effects of clopidogrel and aspirin detected with the PFA-100 in stroke patients.  Stroke. 2003;  34 849-854
• 117 Lepäntalo A, Virtanen K S, Heikkilä J, Wartiovaara U, Lassila R. Limited early antiplatelet effect of 300 mg clopidogrel in patients with aspirin therapy undergoing percutaneous coronary interventions.  Eur Heart J. 2004;  25 476-483
• 118 Raman S, Jilma B. Time lag in platelet function inhibition by clopidogrel in stroke patients as measured by PFA-100.  J Thromb Haemost. 2004;  2 2278-2279
• 119 Geiger J, Teichmann L, Grossmann R et al.. Monitoring of clopidogrel action: comparison of methods.  Clin Chem. 2005;  51 957-965
• 120 Mani H, Linnemann B, Luxembourg B, Kirchmayr K, Lindhoff-Last E. Response to aspirin and clopidogrel monitored with different platelet function methods.  Platelets. 2006;  17 303-310
• 121 Agarwal S, Coakley M, Reddy K, Riddell A, Mallett S. Quantifying the effect of antiplatelet therapy: a comparison of the platelet function analyzer (PFA-100) and modified thromboelastography (mTEG) with light transmission platelet aggregometry.  Anesthesiology. 2006;  105 676-683
• 122 Alström U, Tydén H, Oldgren J, Siegbahn A, Ståhle E. The platelet inhibiting effect of a clopidogrel bolus dose in patients on long-term acetylsalicylic acid treatment.  Thromb Res. 2007;  120 353-359
• 123 Serebruany V L, Malinin A I, Atar D. Combination antiplatelet therapy with aspirin and clopidogrel: the role of antecedent and concomitant doses of aspirin. An analysis of 711 patients.  Cardiology. 2007;  107 307-312
• 124 Lev E I, Ramchandani M, Garg R et al.. Response to aspirin and clopidogrel in patients scheduled to undergo cardiovascular surgery.  J Thromb Thrombolysis. 2007;  24 15-21
• 125 Malek L A, Grabowski M, Spiewak M et al.. Relation between impaired antiplatelet response to clopidogrel and possible pleiotropic effects.  J Thromb Thrombolysis. 2007;  24 301-305
• 126 Kotzailias N, Elwischger K, Sycha T et al.. Clopidogrel-induced platelet inhibition cannot be detected by the platelet function analyzer-100 system in stroke patients.  J Stroke Cerebrovasc Dis. 2007;  16 199-202
• 127 Dyszkiewicz-Korpanty A, Olteanu H, Frenkel E P, Sarode R. Clopidogrel anti-platelet effect: an evaluation by optical aggregometry, impedance aggregometry, and the platelet function analyzer (PFA-100).  Platelets. 2007;  18 491-496
• 128 Konopka A, Spychalska J, Sitkiewicz D et al.. Expression of platelet surface receptors and early changes in platelet function in patients with STEMI treated with abciximab and clopidogrel versus clopidogrel alone.  Am J Cardiovasc Drugs. 2007;  7 433-439
• 129 Serebruany V L, Malinin A I, Pokov A, Barsness G, Hanley D F. Effects of clopidogrel and aspirin in combination versus aspirin alone on platelet activation and major receptor expression in diabetic patients: the PLavix Use for Treatment Of Diabetes (PLUTO-Diabetes) trial.  Am Heart J. 2008;  155 93.e1-97
• 130 Fehr M, Galliard-Grigioni K S, Reinhart W H. Influence of acute alcohol exposure on hemorheological parameters and platelet function in vivo and in vitro.  Clin Hemorheol Microcirc. 2008;  39 351-358
• 131 Pearson D A, Paglieroni T G, Rein D et al.. The effects of flavanol-rich cocoa and aspirin on ex vivo platelet function.  Thromb Res. 2002;  106 191-197
• 132 Bordeaux B, Yanek L R, Moy T F et al.. Casual chocolate consumption and inhibition of platelet function.  Prev Cardiol. 2007;  10 175-180
• 133 Scharbert G, Kalb M L, Duris M, Marschalek C, Kozek-Langenecker S A. Garlic at dietary doses does not impair platelet function.  Anesth Analg. 2007;  105 1214-1218
• 134 Beckert B W, Concannon M J, Henry S L, Smith D S, Puckett C L. The effect of herbal medicines on platelet function: an in vivo experiment and review of the literature.  Plast Reconstr Surg. 2007;  120 2044-2050
• 135 Kwok Y, Ng K F, Li C C, Lam C C, Man R Y. A prospective, randomized, double-blind, placebo-controlled study of the platelet and global hemostatic effects of Ganoderma lucidum (Ling-Zhi) in healthy volunteers.  Anesth Analg. 2005;  101 423-426
• 136 Golański J, Muchova J, Golański R, Durackova Z, Markuszewski L, Watała C. Does pycnogenol intensify the efficacy of acetylsalicylic acid in the inhibition of platelet function? In vitro experience.  Postepy Hig Med Dosw (Online). 2006;  60 316-321
• 137 Lippi G, Montagnana M, Franchini M, Favaloro E J, Targher G. Dark chocolate: consumption for pleasure or therapy?.  J Thromb Thrombolysis. 2008;  , Sept 23 [Epub ahead of print]
• 138 Kloner R A, Rezkalla S H. To drink or not to drink? That is the question.  Circulation. 2007;  116 1306-1317
• 139 Marietta M, Castelli I, Piccinini F et al.. The PFA-100 system for the assessment of platelet function in normotensive and hypertensive pregnancies.  Clin Lab Haematol. 2001;  23 131-134
• 140 Vincelot A, Nathan N, Collet D, Mehaddi Y, Grandchamp P, Julia A. Platelet function during pregnancy: an evaluation using the PFA-100 analyser.  Br J Anaesth. 2001;  87 890-893
• 141 Davies J R, Fernando R, Hallworth S P. Hemostatic function in healthy pregnant and preeclamptic women: an assessment using the platelet function analyzer (PFA-100) and thromboelastograph.  Anesth Analg. 2007;  104 416-420
• 142 Nemmar A, Hoylaerts M F, Hoet P H, Vermylen J, Nemery B. Size effect of intratracheally instilled particles on pulmonary inflammation and vascular thrombosis.  Toxicol Appl Pharmacol. 2003;  186 38-45
• 143 Nemmar A, Hoet P H, Dinsdale D, Vermylen J, Hoylaerts M F, Nemery B. Diesel exhaust particles in lung acutely enhance experimental peripheral thrombosis.  Circulation. 2003;  107 1202-1208
• 144 Nemmar A, Nemery B, Hoet P H, Vermylen J, Hoylaerts M F. Pulmonary inflammation and thrombogenicity caused by diesel particles in hamsters: role of histamine.  Am J Respir Crit Care Med. 2003;  168 1366-1372
• 145 Nemmar A, Hoylaerts M F, Hoet P H, Nemery B. Possible mechanisms of the cardiovascular effects of inhaled particles: systemic translocation and prothrombotic effects.  Toxicol Lett. 2004;  149 243-253
• 146 Lippi G, Favaloro E J, Franchini M, Guidi G C. Air pollution and coagulation testing: a new source of biological variability?.  Thromb Res. 2008;  123 50-54
• 147 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;  84 614-619
• 148 Pihusch R, Rank A, Göhring P, Pihusch M, Hiller E, Beuers U. Platelet function rather than plasmatic coagulation explains hypercoagulable state in cholestatic liver disease.  J Hepatol. 2002;  37 548-555
• 149 Bilgin A U, Karadogan I, Artac M, Kizilors A, Bligin R, Undar L. Hemodialysis shortens long in vitro closure times as measured by the PFA-100.  Med Sci Monit. 2007;  13 CR141-CR145
• 150 Frossard M, Fuchs I, Leitner J M et al.. Platelet function predicts myocardial damage in patients with acute myocardial infarction.  Circulation. 2004;  110 1392-1397
• 151 Sestito A, Sgueglia G A, Spinelli A et al.. Increased platelet reactivity in unstable angina patients is not related to C-reactive protein levels.  Platelets. 2006;  17 336-339
• 152 Yee D L, Bergeron A L, Sun C W, Dong J F, Bray P F. Platelet hyperreactivity generalizes to multiple forms of stimulation.  J Thromb Haemost. 2006;  4 2043-2050
• 153 Fuchs I, Frossard M, Spiel A, Riedmüller E, Laggner A N, Jilma B. Platelet function in patients with acute coronary syndrome (ACS) predicts recurrent ACS.  J Thromb Haemost. 2006;  4 2547-2552
• 154 Giusti B, Gori A M, Marcucci R et al.. Role of glycoprotein Ia gene polymorphisms in determining platelet function in myocardial infarction patients undergoing percutaneous coronary intervention on dual antiplatelet treatment.  Atherosclerosis. 2008;  196 341-348
• 155 Linden M D, Furman M I, Frelinger III A L et al.. Indices of platelet activation and the stability of coronary artery disease.  J Thromb Haemost. 2007;  5 761-765
• 156 Serebruany V L, Malinin A, Ong S, Atar D. Patients with metabolic syndrome exhibit higher platelet activity than those with conventional risk factors for vascular disease.  J Thromb Thrombolysis. 2008;  25 207-213
• 157 Jacopo G, Elisabetta V, Silverio S et al.. Identification of platelet hyper-reactivity measured with a portable device immediately after percutaneous coronary intervention predicts in stent thrombosis.  Thromb Res. 2007;  121 407-412
• 158 Jilma-Stohlawetz P, Jilma B, Mannhalter C et al.. Platelet glycoprotein Ibalpha polymorphisms and function evaluated by the platelet function analyzer PFA-100 in patients with lupus anticoagulant: the association with thromboembolic disease.  Ann Hematol. 2007;  86 719-725
• 159 Harrison P, Mackie I, Mathur A et al.. Platelet hyper-function in acute coronary syndromes.  Blood Coagul Fibrinolysis. 2005;  16 557-562
• 160 Franchini M, Lippi G. Von Willebrand factor and thrombosis.  Ann Hematol. 2006;  85 415-423
• 161 Franchini M, Mannucci P M. Von Willebrand factor: another Janus-faced hemostasis protein.  Semin Thromb Hemost. 2008;  34 663-669
• 162 Chakroun T, Gerotziafas G, Robert F et al.. In vitro aspirin resistance detected by PFA-100 closure time: pivotal role of plasma von Willebrand factor.  Br J Haematol. 2004;  124 80-85
• 163 Kilanowska J, Favaloro E J, Lippi G. Aspirin ‘responsiveness,’ ‘non-responsiveness’ or ‘resistance’: a putative role for von Willebrand factor?.  Blood Coagul Fibrinolysis. 2008;  19 823-824
• 164 Favaloro E J. An update on the von Willebrand factor collagen binding (VWF:CB) assay: 21 years of age and beyond adolescence, but not yet a mature adult.  Semin Thromb Hemost. 2007;  33 727-744
• 165 Favaloro E J, Lippi G, Franchini M. Preface: laboratory diagnostics in thrombosis and hemostasis: the past, the present, and the future.  Semin Thromb Hemost. 2008;  34 579-584
• 166 Lippi G, Favaloro E J. Activated partial thromboplastin time: new tricks for an old dogma.  Semin Thromb Hemost. 2008;  34 604-611
• 167 Watson H G, Greaves M. Can we predict bleeding?.  Semin Thromb Hemost. 2008;  34 97-103
• 168 Chee Y L, Crawford J C, Watson H G, Greaves M. Guidelines on the assessment of bleeding risk prior to surgery or invasive procedures. British Committee for Standards in Haematology.  Br J Haematol. 2008;  140 496-504
• 169 Karon B S, Wockenfus A, Scott R et al.. Aspirin responsiveness in healthy volunteers measured with multiple assay platforms.  Clin Chem. 2008;  54 1060-1065
• 170 Klein Gunnewiek J M, Hovestad-Witterland A H, Vollaard E J, Fleuren H W, de Metz M. The influence of acetylsalicylic acid intake by healthy volunteers on duplicate PFA-100 measurements.  Blood Coagul Fibrinolysis. 2005;  16 337-340
• 171 Haubelt H, Anders C, Vogt A, Hoerdt P, Seyfert U T, Hellstern P. Variables influencing Platelet Function Analyzer-100 closure times in healthy individuals.  Br J Haematol. 2005;  130 759-767
• 172 Poulsen T S, Mickley H, Korsholm L, Licht P B, Haghfelt T, Jørgensen B. Using the Platelet Function Analyzer-100 for monitoring aspirin therapy.  Thromb Res. 2007;  120 161-172
• 173 Carcao M D, Blanchette V S, Stephens D et al.. Assessment of thrombocytopenic disorders using the Platelet Function Analyzer (PFA-100).  Br J Haematol. 2002;  117 961-964
• 174 Kretschmer V, Bade S, Weippert-Kretschmer M, Kratzer M A. Measurement of primary haemostasis using a pressure clamp technique.  Platelets. 2001;  12 462-470