Impaired Platelet Function among Platelet Donors

Petra Jilma-Stohlawetz; Nicole Hergovich; Monika Homoncik; Larisa Dzirlo; Michaela Horvath; Michael Janisiw; Simon Panzer; Bernd Jilma

doi:10.1055/s-0037-1616146

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2001; 86(03): 880-886
DOI: 10.1055/s-0037-1616146

Review Articles

Schattauer GmbH

Impaired Platelet Function among Platelet Donors

Petra Jilma-Stohlawetz

²Department of Blood Group Serology and Transfusion Medicine, Division of Transfusion Medicine, Vienna University, Vienna, Austria

,

Nicole Hergovich

¹Departments of Clinical Pharmacology-TARGET

,

Monika Homoncik

¹Departments of Clinical Pharmacology-TARGET

,

Larisa Dzirlo

¹Departments of Clinical Pharmacology-TARGET

,

Michaela Horvath

²Department of Blood Group Serology and Transfusion Medicine, Division of Transfusion Medicine, Vienna University, Vienna, Austria

,

Michael Janisiw

²Department of Blood Group Serology and Transfusion Medicine, Division of Transfusion Medicine, Vienna University, Vienna, Austria

,

Simon Panzer

²Department of Blood Group Serology and Transfusion Medicine, Division of Transfusion Medicine, Vienna University, Vienna, Austria

,

Bernd Jilma

¹Departments of Clinical Pharmacology-TARGET

› Institutsangaben

Abstract

Summary

Background: Platelet transfusions are effective for the prevention and treatment of bleeding in patients with disorders of platelet number and/or function. In recent years plateletpheresis concentrates have outnumbered pooled platelet concentrates, albeit with significant differences between nations. Thus, the platelet quality of individual donors has become increasingly important. The aim of this study was to gain an estimate for the prevalence of impaired platelet function among platelet donors. Study design and methods: We determined the inter-donor variability in platelet plug formation with a PFA-100 analyzer, the prevalence of impaired thromboxane formation, and effects of the density in alpha2 integrin polymorphism and density. Results: (i) Collagen-epinephrine induced closure time (CEPI-CT) showed a great inter-subject variability in platelet donors and was higher than in healthy controls (p = 0.008). One-fifth of donors had abnormal CEPI-CT values and 11% exceeded >300 s (max measurable value). (ii) Decreased serum thromboxane B₂ levels were found in 9% of all donors, compatible with surreptitious intake of cyclooxygenase inhibitors or with an aspirin-like defect. CEPI-CT correlated inversely with TxB₂-levels in donors and controls. (iii) The density of the alpha_2-integrin correlated negatively with CEPI-CT and CADP-CT values in controls, but was not responsible for the observed impaired platelet function in donors. (iv) Finally, the ABO blood group system modulates closure times. Conclusion: In sum, a large number of platelet donors present with prolonged closure times. Decreased thromboxane formation and frequent platelet donation partly account for this observation.

Abbreviations: 807 CC/CT/TT polymorphisms of the alpha2-integrin gene, CD36… GPIIIb, an alternative collagen receptor, CD42b… GpIb, the von Willebrand receptor, CD49b… alpha2-integrin, subunit of the main collagen receptor, CADP-CT… collagen adenosine diphosphate induced closure time, CEPI-CT… collagen/epinephrine induced closure time, PFA-100… platelet function analyzer, vWF-Ag… von Willebrand factor antigen, TXB2… thromboxane B2

Key words

Platelet function - vWF - PFA-100 - aspirin-like defect - thromboxane B₂

Volltext

Referenzen

References
1 Machin SJ, Kelsey H, Seghatchian MJ, Warwick R, Mackie IJ. Platelet transfusion. Thromb Haemost 1995; 74 (Suppl. 01) 246-52.
2 Norfolk DR, Ancliffe PJ, Contreras M, Hunt BJ, Machin SJ, Murphy WG, Williamson L. Consensus Conference on Platelet Transfusion, Royal College of Physicians of Edinburgh, 27-28 November 1997. Synopsis of background papers. Br J Haematol 1998; 101: 609-17.
3 Wallace EL, Churchill WH, Surgenor DM, Cho GS, McGurk S. Collection and transfusion of blood and blood components in the United States, 1994. Transfusion 1998; 38: 625-36.
4 Ness PM, Braine HG, King KE, Barsasso C, Kennedy SD. Single donor platelets reduce the risk of septic transfusion reactions. Transfusion 1999; 39: 89S (Abstract).
5 Chernoff A, Snyder EL. The cellular and molecular basis of the platelet storage lesion: a symposium summary. Transfusion 1992; 32: 386-90.
6 Francis JL. Platelet dysfunction detected at high shear in patients with heart valve disease. Platelets 2000; 11: 133-6.
7 von Pape KW, Aland E, Stegmann T, Bohner J. Monitoring of primary hemostasis in patients undergoing coronary artery bypass grafting. Ann Hematol 2000; 79S: A68 (Abstract).
8 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.
9 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.
10 Kundu SK, Heilmann EJ, Sio R, Garcia C, Davidson RM, Ostgaard RA. Description of an in vitro platelet function analyzer – PFA-100. Semin Thromb Hemost 1995; 21 (Suppl. 02) 106-12.
11 Fressinaud E, Veyradier A, Sigaud M, Boyer-Neumann C, Le BC, 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.
12 Cattaneo M, Federici AB, Lecchi A, Agati B, Lombardi R, Stabile F, Bucciarelli P. Evaluation of the PFA-100 system in the diagnosis and therapeutic monitoring of patients with von Willebrand disease. Thromb Haemost 1999; 82: 35-9.
13 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: 132-6.
14 Marshall PW, Williams AJ, Dixon RM, Growcott JW, Warburton S, Armstrong J, Moores J. 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.
15 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.
16 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.
17 Bradlow BA, Chetty N. Dosage frequency for suppression of platelet function by low dose aspirin therapy. Thromb Res 1982; 27: 99-110.
18 Patrono C, Ciabattoni G, Patrignani P, Pugliese F, Filabozzi P, Catella F, Davi G, Forni L. Clinical pharmacology of platelet cyclooxygenase inhibition. Circulation 1985; 72: 1177-84.
19 Stohlawetz P, Horvath M, Pernerstorfer T, Nguyen H, Vondrovec B, Robisch A, Eichler HG, Spitzauer S, Jilma B. Effects of nitric oxide on platelet activation during plateletpheresis and in vivo tracking of biotinylated platelets in humans. Transfusion 1999; 39: 506-14.
20 Stohlawetz P, Hergovich N, Stiegler G, Eichler HG, Hocker P, Kapiotis S, Jilma B. Differential induction of P-selectin expression on platelets by two cell separators during plateletpheresis and the effect of gender on the release of soluble P-selectin. Transfusion 1998; 38: 24-30.
21 Bock M, De Haan J, Beck KH, Gutensohn K, Hertfelder HJ, Karger R, Heim MU, Beeser H, Weber D, Kretschmer V. 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.
22 Hansen JB, Wilsgard J, Olsen JO, Svensson B, Osterud B. The effect of lipopolysaccharides (LPS) on generation of thromboxane A2 and thromboplastin activity in whole blood of males, females and females on oral contraceptives. Thromb Haemost 1989; 61: 493-6.
23 Reiner AP, Aramaki KM, Teramura G, Gaur L. Analysis of platelet glycoprotein Ia (alpha2 integrin) allele frequencies in three North American populations reveals genetic association between nucleotide 807C/T and amino acid 505 Glu/Lys (HPA- 5) dimorphisms. Thromb Haemost 1998; 80: 449-56.
24 Homoncik M, Blann AD, Hollenstein U, Pernerstorfer Eichler HG, Jilma B. Systemic inflammation increasesshear induced platelet plug formation measured by the PFA-100. Br J Haematol 2000; 111: 1250-2.
25 Blann AD, Daly RJ, Amiral J. The influence of age, gender and ABO blood group on soluble endothelial cell markers and adhesion molecules. Br J Haematol 1996; 92: 498-500.
26 Lasne D, Fiemeyer A, Chatellier G, Chammas C, Baron JF, 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: 794-9.
27 Borzini P, Lazzaro A, Mazzucco L. Evaluation of the hemostatic function of stored platelet concentrates using the platelet function analyzer (PFA-100). Haematologica 1999; 84: 1104-9.
28 Wong EC, Oblitas J, Leitman SF, Stroncek DF. Whole blood platelet von Willebrand bead reactivity in plateletpheresis donors: effect of age, gender and medications. Transfusion 1999; 39: 38S (Abstract).
29 Borzini P, Lazzaro A, Mazzucco L, Schiavo R, Connor J, Siena S. Platelet cryopreservation using second-messenger effector and low-dose (2%) dimethyl sulfoxide. In vitro evaluation of post-thawing platelet activity with the platelet function analyzer. Haematologica 2000; 85: 885-7.
30 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.
31 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.
32 Schlammadinger A, Kerenyi A, Muszbek L, Boda Z. Comparison of the O’Brien filter test and the PFA-100 platelet analyzer in the laboratory diagnosis of von Willebrand’s disease. Thromb Haemost 2000; 84: 88-92.
33 Hergovich N, Aigner M, Eichler HG, Entlicher J, Mensik C, Jilma B. Paroxetine decreases platelet serotonin contents and platelet function in human beings. Clin Pharmacol Ther 2000; 68: 435-42.
34 Francis JL. Platelet dysfunction detected at high shear in patients with heart valve disease. Platelets 2000; 11: 133-6.
35 Kitchen L, Erichson RB, Sideropoulos H. Effect of drug-induced platelet dysfunction on surgical bleeding. Am J Surg. 1982; 143: 215-7.
36 Green D, Davies RO, Holmes GI, Holmes GI, Kohl H, Lee RB, Reynolds N, Schmid FR. Effects of diflunisal on platelet function and fecal blood loss. Clin Pharmacol Ther 1981; 30: 378-84.
37 Vostal JG, Reid TJ, Mondoro TH. Summary of a workshop on in vivo efficacy of transfused platelet components and platelet substitutes. Transfusion 2000; 40: 742-50.
38 Di Paola J, Federici AB, Mannucci PM, Canciani MT, Kritzik M, Kunicki TJ, Nugent D. Low platelet alpha2beta1 levels in type I von Willebrand disease correlate with impaired platelet function in a high shear stress system. Blood 1999; 93: 3578-82.
39 Moeller A, Weippert-Kretschmer M, Prinz H, and Kretschmer V. Influence of ABO groups on primary hemostasis. Transfusion 2001; 41: 56-60.
40 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: 369-70.