Platelet hyperreactivity in hemodialysis patients with frequently occluded vascular access

Kang-Ju Chou; Chung-Ren Jan; Po-Tsang Lee; Chien-Liang Chen; Hsiao-Min Chung; Yueh-Yen Hwang; Jing-Dung Chou; Hua-Chang Fang

doi:10.1160/TH04-01-0048

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 92(03): 621-626
DOI: 10.1160/TH04-01-0048

Platelets and Blood Cells

Schattauer GmbH

Platelet hyperreactivity in hemodialysis patients with frequently occluded vascular access

Authors

Kang-Ju Chou

¹Division of Nephrology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

²National Yang-Ming University, School of Medicine, Taipei, Taiwan
Chung-Ren Jan

³Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung Taiwan
Po-Tsang Lee

¹Division of Nephrology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

²National Yang-Ming University, School of Medicine, Taipei, Taiwan
Chien-Liang Chen

¹Division of Nephrology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

²National Yang-Ming University, School of Medicine, Taipei, Taiwan
Hsiao-Min Chung

¹Division of Nephrology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

²National Yang-Ming University, School of Medicine, Taipei, Taiwan
Yueh-Yen Hwang

¹Division of Nephrology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
Jing-Dung Chou

¹Division of Nephrology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
Hua-Chang Fang

¹Division of Nephrology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

²National Yang-Ming University, School of Medicine, Taipei, Taiwan

Abstract

Summary

It is known that thrombosis is a leading cause of vascular access failure and that the formation of thrombus requires platelets. The activation of platelets induces the increase in intracellular Ca²⁺ levels ([Ca²⁺]_i) leading to aggregation and thrombosis. We compared the platelet [Ca²⁺]_i before and after stimulation between the patients with and without easily occluded vascular access. Our study included two groups of hemodialysis patients. Group 1 consisted of 21 patients who had received chronic hemodialysis therapy for more than 6 months. They had had more than three events (including three) of vascular access failures during the past year. Group 2 consisted of 21 hemodialysis patients with age, sex, and diabetes mellitus matched who had never suffered from any event of vascular access failure. We measured the basal and stimulated platelet [Ca²⁺]_i after stimulation with 1 U/ml thrombin, 1 µM arachidonic acid, 1 µM platelet activation factor (PAF), and 10 µM adenosine diphosphate (ADP), respectively. Our results showed that in Ca²⁺-containing media, there was no significant differences in the basal [Ca²⁺]_i _, but the maximal increases of [Ca²⁺]_i of platelets were higher (p <0.05) in group 1 than in group 2 after stimulating with PAF and ADP, but not with thrombin and arachidonic acid. We concluded that the causes for the susceptibility of some hemodialysis patients to vascular access occlusion were multifactorial. In addition to previously reported plasma factors, there was a subgroup of patients who showed greater elevations of agonists stimulated platelet intracellular calcium levels.

Keywords

Agonists - hemodialysis - intracellular calcium - platelet - vascular access failure

Full Text

References

References
1 Fan PY, Schwab SJ. Vascular access: concepts for the 1990s. J Am Soc Nephrol 1992; 03: 1-11.
2 Windus DW. Permanent vascular access: a nephrologist’s view. Am J Kidney Dis 1993; 21: 457-71.
3 Porile JL, Richter M. Preservation of vascular access. J Am Soc Nephrol 1993; 04: 997-1003.
4 Feldman HI, Kobrin S, Wasserstein A. Hemodialysis vascular access morbidity. J Am Soc Nephrol 1996; 07: 523-35.
5 Mysliwiec M. Vascular access thrombosiswhat are the possibilities of intervention?. Nephrol Dial Transplant 1997; 12: 876-78.
6 Massini P, Luscher EF. On the significance of the influx of calcium ions into stimulated human blood platelets. Biochim Biophys Acta 1976; 436: 652-63.
7 Massini P, Kaser-Glanzmann R, Luscher EF. Movement of calcium ions and their role in the activation of platelets. Thromb Haemost 1978; 40: 212-8.
8 Feinstein MB. Role of Ca2+-ions in the regulation of platelet function. Bibl Haematol 1978; 45: 1-8.
9 Steer ML, Salzman EW. Cyclic nucleotides in hemostasis and thrombosis. Adv Cyclic Nucleotide Res 1980; 12: 71-92.
10 Feinstein MB. The role of calmodulin in hemostasis. Prog Hemost Thromb 1982; 06: 25-61.
11 Zucker MB, Nachmias VT. Platelet activation. Arteriosclerosis 1985; 05: 2-18.
12 Rink TJ. Cytosolic calcium in platelet activation. Experientia 1988; 44: 97-100.
13 Dmoszynska-Giannopoulou A, Krawczyk W. The role of calcium ions and inositol phospholipids in platelet activation Acta Haematol Pol. 1991; 22: 336-45.
14 Geiger J, Nolte C, Butt E. et al. Role of cGMP and cGMP-dependent protein kinase in nitrovasodilator inhibition of agonist-evoked calcium elevation in human platelets. Proc Natl Acad Sci U S A 1992; 89: 1031-5.
15 Jin J, Daniel JL, Kunapuli SP. Molecular Basis for ADP-induced Platelet Activation J Biol Chem. 1998; 273: 2030-4.
16 Hussain JH, Mahaut-Smith MP. Reversible and irreversible intracellular Ca²⁺ spiking in single isolated human platelets. J Physiol 1999; 514: 713-8.
17 Grynkiewicz G, Poenie M, Tsien RY. A new generation of Ca²⁺ indicators with greatly improved fluorescence properties. J Biol Chem 1985; 260: 3440-50.
18 De Marchi S, Falleti E, Giacomello R. et al. Risk factors for vascular disease and arteriovenous fistula dysfunction in hemodialysis patients. J Am Soc Nephrol 1996; 07: 1169-77.
19 Tsien RY. New calcium indicators and buffers with high selectivity against magnesium and protons: Design synthesis and properties of prototype structures. Biochemistry 1980; 19: 2396-404.
20 Rink TJ, Smith SW, Tsien RY. Cytoplasmic free Ca2+ in human platelets: Ca2+ thresholds and Ca-independent activation for shapechange and secretion. FEBS Lett 1982; 148: 21-6.
21 Poenie M, Alderton J, Tsien RY. et al. Changes of free calcium levels with stages of the cell division cycle. Nature 1985; 315: 147-9.
22 Siess W. Molecular mechanisms of platelet activation. Physiological Reviews 1989; 69: 58-178.
23 Tao J, Rose B, Haynes DH. Variability of the thrombin-and ADP-induced Ca2+ response among human platelets measured using fluo-3 and fluorescent videomicroscopy. Biochim Biophys Acta 1996; 1311: 164-74.
24 Shukla SD. Platelet-activating factor receptor and signal transduction mechanisms. FASEB J 1992; 06: 2296-301.
25 Logan JE, Roudebush WE. Platelet-activating factor increases intracellular calcium levels in preimplantation stage embryos. Early Pregnancy 2000; 04: 30-8.
26 Brace LD, Venton DL, Le Breton GC. Thromboxane A2/prostaglandin H2 mobilizes calcium in human blood platelets. Am J Physiol 1985; 249 1 Pt 2 H1-7.
27 Vu TK, Hung DT, Wheaton VI. et al. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell 1991; 64: 1057-68.
28 Ishihara H, Connolly AJ, Zeng D. et al. Protease-activated receptor 3 is a second thrombin receptor in humans. Nature 1997; 386: 502-6.
29 Xu WF, Andersen H, Foster DC. Cloning and characterization of human protease-activated receptor 4. Proc Natl Acad Sci USA 1998; 95: 6642-6.
30 Parise LV, Venton DL, Le Breton GC. Arachidonic acid-induced platelet aggregation is mediated by a thromboxane A2/prostaglandin H2 receptor interaction. J Pharmacol Exp Ther 1984; 228: 240-4.
31 Ishii S, Nagase T, Shimizu T. Platelet-activating factor receptor. Prostaglandins Other Lipid Mediat 2002; 68-69: 599-609.
32 MacKenzie AB, Mahaut-Smith MP, Sage SO. Activation of receptor-operated cation channels via P2X1 not P2T purinoceptors in human platelets. J Biol Chem 1996; 271: 2879-81.
33 Daniel JL, Dangelmaier C, Jin J. et al. Molecular basis for ADP-induced platelet activation. I. Evidence for three distinct ADP receptors on human platelets. J Biol Chem 1998; 273: 2024-9.
34 Schaberg T, Haller H, Lode H. Evidence for a platelet-activating factor receptor on human alveolar macrophages. Biochem Biophys Res Commun 1991; 177: 704-10.
35 Nomura S. Function and clinical significance of platelet-derived microparticles. Int J Hematol 2001; 74: 397-404.
36 Dopheide SM, Yap CL, Jackson SP. Dynamic aspects of platelet adhesion under flow. Clin Exp Pharmacol Physiol 2001; 28: 355-63.