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Effects of Hydroxyethyl Starch and Calcium on Platelet Activation

Nielsen, Vance G. MD

doi: 10.1213/01.ANE.0000149041.17161.FF
Letters to the Editor: Letters & Announcements

Department of Anesthesiology; The University of Alabama at Birmingham; Birmingham, AL;

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To the Editor:

I read with great interest the article by Deusch et al. (1) wherein citrate anticoagulated blood diluted 20% with Hextend® (Abbott Laboratories, Chicago, IL) had greater platelet activation than other hydroxyethyl starch solutions devoid of calcium. Furthermore, blood samples diluted with a 600 kd-containing hydroxyethyl starch solution with addition of calcium equivalent to Hextend® also had an increase in platelet activation. My concern with these results was that blood sample calcium concentrations could be sufficiently increased by Hextend® to initiated thrombin generation. To test this, pooled, citrated control plasma (Trinity Biotech, Ventura, CA) was either undiluted, diluted 20% with 6% hetastarch in 0.9% NaCl (Abbott) or with Hextend® (n = 3 per condition) at room temperature for 5 min prior to calcium determination with an analyzer (model 1306, Instrumentation Laboratory, Lexington, MA). Calcium values were as follows (mM): undiluted = 0.02 ± 0.01, hetastarch = 0.01 ± 0.00, Hextend® = 0.04 ± 0.01. One-way analysis of variance demonstrated that the plasma diluted with Hextend® had a significantly greater calcium concentration than the other fluids. Nevertheless, this concentration is far below the threshold required for thrombin generation. What other mechanism underlying calcium-mediated platelet activation would the authors suggest?

Another issue is the citation by Deusch and colleagues (1) of a study wherein Hextend® administration resulted in enhanced hemostasis assessed by thrombelastography (decreased R time) in a rabbit model of hemorrhagic shock (2). Deusch et al. (1) in their discussion imply that our findings were explained by calcium contained in Hextend®—a conclusion that is not true, as Hextend® decreased endogenous heparinoid release and did not affect blood calcium concentration (2). In fact, there has never been a significant change in blood calcium concentration documented in any of our in vivo rabbit studies involving hemodilution (3,4). However, while 40% dilution with Hextend® did not change R values (3), 75% dilution did significantly decrease R values in rabbits (4).

Vance G. Nielsen, MD

Department of Anesthesiology; The University of Alabama at Birmingham; Birmingham, AL;

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1. Deusch E, Thaler U, Kozek-Langenecker SA. The effects of high molecular weight hydroxyethyl starch solutions on platelets. Anesth Analg 2004;99:665–8.
2. Nielsen VG. Resuscitation with Hextend® decreases endogenous circulating heparin activity and accelerates clot initiation after hemorrhage in the rabbit. Anesth Analg 2001;93:1106–10.
3. McCammon AT, Wright JP, Figueroa M, Nielsen VG. Hemodilution with albumin, but not Hextend®, results in hypercoagulability as assessed by thrombelastography in rabbits: role of heparin-dependent serpins and factor VIII complex. Anesth Analg 2002;95:844–50.
4. Nielsen VG, Baird MS. Extreme hemodilution in rabbits: an in vitro and in vivo thrombelastographic analysis. Anesth Analg 2000;90:541–5.
© 2005 International Anesthesia Research Society