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LETTER TO THE EDITOR

Hydroxyethyl Starch and Risk of Bleeding: The Missing Links

Department of Anesthesiology, Critical Care Medicine, Pain Management, and Hyperbaric Medicine, Englewood Hospital, Englewood, NJ, aryeh.shander{at}ehmc.com

To the Editor:

Arellano et al. (1) compared hydroxyethyl starch (HES) 264/0.45 (Pentaspan®; Bristol-Myers Squibb, St. Laurent, Quebec) to 5% albumin in major reconstructive surgery and raised some interesting points. The authors' well-designed trial falls short because of inherent flaws and skewed randomization. As such, evidence regarding HES and its clinical effect on bleeding is inconclusive.

The effects of HES on platelets, factor VIII activity, and von Willebrand factor are well-defined in vivo (2–4). This study showed a dose-related significant prolongation of activated partial thromboplastin time, international normalized ratio, and reduction in von Willebrand factor A, von Willebrand factor L, and factor VIII activity in the HES group. The poor predictability of these tests for surgical bleeding has been established (5–7). Estimated blood loss and correlation between the worst test results and blood loss or transfusion were absent. No patient required re-exploration for microvascular coagulopathy. Thrombin time, which is negatively affected by albumin, was not assayed for or reported (8,9).

The demographic imbalances between the two groups may explain the increased transfusion rate in the HES group. The larger number of women in the HES group (58% versus 17%; P = 0.003) accounted for the differences in weight (P = 0.0003) and height (P = 0.02) between the groups. Smaller body mass and smaller blood volumes lead to higher transfusion rates. A larger sample could eliminate the gender and transfusion difference. The HES group received 15% more colloid (P = 0.003) and 20 mL/kg more of crystalloid (P = 0.12). This further dilutes clotting factors and increases activated partial thromboplastin time and international normalized ratio. Finally, estimated blood loss and the amount of transfused blood products were not reported.

The concern regarding the effect of starches on coagulation remains in question. The thought that coagulopathy from HES led to bleeding is difficult to conclude from this article. In vitro assessment of both albumin and starch show prolongation of clotting parameters but the clinical impact is unclear. Finally, transfusion of blood products is not an accurate measure of bleeding (10,11). As more information on the effects of colloids on coagulation accrues, condemnation of one product or another based on questionable evidence reduces the limited repertoire of fluids to be used for intravascular volume resuscitation.

References

1. Arellano R, Gan BS, Salpeter MJ, et al. A triple-blinded randomized trial comparing the hemostatic effects of large-dose 10% hydroxyethyl starch 264/0.45 versus 5% albumin during major reconstructive surgery. Anesth Analg 2005;100:1846–53.[Abstract/Free Full Text]
2. Kapiotis S, Quehenberger P, Eichler HG, et al. Effect of hydroxyethyl starch on the activity of blood coagulation and fibrinolysis in healthy volunteers: comparison with albumin. Crit Care Med 1994;22:606–12.[Web of Science][Medline]
3. Claes Y, Van Hemelrijck J, Van Gerven M, et al. Influence of hydroxyethyl starch on coagulation in patients during the perioperative period. Anesth Analg 1992;75:24–30.[Abstract/Free Full Text]
4. Omar MN, Shouk TA, Khaleq MA. Activity of blood coagulation and fibrinolysis during and after hydroxyethyl starch (HES) colloidal volume replacement. Clin Biochem 1999;32:269–74.[Web of Science][Medline]
5. Wahba A, Rothe G, Lodes H, et al. Predictors of blood loss after coronary artery bypass grafting. J Cardiothorac Vasc Anesth 1997;11:824–7.[Medline]
6. Gelb AB, Roth RI, Levin J, et al. Changes in blood coagulation during and following cardiopulmonary bypass: lack of correlation with clinical bleeding. Am J Clin Pathol 1996;106:87–99.[Web of Science][Medline]
7. Gravlee GP, Arora S, Lavender SW et al. Predictive value of blood clotting tests in cardiac surgical patients. Ann Thorac Surg 1994;58:216–21.[Abstract]
8. Galanakis DK, Lane BP, Simon SR. Albumin modulates lateral assembly of fibrin polymers: evidence of enhanced fine fibril formation and of unique synergism with fibrinogen. Biochemistry 1987;26:2389–400.[Medline]
9. Galanakis DK. Anticoagulant albumin fragments that bind to fibrinogen/fibrin: possible implications. Semin Thromb Hemost 1992;18:44–52.[Medline]
10. Ozier Y, Pessione F, Samain E, et al. Institutional variability in transfusion practice for liver transplantation. Anesth Analg. 2003;97:671–9.[Abstract/Free Full Text]
11. Hutton B, Fergusson D, Tinmouth A, et al. Transfusion rates vary significantly amongst Canadian medical centers Can J Anaesth 2005;52:581–90.[Medline]

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