Semin Thromb Hemost 2007; 33(8): 810-815
DOI: 10.1055/s-2007-1000370
© Thieme Medical Publishers

Clinical Relevance of the Effects of Plasma Expanders on Coagulation

Marcel Levi1 , Evert de Jonge2
  • 1Department of Vascular Medicine/Internal Medicine, Amsterdam, The Netherlands
  • 2Department of Intensive Care, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
Further Information

Publication History

Publication Date:
04 January 2008 (online)

ABSTRACT

Patients with severe bleeding are often treated with colloids as plasma replacement fluids, including dextrans, gelatin-based solutions, or starches. Many of these agents will affect the hemostatic system beyond their effect on hemodilution. Obviously, the ensuing impairment of coagulation is not desirable in patients with major blood loss. However, there is considerable controversy whether the anticoagulant effects of the various compounds will truly translate into clinically relevant effects, such as increased blood loss or, even more importantly, transfusion requirements, the need for surgical (re) exploration, organ dysfunction, or mortality. In this overview, we discuss the effects of various plasma replacement solutions on the coagulation system and review the controlled clinical studies with different plasma expanders on clinically significant end points. We conclude that most plasma expanders have indeed marked effects at various points in the hemostatic system and that there are significant differences between various plasma replacement fluids but that clinically relevant effects on bleeding are mostly present if large volumes (i.e., > 1.5 L) are infused or if the patient has a concomitant or preexistent hemostatic impairment.

REFERENCES

  • 1 de Jonge E, Levi M. Effects of different plasma substitutes on blood coagulation: a comparative review.  Crit Care Med. 2001;  29 1261-1267
  • 2 Marik P E, Iglesias J. Would the colloid detractors please sit down!.  Crit Care Med. 2000;  28 2652-2654
  • 3 Choi P T, Yip G, Quinonez L G, Cook D J. Crystalloids vs. colloids in fluid resuscitation: a systematic review.  Crit Care Med. 1999;  27 200-210
  • 4 Treib J, Baron J F, Grauer M T, Strauss R G. An international view of hydroxyethyl starches.  Intensive Care Med. 1999;  25 258-268
  • 5 Salmon J B, Mythen M G. Pharmacology and physiology of colloids.  Blood Rev. 1993;  7 114-120
  • 6 Lundsgaard-Hansen P, Tschirren B. Clinical experience with 120,000 units of modified fluid gelatin.  Dev Biol Stand. 1980;  48 251-256
  • 7 Mardel S N, Saunders F M, Allen H et al.. Reduced quality of clot formation with gelatin-based plasma substitutes.  Br J Anaesth. 1998;  80 204-207
  • 8 Ruttmann T G, James M F, Viljoen J F. Haemodilution induces a hypercoagulable state.  Br J Anaesth. 1996;  76 412-414
  • 9 Tabuchi N, de Haan J, Gallandat Huet R C, Boonstra P W, van Oeveren W. Gelatin use impairs platelet adhesion during cardiac surgery.  Thromb Haemost. 1995;  74 1447-1451
  • 10 de Jonge E, Levi M, Berends F et al.. Impaired haemostasis by intravenous administration of a gelatin-based plasma expander in human subjects.  Thromb Haemost. 1998;  79 286-290
  • 11 Clagett G P, Anderson Jr F A, Heit J, Levine M, Wheeler H B. Prevention of venous thromboembolism.  Chest. 1995;  108 312S-334S
  • 12 Batlle J, del Rio F, Lopez Fernandez M F, Martin R, Lopez B A. Effect of dextran on factor VIII/von Willebrand factor structure and function.  Thromb Haemost. 1985;  54 697-699
  • 13 Zhang B, Wieslander J B. Dextran's antithrombotic properties in small arteries are not altered by low-molecular-weight heparin or the fibrinolytic inhibitor tranexamic acid: an experimental study.  Microsurgery. 1993;  14 289-295
  • 14 Bergman A, Andreen M, Blomback M. Plasma substitution with 3% dextran-60 in orthopaedic surgery: influence on plasma colloid osmotic pressure, coagulation parameters, immunoglobulins and other plasma constituents.  Acta Anaesthesiol Scand. 1990;  34 21-29
  • 15 Lethagen S, Rugarn P, Aberg M, Nilsson I M. Effects of desmopressin acetate (DDAVP) and dextran on hemostatic and thromboprophylactic mechanisms.  Acta Chir Scand. 1990;  156 597-602
  • 16 Eriksson M, Saldeen T. Effect of dextran on plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) during surgery.  Acta Anaesthesiol Scand. 1995;  39 163-166
  • 17 Carr M E, Gabriel D A. The effect of dextran 70 on the structure of plasma-derived fibrin gels.  J Lab Clin Med. 1980;  96 985-993
  • 18 Dalrymple-Hay M, Aitchison R, Collins P, Sekhar M, Colvin B. Hydroxyethyl starch induced acquired von Willebrand's disease.  Clin Lab Haematol. 1992;  14 209-211
  • 19 Damon L, Adams M, Stricker R B, Ries C. Intracranial bleeding during treatment with hydroxyethyl starch.  N Engl J Med. 1987;  317 964-965
  • 20 Cope J T, Banks D, Mauney M C et al.. Intraoperative hetastarch infusion impairs hemostasis after cardiac operations.  Ann Thorac Surg. 1997;  63 78-82
  • 21 Stump D C, Strauss R G, Henriksen R A, Petersen R E, Saunders R. Effects of hydroxyethyl starch on blood coagulation, particularly factor VIII.  Transfusion. 1985;  25 349-354
  • 22 Kapiotis S, Quehenberger P, Eichler H G et al.. Effect of hydroxyethyl starch on the activity of blood coagulation and fibrinolysis in healthy volunteers: comparison with albumin.  Crit Care Med. 1994;  22 606-612
  • 23 Thyes C, Madjdpour C, Frascarolo P et al.. Effect of high- and low-molecular-weight low-substituted hydroxyethyl starch on blood coagulation during acute normovolemic hemodilution in pigs.  Anesthesiology. 2006;  105 1228-1237
  • 24 Tigchelaar I, Gallandat Huet R C, Korsten J, Boonstra P W, van Oeveren W. Hemostatic effects of three colloid plasma substitutes for priming solution in cardiopulmonary bypass.  Eur J Cardiothorac Surg. 1997;  11 626-632
  • 25 Treib J, Haass A, Pindur G et al.. All medium starches are not the same: influence of the degree of hydroxyethyl substitution of hydroxyethyl starch on plasma volume, hemorrheologic conditions, and coagulation.  Transfusion. 1996;  36 450-455
  • 26 de Jonge E, Levi M, Buller R, Berends F, Kesecioglu J. Decreased circulating levels of von Willebrand factor after intravenous administration of a rapidly degradable hydroxyethyl starch (HES 200/0.5/6) in healthy human subjects.  Intensive Care Med. 2001;  27 1825-1829
  • 27 Rackow E C, Mecher C, Astiz M E et al.. Effects of pentastarch and albumin infusion on cardiorespiratory function and coagulation in patients with severe sepsis and systemic hypoperfusion.  Crit Care Med. 1989;  17 394-398
  • 28 Strauss R G, Stump D C, Henriksen R A, Saunders R. Effects of hydroxyethyl starch on fibrinogen, fibrin clot formation, and fibrinolysis.  Transfusion. 1985;  25 230-234
  • 29 Ruttmann T G, James M F, Aronson I. In vivo investigation into the effects of haemodilution with hydroxyethyl starch (200/0.5) and normal saline on coagulation.  Br J Anaesth. 1998;  80 612-616
  • 30 Nielsen V G. High-molecular-weight hydroxyethyl starch accelerates kallikrein-dependent clot initiation.  J Trauma. 2007;  62 1491-1494
  • 31 Egli G A, Zollinger A, Seifert B et al.. Effect of progressive haemodilution with hydroxyethyl starch, gelatin and albumin on blood coagulation.  Br J Anaesth. 1997;  78 684-689
  • 32 Gandhi S D, Weiskopf R B, Jungheinrich C et al.. Volume replacement therapy during major orthopedic surgery using Voluven (hydroxyethyl starch 130/0.4) or hetastarch.  Anesthesiology. 2007;  106 1120-1127
  • 33 Boldt J, Muller M, Heesen M, Heyn O, Hempelmann G. Influence of different volume therapies on platelet function in the critically ill.  Intensive Care Med. 1996;  22 1075-1081
  • 34 Brummel-Ziedins K, Whelihan M F, Ziedins E G, Mann K G. The resuscitative fluid you choose may potentiate bleeding.  J Trauma. 2006;  61 1350-1358
  • 35 Hjertberg H, Olsson J, Ekstrom T, Lisander B. Do low molecular weight heparin and dextran increase the blood loss in transurethral resection of the prostate?.  Br J Urol. 1996;  78 897-900
  • 36 Bergqvist D, Kettunen K, Fredin H et al.. Thromboprophylaxis in patients with hip fractures: a prospective, randomized, comparative study between Org 10172 and dextran 70.  Surgery. 1991;  109 617-622
  • 37 Lisander B, Jacobsson S A, Ivarsson I, Vegfors M, Engdahl O. Giving both enoxaparin and dextran increases the need for transfusion in revision hip arthroplasty.  Eur J Surg. 1996;  162 861-866
  • 38 Boldt J, Knothe C, Zickmann B et al.. Influence of different intravascular volume therapies on platelet function in patients undergoing cardiopulmonary bypass.  Anesth Analg. 1993;  76 1185-1190
  • 39 Niemi T T, Suojaranta-Ylinen R T, Kukkonen S I, Kuitunen A H. Gelatin and hydroxyethyl starch, but not albumin, impair hemostasis after cardiac surgery.  Anesth Analg. 2006;  102 998-1006
  • 40 Boldt J, Scholhorn T, Mayer J, Piper S, Suttner S. The value of an albumin-based intravascular volume replacement strategy in elderly patients undergoing major abdominal surgery.  Anesth Analg. 2006;  103 191-199
  • 41 Mortelmans Y J, Vermaut G, Verbruggen A M et al.. Effects of 6% hydroxyethyl starch and 3% modified fluid gelatin on intravascular volume and coagulation during intraoperative hemodilution.  Anesth Analg. 1995;  81 1235-1242
  • 42 Arellano R, Gan B S, Salpeter M J 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 1846-1853

Marcel LeviM.D. 

Department of Internal Medicine, Academic Medical Centre F-4

Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

Email: m.m.levi@amc.uva.nl

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