Skip to main content
Log in

RETRACTED ARTICLE: Does long-term continous administration of pentoxifylline affect platelet function in the critically ill patient?

  • Original
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

This article was retracted on 19 June 2023

This article has been updated

Abstract

Objective

The methylxanthine derivative pentoxifylline (PTX) is one of those promising substances which are under current investigation to modify or limit inflammatory response. Antiaggregation activity has also been described that may contribute to the beneficial effects of this substance. Long-term effects on platelet function have not been elucidated yet.

Design

Prospective, randomized study.

Setting

Clinical investigation on a surgical intensive care unit of a university hospital.

Patients

26 trauma patients and 26 patients suffering from sepsis secondary to major operations were consecutively studied.

Interventions

The patients prospectively received either 1.5 mg/kg per h pentoxifylline continuously for 5 days (after a loading dose of 600 mg) (trauma-PTX,n=13; sepsis-PTX,n=13) or saline solution as placebo (trauma-control;n=13; sepsis-control,n=13).

Measurements

On the day of admission (trauma patients) or day of the diagnosis of sepsis and at 12:00 p.m. during the next 5 days, platelet aggregation induced by adenosine diphosphate (ADP 2.0 μmol/l), collagen (4 μl/ml), and epinephrine (25 μmol/l) was determined by a turbidimetric method from arterial blood samples. Standard coagulation screen was also monitored.

Main results

In untreated trauma and sepsis patients, maximum platelet aggregation induced by all three agonists decreased during the first few days after inclusion in the study [trauma: ADP −17.1±8.0 rel% (% change from baseline); sepsis: ADP −26.1±5.6 rel%]. In due course, maximum platelet aggregation recovered, reaching the baseline value or even exceeding it (trauma patients). In the PTX-treated patients, platelet aggregation was significantly less impaired (sepsis group: ADP −4.4±3.3 rel%) or even increased beyond baseline values in the first few days of the study (trauma group: ADP 16.1±8.0 rel%). Fibrinogen plasma levels were lower in the non-treated control groups (p<0.05) than in the PTX groups.

Conclusions

Continuous infusion of PTX for 5 days did not impair platelet function in critically ill patients. In both trauma and sepsis patients, the usual deterioration in platelet function was even attenuated, which may be due to the effects of PTX on cytokine release (e.g., reduction in tumor necrosis factor and interleukin-1), improvement in microcirculation, or additional fibrinolytic effects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Change history

References

  1. Bick RL (1992) Platelet function defects: a clinical review. Sem Thromb Hemost 18:167–185

    Article  CAS  Google Scholar 

  2. Fourrier F, Chopin C, Goudemand J, Hendrycx S, Caron C, Rime A, Marey A, Lestavel P (1992) Septic shock, multiple organ failure, and disseminated intravascular coagulation. Chest 101:816–823

    Article  CAS  PubMed  Google Scholar 

  3. Hines R (1989) Infusion of sodium nitroprusside induces platelet dysfunction in vitro. Anesthesiology 70:611–615

    Article  CAS  PubMed  Google Scholar 

  4. Weiss HJ (1982) Antiplatelet drugs: pharmacological aspects. In: Weiss HJ (ed) Platelets: pathophysiology and antiplatelet drug therapy. Liss, New York, pp 45–58

    Google Scholar 

  5. Campbell FW, Addonizio VP Jr (1988) Platelet function alterations during cardiac surgery. In: Ellison N, Jobes DR (eds) Effective hemostasis in cardiac surgery. Saunders, Philadelphia, pp 85–109

    Google Scholar 

  6. Suffredini AF (1994) Current prospects for the treatment of clinical sepsis. Crit Care Med 22:S 12-S 18

    CAS  Google Scholar 

  7. Schade UF (1990) Pentoxifylline increases survival in murine endotoxin shock and decreases formation of tumor necrosis factor. Circ Shock 31:171–181

    CAS  PubMed  Google Scholar 

  8. Coccia MT, Waxman K, Soliman MH, Tominaga G, Pindereski L (1989) Pentoxifylline improves survival following hemorrhagic shock. Crit Care Med 17:36–38

    Article  CAS  PubMed  Google Scholar 

  9. Sato K, Stelzner TJ, O'Brien RF, Weil JV, Welsh CH (1991) Pentoxifylline lessens the endotoxin-induced increase in albumin clearance across pulmonary artery endothelial monolayers with and without neutrophils. Am J Respir Cell Mol Biol 4:219–227

    Article  CAS  PubMed  Google Scholar 

  10. Sullivan GW, Carper HT, Novick WJ, Mandell GL (1988) Inhibition of the inflammatory action of interleukin-1 and tumor necrosis factor (alpha) on neutrophil function by pentoxifylline. Infect Immun 56:1722–1729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Josaki K, Contrino J, Kristie J, Krause P, Kreutzer DL (1990) Pentoxifyllineinduced modulation of human leukocyte function in vitro. Am J Pathol 136:623–630

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Ward A, Clissold SP (1987) Pentoxifylline — a review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic efficacy. Drugs 34:50–97

    Article  CAS  PubMed  Google Scholar 

  13. Lapetina EG, Schitges A, Chandrabose K (1977) Cyclic adenosine 3′5′-monophosphatase and prostacyclin inhibit membrane phospholipase activity in platelets. Biochem Biophys Res Commun 14:39–50

    Google Scholar 

  14. Kaser-Glanzmann R, Jakabova M, George JN, Luscher EF (1977) Stimulation of calcium uptake in platelet membrane vesicles by adenosine 3′5′-monophosphate and protein kinase. Biochim Biophys Acta 466:429–440

    Article  CAS  PubMed  Google Scholar 

  15. Baker SP, O'Neill B (1976) The injury severity score: an update. J Trauma 16:882–888

    Article  CAS  PubMed  Google Scholar 

  16. Members of the American College of Chest Physicians/Society of Critical Care Medicine Conference Committee (1992) American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20:864–874

    Article  Google Scholar 

  17. Born GVR (1962) Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 194:927–929

    Article  CAS  PubMed  Google Scholar 

  18. Bone RC (1992) Sepsis and coagulation. An important link. Chest 101:594–595

    Article  CAS  PubMed  Google Scholar 

  19. Weithmann KU (1983) Reduced platelet aggregation by effects of pentoxifylline on vascular prostacyclin isomerase and platelet cyclic AMP. Gen Pharmacol 14:161–162

    Article  CAS  PubMed  Google Scholar 

  20. Hammerschmidt DE, Vercellotti GM (1987) Mechanism of action of pentoxifylline (PTX) in peripheral vascular disease: inhibition of platelet and granulocyte responsiveness. Clin Hemorheol 7:529–533

    Google Scholar 

  21. Schönharting M, Musikic P, Müller R (1988) The hemorheological and antithrombotic potential of pentoxifylline (Trental). Pharmatherapeutica 5:159–169

    PubMed  Google Scholar 

  22. Levi M, ten Cate, Bauer KA, van der Poll, Edgington TS, Buller HR, van Deventer SJ, Hack CE, ten Cate JW, Rosenberg RD (1994) Inhibition of endotoxin-induced activation of coagulation and fibrinolysis by pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees. J Clin Invest 93:114–120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gordon JL (1985) Endothelium as a modulator of platelet reactivity. Adv Exp Med Biol 192:419–425

    Article  CAS  PubMed  Google Scholar 

  24. Noel P, Nelson S, Bokulic R (1989) Pentoxifylline inhibits lipopolysaccharideinduced serum tumor necrosis factor and mortality. Am Rev Resp Dis 139:A222

    Google Scholar 

  25. Lechner AJ, Rouben LR, Potthoff LH, Tredway TL, Matuschak GM (1993) Effects of pentoxifylline on tumor necrosis production and survival during lethalE. coli sepsis vs. disseminated candidiasis with fungal septic shock. Circ Shock 39:306–315

    CAS  PubMed  Google Scholar 

  26. Toung T, Kirsch J, Maruki Y, Traystman RJ (1994) Effects of pentoxifylline on cerebral blood flow, metabolism, and evoked response after total cerebral ischemia in dogs. Crit Care Med 22:273–281

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

About this article

Cite this article

Boldt, J., Müller, M., Heesen, M. et al. RETRACTED ARTICLE: Does long-term continous administration of pentoxifylline affect platelet function in the critically ill patient?. Intensive Care Med 22, 644–650 (1996). https://doi.org/10.1007/BF01709740

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01709740

Key words

Navigation