Download PDF
Thromb Haemost 1999; 81(04): 613-617
DOI: 10.1055/s-0037-1614534
Rapid Communication
Schattauer GmbH

Effects of Endotoxemia on Thrombopoiesis in Men

Petra Stohlawetz
2   Clinic of Blood Group Serology and Transfusion Medicine, Transfusion Medicine, Vienna University School of Medicine, Vienna, Austria
,
Claudia C. Folman
3   Department of Hematology, Div. of Internal Medicine Academic Medical Center, University of Amsterdam, Central Laboratory of Experimental and Clinical Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
Albert E. G. Kr. von dem Borne
3   Department of Hematology, Div. of Internal Medicine Academic Medical Center, University of Amsterdam, Central Laboratory of Experimental and Clinical Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
Thomas Pernerstorfer
1   From the Departments of Clinical Pharmacology, the Adhesion Research Group Elaborating Therapeutics, Vienna, Austria
,
Hans-Georg Eichler
3   Department of Hematology, Div. of Internal Medicine Academic Medical Center, University of Amsterdam, Central Laboratory of Experimental and Clinical Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
Simon Panzer
2   Clinic of Blood Group Serology and Transfusion Medicine, Transfusion Medicine, Vienna University School of Medicine, Vienna, Austria
,
Bernd Jilma
1   From the Departments of Clinical Pharmacology, the Adhesion Research Group Elaborating Therapeutics, Vienna, Austria
› Author AffiliationsThis work was supported by a grant from the Kamillo-Eisner-Stiftung, CH.
Further Information

Publication History

Received 22 September 1998

Accepted after revision 05 January 1999

Publication Date:
09 December 2017 (online)

    Permissions and Reprints

Summary

Background. Febrile conditions are often associated with increased platelet turnover and refractoriness to platelet transfusions, although several pyrogenic cytokines enhance thrombopoiesis. This study aimed to characterize the effects of experimental human endotoxemia on platelet turnover and thrombopoiesis. Methods. Endotoxin (4 ng/kg) was infused into 30 healthy men to study the regulation of thrombopoiesis in systemic human inflammation. Platelet counts, plasma thrombopoietin (TPO) and glycocalicin levels, and reticulated platelets (RP) were measured to evaluate the effect of acute endotoxemia on thrombopoiesis. Ten subjects received pretreatment with 1000 mg aspirin po. to evaluate possible effects of aspirin on platelet turnover, and ten subjects received paracetamol to control for effects of anti-pyresis. Results. Platelet counts dropped by about 15% (p <0.001) one hour after LPS infusion, began to recover at 24 h, and exceeded baseline values by 8% (CI: 5-12; p <0.001) at 7 days after LPS iv. Reticulated platelet counts increased from 1.62% (CI: 1.24-2.0) to a maximum of 2.39% (CI: 1.81-2.98; p = 0.003) at 6 h. TPO levels increased from baseline values of 10 A.U/ml (CI: 8.8-11.2) to 15.5 A.U/ml (CI: 13.6-17.3) at 24 h (p <0.001), whereas plasma glycocalicin was not changed (p >0.05). The number of circulating platelet-neutrophil aggregates increased more than 100% at 6 h (p <0.001). Neither aspirin nor paracetamol affected changes in any of the parameters measured. Conclusion. Low grade endotoxemia induces a rapid fall of platelet counts, which is followed by an early increase in reticulated platelets and TPO levels but not of glycocalicin levels. Finally peripheral platelet counts increase several days after LPS infusion.

 

  • References

  • 1 Nagata Y, Shozaki Y, Nagahisa H, Nagasawa T, Abe T, Todokoro K. Serum thrombopoietin level is not regulated by transcription but by the total counts of both megakaryocytes and platelets during thrombocytopenia and thrombocytosis. Thromb Haemost 1997; 77: 808-14.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Gewirtz AM. Megakaryocytopoiesis: the state of the art. Thromb Haemost 1995; 74: 204-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Burstein SA. Cytokines, platelet production and hemostasis. Platelets 1997; 8: 93-104.
    CrossrefPubMedGoogle Scholar
  • 4 Vainchenker W, Methia N, Debili N, Titeux M, Wendling F. c-mpl, the thrombopoietin receptor. Thromb Haemost 1995; 74: 526-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Gurney AL, Carver Moore K, de Sauvage FJ, Moore MW. Thrombocytopenia in c-mpl-deficient mice. Science 1994; 265: 1445-7.
    CrossrefPubMedGoogle Scholar
  • 6 Sheridan WP, Choi E, Toombs CF, Nichol J, Fanucchi M, Basser I R. Biology of thrombopoiesis and the role of Mpl ligand in the production and function of platelets. Platelets 1997; 8: 319-32.
    CrossrefPubMedGoogle Scholar
  • 7 Schrezenmeier H, Marsh JC, Stromeyer P, Muller H, Heimpel H, Gordon-Smith EC, Raghavachar A. A phase I/II trial of recombinant human interleukin-6 in patients with aplastic anemia. Br J Haematol 1995; 90: 283-92.
    CrossrefPubMedGoogle Scholar
  • 8 Pettengell R, Luft T, de Wynter E, Coutinho L, Young R, Fitzsimmons L, Scarffe JH, Testa NG. Effects of interleukin-6 on mobilization of primitive haemopoietic cells into the circulation. Br J Haematol 1995; 89: 237-42.
    CrossrefPubMedGoogle Scholar
  • 9 Hollen CW, Henthorn J, Koziol JA, Burstein SA. Elevated serum interleukin-6 levels in patients with reactive thrombocytosis. Br J Haematol 1991; 79: 286-90.
    CrossrefPubMedGoogle Scholar
  • 10 Ishiguro A, Ishikita T, Shimbo T, Matsubara K, Baba K, Hayashi Y, Naritaka S, Nakahata T. Elevation of serum thrombopoietin precedes thrombocytosis in Kawasaki disease. Thromb Haemost 1998; 79: 1096-100.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Gastl G, Plante M, Finstad CL, Wong GY, Federici MG, Bander NH, Rubin SC. High IL-6 levels in ascitic fluid correlate with reactive thrombocytosis in patients with epithelial ovarian cancer. Br J Haematol 1993; 83: 433-41.
    CrossrefPubMedGoogle Scholar
  • 12 Michelmann I, Bockmann D, Nurnberger W, Eckhof Donovan S, Burdach S, Gobel U. Thrombocytopenia and complement activation under recombinant TNF alpha/IFN gamma therapy in man. Ann Hematol 1997; 74: 179-84.
    CrossrefPubMedGoogle Scholar
  • 13 Alcorta I, Pereira A, Ordinas A. Clinical and laboratory factors associated with platelet transfusion refractoriness: a case-control study. Br J Haematol 1996; 93: 220-4.
    CrossrefPubMedGoogle Scholar
  • 14 Martich GD, Boujoukos AJ, Suffredini AF. Response of man to endotoxin. Immunobiology 1993; 187: 403-16.
    CrossrefPubMedGoogle Scholar
  • 15 Harrison P, Robinson MSC, Mackie IJ, Machin SJ. Reticulated platelets. Platelets 1997; 8: 319-22.
    CrossrefPubMedGoogle Scholar
  • 16 Jilma B, Blann AD, Pernerstorfer T, Stohlawetz P, Eichler HG, Vondrovec B, Amiral J, Richter V, Wagner OF. Regulation of adhesion molecules during human endotoxemia: no acute effects of aspirin. Am J Respir Crit Care Med 1999: 159 in press.
    PubMedGoogle Scholar
  • 17 Jilma B, Voltmann J, Albinni S, Stohlawetz P, Schwarzinger I, Gleiter CH, Rauch A, Eichler HG, Wagner OF. Dexamethasone down-regulates the expression of L-selectin on the surface of neutrophils and lymphocytes in humans. Clin Pharmacol Ther 1997; 62: 562-8.
    CrossrefPubMedGoogle Scholar
  • 18 Folman CC, von dem Borne AE, Rensink IH, Gerritsen W, van der Schoot CE, de Haas M, Aarden L. Sensitive measurement of thrombopoietin by amonoclonal antibody based sandwich enzyme-linked immunosorbent assay. Thromb Haemost 1997; 78: 1262-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Porcelijn J, Folman CC, Bossers B, Huiskes E, Overbeeke MAM, vd Schoot CE, de Haas M, von dem Borne AEGK. The diagnostic value of thrombopoietin level measurements in thrombocytopenia. Thromb Haemost 1998; 79: 1101-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Jilma B, Dirnberger E, Löscher I, Rumplmayr A, Hildebrandt J, Eichler HG, Kapiotis S, Wagner OF. Menstrual cycle associated changes in blood levels of interleukin-6, a1 acid glycoprotein, and C-reactive protein. J Lab Clin Med 1997; 130: 69-75.
    CrossrefPubMedGoogle Scholar
  • 21 Kapiotis S, Jilma B, Pernerstorfer T, Stohlawetz P, Eichler HG, Speiser W. Plasma levels of activated Factor VII are higher in young men than in premenopausal women and decrease during the menstrual cycle. Thromb Haemost 1998; 80: 588-91.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 van der Poll T, Coyle SM, Levi M, Jansen PM, Dentener M, Barbosa K, Buurman WA, Hack CE, ten Cate JW, Agosti JM. et al Effect of a recombinant dimeric tumor necrosis factor receptor on inflammatory responses to intravenous endotoxin in normal humans. Blood 1997; 89: 3727-34.
    PubMedGoogle Scholar
  • 23 Stohlawetz P, Stiegler G, Jilma B, Dettke M, Höcker P, Panzer S. Measurement of the levels of reticulated platelets after plateletpheresis to monitor activity of thrombopoiesis. Transfusion 1998; 38: 454-8.
    CrossrefPubMedGoogle Scholar
  • 24 Stiegler G, Stohlawetz P, Jilma B, Brugger S, Vierhapper H, Höcker P, Panzer S. Elevated numbers of reticulated platelets in hyperthyroidism: direct evidence for an increase of thrombopoiesis. Br J Haematol 1998; 101: 656-8.
    CrossrefPubMedGoogle Scholar
  • 25 Schmitz G, Rothe G, Ruf A, Barlage S, Tschöpe D, Clemetson KJ, Goodall AL, Michelson AD, Nurden AT, Shankey TV. European Working Group on Clinical Cell Analysis: Consensus protocol for the flow cytometric characterisation of platelet function. Thromb Haemost 1998; 79: 885-96.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Ault KA, Rinder HM, Mitchell J, Carmody MB, Vary CP, Hillman RS. The significance of platelets with increased RNA content (reticulated platelets). A measure of the rate of thrombopoiesis. Am J Clin Pathol 1992; 98: 637-46.
    CrossrefPubMedGoogle Scholar
  • 27 Gawaz M, Fateh Moghadam S, Pilz G, Gurland HJ, Werdan K. Platelet activation and interaction with leucocytes in patients with sepsis or multiple organ failure. Eur J Clin Invest 1995; 25: 843-51.
    CrossrefPubMedGoogle Scholar
  • 28 DeLa Cadena RA, Majluf-Cruz A, Stadnicki A, Tropea M, Reda D, Agosti JM, Colman RW, Suffredini AF. Recombinant tumor necrosis factor receptor p75 fusion protein (TNFR:Fc) alters endotoxin-induced activation of the kinin, fibrinolytic and coagulation systems in normal humans. Thromb Haemost 1998; 114-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Drake TA, Cheng J, Chang A, Taylor , Jr FB. Expression of tissue factor, thrombomodulin, and E-selectin in baboons with lethal Escherichia coli sepsis. Am J Pathol 1993; 142: 1458-70.
    PubMedGoogle Scholar
  • 30 Celi A, Lorenzet R, Furie B, Furie BC. Platelet-leukocyte-endothelial cell interaction on the blood vessel wall. Semin Hematol 1997; 34: 327-35.
    PubMedGoogle Scholar
  • 31 Ault KA, Knowles C. In vivo biotinylation demonstrates that reticulated platelets are the youngest platelets in circulation. Exp Hematol 1995; 23: 996-1001.
    PubMedGoogle Scholar
  • 32 Watanabe K, Takeuchi K, Kawai Y, Ikeda Y, Kubota F, Nakamoto H. Automated measurement of reticulated platelets in estimating thrombopoiesis. Eur J Haematol 1995; 54: 163-71.
    PubMedGoogle Scholar
  • 33 Richards EM, Baglin TP. Quantitation of reticulated platelets: methodology and clinical application. Br J Haematol 1995; 91: 445-51.
    CrossrefPubMedGoogle Scholar
  • 34 Begley CG. Clinical studies with megakaryocyte growth and development factor. Thromb Haemost 1997; 78: 42-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 35 Cohen Solal K, Debili N, Vainchenker W, Wendling F. Thrombopoietin (Mpl-ligand) and the regulation of platelet production. Thromb Haemost 1997; 78: 37-41.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 36 Peng J, Friese P, Wolf RF, Harrison P, Downs T, Lok S, Dale GL, Burstein SA. Relative reactivity of platelets from thrombopoietin- and interleukin-6-treated dogs. Blood 1996; 87: 4158-63.
    PubMedGoogle Scholar
  • 37 Mukai HY, Kojima H, Todokoro K, Tahara T, Kato T, Hasegawa Y, Kobayashi T, Ninomiya H, Nagasawa T, Abe T. Serum thrombopoietin (TPO) levels in patients with amegakaryocytic thrombocytopenia are much higher than those with immune thrombocytopenic purpura. Thromb Haemost 1996; 76: 675-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 38 Schrezenmeier H, Griesshammer M, Hornkohl A, Nichol JL, Hecht T, Heimpel H, Kubanek B, Raghavachar A. Thrombopoietin serum levels in patients with aplastic anaemia: correlation with platelet count and persistent elevation in remission. Br J Haematol 1998; 100: 571-6.
    CrossrefPubMedGoogle Scholar
  • 39 Folman CC, Linthorst GE, Levi M, deJonge E, vd Schoot CE, de Haas M, von dem Borne AEGK. Thrombopoietin release by activated platelets; implications for platelet disorders. Blood 1998; 92: 3255A
    PubMedGoogle Scholar
  • 40 Hiyoyama K, Wada H, Shimura T, Nakasaki T, Katayama N, Nishikawa M, Shiku H, Tahara T, Kato T. Increased serum levels of thrombopoietin in patients with thrombotic thrombocytopenic purpura, idiopathic thrombocytopenic purpura, or disseminated intravascular coagulation. Blood Coagul Fibrinolysis 1997; 8: 345-9.
    CrossrefPubMedGoogle Scholar
  • 41 Steinberg MH, Kelton JG, Coller BS. Plasma glycocalicin: an aid in the classification of thrombocytopenic disorders. N Engl J Med 1987; 317: 1037-42.
    CrossrefPubMedGoogle Scholar
  • 42 Oleksowicz L, Mrowiec Z, Zuckerman D, Isaacs R, Dutcher J, Puszkin E. Platelet activation induced by interleukin-6: evidence for a mechanism involving arachidonic acid metabolism. Thromb Haemost 1994; 72: 302-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 43 Osnes LT, Foss KB, Joo GB, Okkenhaug C, Westvik AB, Ovstebo R, Kierulf P. Acetylsalicylic acid and sodium salicylate inhibit LPS-induced NF-kappa B/c-Rel nuclear translocation, and synthesis of tissue factor (TF) and tumor necrosis factor alfa (TNF-alpha) in human monocytes. Thromb Haemost 1996; 76: 970-6.
    Article in Thieme ConnectPubMedGoogle Scholar