Diabetes does not influence activation of coagulation, fibrinolysis or anticoagulant pathways in Gram-negative sepsis (melioidosis)

Gavin C. K. W Koh; Joost C. M. Meijers; Rapeephan R. Maude; Direk Limmathurotsakul; Nicholas P. J. Day; Sharon J. Peacock; Tom van der Poll; Willem J. Wiersinga

doi:10.1160/TH11-07-0504

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2011; 106(06): 1139-1148
DOI: 10.1160/TH11-07-0504

Wound Healing and Inflammation/Infection

Schattauer GmbH

Diabetes does not influence activation of coagulation, fibrinolysis or anticoagulant pathways in Gram-negative sepsis (melioidosis)

Authors

Gavin C. K. W Koh

¹Center for Experimental and Molecular Medicine, Department of Infectious Diseases, Tropical Medicine & AIDS, Academic Medical Center, Amsterdam, The Netherlands

²Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

³Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK

⁴Department of Infection and Tropical Medicine, Heartlands Hospital, Birmingham, UK

⁵Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
Joost C. M. Meijers

⁶Departments of Experimental Vascular Medicine and of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
Rapeephan R. Maude

²Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
Direk Limmathurotsakul

²Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
Nicholas P. J. Day

²Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

⁷The Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Churchill Hospital, Oxford, UK
Sharon J. Peacock

²Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

³Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK

⁵Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
Tom van der Poll

¹Center for Experimental and Molecular Medicine, Department of Infectious Diseases, Tropical Medicine & AIDS, Academic Medical Center, Amsterdam, The Netherlands
Willem J. Wiersinga

¹Center for Experimental and Molecular Medicine, Department of Infectious Diseases, Tropical Medicine & AIDS, Academic Medical Center, Amsterdam, The Netherlands

Abstract

Summary

Diabetes is associated with a disturbance of the haemostatic balance and is an important risk factor for sepsis, but the influence of diabetes on the pathogenesis of sepsis remains unclear. Melioidosis (Burkholderia pseudomallei infection) is a common cause of community-acquired sepsis in Southeast Asia and northern Australia. We sought to investigate the impact of pre-existing diabetes on the coagulation and fibrinolytic systems during sepsis caused by B. pseudomallei. We recruited a cohort of 44 patients (34 with diabetes and 10 without diabetes) with culture-proven melioidosis. Diabetes was defined as a pre-admission diagnosis of diabetes or an HbA_1c>7.8% at enrolment. Thirty healthy blood donors and 52 otherwise healthy diabetes patients served as controls. Citrated plasma was collected from all subjects; additionally in melioidosis patients follow-up specimens were collected seven and ≥28 days after enrolment where possible. Relative to uninfected healthy controls, diabetes per se (i.e. in the absence of infection) was Characterised by a procoagulant effect. Melioidosis was associated with activation of coagulation (thrombin-antithrombin complexes (TAT), prothrombin fragment F₁₊₂ and fibrinogen concentrations were elevated; PT and PTT prolonged), suppression of anti-coagulation (antithrombin, protein C, total and free protein S levels were depressed) and abnormalities of fibrinolysis (D-dimer and plasmin-antiplasmin complex [PAP] were elevated). Remarkably, none of these haemostatic alterations were influenced by pre-existing diabetes. In conclusion, although diabetes is associated with multiple abnormalities of coagulation, anticoagulation and fibrinolysis, these changes are not detectable when superimposed on the background of larger abnormalities attributable to B. pseudomallei sepsis.

Keywords

Diabetes mellitus - Burkholderia pseudomallei - melioidosis - coagulation - fibrinolysis

Full Text

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