PMID- 17944999
OWN - NLM
STAT- MEDLINE
DCOM- 20080228
LR  - 20230829
IS  - 1538-7933 (Print)
IS  - 1538-7836 (Linking)
VI  - 6
IP  - 1
DP  - 2008 Jan
TI  - Activation of coagulation with concurrent impairment of anticoagulant mechanisms 
      correlates with a poor outcome in severe melioidosis.
PG  - 32-9
AB  - BACKGROUND: Melioidosis, which is caused by infection with the Gram-negative 
      bacterium Burkholderia pseudomallei, is an important cause of sepsis in 
      South-East Asia with a mortality of up to 40%. Knowledge of the involvement of 
      coagulation and fibrinolysis in the pathogenesis of melioidosis is highly 
      limited. OBJECTIVE: To define the involvement of the coagulation and fibrinolytic 
      systems in patients with severe melioidosis. METHODS: Parameters of coagulation 
      and fibrinolysis were measured in 34 patients with culture proven septic 
      melioidosis and 32 healthy controls. RESULTS: Patients demonstrated strong 
      activation of the coagulation system, as reflected by high plasma levels of 
      soluble tissue factor, the prothrombin fragment F(1+2) and thrombin-antithrombin 
      complexes (TATc), and consumption of coagulation factors resulting in a prolonged 
      prothrombin time and activated partial thromboplastin time. Concurrently, 
      anticoagulant pathways were downregulated in patients: protein C, protein S, and 
      antithrombin levels were all decreased when compared to controls. Patients also 
      demonstrated evidence of activation and inhibition of fibrinolysis, as reflected 
      by elevated concentrations of tissue-type plasminogen activator (tPA), 
      plasminogen activator inhibitor type 1, plasmin-alpha2-antiplasmin complexes 
      (PAPc) and D-dimer. High TATc/PAPc ratios in patients pointed to a predominance 
      of the prothrombotic pathway in melioidosis. Furthermore, soluble thrombomodulin 
      levels were increased. The extent of coagulation activation correlated with 
      mortality; patients who went on to die had higher TATc, F(1+2), tPA and PAPc and 
      lower protein C and antithrombin levels on admission than patients who survived. 
      CONCLUSIONS: The coagulation system is strongly activated during melioidosis. A 
      high degree of activation of the coagulation system is an indicator of poor 
      outcome in patients with melioidosis.
FAU - Wiersinga, W J
AU  - Wiersinga WJ
AD  - Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, 
      University of Amsterdam, Amsterdam, The Netherlands. w.j.wiersinga@amc.uva.nl
FAU - Meijers, J C M
AU  - Meijers JC
FAU - Levi, M
AU  - Levi M
FAU - Van 't Veer, C
AU  - Van 't Veer C
FAU - Day, N P
AU  - Day NP
FAU - Peacock, S J
AU  - Peacock SJ
FAU - van der Poll, T
AU  - van der Poll T
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071012
PL  - England
TA  - J Thromb Haemost
JT  - Journal of thrombosis and haemostasis : JTH
JID - 101170508
RN  - 0 (Biomarkers)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers/blood
MH  - *Blood Coagulation
MH  - Blood Coagulation Tests
MH  - Case-Control Studies
MH  - Female
MH  - *Fibrinolysis
MH  - Humans
MH  - Male
MH  - Melioidosis/*blood/*diagnosis/mortality
MH  - Middle Aged
MH  - Prognosis
MH  - Sepsis
MH  - Survival Rate
MH  - Treatment Outcome
EDAT- 2007/10/20 09:00
MHDA- 2008/02/29 09:00
CRDT- 2007/10/20 09:00
PHST- 2007/10/20 09:00 [pubmed]
PHST- 2008/02/29 09:00 [medline]
PHST- 2007/10/20 09:00 [entrez]
AID - S1538-7836(22)13175-2 [pii]
AID - 10.1111/j.1538-7836.2007.02796.x [doi]
PST - ppublish
SO  - J Thromb Haemost. 2008 Jan;6(1):32-9. doi: 10.1111/j.1538-7836.2007.02796.x. Epub 
      2007 Oct 12.