Activation of coagulation and endothelium with concurrent impairment of anticoagulant mechanisms in patients with typhoid fever.

Hanna K. de Jong; Christopher Parry; Thomas W. van der Vaart; Liesbeth M. Kager; Stannie J. van den Ende; Rapeephan R. Maude; Lalith Wijedoru; Aniruddha Ghose; Mohammed U. Hassan; Mohammed A. Hossain; Arjan M. Dondorp; Steve Baker; M. Abul Faiz; Joost C.M. Meijers; W. Joost Wiersinga

doi:10.1016/j.jinf.2018.03.008

Activation of coagulation and endothelium with concurrent impairment of anticoagulant mechanisms in patients with typhoid fever.

Hanna K. de Jong, Christopher Parry, Thomas W. van der Vaart, Liesbeth M. Kager, Stannie J. van den Ende, Rapeephan R. Maude, Lalith Wijedoru, Aniruddha Ghose, Mohammed U. Hassan, Mohammed A. Hossain, Arjan M. Dondorp, Steve Baker, M. Abul Faiz, Joost C.M. Meijers, W. Joost Wiersinga

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

OBJECTIVES

Typhoid fever caused by Salmonella Typhi remains a major burden worldwide. Gastrointestinal bleeding can be seen in up to 10 percent of patients and may be fatal. The coagulopathy, which may be the driver of this severe complication in patients with typhoid fever, however is ill defined. The aim of this study was to evaluate the activation of coagulation, anticoagulation, and fibrinolysis in patients with acute typhoid fever.

METHODS

Parameters of coagulation and fibrinolysis were measured in 28 hospitalized patients with culture-confirmed or PCR-confirmed typhoid fever and compared to 38 age- and sex-matched healthy volunteers.

RESULTS

Patients demonstrated activation of the coagulation system, as reflected by elevated in vitro thrombin generation and high plasma levels of fibrinogen, D-dimer and prothrombin fragment F1+2 in concert with consumption of coagulation factors resulting in a prolonged prothrombin-time and activated-partial-thromboplastin-time. Concurrently, the anticoagulant proteins, protein C and antithrombin, were significantly lower in comparison to healthy controls. Patients also demonstrated evidence of activation and inhibition of fibrinolysis and a marked activation of endothelial cells. The extent of coagulation activation was associated with the course of the disease, repeated testing during convalescence showed a return toward normal values.

CONCLUSIONS

Activation of coagulation is an important clinical feature of typhoid fever and is associated with severity of disease.

Original language	English
Pages (from-to)	60-67
Number of pages	8
Journal	Journal of Infection
Volume	77
Issue number	1
Early online date	7 May 2018
DOIs	https://doi.org/10.1016/j.jinf.2018.03.008
Publication status	Published - 1 Jul 2018

Keywords

Disseminated intravascular coagulation (DIC)
Endocan
Fibrinolytic disorders
Protein C
Salmonella Typhi
Thrombin

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jinf.2018.03.008Licence: CC BY-NC-ND

Accepted journal of infection parryFinal published version, 1.12 MBLicence: CC BY-NC-ND
J Infection 77 1 60-67 2018Final published version, 1.41 MBLicence: CC BY-NC-ND

Cite this

de Jong, H. K., Parry, C., van der Vaart, T. W., Kager, L. M., van den Ende, S. J., Maude, R. R., Wijedoru, L., Ghose, A., Hassan, M. U., Hossain, M. A., Dondorp, A. M., Baker, S., Faiz, M. A., Meijers, J. C. M., & Wiersinga, W. J. (2018). Activation of coagulation and endothelium with concurrent impairment of anticoagulant mechanisms in patients with typhoid fever. Journal of Infection, 77(1), 60-67. https://doi.org/10.1016/j.jinf.2018.03.008

@article{b1589dff27804ce3a460367e0b6a47c8,

title = "Activation of coagulation and endothelium with concurrent impairment of anticoagulant mechanisms in patients with typhoid fever.",

abstract = "OBJECTIVESTyphoid fever caused by Salmonella Typhi remains a major burden worldwide. Gastrointestinal bleeding can be seen in up to 10 percent of patients and may be fatal. The coagulopathy, which may be the driver of this severe complication in patients with typhoid fever, however is ill defined. The aim of this study was to evaluate the activation of coagulation, anticoagulation, and fibrinolysis in patients with acute typhoid fever.METHODSParameters of coagulation and fibrinolysis were measured in 28 hospitalized patients with culture-confirmed or PCR-confirmed typhoid fever and compared to 38 age- and sex-matched healthy volunteers.RESULTSPatients demonstrated activation of the coagulation system, as reflected by elevated in vitro thrombin generation and high plasma levels of fibrinogen, D-dimer and prothrombin fragment F1+2 in concert with consumption of coagulation factors resulting in a prolonged prothrombin-time and activated-partial-thromboplastin-time. Concurrently, the anticoagulant proteins, protein C and antithrombin, were significantly lower in comparison to healthy controls. Patients also demonstrated evidence of activation and inhibition of fibrinolysis and a marked activation of endothelial cells. The extent of coagulation activation was associated with the course of the disease, repeated testing during convalescence showed a return toward normal values.CONCLUSIONSActivation of coagulation is an important clinical feature of typhoid fever and is associated with severity of disease.",

keywords = "Disseminated intravascular coagulation (DIC), Endocan, Fibrinolytic disorders, Protein C, Salmonella Typhi, Thrombin",

author = "\{de Jong\}, \{Hanna K.\} and Christopher Parry and \{van der Vaart\}, \{Thomas W.\} and Kager, \{Liesbeth M.\} and \{van den Ende\}, \{Stannie J.\} and Maude, \{Rapeephan R.\} and Lalith Wijedoru and Aniruddha Ghose and Hassan, \{Mohammed U.\} and Hossain, \{Mohammed A.\} and Dondorp, \{Arjan M.\} and Steve Baker and Faiz, \{M. Abul\} and Meijers, \{Joost C.M.\} and Wiersinga, \{W. Joost\}",

year = "2018",

month = jul,

day = "1",

doi = "10.1016/j.jinf.2018.03.008",

language = "English",

volume = "77",

pages = "60--67",

journal = "Journal of Infection",

issn = "0163-4453",

publisher = "W.B. Saunders Ltd",

number = "1",

}

de Jong, HK, Parry, C, van der Vaart, TW, Kager, LM, van den Ende, SJ, Maude, RR, Wijedoru, L, Ghose, A, Hassan, MU, Hossain, MA, Dondorp, AM, Baker, S, Faiz, MA, Meijers, JCM & Wiersinga, WJ 2018, 'Activation of coagulation and endothelium with concurrent impairment of anticoagulant mechanisms in patients with typhoid fever.', Journal of Infection, vol. 77, no. 1, pp. 60-67. https://doi.org/10.1016/j.jinf.2018.03.008

TY - JOUR

T1 - Activation of coagulation and endothelium with concurrent impairment of anticoagulant mechanisms in patients with typhoid fever.

AU - de Jong, Hanna K.

AU - Parry, Christopher

AU - van der Vaart, Thomas W.

AU - Kager, Liesbeth M.

AU - van den Ende, Stannie J.

AU - Maude, Rapeephan R.

AU - Wijedoru, Lalith

AU - Ghose, Aniruddha

AU - Hassan, Mohammed U.

AU - Hossain, Mohammed A.

AU - Dondorp, Arjan M.

AU - Baker, Steve

AU - Faiz, M. Abul

AU - Meijers, Joost C.M.

AU - Wiersinga, W. Joost

PY - 2018/7/1

Y1 - 2018/7/1

N2 - OBJECTIVESTyphoid fever caused by Salmonella Typhi remains a major burden worldwide. Gastrointestinal bleeding can be seen in up to 10 percent of patients and may be fatal. The coagulopathy, which may be the driver of this severe complication in patients with typhoid fever, however is ill defined. The aim of this study was to evaluate the activation of coagulation, anticoagulation, and fibrinolysis in patients with acute typhoid fever.METHODSParameters of coagulation and fibrinolysis were measured in 28 hospitalized patients with culture-confirmed or PCR-confirmed typhoid fever and compared to 38 age- and sex-matched healthy volunteers.RESULTSPatients demonstrated activation of the coagulation system, as reflected by elevated in vitro thrombin generation and high plasma levels of fibrinogen, D-dimer and prothrombin fragment F1+2 in concert with consumption of coagulation factors resulting in a prolonged prothrombin-time and activated-partial-thromboplastin-time. Concurrently, the anticoagulant proteins, protein C and antithrombin, were significantly lower in comparison to healthy controls. Patients also demonstrated evidence of activation and inhibition of fibrinolysis and a marked activation of endothelial cells. The extent of coagulation activation was associated with the course of the disease, repeated testing during convalescence showed a return toward normal values.CONCLUSIONSActivation of coagulation is an important clinical feature of typhoid fever and is associated with severity of disease.

AB - OBJECTIVESTyphoid fever caused by Salmonella Typhi remains a major burden worldwide. Gastrointestinal bleeding can be seen in up to 10 percent of patients and may be fatal. The coagulopathy, which may be the driver of this severe complication in patients with typhoid fever, however is ill defined. The aim of this study was to evaluate the activation of coagulation, anticoagulation, and fibrinolysis in patients with acute typhoid fever.METHODSParameters of coagulation and fibrinolysis were measured in 28 hospitalized patients with culture-confirmed or PCR-confirmed typhoid fever and compared to 38 age- and sex-matched healthy volunteers.RESULTSPatients demonstrated activation of the coagulation system, as reflected by elevated in vitro thrombin generation and high plasma levels of fibrinogen, D-dimer and prothrombin fragment F1+2 in concert with consumption of coagulation factors resulting in a prolonged prothrombin-time and activated-partial-thromboplastin-time. Concurrently, the anticoagulant proteins, protein C and antithrombin, were significantly lower in comparison to healthy controls. Patients also demonstrated evidence of activation and inhibition of fibrinolysis and a marked activation of endothelial cells. The extent of coagulation activation was associated with the course of the disease, repeated testing during convalescence showed a return toward normal values.CONCLUSIONSActivation of coagulation is an important clinical feature of typhoid fever and is associated with severity of disease.

KW - Disseminated intravascular coagulation (DIC)

KW - Endocan

KW - Fibrinolytic disorders

KW - Protein C

KW - Salmonella Typhi

KW - Thrombin

U2 - 10.1016/j.jinf.2018.03.008

DO - 10.1016/j.jinf.2018.03.008

M3 - Article

SN - 0163-4453

VL - 77

SP - 60

EP - 67

JO - Journal of Infection

JF - Journal of Infection

IS - 1

ER -

Activation of coagulation and endothelium with concurrent impairment of anticoagulant mechanisms in patients with typhoid fever.

Abstract

Keywords

UN SDGs

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