The Coagulopathy in Sepsis: Significance  and Implications for Treatment

Saracco, Paola; Vitale, Pasquale; Scolfaro, Carlo; Pollio, Berardino; Pagliarino, Mauro; Timeus, Fabio

doi:10.4081/pr.2011.e30

Cited by 49 publications

(40 citation statements)

References 27 publications

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“…(64, 128, 527, 741, 1056–1068)]. In the worst cases, these are the very frightening DIC (1047, 1069–1073) that can, of course, also emerge as a consequence of sepsis (1074–1080). Variations in the plasminogen activator inhibitor-1 may contribute to the hypofibrinolysis observed (1081–1083).…”

Section: Clotting Coagulopathies and Fibrinogen In Pementioning

confidence: 99%

A Dormant Microbial Component in the Development of Preeclampsia

Kell

Kenny

2016

Front. Med.

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Preeclampsia (PE) is a complex, multisystem disorder that remains a leading cause of morbidity and mortality in pregnancy. Four main classes of dysregulation accompany PE and are widely considered to contribute to its severity. These are abnormal trophoblast invasion of the placenta, anti-angiogenic responses, oxidative stress, and inflammation. What is lacking, however, is an explanation of how these themselves are caused. We here develop the unifying idea, and the considerable evidence for it, that the originating cause of PE (and of the four classes of dysregulation) is, in fact, microbial infection, that most such microbes are dormant and hence resist detection by conventional (replication-dependent) microbiology, and that by occasional resuscitation and growth it is they that are responsible for all the observable sequelae, including the continuing, chronic inflammation. In particular, bacterial products such as lipopolysaccharide (LPS), also known as endotoxin, are well known as highly inflammagenic and stimulate an innate (and possibly trained) immune response that exacerbates the inflammation further. The known need of microbes for free iron can explain the iron dysregulation that accompanies PE. We describe the main routes of infection (gut, oral, and urinary tract infection) and the regularly observed presence of microbes in placental and other tissues in PE. Every known proteomic biomarker of “preeclampsia” that we assessed has, in fact, also been shown to be raised in response to infection. An infectious component to PE fulfills the Bradford Hill criteria for ascribing a disease to an environmental cause and suggests a number of treatments, some of which have, in fact, been shown to be successful. PE was classically referred to as endotoxemia or toxemia of pregnancy, and it is ironic that it seems that LPS and other microbial endotoxins really are involved. Overall, the recognition of an infectious component in the etiology of PE mirrors that for ulcers and other diseases that were previously considered to lack one.

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Section: Clotting Coagulopathies and Fibrinogen In Pementioning

confidence: 99%

A Dormant Microbial Component in the Development of Preeclampsia

Kell

Kenny

2016

Front. Med.

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“…[25; 121; 511; 692; 988–1000]). In the worst cases these are the very frightening Disseminated Intravascular Coagulation (DIC) [980; 1001–1005], that can, of course, also emerge as a consequence of sepsis [1006–1012]. Variations in the plasminogen activator inhibitor-1 may contribute to the hypofibrinolysis observed [1013–1015].…”

Section: Clotting Coagulopathies and Fibrinogen In Pementioning

confidence: 99%

A Dormant Microbial Component in the Development of Pre-Eclampsia¹

Kell

Kenny

2016

Preprint

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Pre-eclampsia (PE) is a complex, multi-system disorder that remains a leading cause of morbidity and mortality in pregnancy. Four main classes of dysregulation accompany PE, and are widely considered to contribute to its severity. These are abnormal trophoblast invasion of the placenta, anti-angiogenic responses, oxidative stress, and inflammation. What is lacking, however, is an explanation of how these themselves are caused.We here develop the unifying idea, and the considerable evidence for it, that the originating cause of PE (and of the four classes of dysregulation) is in fact microbial infection, that most such microbes are dormant and hence resist detection by conventional (replication-dependent) microbiology, and that by occasional resuscitation and growth it is they that are responsible for all the observable sequelae, including the continuing, chronic inflammation. In particular, bacterial products such as lipopolysaccharide (LPS), also known as endotoxin, are well known as highly inflammagenic and stimulate an innate (and possibly trained) immune response that exacerbates the inflammation further. The known need of microbes for free iron can explain the iron dysregulation that accompanies PE. We describe the main routes of infection (gut, oral, urinary tract infection) and the regularly observed presence of microbes in placental and other tissues in PE. Every known proteomic biomarker of “pre-eclampsia” that we assessed has in fact also been shown to be raised in response to infection. An infectious component to PE fulfils the Bradford Hill criteria for ascribing a disease to an environmental cause, and suggests a number of treatments, some of which have in fact been shown to be successful.PE was classically referred to as endotoxaemia or toxaemia of pregnancy, and it is ironic that it seems that LPS and other microbial endotoxins really are involved. Overall, the recognition of an infectious component in the aetiology of PE mirrors that for ulcers and other diseases that were previously considered to lack one.Insight, innovation, integrationMany descriptors of pre-eclampsia are widely accepted (e.g. abnormal trophoblast invasion, oxidative stress, inflammation and altered immune response, and anti-angiogenic responses). However, without knowing what causes them, they do not explain the syndrome. The Biological Insight of this manuscript is that there is considerable evidence to the effect that each of these phenomena (hence PE) are caused by the resuscitation of dormant bacteria that shed (known and potent) inflammagens such as LPS, often as a consequence of iron availability. PE is thus seen as a milder form of sepsis. The Technological Innovations come from the use of molecular markers (of microbes and omics more generally, as well as novel markers of coagulopathies) to measure this. The Benefit of Integration comes from bringing together a huge number of disparate observations into a unifying theme.

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“…For patients receiving heparin, the PT/INR is useful for determining the effects of disease on the liver-independent of lower doses of heparin. Patients who are septic typically exhibit an elevated INR due to derangement of the clotting cascade from multiple areas associated with sepsis and/or liver dysfunction [143]. Thus, the goal INR for a patient on ECMO receiving heparin therapy should be less than 1.5.…”

Section: Prothrombin Time (Pt)mentioning

confidence: 99%

ECMO Biocompatibility: Surface Coatings, Anticoagulation, and Coagulation Monitoring

Maul¹,

Massicotte²,

Wearden³

2016

Extracorporeal Membrane Oxygenation: Advances in Therapy

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The interaction between the patient and the ECMO (extracorporeal membrane oxygenation) circuit initiates a significant coagulation and inflammatory response due to the large surface area of foreign material contained within the circuit. This response can be blunted with the appropriate mix of biocompatible materials and anticoagulation therapy. The use of anticoagulants, in turn, requires appropriate laboratory testing to determine whether the patient is appropriately anticoagulated. Physicians must balance the risks of bleeding with the risks of thrombosis; the proper interpretation of these tests is often shrouded in mystery. It is the purpose of this chapter to help demystify the coagulation system, anticoagulants, biocompatible surfaces, and coagulation testing so that ECMO practitioners can make informed decisions about their patients and to spur coordinated efforts for future research to improve our understanding of these complex processes.

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The Coagulopathy in Sepsis: Significance and Implications for Treatment

Cited by 49 publications

References 27 publications

A Dormant Microbial Component in the Development of Preeclampsia

A Dormant Microbial Component in the Development of Preeclampsia

A Dormant Microbial Component in the Development of Pre-Eclampsia¹

ECMO Biocompatibility: Surface Coatings, Anticoagulation, and Coagulation Monitoring

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The Coagulopathy in Sepsis: Significance and Implications for Treatment

Cited by 49 publications

References 27 publications

A Dormant Microbial Component in the Development of Preeclampsia

A Dormant Microbial Component in the Development of Preeclampsia

A Dormant Microbial Component in the Development of Pre-Eclampsia1

ECMO Biocompatibility: Surface Coatings, Anticoagulation, and Coagulation Monitoring

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Product

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A Dormant Microbial Component in the Development of Pre-Eclampsia¹