Should all septic patients be given systemic anticoagulation? No

Poll, Tom van der; Opal, Steven M.

doi:10.1007/s00134-016-4607-x

Cited by 18 publications

(16 citation statements)

References 16 publications

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“…The potential bleeding risk is a serious concern when heparin is given to septic patients. 45 Nonanticoagulant CS-E 19-mer would eliminate this bleeding concern. Second, HIT is an immunological disorder resulting from the production of antibodies against a complex of heparin with platelet factor 4 (PF4) 46 and is the major nonbleeding side effect associated with the use of heparin resulting in five to six deaths every day in the United States.…”

Section: Discussionmentioning

confidence: 99%

Enzymatic Synthesis of Chondroitin Sulfate E to Attenuate Bacteria Lipopolysaccharide-Induced Organ Damage

Sparkenbaugh

et al. 2020

ACS Cent. Sci.

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Chondroitin sulfate E (CS-E) is a sulfated polysaccharide that contains repeating disaccharides of 4,6-disulfated N -acetylgalactosamine and glucuronic acid residues. Here, we report the enzymatic synthesis of three homogeneous CS-E oligosaccharides, including CS-E heptasaccharide ( CS-E 7-mer ), CS-E tridecasaccharide ( CS-E13-mer ), and CS-E nonadecasaccharide ( CS-E 19-mer ). The anti-inflammatory effect of CS-E 19-mer was investigated in this study. CS-E 19-mer neutralizes the cytotoxic effect of histones in a cell-based assay and in mice. We also demonstrate that CS-E 19-mer treatment improves survival and protects against organ damage in a mouse model of endotoxemia induced by bacterial lipopolysaccharide (LPS). CS-E19-mer directly interacts with circulating histones in the plasma from LPS-challenged mice. CS-E 19-mer does not display anticoagulant activity nor react with heparin-induced thrombocytopenia antibodies isolated from patients. The successful synthesis of CS-E oligosaccharides provides structurally defined carbohydrates for advancing CS-E research and offers a potential therapeutic agent to treat life-threatening systemic inflammation.

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Section: Discussionmentioning

confidence: 99%

Enzymatic Synthesis of Chondroitin Sulfate E to Attenuate Bacteria Lipopolysaccharide-Induced Organ Damage

Sparkenbaugh

et al. 2020

ACS Cent. Sci.

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“…Negative therapeutic interventions [ 135 , 136 ], drotrecogin alfa withdrawal [ 137 ], but also emerging concept of immunothrombosis [ 14 ] could argue for a radical “tabula rasa” regarding coagulation during septic shock. The debate is still open and can be summarised in one question: “Should all patients with sepsis receive anticoagulation?” [ 138 , 139 ]. Finally, whether immunohaemostasis/DIC clinical assessment is reliable remains a major issue (Fig.…”

Section: New Therapeutic Opportunities?mentioning

confidence: 99%

Immunohaemostasis: a new view on haemostasis during sepsis

Delabranche

Boisramé-Helms

Meziani

2017

Ann. Intensive Care

112

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Host infection by a micro-organism triggers systemic inflammation, innate immunity and complement pathways, but also haemostasis activation. The role of thrombin and fibrin generation in host defence is now recognised, and thrombin has become a partner for survival, while it was seen only as one of the “principal suspects” of multiple organ failure and death during septic shock. This review is first focused on pathophysiology. The role of contact activation system, polyphosphates and neutrophil extracellular traps has emerged, offering new potential therapeutic targets. Interestingly, newly recognised host defence peptides (HDPs), derived from thrombin and other “coagulation” factors, are potent inhibitors of bacterial growth. Inhibition of thrombin generation could promote bacterial growth, while HDPs could become novel therapeutic agents against pathogens when resistance to conventional therapies grows. In a second part, we focused on sepsis-induced coagulopathy diagnostic challenge and stratification from “adaptive” haemostasis to “noxious” disseminated intravascular coagulation (DIC) either thrombotic or haemorrhagic. Besides usual coagulation tests, we discussed cellular haemostasis assessment including neutrophil, platelet and endothelial cell activation. Then, we examined therapeutic opportunities to prevent or to reduce “excess” thrombin generation, while preserving “adaptive” haemostasis. The fail of international randomised trials involving anticoagulants during septic shock may modify the hypothesis considering the end of haemostasis as a target to improve survival. On the one hand, patients at low risk of mortality may not be treated to preserve “immunothrombosis” as a defence when, on the other hand, patients at high risk with patent excess thrombin and fibrin generation could benefit from available (antithrombin, soluble thrombomodulin) or ongoing (FXI and FXII inhibitors) therapies. We propose to better assess coagulation response during infection by an improved knowledge of pathophysiology and systematic testing including determination of DIC scores. This is one of the clues to allocate the right treatment for the right patient at the right moment.Electronic supplementary materialThe online version of this article (10.1186/s13613-017-0339-5) contains supplementary material, which is available to authorized users.

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“…Recently, the Intensive Care Medicine published a pro and con debate entitled ‘Should all patients with sepsis receive anticoagulation?’ [1, 2]. We read the above articles with surprise since the anticoagulant therapies had been almost ignored in the countries other than Japan.…”

Section: Main Textmentioning

confidence: 99%

“…Numbers of randomized controlled trials (RCT) failed to show the benefit of multiple agents. From the standpoint of cons, van der Poll et al [2] asserted that the universal administration of anticoagulants cannot be recommenced because of the increased risk of bleeding and the possibility of hampering coagulation-assisted clearance of pathogens. Well, we agree on both opinions and suppose that the selection of the right target is the fundamental condition for the success in the treatment.…”

Section: Main Textmentioning

confidence: 99%

The application of anticoagulant therapy to sepsis

Thachil

Iba

2017

j intensive care

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Since the withdrawal of recombinant-activated protein C, the anticoagulant therapy for sepsis was taken no notice. For instance, the international sepsis guidelines did not share a space for this therapy. However, we can see the signs of change recently. The Surviving Sepsis Campaign Guidelines 2016 introduced the development of recombinant thrombomodulin, and the European Society of Intensive Care Medicine released comments on this subject. However, since small but important discrepancy was recognized between the standpoints of Japan (more aggressive) and other countries (rather conservative), we intend to discuss on this point.

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Should all septic patients be given systemic anticoagulation? No

Cited by 18 publications

References 16 publications

Enzymatic Synthesis of Chondroitin Sulfate E to Attenuate Bacteria Lipopolysaccharide-Induced Organ Damage

Enzymatic Synthesis of Chondroitin Sulfate E to Attenuate Bacteria Lipopolysaccharide-Induced Organ Damage

Immunohaemostasis: a new view on haemostasis during sepsis

The application of anticoagulant therapy to sepsis

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