Sepsis and Thrombosis

Levi, Marcel; Schultz, Marcus J.; Poll, Tom van der

doi:10.1055/s-0033-1343894

Cited by 171 publications

(74 citation statements)

References 77 publications

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“…This event might seem inconsistent with the previous statements regarding a sepsis-induced hypercoagulation and fibrin deposition, but the process is thought to occur secondary to a consumptive thrombocytopaenia and depletion of clotting factors 10 . The transition from a hypercoagulable state to DIC is characterized by fibrinolysis with increased circulating fibrin degradation products, thrombocytopaenia and exhaustion of liver-derived prothrombin, fibrinogen, factor X and factor V reserves.…”

Section: Mechanisms/pathophysiologycontrasting

confidence: 78%

“…The local cytokine milieu in this stage of inflammation induces cell-surface receptors for myeloid cells, lymphocytes and platelets. Platelets bind to fibrin strands and provide a ready source of P-selectin for neutrophil attachment; activated neutrophils produce NETs that provide a scaffold for more clot formation and this process self-amplifies 10,86 . This cooperative interaction serves to ‘wall off’ sites of injury from the rest of the host, limiting infection risk.…”

Section: Mechanisms/pathophysiologymentioning

confidence: 99%

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Sepsis and septic shock

Hotchkiss

Moldawer

Opal

et al. 2016

Nat Rev Dis Primers

1,191

1,005

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For more than two decades, sepsis was defined as a microbial infection that produces fever (or hypothermia), tachycardia, tachypnoea and blood leukocyte changes. Sepsis is now increasingly being considered a dysregulated systemic inflammatory and immune response to microbial invasion that produces organ injury for which mortality rates are declining to 15–25%. Septic shock remains defined as sepsis with hyperlactataemia and concurrent hypotension requiring vasopressor therapy, with in-hospital mortality rates approaching 30–50%. With earlier recognition and more compliance to best practices, sepsis has become less of an immediate life-threatening disorder and more of a long-term chronic critical illness, often associated with prolonged inflammation, immune suppression, organ injury and lean tissue wasting. Furthermore, patients who survive sepsis have continuing risk of mortality after discharge, as well as long-term cognitive and functional deficits. Earlier recognition and improved implementation of best practices have reduced in-hospital mortality, but results from the use of immunomodulatory agents to date have been disappointing. Similarly, no biomarker can definitely diagnose sepsis or predict its clinical outcome. Because of its complexity, improvements in sepsis outcomes are likely to continue to be slow and incremental.

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Section: Mechanisms/pathophysiologycontrasting

confidence: 78%

Section: Mechanisms/pathophysiologymentioning

confidence: 99%

Sepsis and septic shock

Hotchkiss

Moldawer

Opal

et al. 2016

Nat Rev Dis Primers

1,191

1,005

View full text Add to dashboard Cite

show abstract

“…In sepsis, microthrombi form in the blood capillaries (10). As with IE, this phenomenon was attributed to the inflammatory environment that promoted platelet aggregation.…”

Section: Platelets and Bacterial Infectionsmentioning

confidence: 99%

“…Patients with sepsis have a strong release of PAI-1, a natural plasmin inhibitor. There is also a reduction in protein C, the active form of which is an inhibitor of coagulation factors Va and VIIIa (10, 129–133). In addition, these natural anticoagulants have their role in thrombin generation, with anti-inflammatory properties influencing nuclear factor κB (NFκB) (134).…”

Section: Role Of Platelets In the Pathophysiology Of Sepsismentioning

confidence: 99%

Platelets and Infections â€“ Complex Interactions with Bacteria

et al. 2015

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Platelets can be considered sentinels of vascular system due to their high number in the circulation and to the range of functional immunoreceptors they express. Platelets express a wide range of potential bacterial receptors, including complement receptors, FcγRII, Toll-like receptors but also integrins conventionally described in the hemostatic response, such as GPIIb–IIIa or GPIb. Bacteria bind these receptors either directly, or indirectly via fibrinogen, fibronectin, the first complement C1q, the von Willebrand Factor, etc. The fate of platelet-bound bacteria is questioned. Several studies reported the ability of activated platelets to internalize bacteria such as Staphylococcus aureus or Porphyromonas gingivalis, though there is no clue on what happens thereafter. Are they sheltered from the immune system in the cytoplasm of platelets or are they lysed? Indeed, while the presence of phagolysosome has not been demonstrated in platelets, they contain antimicrobial peptides that were shown to be efficient on S. aureus. Besides, the fact that bacteria can bind to platelets via receptors involved in hemostasis suggests that they may induce aggregation; this has indeed been described for Streptococcus sanguinis, S. epidermidis, or C. pneumoniae. On the other hand, platelets are able to display an inflammatory response to an infectious triggering. We, and others, have shown that platelet release soluble immunomodulatory factors upon stimulation by bacterial components. Moreover, interactions between bacteria and platelets are not limited to only these two partners. Indeed, platelets are also essential for the formation of neutrophil extracellular traps by neutrophils, resulting in bacterial clearance by trapping bacteria and concentrating antibacterial factors but in enhancing thrombosis. In conclusion, the platelet–bacteria interplay is a complex game; its fine analysis is complicated by the fact that the inflammatory component adds to the aggregation response.

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“…However, on the contrary, activation of coagulation frequently occurs in sepsis [17]. Therefore, platelet OXPHOS dysfunction observed in sepsis patients probably is not enough to alter platelet function and increase mortality.…”

Section: Discussionmentioning

confidence: 99%

Higher platelet cytochrome oxidase specific activity in surviving than in non-surviving septic patients

et al. 2014

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IntroductionIn a previous study with 96 septic patients, we found that circulating platelets in 6-months surviving septic patients showed higher activity and quantity of cytochrome c oxidase (COX) normalized by citrate synthase (CS) activity at moment of severe sepsis diagnosis than non-surviving septic patients. The objective of this study was to estimate whether COX specific activity during the first week predicts 1-month sepsis survival in a larger cohort of patients.MethodsUsing a prospective, multicenter, observational study carried out in six Spanish intensive care units with 198 severe septic patients, we determined COX activity per proteins (COXact/Prot) in circulating platelets at day 1, 4 and 8 of the severe sepsis diagnosis. Endpoints were 1-month and 6-months mortality.ResultsSurvivor patients (n = 130) showed higher COXact/Prot (P < 0.001) than non-survivors (n = 68) at day 1, 4 and 8 of severe sepsis diagnosis. More than a half of the 6-months survivor patients showed an increase in their COXact/Prot from day 1 to 8. However, most of the 1-month non-survivors exhibited a decrease in their COXact/Prot from day 1 to 8. Multiple logistic regression analyses showed that of platelet COXact/Prot > 0.30 mOD/min/mg at day 1 (P = 0.002), 4 (P = 0.006) and 8 (P = 0.02) was associated independently with 1-month mortality. Area under the curve of COXact/Prot at day 1, 4 and 8 to predict 30-day survival were 0.70 (95% CI = 0.63-0.76; P < 0.001), 0.71 (95% CI = 0.64-0.77; P < 0.001) and 0.71 (95% CI = 0.64-0.78; P < 0.001), respectively.ConclusionsThe new findings of our study, to our knowledge the largest series reporting data about mitochondrial function during follow-up in septic patients, were that septic patients that survive 1-month have a higher platelet cytochrome oxidase activity at moment of sepsis diagnosis and during the first week than non-survivors, and that platelet cytochrome oxidase activity at moment of sepsis diagnosis and during the first week could be used as biomarker to predict the clinical outcome in septic patients.

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Sepsis and Thrombosis

Cited by 171 publications

References 77 publications

Sepsis and septic shock

Sepsis and septic shock

Platelets and Infections â€“ Complex Interactions with Bacteria

Higher platelet cytochrome oxidase specific activity in surviving than in non-surviving septic patients

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