Fibrin/fibrinogen degradation products (FDP) at hospital admission predict neurological outcomes in out-of-hospital cardiac arrest patients

Ono, Yuichi; Hayakawa, Mineji; Maekawa, Kunihiko; Kodate, Akira; Sadamoto, Yoshihiro; Tominaga, Naoki; Murakami, Hiromoto; Yoshida, Tetsu; Katabami, Kenichi; Wada, Takeshi; Sageshima, Hisako; Sawamura, Atsushi; Gando, Satoshi

doi:10.1016/j.resuscitation.2016.11.017

Cited by 26 publications

(32 citation statements)

References 40 publications

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“…In addition, the TFPI levels did not match the increased levels of tissue factor from arrival at the ED to 24 hours after admission in patients with ROSC after cardiac arrest. Low levels of antithrombin were also confirmed in patients after cardiac arrest and resuscitation, especially in non‐survivors and patients with DIC . An experimental study supported these results, showing that antithrombin levels decrease with mirror‐image increases in TAT levels after CPR in a pig cardiac arrest model …”

Section: Impairment Of Anticoagulation Pathwaysmentioning

confidence: 62%

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Disseminated intravascular coagulation in cardiac arrest and resuscitation

Gando

Wada

2019

Journal of Thrombosis and Haemostasis

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The aims of this review are to demonstrate that the changes in coagulation and fibrinolysis observed in cardiac arrest and resuscitation can be recognized as disseminated intravascular coagulation (DIC), and to discuss the probability of DIC being a therapeutic target. The appearance of triggers of DIC, such as damage-associated molecular patterns, inflammatory cytokines, and adrenaline, is associated with platelet activation, marked thrombin generation and fibrin formation, insufficient anticoagulation pathways, and increased fibrinolysis by tissue-type plasminogen activator, followed by the suppression of fibrinolysis by plasminogen activator inhibitor-1, in patients with cardiac arrest and resuscitation. Simultaneous neutrophil activation and endothelial injury associated with glycocalyx perturbation have been observed in these patients. The degree of these changes is more severe in patients with prolonged precardiac arrest hypoxia and long no-flow and low-flow times, patients without return of spontaneous circulation, and non-survivors. Animal and clinical studies have confirmed decreased cerebral blood flow and microvascular fibrin thrombosis in vital organs, including the brain. The clinical diagnosis of DIC in patients with cardiac arrest and resuscitation is associated with multiple organ dysfunction, as assessed with the sequential organ failure assessment score, and increased mortality. This review confirms that the coagulofibrinolytic changes in cardiac arrest and resuscitation meet the definition of DIC proposed by the ISTH, and that DIC is associated with organ dysfunction and poor patient outcomes. This evidence implies that established DIC should be considered to be one of the main therapeutic targets in post-cardiac arrest syndrome. K E Y W O R D Scardiac arrest, disseminated intravascular coagulation, fibrinolysis, inflammation, resuscitation

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Section: Impairment Of Anticoagulation Pathwaysmentioning

confidence: 62%

“…These results support the hypothesis that DIC is involved in organ dysfunction and a poor outcome of patients with post–cardiac arrest syndrome . In addition, the associations of DIC status, increased DIC scores and FDPs with a poor neurologic outcome were confirmed …”

Section: Dic and The Prognosis Of The Patientsmentioning

confidence: 71%

Disseminated intravascular coagulation in cardiac arrest and resuscitation

Gando

Wada

2019

Journal of Thrombosis and Haemostasis

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“…Antithrombin, which forms complexes with thrombin and inhibits thrombin and FXa, is one of the important anticoagulant factors. Previous studies have confirmed reduced levels of antithrombin in PCAS patients ( 11 , 52 ), particularly those with DIC ( 53 ), with a poor outcome ( 54 ), and with refractory shock ( 11 ). The reduction in the antithrombin levels may be caused by not only consumption through the formation of complexes with thrombin and protease but also extravascular loss due to increased vascular permeability ( 20 , 55 ).…”

Section: Pathophysiologymentioning

confidence: 80%

Coagulofibrinolytic Changes in Patients with Post-cardiac Arrest Syndrome

Wada

2017

Front. Med.

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Whole-body ischemia and reperfusion due to cardiac arrest and subsequent return of spontaneous circulation constitute post-cardiac arrest syndrome (PCAS), which consists of four syndromes including systemic ischemia/reperfusion responses and post-cardiac arrest brain injury. The major pathophysiologies underlying systemic ischemia/reperfusion responses are systemic inflammatory response syndrome and increased coagulation, leading to disseminated intravascular coagulation (DIC), which clinically manifests as obstruction of microcirculation and multiple organ dysfunction. In particular, thrombotic occlusion in the brain due to DIC, referred to as the “no-reflow phenomenon,” may be deeply involved in post-cardiac arrest brain injury, which is the leading cause of mortality in patients with PCAS. Coagulofibrinolytic changes in patients with PCAS are characterized by tissue factor-dependent coagulation, which is accelerated by impaired anticoagulant mechanisms, including antithrombin, protein C, thrombomodulin, and tissue factor pathway inhibitor. Damage-associated molecular patterns (DAMPs) accelerate not only tissue factor-dependent coagulation but also the factor XII- and factor XI-dependent activation of coagulation. Inflammatory cytokines are also involved in these changes via the expression of tissue factor on endothelial cells and monocytes, the inhibition of anticoagulant systems, and the release of neutrophil elastase from neutrophils activated by inflammatory cytokines. Hyperfibrinolysis in the early phase of PCAS is followed by inadequate endogenous fibrinolysis and fibrinolytic shutdown by plasminogen activator inhibitor-1. Moreover, cell-free DNA, which is also a DAMP, plays a pivotal role in the inhibition of fibrinolysis. DIC diagnosis criteria or fibrinolysis markers, including d-dimer and fibrin/fibrinogen degradation products, which are commonly tested in patients and easily accessible, can be used to predict the mortality or neurological outcome of PCAS patients with high accuracy. A number of studies have explored therapy for this unique pathophysiology since the first report on “no-reflow phenomenon” was published roughly 50 years ago. However, the optimum therapeutic strategy focusing on the coagulofibrinolytic changes in cardiac arrest or PCAS patients has not yet been established. The elucidation of more precise pathomechanisms of coagulofibrinolytic changes in PCAS may aid in the development of novel therapeutic targets, leading to an improvement in the outcomes of PCAS patients.

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“…The systemic and sterile in ammation is the most important component of PCAS [8,25]. Second, whole-body ischemia/reperfusion induced by endothelial injury contributes to thrombotic occlusion of the vessels following activation of coagulation and impairment of brinolysis [26,27]. Several studies have demonstrated that aggregation, deformability, and the shape of RBC are altered in critical illness and different diseases [28].…”

Section: Discussionmentioning

confidence: 99%

Thrombotic Microangiopathy Score as a New Predictor for Neurologic Outcome in Patients Undergoing Targeted Temperature Management After Out-of-hospital Cardiac Arrest

Kong

Lee

Jeon

et al. 2020

Preprint

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Abstract Background: Given the morphological characteristics of schistocytes, thrombotic microangiopathy (TMA) score can be beneficial as it can be quickly and serially measured without additional effort or costs. This study aimed to investigate whether the serial TMA scores until 48 h post admission are associated with clinical outcomes in patients undergoing targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA). Methods:We retrospectively evaluated a cohort of 185 patients using a prospective registry. We analyzed the TMA score at admission and after 12, 24, and 48 hours. The primary outcome measures were poor neurologic outcome at discharge and 30-day mortality. Results:Increased TMA scores at all measured time points were independent predictors of poor neurologic outcomes and 30-day mortality, with the TMA score at time-12 showing the strongest correlation (OR, 3.008; 95% CI, 1.707–5.3; p=0.001 and HR, 1.517; 95% CI, 1.196–1.925; p=0.001.Specifically, TMA score ≥2 at time-12 was closely associated with increased predictability of poor neurologic outcome (OR, 6.302; 95% CI: 2.841–13.976; p<0.001) and 30-day mortality (HR, 2.656; 95% CI: 1.675–4.211; p<0.001).Conclusions: Increased TMA scores predicted the neurologic outcome and 30-day mortalityin patients undergoing TTM after OHCA. In addition to the benefit of being quickly and serially measured by using an automated hematology analyzer without additional effort or costs, this finding indicates that the TMA score may be a helpful tool for rapid risk stratification and identification of the need for intensive care in patients with ROSC after OHCA.

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Fibrin/fibrinogen degradation products (FDP) at hospital admission predict neurological outcomes in out-of-hospital cardiac arrest patients

Cited by 26 publications

References 40 publications

Disseminated intravascular coagulation in cardiac arrest and resuscitation

Disseminated intravascular coagulation in cardiac arrest and resuscitation

Coagulofibrinolytic Changes in Patients with Post-cardiac Arrest Syndrome

Thrombotic Microangiopathy Score as a New Predictor for Neurologic Outcome in Patients Undergoing Targeted Temperature Management After Out-of-hospital Cardiac Arrest

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