Differences in coagulofibrinolytic changes between post‐cardiac arrest syndrome of cardiac causes and hypoxic insults: a pilot study

Wada, Takeshi; Gando, Satoshi; Mizugaki, Asumi; Kodate, Akira; Sadamoto, Yoshihiro; Murakami, Hiromoto; Maekawa, Kunihiko; Katabami, Kenichi; Ono, Yuichi; Hayakawa, Mineji; Sawamura, Atsushi; Jesmin, Subrina; Ieko, Masahiro

doi:10.1002/ams2.270

Cited by 8 publications

(7 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A basic study supported this hypothesis by showing that clotting derangement reflecting post‐arrest DIC was more severe after longer cardiac arrest . Furthermore, precardiac arrest conditions associated with long hypoxic states (e.g., asphyxia, drowning, shock, and exsanguination) are important factors that lead to the development of DIC . This may be one of the reasons for the good prognosis of patients with cardiac arrest of cardiac origin, which can cause immediate ischemia after a very short period of hypoxia (or without hypoxia) during precardiac arrest.…”

Section: Dic and The Prognosis Of The Patientsmentioning

confidence: 89%

“…Increased thrombin levels, as assessed by the measurement of thrombin‐antithrombin complex (TAT), fibrin monomers, and soluble fibrin, were also confirmed in patients after cardiac arrest and resuscitation, from the prehospital setting until 3 days after successful CPR . Importantly, thrombin generation was greater in patients who died without achieving ROSC or in the hospital and patients with a long no‐flow time (in cardiac arrest without CPR) or low‐flow time than in survivors and patients with a short low‐flow time …”

Section: Tissue Factor and Massive Thrombin Generationmentioning

confidence: 90%

See 1 more Smart Citation

Disseminated intravascular coagulation in cardiac arrest and resuscitation

Gando

Wada

2019

Journal of Thrombosis and Haemostasis

Self Cite

View full text Add to dashboard Cite

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

show abstract

Section: Dic and The Prognosis Of The Patientsmentioning

confidence: 89%

Section: Tissue Factor and Massive Thrombin Generationmentioning

confidence: 90%

Disseminated intravascular coagulation in cardiac arrest and resuscitation

Gando

Wada

2019

Journal of Thrombosis and Haemostasis

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, the interval between the receipt of the emergency call and the commencement of ROSC or VA-ECMO in the VA-ECMO+ group was much longer than that in the VA-ECMO- group ( Table 2 ). A previous study indicated that the degree of hypoxia, defined as the time from the onset of cardiac arrest to first CPR, and the duration of CPR were significant determinants of the severity of coagulopathy associated with PCAS ( 3 , 15 , 16 ). The current study showed that the patients who received VA-ECMO had significantly more severe coagulopathy than those who did not receive VA-ECMO, even after adjusting for the cardiac arrest time.…”

Section: Discussionmentioning

confidence: 99%

Coagulopathy Induced by Veno-Arterial Extracorporeal Membrane Oxygenation Is Associated With a Poor Outcome in Patients With Out-of-Hospital Cardiac Arrest

2021

Self Cite

View full text Add to dashboard Cite

Background: In recent years, the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in patients with cardiopulmonary arrest who do not respond to conventional resuscitation, has increased. However, despite the development of VA-ECMO, the outcomes of resuscitated patients remain poor. The poor prognosis may be attributed to deterioration owing to the post-cardiac arrest syndrome (PCAS); this includes the systemic inflammatory response and coagulation activation caused by the extracorporeal circulation (VA-ECMO circuit) itself. This study aimed to evaluate the coagulofibrinolytic changes caused by VA-ECMO and to identify predictive factors of poor prognosis.Methods: We analyzed 151 cases of PCAS with witnessed cardiac arrest. As biomarkers, platelet counts, prothrombin time ratio, fibrin/fibrinogen degradation products, fibrinogen, antithrombin, and lactate were recorded from blood samples from the time of delivery to the third day of hospitalization. The maximum (max) and minimum (min) values of each factor during the study period were calculated. To evaluate the impact of VA-ECMO on patients with PCAS, we performed propensity score matching between the patients who received and did not receive VA-ECMO. Sub-analysis was performed for the group with VA-ECMO.Results: There were significant differences in all baseline characteristics and demographics except the time from detection to hospital arrival, percentage of cardiopulmonary resuscitations (CPR) by witnesses, and the initial rhythm between the groups. Propensity score matching adjusted for prehospital factors demonstrated that the patients who received VA-ECMO developed significantly severe coagulation disorders. In a sub-analysis, significant differences were noted in the prothrombin time ratio min, fibrinogen max, antithrombin max, and lactate min between survivors and non-survivors. In particular, the prothrombin time ratio min and antithrombin max were strongly correlated with poor outcome.Conclusion: In the present study, significant coagulopathy was observed in patients who received VA-ECMO for CPR. In particular, in patients receiving VA-ECMO, the minimum prothrombin time ratio and maximum antithrombin by day 3 of hospitalization were strongly correlated with poor outcomes. These results suggest that VA-ECMO-induced coagulopathy can be a promising therapeutic target for patients resuscitated by VA-ECMO.

show abstract

“…A recent study indicated that PCAS patients who suffer from cardiac arrest due to a hypoxic event exhibited severe thrombin activation and hyperfibrinolysis in comparison to patients who experience cardiac arrest due to a cardiogenic cause (Figure 3 ) ( 70 ). This result coincides with a previous report showing that asphyxia by drowning leads to severe hemorrhage due to hyperfibrinolytic DIC ( 62 ).…”

Section: Pathophysiologymentioning

confidence: 99%

Coagulofibrinolytic Changes in Patients with Post-cardiac Arrest Syndrome

Wada

2017

Front. Med.

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Differences in coagulofibrinolytic changes between post‐cardiac arrest syndrome of cardiac causes and hypoxic insults: a pilot study

Cited by 8 publications

References 4 publications

Disseminated intravascular coagulation in cardiac arrest and resuscitation

Disseminated intravascular coagulation in cardiac arrest and resuscitation

Coagulopathy Induced by Veno-Arterial Extracorporeal Membrane Oxygenation Is Associated With a Poor Outcome in Patients With Out-of-Hospital Cardiac Arrest

Coagulofibrinolytic Changes in Patients with Post-cardiac Arrest Syndrome

Contact Info

Product

Resources

About