Time course of coagulation and fibrinolytic parameters in pediatric traumatic brain injury

OBJECTIVE Coagulopathy is a well-recognized risk factor for poor outcomes in patients with traumatic brain injury (TBI). Differences in the time courses of coagulation and fibrinolytic parameters between pediatric and adult patients with TBI have not been defined. METHODS Patients with TBI and an Abbreviated Injury Scale of the head score ≥ 3, in whom the prothrombin time (PT)–international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen concentration, and plasma D-dimer levels were measured on arrival and at 3, 6, and 12 hours after injury, were retrospectively analyzed. Propensity score–matched analyses were performed to adjust baseline characteristics between pediatric patients (aged < 16 years) and adult patients (aged ≥ 16 years). RESULTS A total of 468 patients (46 children and 422 adults) were included. Propensity score matching resulted in a matched cohort of 46 pairs. Higher PT-INR and APTT values at 1 to 12 hours after injury and lower fibrinogen concentrations at 1 to 6 hours after injury were observed in the pediatric group compared with the adult group. Plasma levels of D-dimer were elevated in both groups at 1 to 12 hours after injury, but no significant differences were seen between the groups. Multivariate logistic regression analysis of the initial coagulation and fibrinolytic parameters in the pediatric group revealed no prognostic significance of the coagulation parameter values, but elevation of the fibrinolytic parameter D-dimer was an independent negative prognostic factor. CONCLUSIONS In the acute phase of TBI, pediatric patients were characterized by prolongation of PT-INR and APTT and lower fibrinogen concentrations compared with adult patients, but these did not correlate with outcome. D-dimer was an independent prognostic outcome factor in terms of the Glasgow Outcome Scale in pediatric patients with TBI.

Some fibrinolytic parameters in coronary artery disease patients: focus on unstable angina subgroups

Unstable angina is classified into new-onset, progressive, and angina at rest. Though hemostasis plays a crucial role in the pathogenesis of coronary artery disease, including unstable angina, limited data exist regarding peculiarities of fibrinolytic parameters in the above-mentioned types of unstable angina. Our study aims to investigate if there is a difference in the fibrinolytic state between the groups of patients with new-onset, progressive unstable angina in comparison with stable angina patients depending on medical history data, electrocardiographic and hemodynamic features. In our cross-sectional study, we recruited 93 coronary artery disease patients (mean age 62.32 (6.94) years, 41 males (44.1%)). They were divided into 3 groups: stable angina patients (n=22) (control), new-onset unstable angina patients (n=21), and progressive unstable angina patients (n=50). The groups were comparable by baseline characteristics. Blood samples were obtained before treatment onset. The concentrations of tissue plasminogen activator and inhibitor of plasminogen activator (type 1) were measured by the ELISA method. We registered 14 points at the admission department, particularly age, sex, body mass index, smoking, presence of the family history of cardiovascular disorders, ST-segment depression, T-wave variability, arrhythmias, left bundle branch blockage, heart rate, systolic and diastolic blood pressure, Sokolov-Lyon voltage criteria, and unstable angina type (new-onset or progressive). After comparison of fibrinolytic parameters’ concentrations among groups under investigation, we defined the main independent predictors among observed 14 parameters to create optimal regression models for assessment of fibrinolytic parameters concentrations. The groups under investigation differ significantly in concentration of tissue plasminogen activator (P<0.001) and inhibitor of plasminogen activator (type 1) (P<0.001). The tissue plasminogen activator concentration correlated significantly with ST depression (r=0.344, P=0.001), T wave variability (r=-0.233, P=0.02), systolic blood pressure (r=-0.675, P<0.001), diastolic blood pressure (r=-0.655, P<0.001), heart rate (r=-0.568, P<0.001) and clinical unstable angina subgroups (r=-0.706, P<0.001) as well as plasminogen activator inhibitor (type 1) concentration associated with age (r=-0.560, P<0.001), body mass index (r=-0.249, P=0.049), ST-segment depression (r=0.542, P<0.001), arrhythmia (r=0.210, P=0.03), systolic blood pressure (r=0.310, P=0.04), and clinical unstable angina subgroups (r=-0.406, P<0.001). An optimal regression models for tissue plasminogen activator and its inhibitor assessment included systolic blood pressure, heart rate, unstable angina subgroup (R2adj. = 65.0%, P<0.001) and systolic blood pressure, unstable angina subgroup (R2adj. = 42.7%, P<0.001), respectively. Thus, fibrinolytic state among unstable angina clinical types differs significantly independently on observed baseline clinical, electrocardiographic and hemodynamic parameters. This finding confirms the utility of Braunwald unstable angina classification.

Relationship Between Severity of Fibrinolysis Based on Rotational Thromboelastometry and Conventional Fibrinolysis Markers

The association between severity of fibrinolysis, ascertained by rotational thromboelastometry to diagnose hyperfibrinolysis in patients with out-of-hospital cardiac arrest (OHCA), and conventional fibrinolysis markers (ie, tissue-plasminogen activator [t-PA], plasminogen, α2-plasmin inhibitor [α2-PI], and plasminogen activator inhibitor [PAI]) with key roles in the fibrinolytic system was investigated. This prospective observational study included 5 healthy volunteers and 35 patients with OHCA from the Hokkaido University Hospital. Blood samples were drawn immediately upon admission to the emergency department. Assessments of the extrinsic pathway using tissue factor activation (EXTEM) and of fibrinolysis by comparison with EXTEM after aprotinin addition (APTEM) were undertaken. Conventional coagulation and fibrinolysis markers were measured in the stored plasma samples. Significant hyperfibrinolysis observed in EXTEM disappeared in APTEM. Patients exhibited significantly higher levels of fibrinogen/fibrin degradation products, plasmin–α2-PI complex, and t-PA but lower levels of fibrinogen, plasminogen, and α2-PI than healthy controls. The PAI level was unchanged. Fibrinolytic parameters of EXTEM correlated with levels of lactate and conventional fibrinolysis markers, especially t-PA. Increased t-PA activity and decreased plasminogen and α2-PI significantly correlated with increased severity of fibrinolysis (hyperfibrinolysis).

Hemostasis during Extreme Exertion

Exercise is protective against cardiovascular disease, but can also provoke sudden cardiac death, a phenomenon referred to as “the exercise paradox.” Extreme exertion is known to induce a rebalanced hemostatic state by causing hypercoagulability and concomitantly enhanced fibrinolysis. Over the past decade, novel techniques for quantifying hemostasis have been introduced, which may provide new insights into this process. This review summarizes recent literature on the effect of extreme exertion of both short and long duration on coagulation, fibrinolysis, and recovery of hemostatic balance. Extreme exertion introduces a temporary hypercoagulable state, mainly through upregulation of the contact pathway by increased FVIII levels. Additionally, von Willebrand factor levels and platelet activation are increased. Simultaneously, increased fibrinolysis results from increased tissue-type plasminogen activator levels, suggesting a rebalanced hemostasis. The vascular endothelium appears to play a pivotal role in both processes. Data on the effect of exercise on endogenous anticoagulants are scarce. Hypercoagulability persists for hours to a day after prolonged extreme exertion, while fibrinolytic parameters appear to return to baseline levels more quickly. Hence, the balance in the rebalanced hemostatic state may be lost during recovery. Training induces lower amplitude of the hypercoagulable response, and quicker recuperation toward baseline. Repetitive exercise exhausts the endothelium, attenuating procoagulant changes. Additional research is needed to identify if the hemostatic balance is lost during recovery, and if so, when the shift toward thrombosis appears. Moreover, differences between sexes need to be addressed, since women are known to have a different pathophysiological mechanism behind cardiovascular events, but are underrepresented in recent literature.