The Clinical Efficacy of Ginkgo biloba Leaf Preparation on Ischemic Stroke: A Systematic Review and Meta-Analysis

Background. Ginkgo biloba leaf preparations (GLPs) are widely used in ischemic stroke, and uncertainty remains regarding their clinical efficacy. To evaluate systematically the clinical efficacy and safety of GLPs in the treatment of ischemic stroke, we examine evidence from randomized controlled trials (RCTs). Methods. We examine studies published prior to November 2021 that were found from searching the following sources: PubMed, China National Knowledge Infrastructure (CNKI), WANFANG DATA, Chongqing VIP (CQVIP) databases, and Chinese Biomedical Literature (CBM). We evaluated the quality of the included references according to the Cochrane Manual of Systematic Evaluation and Meta-analysis (MA) performed using RevMan 5.2 software. Results. We included a total of 13 RCTs with clinical therapeutic effects, the National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), hemorheology index, and adverse reaction index as evaluation criteria. There were 631 cases in the observation group and 629 cases in the control group. MA results showed the following: NIHSS WMD = −3.89, 95% CI: [−4.22, −3.56], I2 = 19%, P < 0.00001. This index is often used with nerve injury and can also be used to judge the recovery of nerve function. A lower score means less nerve damage and a better chance of recovery. The BI results were WMD = 11.30, 95% CI: [9.83, 12.77], I2 = 7%, P < 0.00001. This index was used to assess patients’ ability to take care of themselves, with a higher score indicating a stronger ability to live independently. Clinical effective rate results were WMD = 3.79, 95% CI: [2.49, 5.78], I2 = 0%, P < 0.00001, and this measure can be used to evaluate the effect of treatment clearly and objectively. Hemorheological index results show that plasma viscosity has WMD = −0.16, 95% CI: [−0.20, −0.12], I2 = 40%, P < 0.00001 and fibrinogen (FIB) has WMD = −1.13, 95% CI: [−1.23, −1.04], I2 = 0%, P < 0.00001. Plasma viscosity is mainly related to the amount of fibrinogen, and fibrinogen degradation is an important function of the fibrinolytic system. The imbalance of the fibrinolytic system plays an important role in the pathogenesis of cerebral infarction. Fibrinogen is a risk factor of ischemic cerebrovascular disease. Studies have shown that the infarct size of patients with secondary cerebral infarction after CEREBRAL infarction is correlated with their FIB level. In addition, FIB elevation is also one of the risk factors for early infarction after thrombolysis. Therefore, FIB can be used as a detection index for the prevention of cerebral infarction recurrence adverse reactions. Our MA results for FIB show WMD = 0.81, 95% CI: [0.38, 1.73], I2 = 0%, P = 0.58, and RR < 1. Conclusion. The existing clinical evidence shows that GLP has a good therapeutic effect on patients with ischemic stroke and can improve their hemorheology indices. In addition, GLP is shown to be relatively safe.

Fibrinolytic system activation immediately following trauma was quickly and intensely suppressed in a rat model of severe blunt trauma

In severe trauma, excessive fibrinolytic activation is associated with an increase in the transfusion volume and mortality rate. However, in the first several hours after a blunt trauma, changes in fibrinolytic activation, suppression, and activation–suppression balance have not yet been elucidated, which the present study aimed to clarify. Anesthetized 9-week-old male Wistar S/T rats experienced severe blunt trauma while being placed inside the Noble–Collip drum. Rats were randomly divided into four groups of seven. The no-trauma group was not exposed to any trauma; the remaining groups were analysed 0, 60, and 180 min after trauma. Immediately following trauma, total tissue-plasminogen activator (tPA) levels significantly increased in the plasma, and the balance of active tPA and active plasminogen activator inhibitor-1 (PAI-1) significantly tipped toward fibrinolytic activation. After trauma, both tPA and PAI-1 levels increased gradually in various organs and active and total PAI-1 levels increased exponentially in the plasma. Total plasma tPA levels 60 min after trauma returned quickly to levels comparable to those in the no-trauma group. In conclusion, fibrinolytic activation was observed only immediately following trauma. Therefore, immediately after trauma, the fibrinolytic system was activated; however, its activation was quickly and intensely suppressed.

Bleeding Disorders in Primary Fibrinolysis

Fibrinolysis is a complex enzymatic process aimed at dissolving blood clots to prevent vascular occlusions. The fibrinolytic system is composed of a number of cofactors that, by regulating fibrin degradation, maintain the hemostatic balance. A dysregulation of fibrinolysis is associated with various pathological processes that result, depending on the type of abnormality, in prothrombotic or hemorrhagic states. This narrative review is focused on the congenital and acquired disorders of primary fibrinolysis in both adults and children characterized by a hyperfibrinolytic state with a bleeding phenotype.

Features of hemostasis before and long-term periods in patients after ovarian apoplexy

The objective: to reveal the features of the parameters of the blood coagulation system in women in dynamics – from the acute period of ovarian apoplexy to the long-term postoperative period.Materials and methods. The study involved 82 women (main group, n=82), operated on for ovarian apoplexy, and 30 patients in the control group (n=30), who had no history of this pathology. All patients underwent a comprehensive examination using clinical, instrumental and laboratory research methods. The groups were homogeneous in age (average age was 26,1±2,3 years) and statistically comparable.Results. During the study, it was found that in the acute period of ovarian apoplexy, pathological changes were found in the plasma, vascular-platelet components and the fibrinolytic system of hemostasis, as evidenced by the lengthening of the thrombin time to 22,3±1,32 seconds, an increase in the concentration of fibrinogen to 6,73±0,64 g/l, SFMC up to 0,7±0,03 g/l and platelet hyperaggregation, stimulated by ADF, ristocetin and collagen, and reaching 80%. The extremely high content of D-dimer in the abdominal cavity in patients with ovarian apoplexy indicated increased thrombus formation in the damaged ovary, followed by activation of the fibrinolytic system and lysis of fibrin clots. Genetic thrombogenicity was found in general in 80,4% of patients, including those with a predominant lesion of the folate cycle enzymes - in every second patient.Positive dynamics with a tendency to normocoagulation was observed in the distant postoperative period. In the reference range were SFMC indices in 86,6% of cases, fibrinogen and thrombin time in 89,1% of cases, ristocetin-stimulated aggregatogram in 95,1% of cases (p<0,05).Conclusions. In women who underwent ovarian apoplexy, in the acute period of the disease, pathological changes in the vascular-platelet link of the hemostasis system were observed. The diagnosed thrombophilic disorders could lead to a deterioration in the rheological properties of blood, a violation of the processes of oxygenation and tissue trophism. The dynamic study of the hemostasis system in the acute and late postoperative periods of patients with ovarian apoplexy, as well as the data obtained on the prevalence of genetic thrombogenicity in the examined patients, should be taken into account when managing women from this risk group.

Fibrinolytic System and Cancer: Diagnostic and Therapeutic Applications

Fibrinolysis is a crucial physiological process that helps to maintain a hemostatic balance by counteracting excessive thrombosis. The components of the fibrinolytic system are well established and are associated with a wide array of physiological and pathophysiological processes. The aberrant expression of several components, especially urokinase-type plasminogen activator (uPA), its cognate receptor uPAR, and plasminogen activator inhibitor-1 (PAI-1), has shown a direct correlation with increased tumor growth, invasiveness, and metastasis. As a result, targeting the fibrinolytic system has been of great interest in the field of cancer biology. Even though there is a plethora of encouraging preclinical evidence on the potential therapeutic benefits of targeting the key oncogenic components of the fibrinolytic system, none of them made it from “bench to bedside” due to a limited number of clinical trials on them. This review summarizes our existing understanding of the various diagnostic and therapeutic strategies targeting the fibrinolytic system during cancer.

Fibrinolytic Alterations in Sepsis: Biomarkers and Future Treatment Targets

Sepsis is a life-threatening condition which develops as a dysregulated immune response in the face of infection and which is associated with profound hemostatic disturbances and in the most extreme cases disseminated intravascular coagulation (DIC). In addition, the fibrinolytic system is subject to alterations during infection and sepsis, and impaired fibrinolysis is currently considered a key player in sepsis-related microthrombus formation and DIC. However, we still lack reliable biomarkers to assess fibrinolysis in the clinical setting. Furthermore, drugs targeting the fibrinolytic system have potential value in sepsis patients with severe fibrinolytic disturbances, but these are still being tested in the preclinical stage. The present review provides an overview of key fibrinolytic changes in sepsis, reviews the current literature on potential laboratory markers of altered fibrinolysis in adult sepsis patients, and discusses future perspectives for diagnosis and treatment of fibrinolytic disturbances in sepsis patients.

Fibrinolysis in Acute and Chronic Cardiovascular Disease

The formation of an obstructive thrombus within an artery remains a major cause of mortality and morbidity worldwide. Despite effective inhibition of platelet function by modern antiplatelet therapies, these agents fail to fully eliminate atherothrombotic risk. This may well be related to extensive vascular disease, beyond the protective abilities of the treatment agents used. However, recent evidence suggests that residual vascular risk in those treated with modern antiplatelet therapies is related, at least in part, to impaired fibrin clot lysis. In this review, we attempt to shed more light on the role of hypofibrinolysis in predisposition to arterial vascular events. We provide a brief overview of the coagulation system followed by addressing the role of impaired fibrin clot lysis in acute and chronic vascular conditions, including coronary artery, cerebrovascular, and peripheral vascular disease. We also discuss the role of combined anticoagulant and antiplatelet therapies to reduce the risk of arterial thrombotic events, addressing both efficacy and safety of such an approach. We conclude that impaired fibrin clot lysis appears to contribute to residual thrombosis risk in individuals with arterial disease on antiplatelet therapy, and targeting proteins in the fibrinolytic system represents a viable strategy to improve outcome in this population. Future work is required to refine the antithrombotic approach by modulating pathological abnormalities in the fibrinolytic system and tailoring therapy according to the need of each individual.