Abnormalities In Coagulation System Research Articles

Clot lysis time and thrombin generation in patients undergoing transcatheter aortic valve implantation.

Aortic valve stenosis (AS) is the most prevalent valvular heart disease and is associated with a significant increase in mortality. AS has been shown to be linked with numerous coagulation system abnormalities, including increased fibrin deposition on the stenotic aortic valves. Transcatheter aortic valve implantation (TAVI) is the primary treatment method for patients at high surgical risk. The aim of the study was to assess the impact of treating severe AS with TAVI on thrombin generation and clot lysis time (CLT). We studied 135 symptomatic AS patients recommended for TAVI by the local Heart Team. All measurements were performed before and 5-7 days after TAVI. Alongside clinical assessment and echocardiographic analysis, we assessed clot lysis time (CLT) and thrombin generation parameters, including lag time, peak thrombin generation, time to peak thrombin generation (ttPeak), and endogenous thrombin potential (ETP). 70 patients were included in the final analysis. After TAVI, there was a significant 9% reduction in CLT despite a 12% increase in fibrinogen concentration. We observed significant increase in lag time and ttPeak (20% and 12%, respectively), and 13% decrease in peak thrombin concentration compared to pre-procedural levels. Multivariable linear regression analysis demonstrated that baseline CLT and C-reactive protein (CRP) levels were independent predictors of significant reduction in mean aortic gradient, defined as TAVI procedure success. CLT and peak thrombin concentration decreased, while Lag time and ttPeak increased significantly after TAVI. Multivariable linear regression analysis demonstrated CLT and CRP levels as independent predictors of achieving a reduction in mean aortic gradient, defining TAVI procedure success.

Thromboembolic and Bleeding Events in Transthyretin Amyloidosis and Coagulation System Abnormalities: A Review.

Transthyretin amyloidosis (ATTR) is a group of diseases caused by the deposition of insoluble fibrils derived from misfolded transthyretin, which compromises the structure and function of various organs, including the heart. Thromboembolic events and increased bleeding risk are among the most important complications of ATTR, though the underlying mechanisms are not yet fully understood. Transthyretin plays a complex role in the coagulation cascade, contributing to the activation and regulation of the coagulation and fibrinolytic systems. The prevalence of atrial fibrillation, cardiac mechanical dysfunction, and atrial myopathy in patients with ATTR may contribute to thrombosis, though such events may also occur in patients with a normal sinus rhythm and rarely in properly anticoagulated patients. Haemorrhagic events are modest and mainly linked to perivascular amyloid deposits with consequent capillary fragility and coagulation anomalies, such as labile international-normalised ratio during anticoagulant therapy. Therefore, it is paramount to carefully stratify the thrombotic and haemorrhagic risks, especially when initiating anticoagulant therapy. Our review aims to ascertain the prevalence of thromboembolic and haemorrhagic events in ATTR and identify potential risk factors and predictors and their impact on antithrombotic therapy.

Moderately severe acute pancreatitis after snake bite: a case report from Southern China.

Venomous snakebites are not rare worldwide, and this is also the situation in the mountainous regions of southern China, where they pose a serious health risk to the local population. Snake venom usually causes a variety of clinical symptoms, such as local pain and swelling, systemic coagulation system abnormalities, and shock, but rarely leads to acute pancreatitis. In this report, we presented a rare case of moderately severe acute pancreatitis caused by snake venom even after prompt antivenom treatment. The patient was relieved, obviously, with effective treatment of acute pancreatitis and was discharged without severe complications. Although acute pancreatitis after snake bite is a rarity, its serious complications and lethality still deserve our utmost attention, and timely and standardized treatment of acute pancreatitis is needed in addition to antivenom treatment.

Integrated analysis to identify the prognostic and immunotherapeutic roles of coagulation-associated gene signature in clear cell renal cell carcinoma.

The coagulation system is closely related to the physiological status and immune response of the body. Recent years, studies focusing on the association between coagulation system abnormalities and tumor progression have been widely reported. In clear cell renal cell carcinoma (ccRCC), poor prognosis often occurs in patients with venous tumor thrombosis and coagulation system abnormalities, and there is a lack of research in related fields. Significant differences in coagulation function were also demonstrated in our clinical sample of patients with high ccRCC stage or grade. Therefore, in this study, we analyzed the biological functions of coagulation-related genes (CRGs) in ccRCC patients using single-cell sequencing and TCGA data to establish the 5-CRGs based diagnostic signature and predictive signature for ccRCC. Univariate and multivariate Cox analyses suggested that prognostic signature could be an independent risk factor. Meanwhile, we applied CRGs for consistent clustering of ccRCC patients, and the two classes showed significant survival and genotype differences. The differences in individualized treatment between the two different subtypes were revealed by pathway enrichment analysis and immune cell infiltration analysis. In summary, we present the first systematic analysis of the significance of CRGs in the diagnosis, prognosis, and individualized treatment of ccRCC patients.

Management strategies for chronic liver disease-related thrombocytopenia

Chronic liver disease causes bleeding and coagulation system abnormalities through a variety of mechanisms. Thrombocytopenia is a common complication of chronic liver disease. Patients with chronic liver disease, especially liver cirrhosis, often face more invasive examinations or surgeries, which brings great challenges to clinical diagnosis and treatment. Traditional platelet transfusion is the main clinical intervention. With the approval of thrombopoietin receptor agonists, the current management standards for chronic liver disease-related thrombocytopenia may face changes. This article reviews the current main non-pharmacological and pharmacological interventions for chronic liver disease-related thrombocytopenia, and put forwards the corresponding clinical management improvement strategies based on the efficacy and limitations of these interventions.

Covid 19 Enfeksiyonu Olan Hastalarda Koagülasyon Sistem Anormallikleri

COVID-19 infection caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) in China led to a pandemic all over the world. Although mortality rate between 4.3% to 14.6%, studies have shown that coagulation dysfunction is a major cause of death in patients with severe COVID-19 infection. The majority of the severely ill patients have underlying disease (i.e. diabetes, cardiovascular disease, hypertension) and initially present with respiratory insufficiency but some of them progress to systemic disease causing multiple organ dysfunction. This manuscript reviews coagulation system abnormalities in patients with COVID-19 infection.

Clinical Features of Visual Disturbances in Leiden Thrombophilia

The hereditary thrombophilias is a well-recognized important risk factor for a systemic and local thromboembolic events development. The case of Leiden thrombophilia family inheritance concomitant by the visual disturbances development are shown in this аrticle. Most commonly in hereditary thrombophilias, venous thrombembolias occur, arterial occlusions which have been reported in the recent literature only as individual clinical cases occur more rarely. In the European population hereditary thrombophilias are associated with a prothrombotic mutation in the coagulation factor V gene (Leiden factor) in a greater degree; herewith the risk of thrombotic complications is increasing significantly in homozygous polymorphism forms. Presence of combined mutations in several clotting factors also leads to risk of thrombembolias increase. Consequence of the Leiden mutation is a V activator resistance to the resolving action of the activated protein C which is a natural endogenous anticoagulant protein. Resistance development leads to a deceleration of V factor inactivation and to increasing of the thrombin amount. In the work presented here, development of the consistent bilateral occlusion of the central retinal artery (CRA) in a middle-aged patient with a heterozygous form of Leiden thrombophilia is the subject of interest. Along with the hereditary hemostatic system abnormality, the patient also had cardiovascular risk factors (hypertensive disease, atherosclerosis) which had a potentiating effect on the occlusion development. Taking into account the autosomal dominant nature of the Leiden mutation inheritance, the patient’s only daughter was examined; brief episodes of amaurosis fugax against the background of headaches similar to migraine were detected due to ophthalmological abnormalities. For verification of the Leiden thrombophilia diagnosis, both patients underwent molecular genetic diagnostics. Currently there are no large prospective studies showing the optimal and economically viable approach for identification of thrombophilia genetic polymorphisms in patients with retinal vascular occlusions in daily clinical experience. Possible additional risk factors for thrombembolias development, prevention services for manifest and recurrent vascular occlusions in patients with hereditary blood coagulation system abnormalities and their relatives are discussed in this article.

A Challenging Case of Coagulopathy in the ICU

SESSION TITLE: Critical Care 2 SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Disseminated Intravascular Coagulation (DIC) is common in critically ill patients and is usually secondary to sepsis. It can potentially confound a diagnosis of a potentially fatal and uncommon disorder such as hemophagocytic lymphohistiocytosis (HLH)1. Both entities are clinicopathologic diagnoses with shared coagulation system abnormalities. We present a case of DIC initially managed supportively as being secondary to sepsis, with workup leaving secondary HLH. CASE PRESENTATION: A 69 year old female with no known past medical history was brought to the hospital by ambulance for worsening shortness of breath and lethargy. The patient was recently treated for pneumonia with oral azithromycin. At presentation, the patient was tachycardiac, hypotensive and hypoxic with a hemoglobin of 13 g/dL, WBC count 2.61 x 109/L, platelets 92 x 109/L, alkaline phosphatase 212 IU/L, AST 166 IU/L, ALT 61 IU/L and a normal coagulation profile. In a week, her pancytopenia worsened PTT was 99 seconds, PT 13.7 seconds and fibrinogen 84 mg/dL. A CT scan of the abdomen showed necrotic right inguinal adenopathy the biopsy of which was non-diagnostic. Infectious disease work up was negative. Further studies showed a ferritin of 32522 ng/mL, haptoglobin of <20 mg/dL, LDH of 982 IU/L and low natural killer cell activity. A bone marrow biopsy showed significant hemophagocytic macrophages and a diagnosis of concomitant DIC and hemophagocytic lymphohistiocytosis was made. Dexamethasone 10 mg/m2 was started and she received two doses of etoposide 150 mg/m2 resulting in a decrease in ferritin to 19947 ng/mL and normalization of coagulation parameters. A repeat excisional inguinal lymph node biopsy was consistent with anaplastic large cell lymphoma. DISCUSSION: Hemophagocytic lymphohistiocytosis results from uncontrolled activation of cytotoxic T cells resulting in a cytokine storm. It can be familial or secondary to an underlying disorder and has a mortality rate of up to 70% from multiorgan failure. Our patient was started on HLH directed therapy based on clinical judgement and later fulfilled five diagnostic criteria CONCLUSIONS: Hemophagocytic lymphohistiocytosis and co-existent DIC is uncommon and can delay a diagnosis of HLH. Prompt recognition and treatment of the underlying disorder is crucial to improving outcomes. Reference #1: Coagulation Disorders and Bleedings in Critically Ill Patients With Hemophagocytic Lymphohistiocytosis.Valade S, Azoulay E, Galicier L, Boutboul D, Zafrani L, Stepanian A, Canet E, Lemiale V. 2015 Oct;94(40):e1692. DISCLOSURE: The following authors have nothing to disclose: Amina Saqib, uroosa Ibrahim, Gwen Garcia, Rabih Maroun, Jean Atallah No Product/Research Disclosure Information

Haemostatic system in inflammatory bowel diseases: New players in gut inflammation

Inflammation and coagulation constantly influence each other and are constantly in balance. Emerging evidence supports this statement in acute inflammatory diseases, such as sepsis, but it also seems to be very important in chronic inflammatory settings, such as inflammatory bowel disease (IBD). Patients with Crohn's disease and ulcerative colitis have an increased risk of thromboembolic events, and several abnormalities concerning coagulation components occur in the endothelial cells of intestinal vessels, where most severe inflammatory abnormalities occur. The aims of this review are to update and classify the type of coagulation system abnormalities in IBD, and analyze the strict and delicate balance between coagulation and inflammation at the mucosal level. Recent studies on possible therapeutic applications arising from investigations on coagulation abnormalities associated with IBD pathogenesis will also be briefly presented and critically reviewed.

PAI-1 and TAFI in inflammatory bowel disease: the yin and yang of the fibrinolytic system

In both Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel disease (IBD), an increased risk of thrombotic events has been demonstrated. Pathogenesis of thrombosis is multifactorial as various primary coagulation system abnormalities other than acquired factors have been reported. The fibrinolytic system has been widely investigated in IBD. Most of the available data report an imbalance in fibrinolytic capacity with a tendency toward a hypofibrinolytic state. Plasma thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 are fundamental inhibitors of the fibrinolytic process and are also considered to be acute-phase reactants. Recent studies have shown an imbalance of plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor, suggesting that these molecules might contribute to thromboembolic events in both forms of IBD.

Evaluation of anticoagulant system in Turkish children with Perthes disease

Perthes Disease (PD) is generally a self-limiting disease of childhood but it causes severe pain and may lead to deformity of the femoral head. Intravascular thrombosis seems to form the main mechanism in the pathogenesis of the disease. The aim of this study was to determine hereditary thrombotic risk factors in Turkish children with PD. In 46 Perthes patients (35 male, 11 female), family history of thrombotic events was investigated, Protein C (PC), free-Protein S (f-PS), antithrombin (AT) activities, fibrinogen level, and resistance to activated Protein C (APC) were measured. The results were compared with a healthy control group of 79 children matched by age and sex. The relationship between the severity of disease and coagulation system abnormalities was evaluated. While the mean PC and AT activities were significantly lower in the patients than those of the controls, the proportions of patients with low AT activity, resistance to APC, and a history of hereditary thrombophilia were significantly higher than those of the controls. No difference was observed in coagulation system disorders relative to severity of the disease and bilateral or unilateral disease involvement. This study shows that a possible association between PD and inherited hypercoagulability. Determination of thrombotic risk factors in these patients may bring a new approach to the treatment. Most importantly, this may be a stimulant to take precautions for other thrombotic events, which patients may face later in life.

Massive Cardiac Thrombosis in a Patient with Sheehan's Syndrome

Growth hormone deficiency (GHD) is a risk factor for increased cardiovascular disease, and it has been recently demonstrated that abnormalities in coagulation system might contribute to the increased cardiovascular morbidity and mortality. However, there is not enough data related to the major thrombotic events in GH-deficient patients. We describe the case of a 62-year-old woman with Sheehan's syndrome who developed massive cardiac thrombosis. She was hospitalized with acute pulmonary edema. ECG revealed high ventricular responsive atrial fibrillation (AF) and T-wave inversion on precordial leads. The ejection fraction of left ventricle (LVEF) was measured as 60% by transthoracic echocardiography (TTE) and there was 2nd degree mitral regurgitation with concentric hypertrophic LV walls. Transesophagial echocardiography (TEE) established thrombi both at right atrium and left atrial appendix. Before anticoagulant therapy several hemostatic and fibrinolytic markers were measured. Except increased D-dimer concentration (763.14 mug/L (0-325)) we did not observe any pathological finding in these parameters. After 14 days of discharge, the patient was admitted to the intensive care unit with upper gastrointestinal bleeding. The warfarin and salicylate were stopped for two months. At the end of two months, the patient was again hospitalized with congestive heart failure and there was a high ventricular responsive AF on ECG. TEE was performed and three thrombi were demonstrated at right atrium (RA), left atrium (LA) and left ventricle (LV). There was no active bleeding on upper GIS endoscopy and anticoagulant therapy was restarted. In this particular case massive cardiac thrombi involving three chambers (LA, RA, LV) were more extensive than expected in AF. Moreover, there was a 2nd degree mitral regurgitation in the patient, and based on previous studies mitral regurgitation has been associated with less prevalent LA spontaneous echo contrast and fewer thromboembolic events. Therefore we hypothesized that severe GHD in the present case might be the major contributing factor in massive cardiac thrombosis. In summary, based on previous data there is increased risk of thromboembolic events in GHD although the mechanism is unclear yet. Our case is the first case showing massive cardiac thrombosis in a severe GH-deficient patient with Sheehan's syndrome. Therefore, patients with GHD should be screened carefully for thrombus in clinical practice, and further studies need to be done to understand the relation between GHD and coagulation system.

The role of protein C, protein S, and resistance to activated protein C in Legg-Perthes disease.

It has been hypothesized that Legg-Perthes disease is caused by repeated vascular interruptions of the blood supply to the proximal femur, which are precipitated by coagulation system abnormalities. To test this theory, we conducted a case-control study among 57 patients with Legg-Perthes disease and an equal number of community controls. We measured protein C and protein S and resistance to activated protein C (APC-R) from plasma. Participants were placed into 1 of 3 mutually exclusive categories based on the control distribution: 1) normal, defined as either above or within 1 standard deviation below the expected mean; 2) low normal, defined as between 1 and 2 standard deviations below the expected mean; and 3) low, defined as >2 standard deviations below the expected mean. DNA was analyzed to determine the presence of a point mutation in the factor V gene that causes APC-R. We observed a statistically significant increased risk of Legg-Perthes disease with decreasing levels of protein C and a nearly significant increased risk with decreasing levels of protein S. The factor V gene defect was present in 5 (9%) of 55 cases and 3 (5%) of 56 controls (odds ratio 1.8, 95% confidence interval: 0.4-7.7), but the mean level on the APC-R plasma test was similar for cases and controls. Nine cases and 1 control had 2 low normal or low test results (odds ratio 13.0, 95% confidence interval: 2.2-75). Our results support the belief that abnormalities of the coagulation system leading to a thrombophilic state play a role in Legg-Perthes disease; however, larger studies are needed before definitive recommendations for coagulation testing can be made.

The Incidence and significance of thromboembolic complications in patients with high-grade gliomas

Coagulation system abnormalities in patients with malignancy ranges from asymptomatic laboratory abnormalities to overt clinical manifestations. To determine the incidence and significance of clinically manifest thromboembolic phenomena in patients with high-grade gliomas, the records were analyzed of 77 patients that presented between January 1985 and June 1988. Fifteen patients (19%) had clinically manifest deep venous thrombosis and/or pulmonary emboli during the course of their disease. All these patients were ambulatory before and at the time of diagnosis of the event. The thromboembolic episodes occurred at the time of initial management of the primary tumor while there was documented clinical improvement in the functional status of the patient or at the time of progression of the disease. One patient died as a result of a pulmonary embolism; in two others, an embolism was a significant contributor to the patient's death. Anticoagulation resulted in complications in two of eight patients treated. Thromboembolic events occur with high frequency in patients with high-grade gliomas and contribute to the high morbidity and mortality seen in these patients. The optimum approach to screening and the treatment of these events has not been determined.