[Coagulation disorders in liver cirrhosis - Diagnostics and management]. / Gerinnungsstörungen bei Leberzirrhose ­ Diagnostik und Management.

Patients with liver cirrhosis often exhibit complex alterations in their hemostatic system that can be associated with both bleeding and thrombotic complications. While prophylactic correction of abnormal coagulation parameters should be avoided, an individualized approach is recommended prior to invasive procedures, whereby specific preventive measures to stabilize hemostasis should be based on the periprocedural bleeding risk. While the haemostatic system of patients with compensated cirrhosis is often in a rebalanced haemostatic state due to a parallel decline in both pro- and anti-haemostatic factors, a decompensation of liver cirrhosis can lead to destabilization of this fragile equilibrium. Since conventional coagulation tests do not adequately capture the complex changes in the hemostatic system in cirrhosis, functional analysis methods such as viscoelastic tests or thrombin generation assays can be used for evaluating the coagulation status. This review describes the underlying pathophysiological changes in the hemostatic system in liver cirrhosis, provides an overview of diagnostic methods and discusses therapeutic measures in case of bleeding and thrombotic complications.

Assessment of Thrombotic Complications among Coronavirus Disease 2019 Positive Hospitalized Patients at One of Government Tertiary Care Centres of Gujarat: A Retrospective Observational Study.

OBJECTIVES: The objectives of the study were to (1) study risk factors of thrombotic complications in coronavirus disease 2019 (COVID-19) pneumonitis, and (2) study progression of thrombotic complications after COVID-19 pneumonitis and its outcome. MATERIALS AND METHODS: A total of 50 COVID-19-positive admitted patients were studied using a purposive random sampling method. A questionnaire was used to collect data from patients' case records. RESULTS: Diabetes (42%) and hypertension (40%) were common comorbidities. The most common presentation of patients was thromboembolism, followed by cerebrovascular accident (CVA) and myocardial infarction (MI). Around 32% of patients died during the course of treatment. Deaths were more commonly seen in the age-group of 56 years or above than in those below 56 years. Death rates were higher among the group of patients with diabetes, hypertension, and ischemic heart diseases than the group of patients without those diseases, respectively. Patients in whom intubation was needed had a higher death rate than those without the need for it. The mean C-reactive protein (CRP) value was higher in patients who died than in those who survived. The death rate was lower in patients who were thrombolysed than in those who were not, in both pulmonary embolism and MI cases. CONCLUSION: The most common age-group admitted to the hospital was 46-55 years. The two most common underlying risk factors were diabetes and hypertension. Three common presentations of patients were thromboembolism, followed by CVA and MI. Around 32% of patients died during the course of treatment. Deaths were more commonly seen in the age-group of 56 years or above than in those below 56 years. Death rates were higher among the group of patients with diabetes, hypertension, and ischemic heart diseases than the group of patients without those diseases, respectively. Patients in whom intubation was needed had a higher death rate than those without the need for it. The mean CRP value was higher in patients who died than in those who survived.

Successful Thrombolysis of an Obstructive Prosthetic Mitral Valve Thrombosis Using Alteplase.

A 48-year-old man with a history of mitral valve replacement (MVR) in March 2019 for rheumatic heart disease (RHD) and ischemic stroke in August 2019 presented with a history of sudden onset angina of 6 hours duration. He admits to defaulting oral anticoagulant (OAC) intake for the last 50 days. On arrival, he had atrial fibrillation with hemodynamic instability [blood pressure (BP) 70/40 mm Hg, saturation of peripheral oxygen (SpO2) 80% at room air and heart rate approx 140/minute], which was managed with intravenous diltiazem and hemodynamic stability achieved (BP 116/72 mm Hg, heart rate 86/minute). Urgent transthoracic echocardiogram (TTE) and fluoroscopy confirmed obstructive prosthetic mitral valve thrombosis. Though available recommendations suggest surgical intervention for the left-sided valve involvement in a stable patient, in view of the nonavailability of a surgical facility, the patient was thrombolyzed with Alteplase, a recombinant tissue plasminogen activator (rtPA). Since the patient was stable, a "long fibrinolytic protocol" of Alteplase 10 mg bolus, 50 mg during the 1st hour, and 20 mg each during the 2nd and 3rd hour (total of 100 mg) was given. Subsequent TTE revealed a mean gradient of 5 mm Hg, and cine fluoroscopy showed improved mitral valve motion, thereby indicating successful thrombolysis. The patient felt symptomatically relieved within 6 hours and is presently on OAC therapy with strict drug compliance.

Neutrophil extracellular traps induce intrahepatic thrombotic tendency and liver damage in cholestatic liver disease.

BACKGROUND: Cholestatic liver diseases induce local and systemic hypercoagulation, with neutrophil extracellular traps (NETs) serving as major drivers. These NETs have been linked to decreased liver function in patients with obstructive jaundice. However, the impact of NETs on liver hypercoagulation in cholestatic liver disease remains unknown. METHODS: We utilized bile duct ligation to create experimental mice and analyzed NETs formation in the liver. Fibrin deposition, tissue factor expression, and inflammation in the liver were visualized through western blot and immunohistochemical techniques. LSECs were incubated with isolated NETs, and we detected endothelial procoagulant activity using coagulation protein production assays and measuring endothelial permeability. In both in vivo and in vitro settings, DNase I was applied to clarify the effect of NETs on intrahepatic hypercoagulability, hepatotoxicity, LSEC, and macrophage activation or injury. RESULTS: Bile duct ligation mice exhibited significantly increased levels of NETs in liver tissue, accompanied by neutrophil infiltration, tissue necrosis, fibrin deposition, and thrombophilia compared to sham mice. Notably, NETs resulted in phosphatidylserine and tissue factor exposure on LSEC, enhancing coagulation Factor Xa and thrombin production. The enhanced procoagulant activity could be reversed by degrading NETs with DNase I. Additionally, NETs-induced permeability changes in LSECs, characterized by increased VE-cadherin expression and F-actin retraction, which could be rescued by DNase I. Meanwhile, NET formation is associated with KC activation and the formation of inflammatory factors. CONCLUSIONS: NETs promote intrahepatic activation of coagulation and inflammation, leading to liver tissue injury. Strategies targeting NET formation may offer a potential therapeutic approach for treating cholestatic liver disease.

Abdominal aneurysm sac thrombus CT density and volume after EVAR: which association with underlying endoleak?

BACKGROUND: Our aim was to analyse abdominal aneurysm sac thrombus density and volume on computed tomography (CT) after endovascular aneurysm repair (EVAR). METHODS: Patients who underwent EVAR between January 2005 and December 2010 and had at least four follow-up CT exams available over the first five years of follow-up were included in this retrospective single-centre study. Thrombus density and aneurysm sac volume were calculated on unenhanced CT scans. Linear mixed models were used for data analysis. RESULTS: Out of 82 patients, 44 (54%) had an endoleak on post-EVAR contrast-enhanced CT. Thrombus density significantly increased over time in both the endoleak and non-endoleak groups, with a slope of 0.159 UH/month (95% confidence interval [CI] 0.115-0.202), p < 0.0001) and 0.052 UH/month (95% CI 0.002-0.102, p = 0.041). In patients without endoleak, a significant decrease in aneurysm sac volume was identified over time (slope -0.891 cc/month, 95% CI -1.200 to -0.581); p < 0.001) compared to patients with endoleak (slope 0.284 cc/month, 95% CI -0.031 to 0.523, p = 0.082). The association between thrombus density and aneurysm sac volume was positive in the endoleak group (slope 1.543 UH/cc, 95% CI 0.948-2.138, p < 0.001) and negative in the non-endoleak group (slope -1.450 UH/cc, 95% CI -2.326 to -0.574, p = 0.001). CONCLUSION: We observed a progressive increase in thrombus density of the aneurysm sac after EVAR in patients with and without endoleak, more pronounced in patients with endoleak. The association between aneurysm volume and thrombus density was positive in patients with and negative in those without endoleak. RELEVANCE STATEMENT: A progressive increase in thrombus density and volume of abdominal aortic aneurysm sac on unenhanced CT might suggest underlying endoleak lately after EVAR. KEY POINTS: Thrombus density of the aneurysm sac after EVAR increased over time. Progressive increase in thrombus density was significantly associated to the underlying endoleak. The association between aneurysm volume and thrombus density was positive in patients with and negative in those without endoleak.

Thrombus aspiration is associated with improved platelet inhibition rate following dual antiplatelet therapy in acute myocardial infarction patients.

BACKGROUND: It is well-established that thrombus aspiration during primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) indicates a higher thrombus burden and necessitates more intensive antithrombotic therapy. The bidirectional association between adverse events in AMI patients and platelet reactivity is typically observed during dual antiplatelet therapy (DAPT). OBJECTIVE: To investigate platelet reactivity after DAPT in AMI patients with thrombus aspiration performed during PCI. METHODS: In this retrospective study, we examined 269 consecutive AMI patients who underwent PCI and recorded their demographic, clinical and laboratory data. The platelet reactivity was measured with thromboelastogram (TEM). RESULTS: Ultimately, 208 patients were included in this study and divided into a Thrombus Aspiration group (N = 97) and a PCI Alone group (N = 111) based on whether thrombus aspiration was performed or not. The adenosine diphosphate (ADP)-induced platelet inhibition rate in the Thrombus Aspiration group was higher than that in the PCI Alone group (P < 0.001). Furthermore, multivariate linear regression analysis revealed that the ADP-induced platelet inhibition rate was independently associated with leukocyte count, thrombus aspiration and the combination of aspirin and ticagrelor as DAPT after adjusting for potential covariates in all AMI patients. CONCLUSION: In conclusion, clinicians should exercise heightened attention towards the bleeding risk among patients undergoing PCI concomitant with Thrombus Aspiration postoperatively.

Treatment of Transcatheter Aortic Valve Thrombosis: JACC Review Topic of the Week.

Transcatheter aortic valve (TAV) thrombosis may manifest as subclinical leaflet thrombosis (SLT) and clinical valve thrombosis. SLT is relatively common (10%-20%) after transcatheter aortic valve replacement, but clinical implications are uncertain. Clinical valve thrombosis is rare (1.2%) and associated with bioprosthetic valve failure, neurologic or thromboembolic events, heart failure, and death. Treatment for TAV thrombosis has been understudied. In principle, anticoagulation may prevent TAV thrombosis. Non-vitamin K oral anticoagulants, as compared to antiplatelet therapy, are associated with reduced incidence of SLT, although at the cost of higher bleeding and all-cause mortality risk. We present an overview of existing literature for management of TAV thrombosis and propose a rational treatment algorithm. Vitamin K antagonists or non-vitamin K oral anticoagulants are the cornerstone of antithrombotic treatment. In therapy-resistant or clinically unstable patients, ultraslow, low-dose infusion of thrombolytics seems effective and safe and may be preferred over redo-transcatheter aortic valve replacement or explant surgery.

Thrombotic antiphospholipid syndrome: From guidelines to clinical management.

Thrombotic manifestations, mainly venous thromboembolism (VTE) and stroke, are the most common and potentially life-threatening presentations of antiphospholipid syndrome (APS). The management of APS requires the assessment of the antiphospholipid antibodies (aPL) profile, of concurrent systemic lupus erythematosus or other systemic autoimmune diseases and the presence of risk factors for cardiovascular disease and bleeding. Anticoagulation with vitamin K antagonists (VKA) remains the cornerstone of therapy for thrombotic APS. As platelets play a central role in APS, low-dose aspirin is the first option for primary thromboprophylaxis in asymptomatic aPL carriers, and also plays a role as combination therapy with VKAs in arterial thrombosis. Treatment with direct oral anticoagulants (DOACs) could be considered in certain low-risk situations, although they are not recommended in patients with arterial thrombosis or triple positive aPL. Adjuvant therapies such as hydroxychloroquine and statins may be useful in complex settings such as thrombotic recurrences or high risk of bleeding. In this article, we review the evidence and the recommendations of the guidelines for the treatment of APS, and provide a critical and practical approach of its management from our clinical perspective.

Catastrophic antiphospholipid syndrome: Lessons from the "CAPS Registry".

The catastrophic antiphospholipid syndrome (CAPS) is a rare life-threatening clinical condition that represents the most severe clinical presentation of the antiphospholipid syndrome (APS). It was first described in 1992 in a group of patients that presented with multiorgan involvement and microangiopathic features of APS. Most of the current knowledge of CAPS comes from the analysis of all cases collected at the "CAPS Registry" that was created in 2000 to perform studies on this condition. Most cases are triggered by a prothrombotic situation that leads to a multiorgan thrombosis and a cytokine storm. The analysis of cases included in the "CAPS Registry" has shown that the triple therapy with anticoagulation, glucocorticoids, and plasma exchange and/or intravenous immunoglobulins is associated to a better prognosis of CAPS. The improvement of the knowledge allowed a decrease from the 50% mortality rate reported in the first series to 25-30% in the most recent publications.

Numerical simulation and in vitro experimental study of the hemodynamic performance of vena cava filters with helical forms.

Inferior vena cava filter (IVCF) implantation is a common method of thrombus capture. By implanting a filter in the inferior vena cava (IVC), microemboli can be effectively blocked from entering the pulmonary circulation, thereby avoiding acute pulmonary embolism (PE). Inspired by the helical flow effect in the human arterial system, we propose a helical retrievable IVCF, which, due to the presence of a helical structure inducing a helical flow pattern of blood in the region near the IVCF, can effectively avoid the deposition of microemboli in the vicinity of the IVCF while promoting the cleavage of the captured thrombus clot. It also reduces the risk of IVCF dislodging and slipping in the vessel because its shape expands in the radial direction, allowing its distal end to fit closely to the IVC wall, and because its contact structure with the inner IVC wall is curved, increasing the contact area and reducing the risk of the vessel wall being punctured by the IVCF support structure. We used ANSYS 2023 software to conduct unidirectional fluid-structure coupling simulation of four different forms of IVCF, combined with microthrombus capture experiments in vitro, to explore the impact of these four forms of IVCF on blood flow patterns and to evaluate the risk of IVCF perforation and IVCF dislocation. It can be seen from the numerical simulation results that the helical structure does have the function of inducing blood flow to undergo helical flow dynamics, and the increase in wall shear stress (WSS) brought about by this function can improve the situation of thrombosis accumulation to a certain extent. Meanwhile, the placement of IVCF will change the flow state of blood flow and lead to the deformation of blood vessels. In in vitro experiments, we found that the density of the helical support rod is a key factor affecting the thrombus trapping efficiency, and in addition, the contact area between the IVCF and the vessel wall has a major influence on the risk of IVCF displacement.

[Thrombosis of portal cavernoma]. / Thrombose du cavernome porte.

Portal cavernoma thrombosis is a complication of portal cavernoma. We describe the case of a 74-year-old patient who presented to the emergency department with abdominal pain. The computed tomography scan showed a mass from the head of the pancreas to the hepatic hilum not enhanced after injection of iodinated contrast. There was no dilatation of the bile ducts. Abdominal magnetic resonance ruled out a tumour and confirmed a portal cavernoma thrombosis. In 50 % of cases the etiology of the portal cavernoma is unknown. It is often asymptomatic. It may be discovered in case of complications of portal hypertension. In rare cases the portal cavernoma can compress the bile ducts. To our knowledge, portal cavernoma thrombosis has only been described in one article. It is important to search for a thrombophilic disorder when such a complication is found. We share this case report in order to raise awareness in the medical community about this rare complication.

La thrombose de cavernome portal est une complication du cavernome porte. Nous décrivons le cas d'un patient de 74 ans qui s'est présenté aux urgences pour des douleurs abdominales. La tomodensitométrie montrait un syndrome de masse de la tête du pancréas jusqu'au hile hépatique non rehaussé après injection de produit de contraste iodé. Il n'y avait pas de dilatation des voies biliaires. Une imagerie par résonance magnétique abdominale a permis d'infirmer l'hypothèse d'une masse tumorale et d'affirmer une thrombose du cavernome porte. Dans 50 % des cas, l'étiologie du cavernome portal est inconnue. Il est souvent asymptomatique. Il peut être découvert en cas de complications à la suite d'une hypertension portale. Dans de rares cas, le cavernome portal peut comprimer les voies biliaires. À notre connaissance, la thrombose de cavernome portal n'a été décrite que dans un seul article. Il est important de rechercher un désordre thrombophilique quand une telle complication est retrouvée. Nous partageons ce cas clinique afin de sensibiliser la communauté médicale à cette rare complication.

Effect of bile duct resection on the prognosis of patients with hepatocellular carcinoma combined with extrahepatic bile duct tumor thrombus.

BACKGROUND: Surgical therapy is the most optimal treatment for hepatocellular carcinoma (HCC) combined with bile duct tumor thrombus (BDTT) patients. However, whether to perform bile duct resection (BDR) is still controversial. The purpose of this multicenter research is to compare the effect of BDR on the prognosis of extrahepatic BDTT patients. METHODS: We collected the data of 111 HCC patients combined with extrahepatic BDTT who underwent radical hepatectomy from June 1, 2004 to December 31, 2021. Those patients had either received hepatectomy with extrahepatic bile duct resection (BDR group) or hepatectomy without bile duct resection (NBDR group). Inverse probability of treatment weighting (IPTW) was used to reduce the potential bias between two groups and balance the influence of confounding factors in baseline data. Then compare the prognosis between the two groups of patients. Cox regression model was used for univariate and multivariate analysis to further determine the independent risk factors that influence the prognosis of HCC-BDTT patients. RESULTS: There were 38 patients in the BDR group and 73 patients in the NBDR group. Before and after IPTW, there were no statistical significance in OS, RFS and intraoperative median blood loss between the two groups (all P > 0.05). Before IPTW, the median postoperative hospital stay in the NBDR group was shorter (P = 0.046) and the grade of postoperative complications was lower than BDR group (P = 0.014). After IPTW, there was no difference in postoperative hospital stay between the two groups (P > 0.05). The complication grade in the NBDR group was still lower than that in the BDR group (P = 0.046). The univariate analysis showed that TNM stage and portal vein tumor thrombus (PVTT) were significantly correlated with OS (both P < 0.05). Preoperative AFP level, TNM stage and prognostic nutritional index (PNI) were significantly correlated with postoperative RFS (all P < 0.05). Multivariate analysis showed that tumor TNM stage was an independent risk factor for the OS rate (P = 0.014). TNM stage, PNI and AFP were independent predictors of RFS after radical hepatectomy (all P < 0.05). CONCLUSIONS: For HCC-BDTT patients, hepatocellular carcinoma resection combined with choledochotomy to remove the tumor thrombus may benefit more.

[Intervention principles for complications of arteriovenous graft].

Stenosis, thrombosis, and infection are major complications of arteriovenous graft (AVG). Endovascular therapy is usually adopted for stenosis, while bypass, interposition, patch angioplasty and other surgical techniques can also be used for special sites. Interventions of AVG thrombosis include removal of thrombus and treatment of the underlying stenosis. The former includes catheter directed thrombolysis, endovascular intervention, surgical treatment, or hybrid treatment. Etiological detection before the application of empirical antibiotics is the first step of infection management. According to different infection ranges, partial graft excision and interposition, total graft excision and partial graft excision can be performed respectively. Active prevention, timely identification, and appropriate intervention of the complications can improve the long-term outcomes of AVG. Personalized interventional strategy should be employed based on the systemic evaluation.

Catheters linked thrombosis in neonates: a single center observational study.

BACKGROUND: Central venous catheters (CVCs) are the major risk factors for neonatal thrombosis that might negatively affect morbidity and mortality in neonates. The aim of the present work was to estimate the incidence of CVC-linked thrombosis, among neonates in the NICU of Alexandria University Maternity Hospital, Egypt, over 1year, and to determine its possible risk factors. METHODS: This observational cohort study involved 134 newborn infants born from July 2020 to July 2021with CVCs insertion during their hospital stay. Patients who had congenital anomalies, had thrombosis unrelated to the implantation of CVCs or died before 7 days of catheter placement were excluded from the analysis. The 134 neonates who met the study's eligibility requirements had 142 CVCs inserted. Serial ultrasound and Doppler scans on site of venous insertion of catheters were performed. RESULTS: Seventeen patients with catheter's thrombosis (12%) were found during the placement of 142 catheters or 1615 CVCs' days, resulting in an overall rate of 10.5 thrombotic events per 1000 catheters' days. We constructed a logistic regression model to identify risk factors behind CVC-linked thrombosis. In univariate analysis, femoral central venous lines (CVLs), catheter dwell-time, sepsis, packed red cells (PRBCs) transfusions and low platelet count were risk factors for CVC-linked thrombosis. Nevertheless, only PRBCs transfusion was significant in the multivariate analysis, with OR and 95% confidence level 5.768 (1.013-32.836). CONCLUSION: Many factors should be considered in prediction of patients at risk of thrombosis including sepsis, femoral line insertion, low platelet count and PRBCs-transfusions. In our analysis, PRBCs-transfusion through peripheral intravenous lines (PIVs) was the strongest factor associated with CVC-linked thrombosis.

Development and validation of a nomogram for catheter-related thrombosis prediction in children with central venous catheter: a retrospective observational study.

BACKGROUND: Catheter-related thrombosis (CRT) is a thrombotic complication associated with using central venous catheters (CVCs). Although risk factors for CRT were identified in children, no nomograms or predictive tools are available for the pediatric population with CVCs. This study aimed to develop and validate a prediction model of asymptomatic CRT in children with CVCs. METHODS: This retrospective observational study included consecutive pediatric patients who admitted to the Children's Hospital Zhejiang University School of Medicine and received CVCs between October and December 2021. RESULTS: This study included 669 patients, 553 (314 males, aged 22.00 [0.36, 180.00] months, 62 with CRT) were in the training set, and 116 (62 males, aged 15.00 [1.13, 156.00] months, 16 with CRT) were in the validation set. Multivariate logistic regression showed that a catheter time of 0-3 days (OR = 0.201, 95%CI: 0.081-0.497, P = 0.001), catheter time of 4-7 days (OR = 0.412, 95%CI: 0.176-0.964, P = 0.041), male (OR = 3.976, 95%CI: 1.864-4.483, P < 0.001), congenital heart diseases (OR = 0.277, 95%CI: 0.078-0.987, P = 0.048), postoperative (OR = 0.161, 95%CI: 0.072-0.360, P < 0.001), and femoral CVC (OR = 2.451, 95%CI: 1.129-5.318, P = 0.002) were independently associated with CRT. The nomogram incorporating these variables showed relatively good discrimination (AUC = 0.77, 95%CI: [0.65, 0.90]) and calibration abilities in the validation set, and the decision curve analysis (DCA) yielded a clinical net benefit. CONCLUSION: A prediction model for CRT in children with CVC was established based on catheter time, sex, diseases, postoperative, and catheter vein. The nomogram based on logistic regression model showed favorable predictive performance.