Severe Coagulopathy Research Articles

Clinical manifestations of alpine pit viper (Trimeresurus gracilis) bites

Introduction The alpine pit viper, Trimeresurus gracilis, is an endemic species in Taiwan. The incidence of human envenoming is rare. Case summaries We present three events in two patients bitten by Trimeresurus gracilis. In the first patient, envenoming inflicted pain, local bleeding, hemorrhagic bulla, and progressive swelling, leading to necrosis of the bite wound. In the second patient, the two snakebites caused pain and progressive swelling. There were no systemic effects such as organ damage or neurological deficits observed. A paraspecific antivenom against Trimeresurus stejnegeri and Protobothrops mucrosquamatus was used to treat both patients, with a favorable outcome in each. Discussion Combined with the clinical manifestations of two previously reported cases of Trimeresurus gracilis envenoming, the known effects of Trimeresurus gracilis venom in humans include local toxicities, severe soft-tissue damage, compartment syndrome, and coagulopathy without spontaneous systemic bleeding. The paraspecific antivenom, which has demonstrable cross-neutralization effects in animal studies, appeared to be effective against the local toxicities as the patients showed prompt cessation of the progression of their swelling. Conclusions The knowledge of clinical manifestations and management approaches to Trimeresurus gracilis envenoming is helpful for patient care. The use of the paraspecific antivenom should be considered in managing such envenoming.

Comprehensive Evaluation of Pulmonary Masses Using Multi-detector CT: Correlating Morphological Features With CT-Guided Histopathological Findings for Enhanced Diagnostic Accuracy.

Lung masses pose a significant diagnostic challenge due to their diverse causes, from benign hamartomas to malignant bronchogenic carcinoma. Multi-detector CT (MDCT) is essential in evaluating these masses, offering detailed morphological insights to help differentiate between benign and malignant lesions. However, a definitive diagnosis often requires histopathological confirmation. CT-guided biopsy is crucial, providing a minimally invasive method to obtain tissue samples and thus guiding clinical management and treatment decisions. The primary objective of this study was to assess the diagnostic accuracy of MDCT in differentiating between benign and malignant lung mass lesions. The study focused on evaluating the characteristic features of lung masses on MDCT that aid in this differentiation, correlating imaging findings with histopathological results from CT-guided biopsies, and determining the overall diagnostic utility of MDCT in thoracic lesions. This hospital-based observational study was conducted over a period of 17 months. The study included 52 patients with thoracic lesions, identified through imaging techniques such as chest radiographs and CT scans. These patients underwent CT-guided biopsy, with tissue samples sent for histopathological examination. Inclusion criteria involved patients with clinically and radiographically diagnosed lung masses, while exclusion criteria included those who did not consent, had contraindications to contrast media, or had conditions such as severe respiratory distress or coagulopathy. The data were analyzed using descriptive statistics, with efficacy measures such as yield and failure rates of CT-guided biopsies and validation measures like sensitivity, specificity, positive predictive value, and negative predictive value for MDCT. The study included 52 patients (50% male, 50% female), aged 16-80, with the most common age group being 51-60 years. Lesions were mainly in the lung parenchyma (65.38%), followed by the mediastinum (15.38%), hilar region (11.54%), and pleura (7.69%). MDCT evaluation classified 84.44% of the lesions as malignant, characterized by irregular contours, inhomogeneous texture, and contrast enhancement, while 15.55% were benign. Histopathology confirmed 42 malignant lesions, with squamous cell carcinoma being the most prevalent. Benign lesions included abscesses, tuberculosis, and pneumonitis. The study achieved a 100% success rate for CT-guided biopsy, with one minor complication (pneumothorax). The diagnostic accuracy of MDCT was notable, with a sensitivity of 100% for detecting malignancies, a specificity of 77.78%, a positive predictive value of 87.50%, and a negative predictive value of 100%, emphasizing its effectiveness in thoracic lesion evaluation. MDCT is a highly effective tool in the evaluation of lung masses, providing critical information that aids in distinguishing between benign and malignant lesions. When combined with CT-guided biopsy, it offers a reliable method for obtaining diagnostic tissue samples, with a high degree of accuracy and a low complication rate. The study underscores the importance of integrating imaging and histopathological findings in the management of thoracic lesions, ultimately enhancing diagnostic precision and informing appropriate clinical interventions.

Bromadiolone may cause severe acute kidney injury through severe disorder of coagulation: a case report

BackgroundBromadiolone is a wide-use long-acting anticoagulant rodenticide known to cause severe coagulation dysfunction. At present, there have been no detailed reports of acute kidney injury (AKI) resulting from bromadiolone poisoning.Case presentationA 27-year-old woman was admitted to the hospital due to severe coagulopathy and severe AKI. Coagulation test revealed a prothrombin time exceeding 120 s and an international normalized ratio (INR) greater than 10. Further examination for coagulation factors showed significantly reduced level of factors II, VII, IX and X, indicating a vitamin K deficiency. The AKI was non-oliguric and characterized by gross dysmorphic hematuria. Following the onset of the disease, the patient’s serum creatinine rose from 0.86 to 6.96 mg/dL. Suspecting anticoagulant rodenticide poisoning, plasma bromadiolone was identified at a concentration of 117 ng/mL via gas chromatography/mass spectrometry. All other potential causes of AKI were excluded, except for the presence of a horseshoe kidney. The patient’s kidney function fully recovered after the coagulopathy was corrected with high doses of vitamin K and plasma transfusion. At a follow-up 160 days post-discharge, the coagulation function had normalized, and the serum creatinine had returned to 0.51 mg/dL.ConclusionBromadiolone can induce AKI through a severe and prolonged coagulation disorder. Kidney function can be restored within days following treatment with high-dose vitamin K1.

Severe Coagulopathy and Intra-Alveolar Haemorrhage Due to Fat Malabsorption in Celiac Disease.

Celiac disease can cause severe coagulopathy due to fat malabsorption and vitamin K deficiency.High suspicion is required for atypical presentations of celiac disease.A gluten-free diet is essential for managing celiac disease and normalising coagulation profiles.

Efficacy of steroid therapy for improving native liver survival after pediatric acute liver failure with immune activation.

Recent evidence suggests that acute liver failure (ALF) in some patients may reflect a dysregulated immune response, and that corticosteroids improve survival of the native liver in ALF patients with high serum alanine aminotransferase levels, which are an indication of liver inflammation. However, it is unclear whether steroids are effective for pediatric acute liver failure (PALF). The aim of this retrospective case-control study is to examine whether steroid therapy for PALF accompanied by immune activation improves the survival of native liver and to identify factors that predict responses to steroid treatment. Of 38 patients with PALF treated at Kyoto University Hospital from February 2006 to August 2022, 19 receiving steroids who met the specific criteria for identifying the pathophysiology of immune activity in the liver (the "Steroid group"), and seven steroid-free patients who also met the criteria ("Nonsteroid group") were enrolled. Patients in the "Steroid group" were categorized as "responders" or "nonresponders" according to treatment outcome. Clinical and histological data were analyzed. Survival of the native liver in the Steroid group was significantly higher than that in the Nonsteroid group (68% vs. 0%, respectively; p=0.0052). Nonresponders were significantly younger, with higher Model for End-stage Liver Disease and pediatric end-stage liver disease scores, higher prothrombin time - international normalized ratio, and higher serum ferritin levels than responders. Massive hepatic necrosis was more common in nonresponders. Steroid therapy is effective for PALF patients with liver inflammation; however, liver transplantation should be prioritized for young children with ALF accompanied by severe coagulopathy or massive hepatic necrosis.

Trauma induced coagulopathy is limited to only one out of four shock induced endotheliopathy (SHINE) phenotypes among moderate-severely injured trauma patients: an exploratory analysis

BackgroundTrauma induced coagulopathy remains to be an important cause of high transfusion requirements and mortality and shock induced endotheliopathy (SHINE) has been implicated.MethodsEuropean multicenter observational study of adult trauma patients with injury severity score ≥ 16 arriving within 2 h from injury to the trauma centers. Admission blood samples obtained were used for analysis of the SHINE biomarkers (syndecan-1, soluble thrombomodulin, adrenaline) and extensive analysis of coagulation, -and fibrinolytic factors together with collection of clinical data. Hierarchical clustering of the SHINE biomarkers was used to identify the SHINE phenotypes.ResultsThe 313 patients clustered into four SHINE phenotypes. Phenotype 2, having the highest glycocalyx shedding, encompassing 22% of the whole cohort, had severe coagulopathy with lower levels of prothrombin, FV, IX, X, XI and severe hyperfibrinolysis with higher plasmin – alpha 2-antiplasmin (PAP) – and tPA levels and lower alpha2 – antiplasmin levels. This phenotype had significantly higher transfusion requirements and higher mortality (39% vs. 23%, 15% and 14%) but similar injury severity score (ISS) compared to the others phenotypes.ConclusionsHierarchical clustering identified four SHINE phenotype in a cohort of trauma patients. Trauma induced coagulopathy was confined to only one of the SHINE phenotypes, encompassing 22% of the total cohort. This phenotype was characterized by severe hypocoagulability and hyperfibrinolysis, which translated to significantly higher transfusion requirements and higher mortality compared to the other SHINE phenotypes with similar injury severity, warranting further investigation.

Delayed Symptoms of Rodenticide Poisoning in a 16-Year-Old: A Case Report

Anticoagulant rodenticides, a key tool in pest control since the 1940s, have undergone significant evolution to overcome resistance and improve efficacy. However, resistance in rodent populations led to the development of second-generation anticoagulants such as Brodifacoum and Difenacoum, which are more potent but pose increased risks to non-target species, including humans. This case report describes the management of a 16-year-old Iranian male who deliberately ingested a super warfarin rodenticide, resulting in severe coagulopathy and delayed clinical presentation. Despite the initial absence of overt symptoms, the patient’s condition required immediate intervention with intravenous vitamin K and blood products, demonstrating the complexity of diagnosing and managing rodenticide poisoning. Recovery was achieved with comprehensive medical and psychological interventions, demonstrating the need for high clinical suspicion and prompt treatment in similar cases. This report highlights the ongoing public health challenges posed by highly potent rodenticides and the critical need for awareness and preparedness among healthcare providers to effectively manage such emergencies.

The Study of Efficacy and Safe of Lamivudine in Patients with Severe Acute Hepatitis B

Objectives: Lamivudin has been approved for the treatment of chronic hepatitis B but experience with lamivudin treatment for acute severe hepatitis B is still limited. Fulminant hepatitis develops in 1% of patients with acute hepatitis B. Severe acute hepatitis B in immunocompetent patients may progress to fulminant hepatitis and death. Aim: To evaluate the efficasy of lamivudine for the treatment of acute severe hepatitis B virus infection in imunocompetent adults in Clinic for infectious diseases Banja Luka. Patients and methods: In the period of 2006-2024 years, 12 immunocompetent patients (4 women, 8 men, age 24-77 years) with severe acute hepatitis B were treated with lamivudin. All 12 patients fulfil at least two of the criteria for severe acute hepatitis B infection: 1. hepatic encephalopathy; 2. total bilirubin 210 micromole per litre; and severe coagulopathy (international normalized ratio-INR was 4.5 ± 6.4 or prothrombin time-PT < 40%). All patients had evidence of severe hepatocyte lysis. Nine patients had rapid increase of total bilirubin and contemporary decrease of alanine aminotransferase level, which escalate risk of development of fulminant hepatitis B. All patients received lamivudin at a dose 100 mg per day. Results: Ten patients responded well to the treatment and their biochemical parameters improved rapidly. Within 1-6 months, the HBsAg was undetectable in 10 out of 12 investigated patients. Protective anti-HBs antibodies developed in 10 of them in 1-6 months. The corticosteroid therapy was short-term in 2 of 12 patients. Two patient developed fulminant hepatitis B and died after the lamivudine therapy was initiated. Lamivudine treatment was well tolerated in all patients. Conclusion: Lamivudin induces a prompt clinical, biochemical and serological response in immunocompetent patients with severe acute hepatitis B. Early treatment with lamivudine probably decreases the risk of progression to fulminant hepatitis in patients with severe acute hepatitis B.

ПРИОБРЕТЕННАЯ ГЕМОФИЛИЯ А В РЕАЛИЯХ СОВРЕМЕННОЙ МЕДИЦИНЫ: ОПЫТ КЛИНИЧЕСКОЙ ПРАКТИКИ

Abstract. Introduction. Acquired hemophilia A is a rare form of severe coagulopathy with an autoimmune mechanism of development. It occurs due to the formation of circulating inhibitory factor VIII (FVIII) antibodies, which leads to impaired activation of factor X and the occurrence of spontaneous bleeding in patients without previous hemostasis system pathology. In about a half of the cases, FVIII autoantibodies appear in patients without any comorbidities. It should be noted that the average age of patients was 74 years at the time of diagnosis. However, the occurrence of the disease in young women is rare and may be associated with pregnancy and childbirth. Given the rarity of this disease, the management of these patients is a challenging clinical problem. Aim. To describe a clinical case of diagnosis and treatment of a patient with the inhibitor form of acquired hemophilia A (AHA). Materials and Methods. A 38–year–old female patient had acute hemorrhagic syndrome of the hematoma type, manifested by large hematomas in different areas of the body. During the patient’s stay in the hospital, standard lab tests were made, the test results were evaluated over time, and instrumental diagnostics was performed. Results and Discussion. The typical hematoma type of bleeding detected during diagnosing, prolongation of coagulation parameters, presence of factor VIII inhibitor (605 BU), and a decrease in factor VIII level down to 0.5%) verified the AHA diagnosis. Methods of substitution, immunosuppressive therapy, and monoclonal antibodies were successfully used to treat AHA in this patient. The patient is followed up by a hematologist at the place of residence. Hematomas did not recur. Conclusions. This clinical observation demonstrates the peculiarities of the course, diagnostic algorithm, and management of patients with AHA without any concomitant pathology, with a history of only prolonged postpartum uterine bleeding, and with no autoimmune or malignant diseases.

Extensive ecchymosis and retroperitoneal hemorrhage due to acquired hemophilia-A following influenza vaccination: A case report.

Acquired hemophilia-A (AHA) is a rare but potentially life-threatening impaired coagulation disorder characterized by the development of autoantibodies against clotting factor VIII. Only a few case reports have been experienced with influenza vaccine-triggered AHA. Here, we report a case of severe hemorrhagic disorder due to AHA following influenza vaccine, which was successfully treated. The patient presented to the emergency department because of several severe, progressively worsening bruises after receiving the influenza vaccination. Consequently, the patient required intubation due to nasal-oral bleeding, which compromised the airway, and retroperitoneal hemorrhage with shock also developed. AHA was confirmed through a coagulation factor assay, including coagulation activity and antibody testing, which is possibly triggered by influenza vaccination. Low-dose cyclophosphamide and hydrocortisone were prescribed until activated partial thromboplastin time showed normal levels. Coagulation factor VIIa was administered, and aggressive blood transfusion was carried out concurrently to address the blood loss. The upper airway bleeding subsided and bleeding tendencies had been corrected to normal. The patient was smoothly weaned from the ventilator and recovered from critical illness. She was then discharged on the 19th day. The activated partial thromboplastin time mixing test can be performed immediately to establish the initial differential diagnosis and treatment plan for severe coagulopathy. AHA may be triggered by vaccination, with the hypothesis of activation of autoantibodies and molecular mimicry; this mechanism should be further studied.

In-depth structure-function profiling of the complex formation between clotting factor VIII and heme

Background and aimsBlood disorders, such as sickle cell disease, and other clinical conditions are often accompanied by intravascular hemolytic events along with the development of severe coagulopathies. Hemolysis, in turn, leads to the accumulation of Fe(II/III)-protoporphyrin IX (heme) in the intravascular compartment, which can trigger a variety of proinflammatory and prothrombotic reactions. As such, heme binding to the blood coagulation proteins factor VIII (FVIII), fibrinogen, and activated protein C with functional consequences has been demonstrated earlier. MethodsWe herein present an in-depth characterization of the FVIII-heme interaction at the molecular level and its (patho-)physiological relevance through the application of biochemical, biophysical, structural biology, bioinformatic, and diagnostic tools. ResultsFVIII has a great heme-binding capacity with seven heme molecules associating with the protein. The respective binding sites were identified by investigating heme binding to FVIII-derived peptides in combination with molecular docking and dynamic simulation studies of the complex as well as cryo-electron microscopy, revealing three high-affinity and four moderate heme-binding motifs (HBMs). Furthermore, the relevance of the FVIII-heme complex formation was characterized in physiologically relevant assay systems, revealing a ~ 50 % inhibition of the FVIII cofactor activity even in the protein-rich environment of blood plasma. ConclusionOur study provides not only novel molecular insights into the FVIII-heme interaction and its physiological relevance, but also strongly suggests the reduction of the intrinsic pathway and the accentuation of the final clotting step (by, for example, fibrinogen crosslinking) in hemolytic conditions as well as a future perspective in the context of FVIII substitution therapy of hemorrhagic events in hemophilia A patients.

Influence of Covid-19 disease on hemostasis dynamics during extracorporeal membrane oxygenation (ECMO)1.

COVID-19 causes a considerable degradation of pulmonary function to the point of an acute respiratory distress syndrome (ARDS). Over the course of the disease the gas exchange capability of the lung can get impaired to such an extent that extracorporeal membrane oxygenation (ECMO) is needed as a life-saving intervention. In patients COVID-19 as well as ECMO may cause severe coagulopathies which manifest themselves in micro and macro thrombosis. Previous studies established D-dimers as a marker for critical thrombosis of the ECMO system while on admission increased D-dimers are associated with a higher mortality in COIVD-19 patients. It is therefore crucial to determine if COVID-19 poses an increased risk of early thrombosis of the vital ECMO system. 40 patients who required ECMO support were enrolled in a retrospective analysis and assigned into 2 groups. The COVID group consist of 20 COVID-19 patients who required ECMO support (n = 20), whereas 20 ECMO patients without COVID-19 were assigned to the control group. D-dimers, fibrinogen, antithrombin III (AT III), lactate dehydrogenase (LDH) and platelet count were analysed using locally weighted scatterplot smoothing and MANOVAs. The analysis of both groups shows highly significant differences in the dynamics of hemostasis. The increase in D-dimers that is associated with thrombosis of the ECMO systems occurs in COVID-19 patients around 2 days earlier (p = 2,8115 10-11) while fibrinogen is consumed steadily. In the control group fibrinogen levels increase rapidly after ten days with a plateau phase of around five days (p = 1,407 10-3). Both groups experience a rapid increase in AT III after start of support by ECMO (p = 5,96 10-15). In the COVID group platelet count decreased from 210 giga/l to 130 giga/l within eight days, while in the same time span in the control group platelets decreased from 180 giga/l to 105 giga/l (p = 1,1 10-15). In both groups a marked increase in LDH beyond 5000 U/l occurs (p = 3,0865 10-15). The early increase in D-dimers and decrease in fibrinogen suggests that COVID-19 patients bear an increased risk of early thrombosis of the ECMO system compared to other diseases treated with ECMO. Additionally, the control group shows signs of severe inflammation 10 days after the start of ECMO which were absent in COVID-19 patients.

Blood Transfusion for Major Trauma in Emergency Department.

Severe bleeding is the leading cause of death in patients with major trauma admitted to the emergency department. It is estimated that about 50% of deaths happen within a few minutes of the traumatic event due to massive hemorrhage; 30% of deaths are related to neurological dysfunction and typically happen within two days of trauma; and approximately 20% of patients died of multiorgan failure and sepsis within days to weeks of the traumatic event. Over the past ten years, there has been an increased understanding of the underlying mechanisms and pathophysiology associated with traumatic bleeding leading to improved management measures. Traumatic events cause significant tissue damage, with the potential for severe blood loss and the release of cytokines and hormones. They are responsible for systemic inflammation, activation of fibrinolysis pathways, and consumption of coagulation factors. As the final results of this (more complex in real life) cascade, patients can develop tissue hypoxia, acidosis, hypothermia, and severe coagulopathy, resulting in a rapid deterioration of general conditions with a high risk of mortality. Prompt and appropriate management of massive bleeding and coagulopathy in patients with trauma remains a significant challenge for emergency physicians in their daily clinical practice. Our review aims to explore literature studies providing evidence on the treatment of hemorrhage with blood support in patients with trauma admitted to the Emergency Department with a high risk of death. Advances in blood transfusion protocols, along with improvements in other resuscitation strategies, have become one of the most important issues to face and a key topic of recent clinical research in this field.

Efficacy and Safety of Double J Stenting (DJS) and Percutaneous Nephrostomy (PCN) in Patients with Obstructive Uropathy

Background: Obstructive uropathy is a condition characterized by the blockage of urine flow, which can lead to renal parenchymal damage and, if left untreated, potentially fatal outcomes. The condition arises from various causes, including stone disease, which remains the predominant factor. Management strategies such as Double J Stenting (DJS) and Percutaneous Nephrostomy (PCN) are employed to temporarily alleviate the obstruction, yet the comparative efficacy and safety profiles of these interventions remain to be thoroughly evaluated. Objective: To compare the efficacy and safety of ultrasound-guided percutaneous nephrostomy and double J stenting in the temporary diversion of urine in patients with obstructive uropathy, with a focus on procedural success rates, complication rates, and overall patient outcomes. Methods: This randomized controlled trial was conducted at the Department of Urology, Lady Reading Hospital, Peshawar, from January 1st, 2023, to December 31st, 2023. A total of 428 patients with obstructive uropathy, aged between 20 and 60 years, were randomized into two groups: the DJS group (n=214) and the PCN group (n=214). Exclusion criteria included severe coagulopathy and uremic encephalopathy. Efficacy was determined by the resolution of obstruction signs, and safety was assessed by the incidence of complications such as trigonalgia, hematuria, and septicemia within four weeks post-procedure. Statistical analysis was performed using IBM SPSS version 25. Results: The DJS group demonstrated a procedural success rate of 96.0%, while the PCN group showed a slightly higher success rate of 97.5%. Complication rates were comparably low across both groups, with trigonalgia (28.0% in DJS vs. 25.0% in PCN), hematuria (16.0% in DJS vs. 14.0% in PCN), and septicemia (6.5% in DJS vs. 8.4% in PCN). The efficacy in alleviating obstructive symptoms was 82.2% for DJS and 86.9% for PCN, with no statistically significant difference between the groups (p=0.180). Conclusion: Both double J stenting and percutaneous nephrostomy are effective and safe methods for temporary urine diversion in patients with obstructive uropathy. Although the PCN group exhibited a slightly higher success rate and a marginally lower complication rate, the differences were not statistically significant, indicating that the choice of procedure can be tailored to the individual patient's condition and the specific clinical scenario.

Anti-Thrombin IgA in a Patient with Multiple Myeloma Leading to In Vitro Interference in Multiple Coagulation Tests and Confounding Diagnosis.

We report the case of a 59-year-old multiple myeloma patient in whom an anti-human thrombin IgA antibody led to prolonged in vitro coagulation times, suggesting inhibitors to all intrinsic coagulation factors in the absence of spontaneous bleeding. Routine and extensive special coagulation tests, in vivo bleeding time, and specific antibody testing were performed. Although the patient did not suffer from spontaneous bleeding and had a normal in vivo bleeding time, the anti-human thrombin IgA autoantibody affected all coagulation assays involving human thrombin in vitro, mimicking inhibitors to intrinsic coagulation factors. As the IgA paraprotein and the IgA antibody virtually disappeared after autologous stem cell transplantation, the coagulation tests also largely normalized. Antibodies to human thrombin may interfere with all coagulation assays involving thrombin, imitating a severe coagulopathy. However, in vivo they do not necessarily lead to strongly increased bleeding tendency. Complex and ambiguous coagulation abnormalities should be evaluated and treated in an interdisciplinary setting, including a highly specialized coagulation laboratory, from the beginning.

Major vascular reconstructions in thoracic oncological surgery.

The replacement of the superior vena cava and thoracic outlet vessels for thoracic malignancies often becomes necessary for radical oncological surgery. The pulmonary artery can be directly infiltrated by the tumor or affected by metastatic hilar lymph nodes. In some cases, it must be resected and reconstructed to achieve oncological radicality and/or avoid pneumonectomy. This study reflects a single-surgeon, retrospective experience spanning 6years (2017-2023). We reviewed data from patients undergoing early anticoagulant therapy after superior vena cava or thoracic outlet vessels bypass and from patients undergoing early antiaggregation therapy following pulmonary artery reconstruction or resection. This series comprises 41 patients treated by a single surgeon. Fourteen patients underwent superior vena cava and thoracic outlet vessel procedures. Among these, eight patients received superior vena cava replacement (six for thymic malignancies and two for lung cancer), and six patients underwent jugular and subclavian artery/vein resection or replacement (all six had sarcomas). There was one death due to respiratory failure, not associated with bleeding or bypass closure. Additionally, there was one graft closure in a patient with severe coagulopathy and three instances of hemothorax (two patients had undiagnosed complex coagulopathies not evident in pre-operative routine blood tests). Following bleeding incidents, anticoagulation was initiated the next day in one case and based on hematological indications in the two coagulopathic patients. In the pulmonary artery series, 27 patients were involved: 20 underwent direct suture after tangential resection, and 7 received pericardial patch reconstruction. Only one case experienced bleeding necessitating redo-surgery. All these patients received early and chronic antiaggregation therapy after pulmonary artery reconstruction. We conclude that major thoracic oncological vascular surgery is safe and feasible with appropriate technical skills. However, achieving optimal results requires integration with correct early anticoagulant therapy or antiaggregation to maintain the patency of bypasses/grafts and prevent life-threatening risks associated with closure of the "new vessels."

No contraindication to internal jugular central venous catheter insertion in patients at increased risk of bleeding: Results from a prospective observational study in a internal medicine department.

Implantation of centrally inserted central venous catheter (CICC) may be complicated by bleedings particularly in patients with severe coagulopathy or taking antithrombotic drugs. It has been shown that the application of the Italian Group for Venous Access Devices (GAVeCeLT) bundle reduces the incidence of bleeding in patients admitted to intensive care units (ICU), but its effectiveness has never been demonstrated in different contexts. In this study we evaluated the incidence of bleeding after urgent internal jugular CICC (J-CICC) implantation in patients with increased or no risk of bleeding complications when recommended preventive strategies are applied systematically. We included 185 patients admitted to Internal Medicine Units who underwent urgent J-CICC implantation from April 2016 to December 2018. The incidence of major and minor bleeding immediately after the procedure and in the following 30 days was recorded. None of the enrolled patients showed major bleeding. The incidence of minor bleedings was 2.1% (95% IC: 0.03-4.2) with two patients requiring line removal and repositioning (1.1%; 95% IC: -0.45 to 2.6). Bleeds were not correlated with age or sex, although they all occurred in female subjects. The incidence of bleeds was not increased in patients with increased risk of bleeding compared with those without (5.0% vs 1.3%; p = 0.16). The use of anti-thrombotic medications was significantly associated with increased risk of minor bleedings (p = 0.03). In this study we demonstrated that the application of the GAVeCeLT suggested bundle can minimize the number of bleeding complications even in patients hospitalized in Internal Medicine Units. Further data are needed in patients taking antithrombotic drugs who appear to be more prone to minor bleeding, however the benefit of completing the procedure appears to significantly outweigh the risk of mechanical complications.

Abstract WP174: A Reassessment of Cost Effectiveness and Clinical Effectiveness of Anticoagulation Reversal in Direct Oral Anticoagulant - Related Intracerebral Hemorrhage

Introduction: Anticoagulation use is associated with increased risk of hematoma expansion (HE) in patients with intracerebral hemorrhage (ICH). We sought to assess rates of HE in patients with ICH on direct oral anticoagulants (DOAC) and annual cost associated with anticoagulation reversal and occurrence of HE. Methods: We performed an observational cohort study on consecutive patients with ICH on DOAC admitted to a Comprehensive Stroke Center over 3 years, using data from an institutional ICH registry. We prospectively collected baseline demographic and clinical variables, neuroimaging data on baseline and follow-up hematoma volumes (HV) and HE and outcomes on discharge via modified Rankin scale (mRS). Hemostatic efficacy on hematoma size was adjudicated based on the Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors-4 (ANNEXA-4) trial, with a ≤20% increase in HV compared to baseline considered “excellent” and a ≤ 35% increase in HV compared to baseline considered “good.” Weighted hematoma expansion cost was estimated based on common odds ratio of mRS increase with HE and distributions of mRS with HE. Results: We identified 103 patients who met inclusion criteria: mean age 75.8 (± 11.4) years, 55.3% female. 92 patients (89.3%) received anticoagulation reversal with prothrombin complex concentrate (PCC), of which 19 (20.7%) had HE. A more severe coagulopathy (antiXa > 0.5) was associated with increased risk of HE (p<0.05). 74 patients (80.4%) achieved good or excellent hemostasis. Use of PCC was associated with a 19.6% hematoma expansion rate using the definition above, which translates into a $6700 increase in annual cost per every ICH patient attributed to HE. Conclusion: Cost effective and clinically effective treatments for anticoagulation reversal are needed to reduce the risk and cost associated with HE in anticoagulation-related ICH.

Severe coagulopathy and inflammation occurred after resection of giant right ventricular intimal sarcoma with cardiopulmonary bypass: a case report

BackgroundPrimary malignant cardiac tumors are rare in clinic, and surgical resection under cardiopulmonary bypass (CPB) remains the main treatment. The non-physiological perfusion process of CPB leads to contact activation, and the resulting coagulopathy and systemic inflammatory response syndrome (SIRS) are common complications. However, it is difficult to predict the impact of foreign tumor fragments on this pathophysiological process once they enter the bloodstream, making this phenomenon more complex and challenging.Case PresentationWe report a case of cardiac intimal sarcoma who developed severe coagulopathy and widespread inflammation after excision of massive right ventricular tumor and replacement of tricuspid valve by median sternotomy under CPB. Although the procedure was expected to cause tumor cell necrosis and precautions were taken, uncontrolled massive postoperative bleeding, persistent fever, abnormally elevated inflammatory markers, and recurrent malignant arrhythmias occurred after surgery. In addition to common factors, the most possible underlying mechanism is contact activation triggered following surgical procedure for intimal sarcoma with CPB.ConclusionPatients with intracardiac malignant tumors are at a high risk for serious contact activation during CPB. Preventive application of comprehensive anti-inflammatory measures such as drugs and adsorptive CPB technology, as well as point-of-care (POC) monitoring of coagulation status will be helpful for individualized guidance and optimization of CPB management, and improvement of patient prognosis.

Transcriptional Profiling of the Rabbit Liver Infected With Eimeria stiedae Reveals Dynamic Host Cell Responses During the Induction and Resolution of Cholangitis

Eimeria stiedae is one of the few eukaryotic pathogens that exclusively infect the liver and serves as a good model to study the host–pathogen interactions in this vital organ. In this study, we show that rabbits infected with E. stiedae develop severe but self‐healing cholangitis. RNA‐seq analysis of the liver gene expression landscapes over the long course of E. stiedae infection identified 912 differentially expressed genes (DEGs) in the prepatent period (794 up‐ and 118 downregulated genes), 2889 DEGs in the early oocyst shedding period (1870 up‐ and 1019 downregulated genes), 2859 DEGs in the peak oocyst shedding period (1923 up‐ and 936 downregulated genes), and 327 DEGs in the recovery period (164 up‐ and 163 downregulated genes). Combined with pathological observations, we identified dynamic changes in host–parasite interactions involving multiple pathways. They showed that E. stiedae infection induced full‐blown inflammatory, Th1 and Th17 immune responses at all time points. This was associated with the strong innate immune responses during the prepatent period, including increased Toll‐like and NOD‐like receptor signaling. Despite mounting several damage control and repair responses, such as PI3K‐Akt signaling, Ras signaling, and extracellular matrix‐receptor interactions, the liver underwent severe metabolic dysfunction, oxidative damage, and coagulopathy after patency and at peak infection, possibly as a result of suppressed peroxisome activities and downregulated PPAR signaling. These responses largely disappeared during late infection, suggesting that the liver self‐heals after severe cholangitis. These data provide new insights into host–pathogen interactions during Eimeria infection and improve our understanding of the pathogenesis of parasitic cholangitis.