[Management of HIT/anti-PF4 disorders].

Heparin-induced thrombocytopenia (HIT) was widely known as a disease characterized by development of thrombosis with thrombocytopenia after heparin exposure. In addition, vaccine-induced immune thrombotic thrombocytopenia (VITT) has been described as a fatal disease involving simultaneous bleeding and thrombosis after COVID-19 adenovirus vector vaccination. These were caused by HIT antibodies and anti-PF4 antibodies, respectively, but both were autoantibodies that recognized PF4, and were found to have the same pathology with different severities. In recent years, many pathologies in which anti-PF4 antibodies are produced have been reported, and a new concept of anti-PF4 disorder has been proposed. Anti-PF4 disorders are often difficult to identify due to their diverse range of causes, and the prognosis varies greatly depending on whether anti-PF4 antibodies can be measured and early treatment performed after observation of thrombocytopenia of unknown cause or thrombosis at an unusual site. To avoid overlooking anti-PF4 disorders, clinicians should become familiar with the classification of these disorders and accurately select the necessary tests.

How Protein Depletion Balances Thrombosis and Bleeding Risk in the Context of Platelet's Activatory and Negative Signaling.

Platelets are small cell fragments that play a crucial role in hemostasis, requiring fast response times and fine signaling pathway regulation. For this regulation, platelets require a balance between two pathway types: the activatory and negative signaling pathways. Activatory signaling mediators are positive responses that enhance stimuli initiated by a receptor in the platelet membrane. Negative signaling regulates and controls the responses downstream of the same receptors to roll back or even avoid spontaneous thrombotic events. Several blood-related pathologies can be observed when these processes are unregulated, such as massive bleeding in activatory signaling inhibition or thrombotic events for negative signaling inhibition. The study of each protein and metabolite in isolation does not help to understand the role of the protein or how it can be contrasted; however, understanding the balance between active and negative signaling could help develop effective therapies to prevent thrombotic events and bleeding disorders.

Correlation Between Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio with Risk Stratification Indicators and Thrombus Burden in Patients with Moderate-to-High Risk Acute Pulmonary Embolism, and Changes After Treatment.

OBJECTIVE: To investigate the correlation between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and risk stratification indicators as well as thrombus burden in patients with moderate-to-high risk acute pulmonary embolism (APE), and to assess the changes in these parameters following interventional therapy. METHODS: This study retrospectively included patients with moderate-to-high risk APE who were admitted to the Department of Interventional Vascular Surgery at Putian First Hospital from May 2020 to May 2024. All patients received anticoagulation therapy, pulmonary artery catheter-directed thrombolysis, and/or mechanical thrombectomy. Patients were further divided into subgroup A if they did not present with any of the following conditions at admission: a) acute inflammatory diseases (including lung infections); b) malignant tumors; c) history of trauma or surgery within the past 2 months. Patients with any of the aforementioned conditions were classified as subgroup B. Additionally, 50 healthy individuals were randomly selected as the healthy control group. RESULTS: The NLR and PLR in subgroup A were significantly lower than those in subgroup B (P < .01). Compared with the healthy control group, the NLR in the APE group and subgroup A was significantly higher (P < .001). There were no significant differences in NLR and PLR between the troponin I-negative and troponin I-positive groups (P > .05), or between the N-terminal pro-B-type natriuretic peptide (NT-proBNP)-negative and NT-proBNP-positive groups (P > .05). There were no significant correlations between NLR and PLR with risk stratification indicators and pulmonary artery embolism index (P > .05). Compared with before treatment, NLR, troponin I, NT-proBNP, right ventricular diameter/left ventricular diameter ratio, and pulmonary artery embolism index were significantly reduced after treatment (P < .05), while there was no significant difference in PLR before and after treatment (P > .05). CONCLUSION: Elevated NLR in patients with APE, which decreases after effective treatment, may be used for assessing disease status and treatment efficacy. However, there is no correlation between NLR and risk stratification indicators or thrombus burden. PLR does not demonstrate significant value in assessing APE.

AB040. A complication of recurrent artery of Huebner infarction after resection of an anterior cerebral artery thrombotic giant intracranial aneurysm: case report and literature review.

BACKGROUND: Giant aneurysms, comprising 3-5% of all intracranial aneurysms, pose a considerable challenge due to their heterogeneity and complex vascular anatomy. Defined as aneurysms exceeding 2.5 cm in diameter, they often develop intraluminal thrombosis. Despite advancements in neurosurgical techniques, managing giant aneurysms remains complex and highly individualized. Thrombotic giant aneurysms are particularly problematic due to their size and thrombosis potential. This case report is unique as it presents the first documented instance of recurrent artery of Heubner (RAH) infarction following surgical resection of a giant thrombotic aneurysm. CASE DESCRIPTION: A 53-year-old man with no prior systemic presented to our emergency department due to progressive left-sided weakness and slurred speech. Magnetic resonance imaging (MRI) of brain revealed a thrombotic giant intracranial aneurysm on right anterior cerebral artery (ACA). Surgical resection was performed using a right pterional craniotomy. During surgery, the aneurysm was confirmed to be completely thrombosed and was excised. Postoperatively, the patient experienced a generalized seizure and was intubated. Brain MRI revealed a new infarction in the RAH territory. Despite initial complications, the patient showed significant recovery with rehabilitation, regaining most motor functions by the 6-month follow-up. CONCLUSIONS: This case emphasizes the critical importance of comprehensive preoperative evaluation, particularly in assessing small perforating branches and collateral circulation. It highlights the challenges in managing giant aneurysms and the necessity of anticipating potential postoperative complications. This report adds valuable insights into the clinical management and surgical planning for giant aneurysms, particularly those involving the ACA and RAH.

Ultraslow low-dose thrombolytic therapy in patients with acute mechanical prosthetic heart valve thrombosis - A prospective cohort study.

BACKGROUND: While surgery still remains the gold standard treatment for mechanical prosthetic valve thrombosis (MPVT) by many guidelines, the ultraslow low-dose thrombolytic regimen has been reported as a promising alternative. METHODS: In this prospective single-center cohort, patients with acute MPVT were treated with an ultraslow low-dose thrombolytic regimen consisting of 25 mg infusion of recombinant tissue-type plasminogen activator (rtPA) over 25 h. The regimen could be repeated in case of failure until resolution/occurrence of adverse events or a maximum cumulative dose of 150 mg. The primary outcome was the complete MPVT resolution rate; other outcomes included first-dose success rate, major bleeding, thromboembolic events, mortality, and total thrombolytic dose/duration. RESULTS: Between April 2018 to January 2024, 135 episodes of acute MPVT were treated with an ultraslow low-dose thrombolytic regimen in 118 patients. In 118/135 (87.4 %) episodes, right-sided prosthetic valve was involved. Complete success was achieved in 88.1 % of cases, with 39.5 % responding after the first dose. The median total dose was 50 mg over a median of 30 h. Only one fatal intracranial hemorrhage occurred (0.7 %), with no other bleeding or thromboembolic complications. CONCLUSION: The ultraslow low-dose thrombolytic regimen appears to exhibit high efficacy and acceptable safety in treating acute MPVT. Further large clinical trials are essential for validating these preliminary findings.

Risk factors for thrombosis in dialysis patients: A comprehensive systematic review and meta-analysis.

AIM: To identify the factors associated with thrombosis in dialysis patients. BACKGROUND: Thrombosis is a leading cause of vascular access failure in dialysis patients. Numerous risk factors contribute to thrombosis in this population. METHODS: A systematic search was conducted across international databases using standardized keywords. The quality of the selected studies was assessed using the STROBE and CONSORT checklists. The findings were summarized in a Garrard table. Meta-analysis was performed using CMA software. The study adhered to the guidelines outlined in the PRISMA statement. RESULTS: A total of 180 articles were reviewed. The odds ratio for thrombosis in patients with arteriovenous grafts compared to arteriovenous fistulas was 10.93 (95 % CI: 9.35-12.78), demonstrating statistical significance (P = 0.001). Similarly, hemodialysis patients had an odds ratio of thrombosis 3.60 times higher than non-hemodialysis patients (95 % CI: 3.54-4.19), with statistical significance (P = 0.001). Patients undergoing single-stage basilic vein transposition had a 1.89 times higher risk of thrombosis compared to those undergoing two-stage transposition (95 % CI: 1.04-3.46), also demonstrating statistical significance (P = 0.038). CONCLUSIONS: Thrombosis in patients with end-stage renal disease undergoing dialysis was significantly associated with various factors, including graft access, single-stage basilic vein transposition, and hemodialysis. Additional contributing factors to thrombosis included diabetes, elevated homocysteine levels, female gender, age over 50, access location, and low access blood flow velocity. The analysis revealed a higher incidence of thrombosis in end-stage renal disease patients undergoing hemodialysis compared to those not undergoing dialysis, as well as in patients with arteriovenous grafts compared to those with arteriovenous fistulas. These findings underscore the importance of recognizing and managing these risk factors to prevent thrombotic events and enhance patient care within the dialysis setting.

Impact of Balloon-Expandable TAVR Valve Deformation and Calcium Distribution on Outcomes in Bicuspid Aortic Valve.

BACKGROUND: Research on the role of transcatheter heart valve (THV) deformation and calcium distribution in patients with bicuspid aortic valves (BAVs) undergoing transcatheter aortic valve replacement (TAVR) remains limited. OBJECTIVES: The aim of this study was to evaluate the impact of THV deformation on clinical outcomes in individuals with BAVs undergoing TAVR and the influence of calcium on these outcomes. METHODS: In total, 229 consecutive patients with BAVs who underwent TAVR with balloon-expandable valves and had computed tomography (CT) performed 30 days post-TAVR were analyzed. Patients were stratified into 3 groups: group 1 (n = 125), with no THV underexpansion or eccentricity; group 2 (n = 69), with underexpansion or eccentricity; and group 3 (n = 35), with both. Calcium distribution was assessed using CT, and its associations with clinical outcomes, including all-cause mortality at 3 years and leaflet thrombosis at 30 days, were determined. A subgroup analysis of patients with type 1 BAVs was conducted. RESULTS: Group 3 exhibited higher rates of all-cause mortality than the other groups, along with the highest risk for hypoattenuated leaflet thickening at 30 days. Multivariate analysis identified annular and left ventricular outflow tract calcification as independent predictors of all-cause mortality and hypoattenuated leaflet thickening. In patients with type 1 BAVs, excessive calcification at the raphe and opposite leaflet were associated with all-cause mortality at 3 years. CONCLUSIONS: THV deformation post-TAVR was significantly linked to all-cause mortality in patients with BAVs. Annular and left ventricular outflow tract calcification correlated with increased risks for all-cause mortality and leaflet thrombosis. (Assessment of Transcatheter and Surgical Aortic Bioprosthetic Valve Thrombosis and Its Treatment With Anticoagulation [RESOLVE]; NCT02318342).

Bridging With Low-Molecular-Weight Heparin Versus Antiplatelet Therapy in Patients Undergoing Noncardiac Surgery After Percutaneous Coronary Intervention: A Comprehensive Review.

BACKGROUND: This review article discussed the use of bridging therapy with low-molecular-weight heparin (LMWH) in patients who undergo noncardiac surgery (NCS) after percutaneous coronary intervention (PCI). HYPOTHESES: Patients who undergo PCI are at an increased risk of thrombotic events due to their underlying cardiovascular disease. However, many of these patients may require NCS at some point in their lives, which poses a significant challenge for clinicians as they balance the risk of thrombotic events against the risk of bleeding associated with antithrombotic therapy. RESULTS: This review evaluates the current evidence on the use of bridging therapy with LMWH in patients undergoing NCS after PCI, focusing on outcomes related to the efficacy and safety of antithrombotic therapy. The article also discusses the limitations of the current evidence and highlights areas where further research is needed to optimize the management of antithrombotic therapy in this patient population. CONCLUSION: The goal of this review was to provide clinicians with a comprehensive summary of the available evidence to guide clinical decision-making and improve patient outcomes.

Exploring the behavioral intentions of PICC-related thrombosis prevention in breast cancer patients undergoing chemotherapy: a qualitative study based on theory of planned behavior.

PURPOSE: To explore the behavioral intention of breast cancer patients undergoing chemotherapy to prevent PICC-related thrombosis based on the theory of planned behavior (TPB). METHODS: This qualitative study employed purposive sampling and conducted semi-structured interviews with 14 breast cancer patients undergoing chemotherapy in the outpatient chemotherapy ward of a tertiary A-level comprehensive hospital in Beijing from July to August 2023. Data were analyzed using Colaizzi's descriptive analysis framework. RESULTS: Data analysis identified 10 themes that were derived from 4 aspects. Regarding behavioral attitude, three themes were condensed: (1) Considering the benefits of preventive measures, (2) Simple and easy preventive measures, and (3) Underestimating the importance of PICC-related thrombosis prophylaxis. Subjective norms yielded two main themes and five sub-themes: (1) Support from those close to the patient motivates adherence to prophylaxis (support from the patient's family, healthcare professionals, and other patients) and (2) Patients are influenced by personal factors to form an internal driving force (physical symptoms, fear of PICC-related thrombosis). Regarding perceived behavioral control, three main themes and four sub-themes were extracted: (1) Obstacles before actual prevention exercise (prevention information, hard-to-remember information), (2) Forgetfulness is the main obstacle factor, and (3) Wanting to overcome barriers to adhere to regular prevention (confidence to overcome obstacles, hope to get support). CONCLUSIONS: The impediments and facilitators identified in this study may provide a scientific foundation for subsequent targeted non-pharmacological preventive interventions for PICC-related thrombosis based on TPB in breast cancer patients undergoing chemotherapy. Special interventions should be designed for the patients in three areas: the patients themselves, the supporters around the patient, and the healthcare professionals.

High Bleeding Risk in Patients Undergoing Coronary and Structural Heart Interventions.

Percutaneous coronary and structural heart interventions are increasingly preferred over cardiac surgery due to reduced rates of periprocedural complications and faster recovery but often require postprocedural antithrombotic therapy for the prevention of local thrombotic events. Antithrombotic therapy is inevitably associated with increased bleeding, the extent of which is proportional to the number, duration, and potency of the antithrombotic agents used. Bleeding complications have important clinical implications, which may outweigh the expected benefit of reducing thrombotic events. Herein, we provide a comprehensive description of the classification and clinical relevance of high bleeding risk in patients undergoing coronary and structural heart interventions.

Antithrombotic Therapy in Patients Undergoing Percutaneous Left Atrial Appendage Occlusion.

Percutaneous left atrial appendage closure (LAAC) is a valid alternative to oral anticoagulation to prevent ischemic stroke in patients with atrial fibrillation.The devices approved in Europe and United States for percutaneous LAAC contain metal and temporary antithrombotic therapy is strongly recommended following implantation to prevent thrombus formation on the atrial device surface. There is still uncertainty regarding to the optimal antithrombotic drug regimen after device implantation for several reasons. Thus, this review aims at summarizing the available evidence and the remaining challenges related to the management of antithrombotic therapy in the context of LAAC procedure.

A large thrombus within a giant coronary artery aneurysm in a child with Kawasaki disease: A case report.

Kawasaki disease (KD) is an acute systemic vasculitis that preferentially involves coronary arteries in young children, and predominantly affects young children. Cardiovascular lesions are the most severe complications of this disease. Even though giant aneurysms are rare, they can complicate thrombus formation, leading to myocardial ischemia, myocardial infarction, and even cardiac death. Later in life, it can lead to steno-occlusive lesions. Follow-up led to coronary artery stenosis. In this article, we report a case of a pediatric patient with KD who presented with a large thrombus within a giant coronary aneurysm as a consequence of delayed treatment with intravenous immunoglobulin (IVIG) and IVIG resistance, which contributed to the formation of coronary artery lesions. Transthoracic echocardiography is a valuable tool for detecting coronary artery abnormalities; however, computed tomography coronary angiography is valuable for precisely delineating coronary anatomy and complications. It is important to maintain a slightly higher international normalized ratio to decrease the risk of thrombosis in coronary artery aneurysms.

Clinical outcomes of acute limb ischaemia caused by femoropopliteal stent thrombosis.

BACKGROUND: Although femoropopliteal-specific stents have durable patency, stent thrombosis (ST) may occur, which can lead to acute limb ischaemia (ALI). AIMS: We aimed to investigate the clinical features and outcomes of ALI caused by femoropopliteal ST in patients with lower extremity artery disease. METHODS: This multicentre retrospective study included 499 patients with ALI - of whom 108 patients had ALI caused by femoropopliteal ST (ST-ALI) and 391 patients had ALI caused by other aetiologies (de novo ALI) - who underwent treatment between September 2011 and March 2023. Clinical features and outcomes were compared between the two groups. The primary outcome measure was 12-month amputation-free survival; factors associated with amputation or death were investigated using multivariate Cox proportional hazards regression analysis. RESULTS: Patients with ST-ALI were significantly more likely to exhibit conventional atherosclerotic risk factors, including diabetes mellitus (63% vs 26%) and haemodialysis (51% vs 10%) compared to patients with de novo ALI, whereas patients with de novo ALI were older (80 years vs 74 years) and more likely to have atrial fibrillation (49% vs 18%) than patients with ST-ALI. The 12-month amputation-free survival rate was significantly lower in the ST-ALI group than that in the de novo ALI group (51% vs 76%; p<0.001). Multivariate analysis revealed that ST-ALI, older age, haemodialysis, atrial fibrillation, the presence of a wound, peak C-reactive protein level, and non-ambulatory status all have an independent, positive association with death or major amputation. CONCLUSIONS: The current study revealed that patients with ST-ALI had worse clinical outcomes than those with de novo ALI, highlighting the need to maximise ST prevention.

Surgery Versus Thrombolytic Therapy for the Management of Left-Sided Prosthetic Valve Thrombosis Without Hemodynamic Compromise: A Systematic Review and Meta-Analysis.

BACKGROUND: The optimal strategy in prosthetic heart valve thrombosis (PVT) remains controversial, with no randomized trials and conflicting observational data. We performed a systematic review and meta-analysis of evidence comparing systemic thrombolysis and cardiac surgery in PVT. METHODS AND RESULTS: We searched PubMed, the Cochrane Library, and Embase for studies on treatment strategies in patients with left-sided PVT since 2000. The primary outcome was death, and the secondary outcomes were major bleeding and thromboembolism during follow-up (International Prospective Register of Systematic Reviews No. CRD42022384092). We identified 2298 studies, of which 16 were included, comprising 1389 patients with PVT (mean age, 50.4±9.3 years; 60.0% women). Among them, 67.2% were New York Heart Association stage III/IV at admission. Overall, 48.1% were treated with systemic thrombolysis and 51.9% with cardiac surgery. The mortality rate was 10.8% in the thrombolysis group and 15.3% in the surgery group. The pooled risk difference for death with systemic thrombolysis was 1.13 (exact CI, 0.74-1.79; ζ2=0.89; P<0.001) versus cardiac surgery. Rates of both transient ischemic attack and non-central nervous system embolism were higher in the thrombolysis group (P=0.002 and P=0.02, respectively). Treatment success, major bleeding, and stroke were similar between groups. Sensitivity analysis including studies that used low-dose or slow-infusion thrombolysis showed that the mortality rate was lower, and treatment success was higher, in patients referred to systemic thrombolysis, with similar rates of other secondary outcomes. CONCLUSIONS: There is evidence to suggest that thrombolysis might be the preferred option for the management of PVT without cardiogenic shock, pending future randomized controlled trials or larger observational studies.

When Anticoagulation Matters: A Case of Large Left Atrial Thrombus After Left Atrial Appendage Ligation.

Atrial fibrillation (AF) is the most frequently encountered arrhythmia in the clinical practice and is associated with stroke. In clinical practice, CHAD2DS2-VASc score is used as a tool to decide whether anticoagulation is needed. In those patients with high bleeding risk or falls, surgical ligation of the left atrial appendage (LAA) or percutaneous closure devices are strategies used to mitigate these challenges. However, there is no guideline advising on what patient's specific factors should be considered in determining initiation or continuation of anticoagulation post LAA ligation. Herein, we report the case of a patient with surgical ligation who developed large atrial thrombus requiring emergent median sternotomy.

Renal Cell Carcinoma with a Catastrophic Thrombus: A Case Report.

INTRODUCTION: Renal cell carcinoma (RCC) is a common malignancy known for its potential to invade the venous system, particularly the inferior vena cava (IVC), leading to tumor thrombus (TT) formation. While the presence of TT in RCC isn't unique, extension of TT above the diaphragm is rare. This case highlights the challenges encountered in diagnosing and managing RCC with extensive TT involvement. CASE REPORT: A 69-year-old man presents with 3-month history of dyspnea and increasing fatigue in the setting of 30 pounds weight loss. Laboratory studies showed anemia and acute kidney injury. CT abdomen and pelvis revealed 6.8cm solid mass within the left perinephric space, enlarged IVC with large thrombus. Kidney biopsy returned positive for clear cell renal carcinoma with metastasis to the liver. Several days into the hospitalization the patient began to experience increased abdominal pain. Repeat ultrasound showed tumor thrombus with extension within the intrahepatic IVC and hepatic veins and reversal of portal venous flow. During the imaging study, the patient suffered a cardiac arrest and expired. Postmortem examination revealed diffuse showering of tumor emboli within the pulmonary arteries, likely contributing to the patient's rapidly progressive respiratory failure, and subsequent cardiovascular collapse. CONCLUSION: This case illustrates the complexity of treating patients with extensive TT. In patients with RCC associated TT, the risk for thromboembolism is increased substantially, however the full benefit of anticoagulation remains controversial. Understanding the intricacies of TT involvement and its potential complications is crucial in guiding treatment decisions in patients with significant tumor thrombus burden.