Search Results (11)

Deep venous thrombosis (DVT) is a pathological condition that develops when a thrombus forms within the deep venous system. Typically, it involves the lower limbs and, less frequently, the upper extremities or other unusual districts such as cerebral or splanchnic veins. While leg DVT itself is rarely fatal and occasionally can lead to limb-threatening implications, its most fearsome complication, namely pulmonary embolism, is potentially fatal and significantly contributes to increased healthcare costs and impaired quality of life in affected patients and caregivers. Thanks to its high accuracy, ease of use, and safety profile, duplex ultrasound (DUS), particularly compression ultrasound (CUS), has emerged as the first-line imaging modality for DVT diagnosis. The evaluation of suspected DVT needs a multifaceted approach, and in this context, CUS rapidly became a key diagnostic tool owing to its many unique advantages. Its central role in the diagnostic algorithm of suspected DVT is clearly established in the latest clinical practice guidelines from the European Society for Vascular Surgery and the American Society of Haematology. Indeed, DUS effectively visualizes blood flow and identifies abnormalities like clot formation with high sensitivity (typically exceeding 90% for proximal DVT) and specificity (often approaching 100% for proximal DVT). Additionally, CUS is non-invasive, readily available at the bedside, and avoids radiation exposure, resulting in an ideal method for various clinical settings. CUS has been shown to have a substantial role not only in the diagnosis of an acute DVT but also in the follow-up of its management. Moreover, this method can provide a prognostic assessment, mostly in terms of risk stratification for recurrent thrombosis and/or for potential complications, such as post-thrombotic syndrome. In summary, given its established benefits, CUS is a technique that many physicians should be familiar with, especially those working in emergency departments, intensive care units, or general wards. When needed, healthcare operators with more advanced US skills (such as radiologists, angiologists, or vascular surgeons) may be called upon to provide a second look in case of uncertainty and/or need for additional information. Full article

Background: Complications, namely, catheter-related thrombosis (CRT) and venous stenosis, are associated with non-cuffed hemodialysis catheters used for emergency vascular access. However, only a few reports have demonstrated changes in the venous lumen and intravenous thrombosis after catheter removal. In this study, we comprehensively investigated the risk factors for residual thrombus 1 month after hemodialysis catheter removal. Methods: This prospective observational study was conducted from June 2021 to October 2022. We included patients with end-stage kidney disease who underwent hemodialysis catheter placement in the internal jugular vein (IJV). After catheter removal, we observed the IJV using vascular ultrasound and evaluated the thrombus and vein properties. Furthermore, we observed thrombosis 1 month after catheter removal, and investigated the risk factors for residual thrombus 1 month after catheter removal. Results: A thrombus was observed at the site of catheter removal in all the cases. Of the 37 patients who were followed up, 11 exhibited a residual thrombus 1 month after catheter removal. Patients with arteriovenous (AV) access dysfunction and enlarged lymph nodes during catheter removal were significantly more likely to have a residual thrombus 1 month after catheter removal. These associations remained significant even after adjusting for age, sex, and diabetes status. Conclusions: In 29.7% of the patients, CRT persisted even 1 month after the removal of the non-cuffed hemodialysis catheter. The provision of early intervention in patients with AV access dysfunction and enlarged lymph nodes during catheter removal may prevent CRT persistence. Full article

Background: The role of residual venous thrombosis (RVT) as a risk factor for recurrent venous thromboembolism (VTE) in patients with cancer-associated thrombosis (CAT) remains controversial. Methods: We conducted a cohort study on consecutive patients with CAT treated with tinzaparin recruited between 2007 and 2022. Primary outcome: RVT. Secondary outcomes: identification of variables associated with RVT and the role of RVT in VTE recurrences or clinically relevant bleeding (CRB). Results: Among 511 patients with CAT (age 64.1 years ± 13.4 years; 53.5% males) followed for 17.6 months (p25–75: 7.9–34), 35.8% (n = 183) presented RVT (at 6 months, 55.5%). Variables identified as being associated with RVT were ECOG performance status > 1, metastasis, and cancer location. Within 5 years, there were 57 CRB (11.2%; 95% CI: 8.6–14.2) and 67 VTE recurrences (13.1%, 95%CI: 10.3–16.4). Competing risk analysis identified that RVT at 6 months was associated with VTE recurrence within 5 years (sub-hazard ratio: 2.1; 95% CI: 1.2–3.7; p = 0.006), but not with CRB. Multivariate analysis confirmed that RVT at 6 months (HR: 2.1; 95% CI: 1.2–3.7) and metastases (HR: 1.7; 95% CI: 1.1–2.9) were associated with VTE recurrence within 5 years. Conclusions: RVT is high in patients with CAT. The presence of RVT at 6 months was associated with an increased risk of recurrent VTE over 5 years. Full article

Inherited defects in the genes of blood coagulation essentially express the severity of the clinical phenotype that is directly correlated to the number of mutated alleles of the candidate leader gene (e.g., heterozygote vs. homozygote) and of possible additional coinherited traits. The F5 gene, which codes for coagulation factor V (FV), plays a two-faced role in the coagulation cascade, exhibiting both procoagulant and anticoagulant functions. Thus, defects in this gene can be predisposed to either bleeding or thrombosis. A Sanger sequence analysis detected a premature stop-codon in exon 13 of the F5 gene (c.3481C>T; p.R1161Ter) in several members of a family characterised by low circulating FV levels and contrasting clinical phenotypes. The propositus, a 29 y.o. male affected by recurrent haemorrhages, was homozygous for the F5 stop-codon and for the F5 c.1691G>A (p.R506Q; FV-Leiden) inherited from the heterozygous parents, which is suggestive of combined cis-segregation. The homozygous condition of the stop-codon completely abolished the F5 gene expression in the propositus (FV:Ag < 1%; FV:C < 1%; assessed by ELISA and PT-based one-stage clotting assay respectively), removing, in turn, any chance for FV-Leiden to act as a prothrombotic molecule. His father (57 y.o.), characterised by severe recurrent venous thromboses, underwent a complete molecular thrombophilic screening, revealing a heterozygous F2 G20210A defect, while his mother (56 y.o.), who was negative for further common coagulation defects, reported fully asymptomatic anamnesis. To dissect these conflicting phenotypes, we performed the ProC^®Global (Siemens Helthineers) coagulation test aimed at assessing the global pro- and anticoagulant balance of each family member, investigating the responses to the activated protein C (APC) by means of an APC-sensitivity ratio (APC-sr). The propositus had an unexpectedly poor response to APC (APC-sr: 1.09; n.v. > 2.25), and his father and mother had an APC-sr of 1.5 and 2.0, respectively. Although ProC^®Global prevalently detects the anticoagulant side of FV, the exceptionally low APC-sr of the propositus and his discordant severe–moderate haemorrhagic phenotype could suggest a residual expression of mutated FV p.506QQ through a natural readthrough or possible alternative splicing mechanisms. The coagulation pathway may be physiologically rebalanced through natural and induced strategies, and the described insights might be able to track the design of novel treatment approaches and rebalancing molecules. Full article

The use of neuromuscular blocking agents (NMBAs) is common in the intensive care unit (ICU). NMBAs have been used in critically ill patients with lung diseases to optimize mechanical ventilation, prevent spontaneous respiratory efforts, reduce the work of breathing and oxygen consumption, and avoid patient–ventilator asynchrony. In patients with acute respiratory distress syndrome (ARDS), NMBAs reduce the risk of barotrauma and improve oxygenation. Nevertheless, current guidelines and evidence are contrasting regarding the routine use of NMBAs. In status asthmaticus and acute exacerbation of chronic obstructive pulmonary disease, NMBAs are used in specific conditions to ameliorate patient–ventilator synchronism and oxygenation, although their routine use is controversial. Indeed, the use of NMBAs has decreased over the last decade due to potential adverse effects, such as immobilization, venous thrombosis, patient awareness during paralysis, development of critical illness myopathy, autonomic interactions, ICU-acquired weakness, and residual paralysis after cessation of NMBAs use. The aim of this review is to highlight current knowledge and synthesize the evidence for the effects of NMBAs for critically ill patients with lung diseases, focusing on patient–ventilator asynchrony, ARDS, status asthmaticus, and chronic obstructive pulmonary disease. Full article

Background: Superficial venous thrombosis (SVT) is a common clinical condition caused by inflammation and the presence of a thrombus inside a superficial vein. It has traditionally been considered a benign and banal disorder, although it can progress or can be associated with thromboembolic disease of deep territories in up to 20%, asymptomatic or symptomatic pulmonary embolism (PE), especially if it affects the main trunk of the internal saphenous vein. The impact of deep vein thrombosis on the quality of life and its sequelae have long been described in the literature; however, they have not been studied in superficial vein thrombosis. Objectives: We aimed to evaluate the risk factors, management, and complications of SVT and its impact on the quality of life of our patients. Methods: Observational, prospective, single-center study to evaluate the management of SVT. The ultrasound (US) was performed initially on symptomatic patients, during treatment with low-molecular-weight heparin (LMWH), at a follow-up, and at the end of 45 days of treatment. A quality-of-life questionnaire was administered to determine the risk factors, management, and complications of SVT at the moment of diagnosis and at the end of treatment. We included patients referred from the emergency department to a monographic consultation for thromboembolic disease, over 18 years of age with a diagnosis of acute SVT symptomatic, without contraindication to initiate anticoagulation. Results: In total, 63 patients were evaluated between October 2020 and April 2022. The mean age was 65.8 years (SD 13.5), of which 35 were women (55.6%), 39 presented cardiovascular risk factors (61.9%), 25 had a history of previous personal venous thromboembolism (VTE) (39.7%), and 10 had obesity (15.9%), 47 had chronic venous insufficiency or varicose veins (74.9%). During follow-up with ultrasound, 39.7% had partial revascularization, and at discharge, 63.5% had permeabilized the thrombosis against 19% who had residual thrombosis or progression of thrombosis. There was a positive correlation between mobility parameters and improvement in the performance of daily activities (rho = 0.35; p = 0.012) and with improvement in pain/discomfort (rho = 0.37; p = 0.007). An improvement in pain parameters was statistically significantly related to a global assessment health perception (rho = 0.48; p < 0.001). Anxiety and depression parameters were related to a global assessment health perception (rho = 0.462; p = 0.001) and to an overall improvement at 12 months (rho = 0.45; p = 0.001). CONCLUSIONS: Superficial venous thrombosis (SVT) is a highly prevalent disease, which is traditionally considered banal and has good evolution, with heterogeneous management in clinical practice and limited information on patient selection for therapies, current treatment routes, and drug use, as well as outcomes. In recent years, the importance of this entity has become evident due to its frequency in clinical practice, its risk of complications, and the impact it has on the quality of life. This study’s results emphasize the importance of the diagnosis, treatment, and follow-up of superficial venous thrombosis. Full article

Venous thromboembolism (VTE) is the third most common cause of death worldwide. The incidence of VTE varies according to different countries, ranging from 1–2 per 1000 person-years in Western Countries, while it is lower in Eastern Countries (<1 per 1000 person-years). Many risk factors have been identified in patients developing VTE, but the relative contribution of each risk factor to thrombotic risk, as well as pathogenetic mechanisms, have not been fully described. Herewith, we provide a comprehensive review of the most common risk factors for VTE, including male sex, diabetes, obesity, smoking, Factor V Leiden, Prothrombin G20210A Gene Mutation, Plasminogen Activator Inhibitor-1, oral contraceptives and hormonal replacement, long-haul flight, residual venous thrombosis, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, trauma and fractures, pregnancy, immobilization, antiphospholipid syndrome, surgery and cancer. Regarding the latter, the incidence of VTE seems highest in pancreatic, liver and non-small cells lung cancer (>70 per 1000 person-years) and lowest in breast, melanoma and prostate cancer (<20 per 1000 person-years). In this comprehensive review, we summarized the prevalence of different risk factors for VTE and the potential molecular mechanisms/pathogenetic mediators leading to VTE. Full article

The main causes of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis are ovarian teratoma and herpes simplex virus (HSV) encephalitis. We present a rare case of suspected anti-NMDAR encephalitis caused by corpus callosotomy (CC). An 18-year-old woman with Lennox-Gastaut syndrome underwent CC. Although left hemiplegic due to cerebral hemorrhage and impaired consciousness due to cerebral venous sinus thrombosis (CVST) appeared postoperatively, anticoagulant therapy quickly improved CVST and impaired consciousness. However, various unexplained symptoms such as insomnia, hallucination, impulsivity, impaired consciousness, and a new type of drug-resistant cluster seizures gradually developed over a 2-month period. Magnetic resonance imaging revealed the gradual extension of a hyperintense area from the right frontal lobe on fluid-attenuated inversion recovery images. Intravenous methylprednisolone pulse was initiated from postoperative day (POD) 74, followed by intravenous immunoglobulin (IVIg) therapy, although white blood cell counts were normal in all three cerebrospinal fluid (CSF) examinations. After IVIg therapy, the above unexplained symptoms promptly improved. On POD 103, antibodies against NMDAR were revealed in both the serum and CSF collected before these immunotherapies. The patient was transferred to a rehabilitation hospital due to residual left hemiplegia. Psychiatric symptoms and a new onset of drug-resistant seizures may be suggestive of postoperative anti-NMDAR encephalitis, even if CSF findings are mild. Full article

Controversies in the treatment of venous thoracic outlet syndrome (VTOS) have been discussed for decades, but still persist. Calls for more objective reporting standards have pushed practice towards comprehensive venous evaluations and interventions after first rib resection (FRR) for all patients. In our practice, we have relied on patient-centered, patient-reported outcomes to guide adjunctive treatment and measure success. Thus, we sought to investigate the use of thrombolysis versus anticoagulation alone, timing of FRR following thrombolysis, post-FRR venous intervention, and FRR for McCleery syndrome (MCS) and their impact on patient symptoms and return to function. All patients undergoing FRR for VTOS at our institution from 4 April 2000 through 31 December 2013 were reviewed. Demographics, symptoms, diagnostic and treatment details, and outcomes were collected. Per “Reporting Standards of the Society for Vascular Surgery for Thoracic Outlet Syndrome”, symptoms were described as swelling/discoloration/heaviness, collaterals, concomitant neurogenic symptoms, and functional impairment. Patient-reported response to treatment was defined as complete (no residual symptoms and return to function), partial (any residual symptoms present but no functional impairment), temporary (initial improvement but subsequent recurrence of any symptoms or functional impairment), or none (persistent symptoms or functional impairment). Sixty FRR were performed on 59 patients. 54.2% were female with a mean age of 34.3 years. Swelling/discoloration/heaviness was present in all but one patient, deep vein thrombosis in 80%, and visible collaterals in 41.7%. Four patients had pulmonary embolus while 65% had concomitant neurogenic symptoms. In addition, 74.6% of patients were anticoagulated and 44.1% also underwent thrombolysis prior to FRR. Complete or partial response occurred in 93.4%. Of the four patients with temporary or no response, further diagnostics revealed residual venous disease in two and occult alternative diagnoses in two. Use of thrombolysis was not related to FRR outcomes (p = 0.600). Performance of FRR less than or greater than six weeks after the initiation of anticoagulation or treatment with thrombolysis was not related to FRR outcomes (p = 1). Whether patients had DVT or MCS was not related to FRR outcomes (p = 1). No patient had recurrent DVT. From a patient-centered, patient-reported standpoint, VTOS is equally effectively treated with FRR regardless of preoperative thrombolysis or timing of surgery after thrombolysis. A conservative approach to venous interrogation and intervention after FRR is safe and effective for symptom control and return to function. Additionally, patients with MCS are effectively treated with FRR. Full article

Thoracic Outlet Syndrome (TOS) describes a set of disorders that arise from compression of the neurovascular structures that exit the thorax and enter the upper extremity. This can present as one of three subtypes: neurogenic, venous, or arterial. The objective of this section is to outline our current practice at a single, high-volume institution for venous and arterial TOS. VTOS: Patients who present within two weeks of acute deep vein thrombosis (DVT) are treated with anticoagulation, venography, and thrombolysis. Those who present later are treated with a transaxillary first rib resection, then a two-week post-operative venoplasty. All patients are anticoagulated for 2 weeks after the post-operative venogram. Those with recurrent thrombosis or residual subclavian vein stenosis undergo repeat thrombolysis or venoplasty, respectively. ATOS: In patients with acute limb ischemia, we proceed with thrombolysis or open thrombectomy if there is evidence of prolonged ischemia. We then perform a staged transaxillary first rib resection followed by reconstruction of the subclavian artery. Patients who present with claudication undergo routine arterial duplex and CT angiogram to determine the pathology of the subclavian artery. They then undergo decompression and subclavian artery repair in a similar staged manner. Full article

Fibrolase is the fibrinolytic enzyme isolated from Agkistrodon contortrix contortrix (southern copperhead snake) venom. The enzyme was purified by a three-step HPLC procedure and was shown to be homogeneous by standard criteria including reverse phase HPLC, molecular sieve chromatography and SDS-PAGE. The purified enzyme is a zinc metalloproteinase containing one mole of zinc. It is composed of 203 amino acids with a blocked amino-terminus due to cyclization of the terminal Gln residue. Fibrolase shares a significant degree of homology with enzymes of the reprolysin sub-family of metalloproteinases including an active site homology of close to 100%; it is rapidly inhibited by chelating agents such as EDTA, and by alpha2-macroglobulin (α2M). The enzyme is a direct-acting thrombolytic agent and does not rely on plasminogen for clot dissolution. Fibrolase rapidly cleaves the A(α)-chain of fibrinogen and the B(β)-chain at a slower rate; it has no activity on the γ-chain. The enzyme exhibits the same specificity with fibrin, cleaving the α-chain more rapidly than the β-chain. Fibrolase was shown to have very effective thrombolytic activity in a reoccluding carotid arterial thrombosis model in the canine. A recombinant version of the enzyme was made in yeast by Amgen, Inc. (Thousand Oaks, CA, USA) and called alfimeprase. Alfimeprase is identical to fibrolase except for a two amino acid truncation at the amino-terminus and the insertion of a new amino-terminal amino acid in the truncated protein; these changes lead to a more stable enzyme for prolonged storage. Alfimeprase was taken into clinical trials by Nuvelo, Inc. (San Carlos, CA), which licensed the enzyme from Amgen. Alfimeprase was successful in Phase I and II clinical trials for peripheral arterial occlusion (PAO) and central venous access device (CVAD) occlusion. However, in Phase III trials alfimeprase did not meet the expected end points in either PAO or CVAD occlusion and in a Phaase II stroke trial, and Nuvelo dropped further development in 2008. Full article