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Venous thromboembolism (VTE) is common in patients with coronavirus disease-2019 (COVID-19). The optimal heparin regimen remains unknown and should balance thromboembolic and bleeding risks. The aim of this study was to evaluate the efficacy and safety of standard or higher heparin regimens for the prevention of VTE in patients hospitalized due to COVID-19. We performed a systematic literature search; studies reporting on hospitalized patients with COVID-19 who received standard heparin prophylaxis vs. high (intermediate or therapeutic) heparin regimens were included if outcome events were reported by treatment group and more than 10 patients were included. Primary study outcome was in-hospital VTE. Secondary study outcomes were major bleeding (MB), all-cause death, fatal bleeding and fatal pulmonary embolism. Overall, 33 studies (11,387 patients) were included. Venous thromboembolic events occurred in 5.2% and in 8.2% of patients who received heparin prophylaxis with at high-dose or standard-dose, respectively (RR 0.71, 95% CI 0.55-0.90, I2 48.8%). MB was significantly higher in patients who received high- compared to the standard-dose (4.2% vs 2.2%, RR 1.94, 95% CI 1.47-2.56, I2 18.1%). Sub-analyses showed a slight benefit associated with high-dose heparin in patients admitted to non-intensive care unit (ICU) but not in those to ICU. No significant differences were observed for mortality outcomes. Heparin prophylaxis at high-dose reduces the risk of VTE, but increased the risk of MB compared to the standard-dose. No clinical benefit for heparin high-dose was observed for ICU setting, but its role in the non-ICU deserves further evaluation. PROSPERO registration number: CRD42021252550.

Background Delayed-onset of headache seems a specific feature of cerebrovascular events after COVID-19 vaccines. Methods All consecutive events reported to the United States Vaccine Adverse Reporting System following COVID-19 vaccines (1 January to 24 June 2021), were assessed. The timing of headache onset post-vaccination in subjects with and without concomitant cerebrovascular events, including cerebral venous thrombosis, ischemic stroke, and intracranial haemorrhage was analysed. The diagnostic accuracy in predicting concurrent cerebrovascular events of the guideline- proposed threshold of three-days from vaccination to headache onset was evaluated. Results There were 314,610 events following 306,907,697 COVID-19 vaccine doses, including 41,700 headaches, and 178/41,700 (0.4%) cerebrovascular events. The median time between the vaccination and the headache onset was shorter in isolated headache (1 day vs. 4 (in cerebral venous thrombosis), 3 (in ischemic stroke), or 10 (in intracranial hemorrhage) days, all P < 0.001). Delayed onset of headache had an area under the curve of 0.83 (95% CI: 0.75–0.97) for cerebral venous thrombosis, 0.70 (95% CI: 0.63–76) for ischemic stroke and 0.76 (95% CI: 0.67–84) for intracranial hemorrhage, and >99% negative predictive value. Conclusion Headache following COVID-19 vaccination occurs within 1 day and is rarely associated with cerebrovascular events. Delayed onset of headache 3 days post-vaccination was an accurate diagnostic biomarker for the occurrence of a concomitant cerebrovascular events.

Purpose To evaluate the usefulness of compressive ultrasound (CUS) for the diagnosis of deep vein thrombosis (DVT) in patients with SARS-CoV-2-related infection. Methods 112 hospitalized patients with confirmed SARS-CoV-2 infection were retrospectively enrolled. CUS was performed within 2 days of admission and consisted in the assessment of the proximal and distal deep venous systems. Lack of compressibility, or direct identification of an endoluminal thrombus, were the criteria used for the diagnosis of DVT. Pulmonary embolism (PE) events were investigated at computed tomography pulmonary angiography (CTPA) within 5 days of follow-up. Logistic binary regression was computed to determine which clinical and radiological parameters were independently associated with PE onset. Results Overall, the incidence of DVT in our cohort was about 43%. The most common district involved was the left lower limb (68.7%) in comparison with the right one (58.3%) while the upper limbs were less frequently involved (4.2% the right one and 2.1% the left one, respectively). On both sides, the distal tract of the popliteal vein was the most common involved (50% right side and 45.8% left side). The presence of DVT in the distal tract of the right popliteal vein (OR = 2.444 95%CIs 1.084–16.624, p = 0.038), in the distal tract of the left popliteal vein (OR = 4.201 95%CIs 1.484–11.885, p = 0.007), and D-dimer values (OR = 2.122 95%CIs 1.030–5.495, p = 0.003) were independently associated with the onset on PE within 5 days. Conclusions CUS should be considered a useful tool to discriminate which category of patients can develop PE within 5 days from admission.

Purpose: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has improved survival for selected patients with peritoneal metastases from colorectal cancer. Previous studies report conflicting rates of postoperative bleeding and venous thromboembolism (VTE) after CRS + HIPEC. The aim of the present study was to systematically review the literature and to estimate the overall 30-day incidence of postoperative bleeding and the overall 90-day incidence of VTE after CRS + HIPEC. Methods: Studies were identified in PubMed, Embase, and Web of Science on 29 April 2021. Data were extracted for a qualitative synthesis and to estimate an overall mean incidence in the meta-analysis. Results: Fourteen studies with a total of 3268 patients were included in the systematic review. Postoperative bleeding incidence rates within 30 days ranged from 1.7 to 8.3% with an overall 30-day postoperative bleeding incidence with [95% CI] at 4.2 [2.6;6.2]%. VTE incidence rates within 90 days ranged from 0.2 to 13.6% with an overall 90-day VTE incidence with [95% CI] at 2.7 [1;5.2]% after CRS + HIPEC. Conclusion: This systematic review and meta-analysis indicate a low risk for postoperative bleeding within 30 days and VTE within 90 days after CRS + HIPEC for peritoneal metastases from colorectal cancer.

Background In intensive-care unit (ICU) patients, pathophysiological changes may affect the pharmacokinetics of enoxaparin and result in underdosing. Objectives To develop a pharmacokinetic model of enoxaparin to predict the time-exposure profiles of various thromboprophylactic regimens in COVID-19 ICU-patients. Methods This was a retrospective study in ICUs of two French hospitals. Anti-Xa activities from consecutive patients with laboratory-confirmed SARS-CoV-2 infection treated with enoxaparin for the prevention or the treatment of venous thrombosis were used to develop a population pharmacokinetic model using non-linear mixed effects techniques. Monte Carlo simulations were then performed to predict enoxaparin exposure at steady-state after three days of administration. Results A total of 391 anti-Xa samples were measured in 95 patients. A one-compartment model with first-order kinetics best fitted the data. The covariate analysis showed that enoxaparin clearance (typical value 1.1 L.h-1) was related to renal function estimated by the CKD-EPI formula and volume of distribution (typical value 17.9 L) to actual body weight. Simulation of anti-Xa activities with enoxaparin 40 mg qd indicated that 64% of the patients had peak levels within the range 0.2 to 0.5 IU.mL-1 and 75% had 12-hour levels above 0.1 IU.mL-1. Administration of a total daily dose of at least 60 mg per day improved the probability of target attainment. Conclusion In ICU COVID-19 patients, exposure to enoxaparin is reduced due to an increase in the volume of distribution and clearance. Consequently, enoxaparin 40 mg qd is suboptimal to attain thromboprophylactic anti-Xa levels.

Patient: Male, 70-year-old Final Diagnosis: Drug induced polycythemia Symptoms: Sural pain Medication: — Clinical Procedure: Endovascular treatment Specialty: Oncology • Pulmonology Objective: Unusual or unexpected effect of treatment Background: Osimertinib is an oral third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) approved as first-line therapy for advanced non-small cell lung cancer (NSCLC) with positive EGFR mutation. Rashes, nail toxicity, and diarrhea are common adverse events. Hematological adverse effects, including anemia, thrombocytopenia, and lymphocytopenia, have been reported. However, erythrocytosis has not been reported as an adverse event. To the best of our knowledge, we report the first case of acute lower extremity thrombosis presumably caused by osimertinib-induced erythrocytosis. Case Report: A 70-year-old man with epidermal EGFR-mutant advanced NSCLC presented with acute left sural pain. The patient’s left foot was cold, and peripheral arterial Doppler signals were absent. He had developed erythrocytosis of unknown etiology during osimertinib therapy. Hemoglobin (Hb) and hematocrit were 22.6 g/dL and 62.5%, respectively. Contrast-enhanced computed tomography showed thrombotic occlusion of the popliteal artery. Other than erythrocytosis, there was no possible cause of arterial thrombosis. Osimertinib was discontinued immediately because the NSCLC started to resist treatment and was presumed to be the cause of erythrocytosis. He received endovascular treatment (EVT). Following serial EVT and debridement, his fourth toe was amputated for necrosis. Erythrocytosis persisted 8 months during osimertinib therapy. Hb levels decreased to 15.4 mg/dL due to blood loss complicated with catheter thrombectomy and remained normal for 20 months after osimertinib discontinuation. The patient died of cancer progression. Conclusions: This case suggests the erythrocytosis was possibly caused by osimertinib. We may need to monitor Hb levels during osimertinib therapy and be alert to thrombosis once Hb starts to rise.

Patient: Male, 40-year-old Final Diagnosis: Sarcoidosis trombophilia pulmonary embolism Symptoms: Chest pain dyspnea cough Medication:— Clinical Procedure: Mediastinoscopy chest angio CT scan laboratory assay Specialty: Pulmonology Objective: Rare co-existance of disease or pathology Background: The association between sarcoidosis and pulmonary embolism (PE) has been described in the literature, but little is known about the origin of hypercoagulability and hypofibrinolysis in sarcoidosis. PE is a multifactorial disease that is rarely caused by a single risk factor, and might be expected in disabling sarcoidosis. No data are available, however, about sarcoidosis being a risk factor for venous thromboembolism in factor V Leiden thrombophilia. Case Report: We describe a case of a 40-year-old man with asymptomatic sarcoidosis. Diagnosis was based on abnormal chest radiology (enlargement of hilar and mediastinal lymph nodes), confirmed by histopathological examination (noncaseating granulomas involving the mediastinal lymph nodes). No therapy was proposed due to good exercise tolerance, normal pulmonary function test, and absence of extrapulmonary involvement. The patient was followed up for 5 years until he developed progressive exertional dyspnea and chest pain. Plasma D-dimers, serum NT-proBNP, and troponin were increased. A computed tomography angiogram confirmed PE. Factor V Leiden thrombophilia was diagnosed following a search for risk factors for thromboembolism. Spontaneous remission of the chest lymphadenopathy was observed on anticoagulation therapy. Different potential mechanisms that relate sarcoidosis to venous thromboembolism are discussed. Conclusions: PE is a potentially fatal condition and may complicate sarcoidosis, a clinically insignificant condition. Sarcoidosis patients with new symptomatology and PE with a high concentration of plasma D-dimers merit extra consideration. In certain clinical situations, sarcoidosis may be considered as a risk factor for deep vein thrombosis/PE. The anti-inflammatory and anti-fibrotic properties of anticoagulation warrant further study.

During the coronavirus disease 2019 (COVID-19) pandemic, numerous reports of ocular anomalies occurring in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged. The most frequently reported pathology is conjunctivitis, which may be the first or only clinical manifestation of the disease. Involvement of SARS-CoV-2 in development of alterations in other ocular structures was suggested, including the cornea, the retina, and blood vessels. Possible mechanisms include direct activity of the viral agent, as well as systemic inflammatory response with accompanying thromboembolic complications. Genetic material of SARS-CoV-2 was detected in ocular secretions of infected individuals, including asymptomatic patients. Moreover, angiotensin-converting enzyme 2 (ACE2), a receptor protein used by the virus to enter the cell, has been found on the surface of various structures of the eye, which indicates a risk of transmission through ocular tissues. Therefore, it is crucial to use eye protection by medical professionals having contact with potentially infected patients. This paper is a review of the literature regarding ocular manifestations of SARS-CoV-2 infection and a summary of the current state of knowledge about possibility of transmission from an ophthalmology point of view. For data collection, a thorough PubMed search was performed, using the key words: "COVID ocular", "COVID eye", "SARS-CoV-2 ocular", and "SARS-CoV-2 eye". Conclusions: SARS-CoV-2 infection may manifest itself in various ocular conditions. Eye protection should not be neglected, as recent studies suggest the eye as a potential route of transmission. Further search for adequate safety measures in ophthalmology practice is required.

Background COVID-19 is still a global challenge in regard for management and therapy. Pulmonary embolism (PE) seems to have a higher prevalence in COVID-19 instead of non-COVID patients. Clinical and laboratory parameters related with PE are still unknown. Methods We conducted a retrospective unicentre study in Alto Vicentino Hospital between March 1st, 2020, and January 31st, 2021 in patients admitted for COVID-19 tested with a RT-PCR nasal swab. Data about patients studied with computed tomography pulmonary angiogram (CTPA) because of PE suspicion were collected, as their clinical and laboratory parameters too. Results 2621 patients were admitted for COVID-19 in Alto Vicentino Hospital between March 1st, 2020, and January 31st, 2021 and in 267 of them a CTPA was performed finding 50 PE (18.7%). Only non-Caucasian race (OR = 5.44; 95% CI 1.22–24.35; p = 0.027) and previous VTE (OR = 5.3; 95% CI 1.09–26.17; p = 0.039) were found to be independently associated with PE. Conclusion PE is a frequent complication of COVID-19 and clinician need high degree of suspicion because clinical and laboratoristic parameters cannot drive diagnosis.

Patient: Male, 43-year-old Final Diagnosis: Heart failure • HIV infection • thrombosis Symptoms: Heart failure Medication: — Clinical Procedure: Echocardiography Specialty: General and Internal Medicine Objective: Unusual clinical course Background: Left ventricular thrombus (LVT) is a complication of left ventricular dysfunction and myocardial infarction (MI) and is associated with systemic thromboembolism. Two-dimensional transthoracic echocardiography (TTE) is considered the first-line diagnostic tool for detection of LVT. Vitamin K antagonists (VKA) targeting an international normalized ratio (INR) from 2 to 3 are the only approved treatments by the Food and Drug Administration (FDA). New emerging observational data support the use of direct oral anticoagulants (DOACs) as an alternative therapeutic option; however, their safety and efficacy have not been assessed in a good-quality randomized controlled trial. Case Report: Here, we present a case of a 43-year-old man diagnosed with human immunodeficiency virus (HIV)-associated dilated cardiomyopathy complicated with an LVT. He was treated with rivaroxaban for 9 consecutive months with no interruption of therapy at any point in time; however, he presented to the emergency department with symptoms of decompensated heart failure. A follow-up TTE demonstrated a significant increase in the size of his LVT. This case questions the efficacy of using factor Xa inhibitor (rivaroxaban) as an alternative option for LVT treatment. Conclusions: This case demonstrates a failure of rivaroxaban in treating LVT in a patient with HIV-associated dilated cardiomyopathy. Good-quality randomized clinical trials or prospective studies are required to establish the efficacy and safety of DOACs for LVT treatment as an alternative to VKA.

Patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have a two- to threefold greater risk of developing venous as well as arterial thrombotic events. Although such thrombotic events are more commonly seen during phases of active AAV, they are also recognized to occur during AAV in remission. Endothelial injury is a key pathogenic event in AAV. Endothelial injury can be caused by neutrophil activation and release of thrombogenic tissue factor into the circulation. Neutrophil activation further results in the formation of neutrophil extracellular traps (NETs). NETs contribute to thrombosis by expressing tissue factor. NETs have also been detected in cutaneous thrombi from patients with AAV induced by hydralazine. Activated neutrophils in AAV patients release thrombogenic microparticles loaded with tissue factor which further enhances clotting of blood. Antiphospholipid antibodies (APLs) have been detected in up to a third of AAV and might also be induced by drugs such as cocaine adulterated with levamisole and propylthiouracil, which are known to trigger AAV. Such APLs further drive the thrombosis in AAV. Once thrombogenesis occurs, the homeostatic mechanisms resulting in clot dissolution are further impaired in AAV due to anti-plasminogen antibodies. The ongoing pandemic of coronavirus disease 2019 (COVID-19) is associated with endothelial injury and NETosis, mechanisms which are in common with AAV. Reports of new-onset AAV following COVID-19 have been described in the literature, and there could be shared mechanisms driving these processes that require further evaluation.

BACKGROUND Congestive heart failure is a challenging problem due to increasing prevalence in developed countries. Patients admitted due to decompensated congestive heart failure symptoms who do not respond to medical treatment require mechanical circulatory support. Patients with biventricular failure are at particularly high mortality risk. MATERIAL AND METHODS We analyzed the function of 49 pumps (POLVAD-MEV, FRK Intra-cordis, Poland) implanted to rescue INTERMACS 1 and 2 profile patients referred to our department due to severe congestive heart failure. All patients were waiting for heart transplantation and were readmitted due to acute decompensations of congestive biventricular heart failure with resistance to medical therapy. RESULTS During the observational period, there were no technical problems in pump function. The mean duration of pump therapy was 30.6±8.3 (5-49) days. The risk for right-sided pump complications included clots formation on the following parts of the pump: outflow tract (1, 2%), membrane (13, 27%), dome (6, 12.5%), and periphery (1, 2%). The overall risk for device thrombosis was 41%. The risk for thromboembolic complications was CRP-dependent regarding conglomerates of fibrin and platelets formation (p

BACKGROUND Since the outbreak of COVID-19 in December 2019, there have been 96 623 laboratory-confirmed cases and 4784 deaths by December 29 in China. We aimed to analyze the risk factors and the incidence of thrombosis from patients with confirmed COVID-19 pneumonia. MATERIAL AND METHODS Eighty-eight inpatients with confirmed COVID-19 pneumonia were reported (31 critical cases, 33 severe cases, and 24 common cases). The thrombosis risk factor assessment, laboratory results, ultrasonographic findings, and prognoses of these patients were analyzed, and compared among groups with different severity. RESULTS Nineteen of the 88 cases developed DVT (12 critical cases, 7 severe cases, and no common cases). In addition, among the 18 patients who died, 5 were diagnosed with DVT. Positive correlations were observed between the increase in D-dimer level (≥5 µg/mL) and the severity of COVID-19 pneumonia (r=0.679, P

The incidence of asymptomatic pulmonary embolism (PE) exceeds 70% in patients with deep venous thrombosis (DVT), even in cases of distal deep vein thrombosis. We report the case of a patient with a diagnosis of DVT in the lower left limb associated with asymptomatic PE who presented late symptoms due to this same PE. The absence of acute symptoms and the late onset of symptoms could have provoked doubts about the most appropriate treatment, resulting in unnecessary interventions, if pulmonary embolism had not already been diagnosed with tomography. In the present case, we demonstrate that computed tomography angiography conducted at the time of DVT diagnosis accurately diagnosed PE and prevented any misinterpretation of recurrent DVT in a patient already being medicated, which could have been mistakenly interpreted as demonstrating failure of anticoagulant therapy. Such a situation could lead to unnecessary intervention to fit an inferior vena cava filter. We cannot suggest that a classic medical conduct should be reformulated simply on the basis of a case report. However, we would be remiss not to suggest that well-designed studies should be carried out in the future to assess the need for this examination in the acute phase. Resumo A ocorrência de embolia pulmonar assintomática em pacientes com trombose venosa profunda tem uma incidência que excede 70%, mesmo nos casos de trombose venosa profunda distal. Relatamos o caso de um paciente com diagnóstico de trombose venosa profunda no membro inferior esquerdo associado a embolia pulmonar assintomática, que apresentou sintomas tardios devido a essa mesma embolia. A ausência de sintomas agudos e o surgimento de sintomas tardios pode suscitar dúvidas quanto ao tratamento mais adequado e resultar em intervenções desnecessárias, se o diagnóstico tomográfico de embolia pulmonar não tiver sido feito anteriormente. No presente caso, demonstramos que uma angiotomografia realizada no momento do diagnóstico de trombose venosa profunda detectou a embolia pulmonar e evitou uma interpretação incorreta de um evento trombótico recorrente na vigência de anticoagulação, o que por engano demonstraria uma falha na terapia anticoagulante. Essa situação pode levar a intervenções desnecessárias, como o implante de filtro de veia cava inferior. Entendemos que apenas um relato de caso não deve mudar uma conduta médica já estabelecida; no entanto, fomenta a discussão e estimula estudos que avaliem a necessidade de um exame diagnóstico pulmonar no momento do diagnóstico de trombose venosa profunda.

Patient: Female, 76-year-old Final Diagnosis: Lower limb ischemia Symptoms: Leg pain Medication: — Clinical Procedure: — Specialty: General and Internal Medicine Objective: Unusual clinical course Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which has become a global pandemic. The typical symptoms are fever, cough, and shortness of breath, but the disease can present with atypical signs, including those associated with a hypercoagulable state. These signs include deep venous thrombosis, pulmonary embolism, ischemic stroke, and acute coronary syndrome. Herein, we present the case of acute bilateral lower-extremity ischemia as a thromboembolic complication in a patient with COVID-19. Case Report: A 76-year-old woman presented with acute bilateral lower-extremity ulcerations covered with eschar formation of several weeks’ duration. During her hospital course, she underwent a test for COVID-19 and the result was positive. An angiogram of the patient’s lower extremities showed occlusions of the right distal posterior tibial artery, right mid-distal anterior tibial artery, right dorsalis pedis artery, left mid-distal anterior tibial artery, left dorsalis pedis artery, and left popliteal vein. Tissue plasminogen activator was administered to treat the occlusions. On the following day, the patient had an acute decline in her neurologic state and was emergently intubated. A computed tomography scan of the brain confirmed a subarachnoid hemorrhage requiring reversal of tissue plasminogen activator. The patient was transitioned to comfort care and ultimately died. Conclusions: In conclusion, acute limb ischemia should be acknowledged as a rare complication associated with COVID-19. It is important to raise awareness of arterial thrombosis as a possible complication of the hypercoagulable state caused by SARS-CoV-2 because prompt recognition is essential for early diagnosis and treatment. These actions could have a significant impact on patients’ overall outcome.

Highlights • Venous Thromboembolic Events after Bariatric Surgery. • This protocol undertakes a systematic review and metanalysis of venous thromboembolic events after bariatric surgery. • Methodology, searches, eligibility, and data extraction for analysis are described. • Following the PRISMA guidelines, it describes the approach for pooled estimates. • Findings will have key clinical consequences for patient care., Introduction Considerably large numbers of bariatric surgery (BS) procedures are undertaken globally, and are projected to increase with the obesity epidemic. Venous thromboembolic events (VTE) comprise an important cause of postoperative morbidity and mortality after BS and an important issue with wide clinical and financial repercussions. Yet, a precise extent of the prevalence of VTE after BS for obesity and its mortality remains uncertain. Methods and analysis In order to respond to this knowledge gap, we will conduct a systematic review and meta-analysis of the prevalence of and mortality associated with VTE after BS. This protocol outlines the methodology that will be used and the search strategies and eligibility criteria that will be utilized to identify and select studies, as well as the method by which data from the selected studies will be extracted for analysis. PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), WHO International Clinical Trials Registry Platform, Cochrane Library, MEDLINE, Scopus, clinicaltrials.gov and Google scholar will be searched from 01 January 1990 through 10th April 2020, for original studies written in English that provided prevalence estimates of VTE after BS. Articles will also be searched for mortality estimates of VTE after BS. STROCSS (Strengthening the Reporting of Cohort Studies in Surgery) criteria will evaluate the methodological quality of the selected studies. The use of fixed effect or random effects model will be subject to the findings of the statistical tests for heterogeneity. Publication bias will be visually estimated by inspecting the funnel plots. Pooled estimates will be computed. Th current protocol conforms to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines and has been submitted to the PROSPERO International Prospective Register of systematic reviews. No ethical clearance is required for this study. This systematic review and meta-analysis will be published in a peer-reviewed journal and presented at national and international conferences.

BACKGROUND Laminaria japonica polysaccharide (LJP), a fucose enriched sulfated polysaccharide has been demonstrated to have excellent anticoagulant and antithrombotic activities. However, the antithrombotic effect of low molecular weight polysaccharide from enzymatically modified of LJP (LMWEP) remains unknown. MATERIAL AND METHODS LMWEP was prepared by fucoidanase enzymatic hydrolysis, and the antithrombotic and anticoagulant activities, and the underlying mechanism were investigated thoroughly. Rats were randomly divided into 6 groups (8 rats in each group): the blank control group, the blank control group treated with LMWEP (20 mg/kg), the model group, the model group treated with heparin (2 mg/kg), the model group treated with LJP (20 mg/kg), and the model group treated with LMWEP (20 mg/kg). After 7 days of intravenous administration, blood was collected for biochemical parameters examinations. RESULTS LMWEP increased the activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), 6-keto prostaglandin F1alpha (6-Keto-PGF1alpha), and endothelial nitric oxide synthase (eNOS). In addition, LMWEP decreased fibrinogen (FIB), endothelin-1 (ET-1), thromboxane B2 (TXB2), erythrocyte sedimentation rate (ESR), and hematocrit (HCT). CONCLUSIONS LMWEP, an enzymatically modified fragment with a molecular weight of 25.8 kDa, is a potential antithrombotic candidate for treatment of thrombosis related diseases.

BackgroundThere is lack of evidence to guide the type, intensity, and the duration of anticoagulation following venous thromboembolism (VTE) in patients with inflammatory bowel disease (IBD).Patients and methodsRegistro Informatizado Enfermedad Trombo Embolica (RIETE) is an ongoing, multicenter, observational registry of consecutive patients with symptomatic, objectively confirmed, acute VTE. We used the RIETE database to compare the rate of VTE recurrences and major bleeding during the course of anticoagulation in noncancer patients with or without IBD.ResultsAs of October 2014, 41927 patients without active cancer have been recruited in RIETE. Of these, 265 (0.63%) had IBD and 85 (32%) had the VTE during an acute flare. The duration of anticoagulation was similar in patients with VTE during an acute flare (8.38.8 months), in remission (9.4 +/- 11.5 months), or without IBD (10.0 +/- 12.8 months). The rate of VTE recurrences [7.25, 95% confidence interval (CI): 1.46-21.2; 8.84, 95% CI: 3.23-19.2; and 5.85, 95% CI: 5.46-6.26 per 100 patient-years, respectively] and major bleeding (7.25, 95% CI: 1.46-21.2; 2.95, 95% CI: 0.33-10.6; and 4.79, 95% CI: 4.44-5.15, respectively) were similar in all three subgroups. Propensity score matching analysis confirmed the absence of differences in the rate of VTE recurrences (rate ratio: 1.16, 95% CI: 0.54-2.47) or major bleeding (rate ratio: 0.84, 95% CI: 0.31-2.23) between patients with or without IBD.ConclusionTherapeutic anticoagulation for patients with IBD and VTE is as safe and effective as for those with VTE without IBD.

BACKGROUND Acute limb ischemia (ALI) is a clinical entity with a high rate of morbidity and mortality. Despite advances and variety of its management, there is still no criterion standard treatment. The goal of this study was to evaluate the effect of tirofiban use on the early and 6-month prognosis of patients with knee and below-knee arterial thrombosis who were treated with percutaneous thrombosuction (PT) within 24 h. MATERIAL AND METHODS Data of consecutive ALI patients who were diagnosed with popliteal and infra-popliteal arterial thrombosis and underwent PT procedure within 24 h between January 2010 and September 2015 were evaluated retrospectively. Patients were separated into 2 groups according to tirofiban usage. RESULTS A total of 105 patients (mean age 67±16; 53% men) were included in the study. Atrial fibrillation (n 64, 61%) and hypertension (n 60, 57%) were the most frequent comorbidities in patients with thromboembolic events. A significantly higher rate of distal embolization (6% vs. 16%; p=0.01) and slow-flow (17% vs. 30%; p

Patient: Male, 21 Final Diagnosis: Massive pulmonary embolism and acromegaly Symptoms: Chest pain and syncope Medication: Thrombolysis and Anticoagulation Clinical Procedure: Computerized tomography pulmonary angiogram and magnetic resonance imaging of pituitary Specialty: Endocrinology and Pulmonology Objective: Unusual clinical course Background: The clinical presentation in acromegaly is usually insidious, with headaches or visual disturbances being the most common symptoms. Previous studies have shown higher fibrinogen levels, lower protein C and S activity values, and enhanced platelet function in patients with acromegaly compared to a normal population. Nevertheless, the link between hypercoagulability and acromegaly is often overlooked and rarely reported in the literature. Case Report: We report a case of a young man with a massive pulmonary embolism as the initial presentation of acromegaly. Extensive workup excluded other causes of thrombophilia. Furthermore, the diagnosis of acromegaly was confirmed by the patient’s clinical features as well as laboratory and radiological testing. A literature review on the link between hypercoagulability and acromegaly was performed. Conclusions: This case report shed light on hypercoagulability as an under-recognized serious complication of acromegaly and paves the road for future studies on this topic.

Background Low-molecular-weight heparins (LMWHs) are the recommended treatment for cancer-associated venous thrombosis (CAT). Recent evidences suggest a role for direct-acting oral anticoagulants (DOACs) in this clinical setting. Methods To evaluate the efficacy and safety of different anticoagulants we performed a network meta-analysis of RCTs including patients with CAT treated with LMWHs, vitamin K antagonists (VKAs) or DOACs. MEDLINE and EMBASE were searched up to February 2018. The primary efficacy and safety outcomes were recurrent VTE and major bleeding, respectively. Results Overall, 4720 CAT patients from 12 studies were included: 1430 from 2 studies comparing DOACs with LMWHs, 1212 from 4 studies comparing DOACs with VKAs and 2078 from 6 studies comparing VKAs to LMWHs. Recurrent VTE occurred in 4.9% of patients receiving DOACs, 9.6% receiving VKAs and 8.4% receiving LMWHs. The network meta-analysis showed a not significant increase of recurrent VTE in patients receiving LMWHs compared to those receiving DOACs (RR 1.3, 95% CI 0.9 to 2.0). The risk of recurrent VTE was higher in patients receiving VKAs compared to LMWHs (RR 1.5, 95% CI 1.0 to 2.0) or DOACs (RR 2.0, 95% CI 1.3 to 3.0) with no heterogeneity. Major bleeding occurred in 4.9, 4.1 and 4.3% of patients with CAT treated with DOAC, VKA or LMWH, respectively. No significant differences were observed from the direct, indirect and network meta-analyses. Conclusion In patients with CAT, DOACs showed a good efficacy and safety profile compared to other anticoagulants and is candidates to be an alternative to LMWHs.

Patient: Male, 55 Final Diagnosis: Disseminated intravascular coagulation Symptoms: Leg pain • short of breath • swelling legs Medication: — Clinical Procedure: — Specialty: Cardiology Objective: Unusual clinical course Background: Coagulation abnormalities can accompany acute congestive heart failure (CHF). However, disseminated intravascular coagulation (DIC) is rarely documented in such patients. DIC is characterized by generalized excessive activation of coagulation pathways followed by their depletion with secondary activation of anticoagulation and fibrinolysis. Treatment of the cause is an integral part of management of DIC; thus, recognition of the cause is critical. Case Report: A 55-year-old previously healthy man presented with breathlessness, swelling of both legs, and left leg pain. His physical exam result was consistent with decompensated heart failure. Further testing revealed multiple deep venous thrombi in the upper and lower extremities, arterial occlusion in the left popliteal artery, and an unusual cyst-like left ventricular thrombus. His laboratory evaluation was consistent with severe acute DIC. The patient was managed aggressively with diuretics, transfusions of platelets, and cryoprecipitate and was subsequently anticoagulated. His platelet count and coagulation parameters normalized and coronary angiography did not reveal any obstructive lesions. On day 22, an echocardiogram revealed and MRI confirmed that the intracardiac thrombus had disappeared. He underwent revascularization of the left leg and was successfully discharged from the hospital. Conclusions: Severe biventricular non-ischemic cardiac dysfunction with intra-cardiac thrombi should be considered in patients presenting with DIC. In addition to anticoagulation, treatment of underlying heart failure is critical in such cases.

Left ventricular assist devices (LVAD) are an increasingly implemented therapeutic intervention for patients with end-stage heart failure. A growing body of evidence, however, has shown an elevated risk of device thrombosis, a major complication jeopardizing the patient’s post-implantation survival. To date, multiple causative factors for LVAD thrombosis have been identified, such as internal shear stress, device material, infection, and inadequate anticoagulation. Understanding the mechanisms leading to LVAD thrombosis will not only enable device optimization, but also allow for better patient handling, hence improving post-implantation outcome. In this review we highlight the most commonly identified factors leading to LVAD thrombosis and discuss their mechanisms.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:57:55Z No. of bitstreams: 1 S0102-76382010000400008.pdf: 195940 bytes, checksum: dcceb252b0a797eebe88b5ef096722a6 (MD5) Made available in DSpace on 2013-08-22T18:57:55Z (GMT). No. of bitstreams: 1 S0102-76382010000400008.pdf: 195940 bytes, checksum: dcceb252b0a797eebe88b5ef096722a6 (MD5) Previous issue date: 2010-12-01 Made available in DSpace on 2013-09-30T19:53:04Z (GMT). No. of bitstreams: 2 S0102-76382010000400008.pdf: 195940 bytes, checksum: dcceb252b0a797eebe88b5ef096722a6 (MD5) S0102-76382010000400008.pdf.txt: 33171 bytes, checksum: 5d020bcff52b1bbe36f94507cbd1c3bc (MD5) Previous issue date: 2010-12-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:32:28Z No. of bitstreams: 2 S0102-76382010000400008.pdf: 195940 bytes, checksum: dcceb252b0a797eebe88b5ef096722a6 (MD5) S0102-76382010000400008.pdf.txt: 33171 bytes, checksum: 5d020bcff52b1bbe36f94507cbd1c3bc (MD5) Made available in DSpace on 2014-05-20T13:32:28Z (GMT). No. of bitstreams: 2 S0102-76382010000400008.pdf: 195940 bytes, checksum: dcceb252b0a797eebe88b5ef096722a6 (MD5) S0102-76382010000400008.pdf.txt: 33171 bytes, checksum: 5d020bcff52b1bbe36f94507cbd1c3bc (MD5) Previous issue date: 2010-12-01 INTRODUÇÃO: Dados da literatura sugerem que as taxas de tromboembolismo e sangramento em pacientes com próteses valvares cardíacas mecânicas podem ser muito reduzidas se a terapia anticoagulante for otimizada. OBJETIVOS: Avaliar a ocorrência de complicações em portadores de próteses valvares cardíacas mecânicas submetidos à terapêutica anticoagulante, otimizada por meio de ambulatório especializado. MÉTODOS: Estudou-se a ocorrência de complicações ao longo de 10 anos em 261 pacientes com próteses valvares cardíacas mecânicas, anticoagulados e acompanhados em ambulatório especializado. Esses pacientes foram divididos em dois grupos conforme porcentual de consultas com tempo de protrombina (RNI) dentro do intervalo desejado: G1-0% a 50,00% e G2-50,01% a 100% das consultas. Foram avaliadas as ocorrências de complicações tromboembólicas e hemorrágicas na sua totalidade, ou subdivididas em maiores e menores, de acordo com a gravidade. Os resultados estão apresentados sob forma de estudo atuarial e de frequência linearizada de ocorrência de eventos. RESULTADOS: O estudo atuarial mostrou que, ao longo do tempo, no grupo G2 (com 50,01% a 100% das consultas com a RNI no intervalo desejado) maior número de pacientes esteve livre da ocorrência de qualquer tipo de evento, de eventos hemorrágicos menores ou da elevação exacerbada da RNI. As frequências linearizadas de ocorrência, em todos os tipos eventos, também foram menores nos pacientes do grupo G2. CONCLUSÕES: O tempo de permanência dentro do intervalo de anticoagulação desejado está diretamente relacionado com a ocorrência de complicações. Entretanto, mesmo com acompanhamento otimizado por meio de ambulatório especializado, apenas cerca de um terço dos pacientes apresentaram nível de anticoagulação adequado em mais da metade das consultas. BACKGROUND: Published data suggest that rates of thromboembolism and bleeding, in patients with mechanical heart valve prostheses, can be very small by optimizing current anticoagulant therapy. OBJECTIVE: To evaluate the occurrence of complications in patients with mechanical heart valve prostheses undergoing anticoagulant therapy optimized through specialized clinics. METHODS: We studied the occurrence of complications over 10 years in 261 anticoagulated patients with mechanical heart valve prostheses, followed in specialized clinics. These patients were divided into two groups according to percentage of queries with prothrombin time (INR) within the desired range: G1-0% to 50.00% and G2-50.01% to 100% of appointments. We evaluated the occurrence of thromboembolic and bleeding complications in their entirety or subdivided into major and minor, according to gravity. The results are presented in an actuarial study and frequency of occurrence of linear events. RESULTS: The actuarial study showed that, over time, more G2 (with 50.01% to 100% of the consultations with INR in desired range) more patients were free of the occurrence of any event, of minor bleeding events or the marked increase of RNI. The linearized frequency of occurrence in all types events, were also lower in group G2. CONCLUSIONS: The period of time that patients that remain within the desired anticoagulation interval has directly relations with occurrence of complications. Even with careful follow-up at a specialized outpatient unit, only approximately one third of the patients showed an adequate anticoagulation level in more than half of the consultations. UNESP Faculdade de Medicina de Botucatu Departamento de Cirurgia e Ortopedia UNESP Faculdade de Medicina de Botucatu Departamento de Cirurgia e Ortopedia

Patient: Female, 45 Final Diagnosis: Chronic thromboembolic pulmonary hypertension (CTEPH) Symptoms: Dyspnea • fatigue • palpitations Medication: — Clinical Procedure: Right heart catheterization • pulmonary endarterectomy Specialty: Pulmonology Objective: Mistake in diagnosis Background: Chronic thromboembolic pulmonary hypertension most often results from obstruction of the pulmonary vascular bed by nonresolving thromboemboli. Misdiagnosis of the disease is common because patients often present with subtle or nonspecific symptoms. Furthermore, some features in chest imaging may mimic parenchymal lung disease. The most clinically important mimic in high-resolution chest tomography is air trapping, which can be seen in a variety of small airway diseases. Case Report: We present the case of a 45-year-old woman with a long history of dyspnea and exercise intolerance, misdiagnosed with allergic alveolitis. The diagnosis of CTEPH was finally established with computed tomography (CT) angiography and hemodynamics. Conclusions: Chronic thromboembolism is under-diagnosed and also frequently misdiagnosed in clinical practice. The present report aims to increase the awareness of clinicians towards an accurate diagnosis of the disease, which is necessary for the early referral of CTEPH patients for operability.

Background The incidence of clinically apparent stroke in transcatheter aortic valve implantation (TAVI) exceeds that of any other procedure performed by interventional cardiologists and, in the index admission, occurs more than twice as frequently with TAVI than with surgical aortic valve replacement (SAVR). However, this represents only a small component of the vast burden of neurological injury that occurs during TAVI, with recent evidence suggesting that many strokes are clinically silent or only subtly apparent. Additionally, insult may manifest as slight neurocognitive dysfunction rather than overt neurological deficits. Characterisation of the incidence and underlying aetiology of these neurological events may lead to identification of currently unrecognised neuroprotective strategies. Methods The Silent and Apparent Neurological Injury in TAVI (SANITY) Study is a prospective, multicentre, observational study comparing the incidence of neurological injury after TAVI versus SAVR. It introduces an intensive, standardised, formal neurologic and neurocognitive disease assessment for all aortic valve recipients, regardless of intervention (SAVR, TAVI), valve-type (bioprosthetic, Edwards SAPIEN-XT) or access route (sternotomy, transfemoral, transapical or transaortic). Comprehensive monitoring of neurological insult will also be recorded to more fully define and compare the neurological burden of the procedures and identify targets for harm minimisation strategies. Discussion The SANITY study undertakes the most rigorous assessment of neurological injury reported in the literature to date. It attempts to accurately characterise the insult and sustained injury associated with both TAVI and SAVR in an attempt to advance understanding of this complication and associations thus allowing for improved patient selection and procedural modification.

Objective To evaluate the efficacy and bleeding complications associated with a low-dose thrombolysis protocol for thromboembolic lower extremity arterial occlusions. Design A retrospective cohort study. Materials and methods A retrospective analysis was performed using data from all consecutive patients who underwent catheter-directed, intra-arterial thrombolysis for thromboembolic lower extremity arterial occlusions between January 2004 and May 2013. All patients were treated on a standard surgical ward. Endpoints were incidence of bleeding complications, duration of thrombolysis, angiographic patency rate, 30-day mortality rate, and amputation-free rate at 6 months. Results Of the 171 cases analyzed, 129 cases underwent low-dose thrombolysis and 42 underwent high-dose thrombolysis. No major bleeding complications occurred in the low-dose group versus 5% in the high-dose group ( p = .01). The median duration of thrombolysis was 67 hours (4–304 hours) in the low-dose and 49 hours (2–171 hours) in the high-dose group ( p = .027). Angiographic patency was restored in 67% of the cases in the low-dose group versus 79% of the high-dose group ( p = .17). The 30-day mortality rates were 1% in the low-dose versus 5% in the high-dose group ( p = .09). However, this higher mortality rate was not related to bleeding complications. Major amputation-free rates at 6 months were 81% in the low-dose group and 88% in the high-dose group ( p = .22). Conclusions Based on this data series, low-dose thrombolysis for thromboembolic lower extremity arterial occlusions is as effective as high-dose thrombolysis; however, the risk of major bleeding complications is substantially lower when using low-dose thrombolysis.

The risk for venous thromboembolism (VTE) in medical patients is high, but risk assessment is rarely performed because there is not yet a good method to identify candidates for prophylaxis. Purpose To perform a systematic review about VTE risk factors (RFs) in hospitalized medical patients and generate recommendations (RECs) for prophylaxis that can be implemented into practice. Data sources A multidisciplinary group of experts from 12 Brazilian Medical Societies searched MEDLINE, Cochrane, and LILACS. Study selection Two experts independently classified the evidence for each RF by its scientific quality in a standardized manner. A risk-assessment algorithm was created based on the results of the review. Data synthesis Several VTE RFs have enough evidence to support RECs for prophylaxis in hospitalized medical patients (eg, increasing age, heart failure, and stroke). Other factors are considered adjuncts of risk (eg, varices, obesity, and infections). According to the algorithm, hospitalized medical patients ≥40 years-old with decreased mobility, and ≥1 RFs should receive chemoprophylaxis with heparin, provided they don’t have contraindications. High prophylactic doses of unfractionated heparin or low-molecular-weight-heparin must be administered and maintained for 6–14 days. Conclusions A multidisciplinary group generated evidence-based RECs and an easy-to-use algorithm to facilitate VTE prophylaxis in medical patients.

Arterial embolization with cyanoacrylate is commonly used for the treatment of arteriovenous malformations. We report the case of a 40 years old man who four days after an embolization with cyanoacrylate, begins with cough, bloody sputum, and right hemithorax pleuritic pain. Pulmonary embolism was confirmed with chest X ray, CT scan and scyntigraphy. The patient received anticoagulation, with adequate response. The most common complications of cerebral embolization are related to central nervous system and pulmonary embolism is exceptional. Considering the high number of embolization procedures done nowadays, this complication must be borne in mind (Rev Méd Chile 2004; 132: 489-92)

Background: Atrial fibrillation is associated to a high risk of systemic embolism and to hypercoagulability. Aim: To evaluate the activation of the coagulation cascade through determinations of the thrombin-antithrombin complex in patients with atrial fibrillation and to correlate this data with the clinical and echocardiographic risk factors for systemic embolism. Patients and Methods: In 53 patients with atrial fibrillation plasma levels of the thrombin-antithrombin complex were determined on admission to a coronary care unit and 30 days later. Using a univariate and multiple regression analysis, the association basal thrombin-antithrombin with the duration of the arrhythmia, age over 70 years, previous use of antiplatelet agents, history of hypertension, mitral valve disease, diabetes, heart failure, previous systemic embolism, left atrial diameter and the presence of spontaneous contrast echo or thrombus in the left atrial appendage, was studied. Results: Basal thrombin-antithrombin values were 40.1±69 mg/L (Median 8.34 [3.0-47.5]) compared to 2.7±3.3 mg/L in healthy controls (p