Incidence of deep venous thrombosis in patients with hemophilia undergoing bilateral simultaneous total knee arthroplasty: a retrospective cohort study.

BACKGROUND: Hemophilic arthropathy usually affects the knees bilaterally. In order to reduce costs and improve rehabilitation, bilateral simultaneous total knee arthroplasty (TKA) can be performed. However, pharmacological prophylaxis for deep venous thrombosis (DVT) remains controversial in patients with severe hemophilia. The purpose of this study was to establish the incidence of DVT in severe hemophilia A patients undergoing bilateral simultaneous TKA without pharmacological thromboprophylaxis. METHODS: Consecutive patients with severe hemophilia A undergoing bilateral simultaneous TKA at a single center between January 2015 and December 2020 were retrospectively reviewed. All patients received a modified coagulation factor substitution regimen. Tranexamic acid (TXA) was used for hemostasis in all patients during surgery. All patients followed a standardized postoperative protocol with routine mechanical thromboprophylaxis, and none received anticoagulation. D-dimer was measured preoperatively, on the day of the operation and on postoperative days 1, 7 and 14. Ultrasound (US) of the lower extremities was performed before (within 3 days of hospitalization) and after surgery (days 3 and 14) to detect asymptomatic DVT. Patients were followed up until 2 years after surgery for the development of symptomatic DVT or pulmonary embolism (PE). RESULTS: 38 male patients with severe hemophilia A underwent 76 simultaneous TKAs. Mean (± standard deviation) age at the time of operation was 41.7 (± 17.1) years. Overall, 47.3% of patients had D-dimer concentrations above the threshold 10 µg/mL on day 7 and 39.5% on day 14. However, none of the patients had DVT detected on postoperative US, nor developed symptomatic DVT or PE during the 2-year follow-up. CONCLUSIONS: The risk of DVT in patients with severe hemophilia A after bilateral simultaneous TKA is relatively low, and routine pharmacological thromboprophylaxis may not be needed.

Navigating through the haemostatic paradox in kidney failure: A practical overview.

Chronic kidney disease (CKD) affects around 9.1% of humankind globally resulting in a significant health burden. Some of these individuals will also require renal replacement therapy with dialysis due to complete kidney failure. Patients with CKD are known to be at increased risk of both bleeding and thrombosis. Often it is very difficult to manage these yin and yang since both risks tend to co-exist. Clinically, very few studies have looked at the effects of antiplatelet agents and anticoagulants in this highly vulnerable subgroup of medical patients and evidence is very limited. This review attempts to explain the current state-of-the-art regarding the basic science of haemostasis in patients with end-stage kidney disease. We also try to transfer this knowledge into the clinics by looking at some common haemostasis challenges that are encountered in this cohort of patients and what evidence and guidance there is for their optimal management.

Anticoagulant therapy for splanchnic vein thrombosis: a systematic review and meta-analysis.

Treatment of splanchnic vein thrombosis (SVT) is challenging, and evidence to guide therapeutic decisions remains scarce. The objective of this systematic review and meta-analysis was to determine the efficacy and safety of anticoagulant therapy for SVT. MEDLINE, EMBASE, and clinicaltrials.gov were searched from inception through December 2019, without language restrictions, to include observational studies and randomized controlled trials reporting radiological or clinical outcomes in patients with SVT. Pooled proportions and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated in a random-effects model. Of 4312 records identified by the search, 97 studies including 7969 patients were analyzed. In patients receiving anticoagulation, the rates of SVT recanalization, SVT progression, recurrent venous thromboembolism (VTE), major bleeding, and overall mortality were 58% (95% CI, 51-64), 5% (95% CI, 3-7), 11% (95% CI, 8-15), 9% (95% CI, 7-12), and 11% (95% CI, 9-14), respectively. The corresponding values in patients without anticoagulation were 22% (95% CI, 15-31), 15% (95% CI, 8-27), 14% (95% CI, 9-21), 16% (95% CI, 13-20), and 25% (95% CI, 20-31). Compared with no treatment, anticoagulant therapy obtained higher recanalization (RR, 2.39; 95% CI, 1.66-3.44) and lower thrombosis progression (RR, 0.24; 95% CI, 0.13-0.42), major bleeding (RR, 0.73; 95% CI, 0.58-0.92), and overall mortality (RR, 0.45; 95% CI, 0.33-0.60). These results demonstrate that anticoagulant therapy improves SVT recanalization and reduces the risk of thrombosis progression without increasing major bleeding. The incidence of recurrent VTE remained substantial in patients receiving anticoagulation, as well. Effects were consistent across the different subgroups of patients. This trial was registered on the PROPERO database at (https://www.crd.york.ac.uk/prospero//display_record.php?ID=CRD42019127870) as #CRD42019127870.

Efficacy and safety of the direct oral anti-coagulants in patients with cerebral vein thrombosis: A systematic review and meta-analysis.

Vitamin K antagonists (VKAs) are the standard oral anti-coagulant treatment for patients with cerebral venous thrombosis (CVT). However, the direct oral anti-coagulants (DOACs) started replacing VKAs also in this setting. We aimed to evaluate safety and efficacy of the DOACs for CVT treatment. We performed a systematic review and meta-analysis (PROSPERO protocol registration number CRD42020191472). The electronic databases MEDLINE, EMBASE and CENTRAL were searched from inception to January 2022. We included randomised controlled trials (RCTs) and observational studies, enrolling at least 10 adult patients with CVT treated with any DOACs. Twenty-three studies were included, for a total of 618 CVT patients treated with DOACs (treatment duration range 3-12 months). Mortality rate was 1.76% [95% confidence interval (CI) 0.70%-3.24%; I2  = 0%; 5/428 patients, 18 studies]; major bleeding 2.41% (95% CI 1.26%-3.91%; I2  = 1.5%; 12/534 patients, 21 studies); recurrent thrombosis 2.05% (95% CI 1.04%-3.37%; I2  = 0%; 10/577 patients, 21 studies); excellent neurological outcome 85.9% (95% CI 79.0%-91.7%; I2  = 63.7%; 289/340 patients, 13 studies); vessel recanalisation 89.0% (95% CI 82.9%-93.9%; I2  = 62.7%; 316/359 patients, 16 studies). No significant differences emerged by study design (RCTs vs. observational studies) or by treatment (DOACs vs. VKAs). This systematic review showed that the DOACs might represent a reasonable oral anti-coagulant treatment option for CVT patients.

High-dose glucocorticoids pulse-therapy for beta-coronaviridae pneumonia: a systematic literature review and case-series of Coronavirus disease-2019.

OBJECTIVES: The results of the RECOVERY trial identified dexamethasone as the first pharmacological therapy that reduces mortality in patients with COVID-19. The aim of this paper is to conduct a systematic literature review on safety and efficacy of pulse glucocorticoid therapy for Severe Acute Respiratory Syndrome (SARS)-CoronaVirus (CoV), Middle East Respiratory Syndrome (MERS)-CoV or SARS-CoV-2 infections and describe a case-series of COVID-19 patients treated with off-label pulse doses of methylprednisolone. METHODS: We performed a systematic literature review on safety and efficacy of pulse therapy for betacoronaviridae infections as described in the protocol registered on PROSPERO (CRD42020190183). All consecutive patients admitted to Arcispedale Santa Maria Nuova di Reggio Emilia or Guastalla Hospital with COVID-19 between March 1st and April 30th, 2020 and treated with methylprednisolone 1 gram/day for at least three days were included in the case series. A retrospective review of available computed tomography (CT) scan and chest x-ray was performed independently by two radiologists blinded to clinical data, and discordances were resolved by consensus. RESULTS: Twenty papers were included for SARS, but only two were comparative and were included in the primary endpoint analysis. Likewise, eleven papers were included for COVID-19, four of which were comparative and were considered for the primary outcome analysis. Included studies for both SARS and COVID-19 are mostly retrospective and highly heterogeneous, with lethality ranging from 0% to 100% and ICU admission rate ranging from 9% to 100%. Fourteen patients were included in our case series, 7 males and 7 females. CONCLUSIONS: No randomised controlled trial is available yet for corticosteroids pulse-therapy defined as at least ≥500mg/day methylprednisolone in patients with emerging coronavirus pneumonia. Lethality among our cohort is high (4/14), but this finding should be interpreted with caution due to the fact that in our setting pulse-steroids were used in patients not eligible for other treatments because of comorbidities or as rescue therapy. The incidence of steroid-related adverse events seems low in our cohort. The quality of the evidence on glucocorticoid pulse-therapy in SARS, MERS and COVID-19 is poor. Randomised controlled trials are greatly needed.

Diagnostic accuracy of inferior vena cava ultrasound for heart failure in patients with acute dyspnoea: a systematic review and meta-analysis.

BACKGROUND: Dyspnoea is the most common sign of heart failure (HF). Patients accessing the ED for HF-related symptoms require fast diagnosis and early treatment. Transthoracic echocardiography has a crucial role in HF diagnosis, but requires qualified staff and adequate time for execution. The measurement of inferior vena cava (IVC) diameter has been recently proposed as a rapid, simple and reliable marker of volume overload. The aim of this systematic review was to assess the accuracy of IVC-ultrasound as a stand-alone test for HF diagnosis in patients presenting to the ED with acute dyspnoea. METHODS: Studies evaluating the diagnostic accuracy of the inferior vena cava collapsibility index (IVC-CIx) for HF diagnosis were systematically searched in the EMBASE and MEDLINE databases (up to January 2018). Quality Assessment of Diagnostic Accuracy Studies 2 tool was used for the quality assessment of the primary studies. A bivariate random-effects regression approach was used for summary estimates of both sensitivity and specificity. RESULTS: Seven studies, for a total of 591 patients, were included. Three studies were at low-risk of bias. All studies used a proper reference test. Weighted mean prevalence of HF was 49.3% at random-effect model (I2 index for heterogeneity=74.7%). IVC-CIx bivariate weighted mean sensitivity was 79.1% (95% CI 68.5% to 86.8%) and bivariate weighted mean specificity was 81.8% (95% CI 75.0% to 87.0%). CONCLUSIONS: Our findings suggest that the sensitivity and specificity of IVC-CIx are suboptimal to rule in or rule out HF diagnosis in patients with acute dyspnoea in the ED setting. Therefore, IVC-CIx is not advisable as a stand-alone test, but may be useful when integrated in a specific diagnostic algorithm for the differential diagnosis of acute dyspnoea.

Abdominal Visceral Infarction in 3 Patients with COVID-19.

A high incidence of thrombotic events has been reported in patients with coronavirus disease (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We report 3 clinical cases of patients in Italy with COVID-19 who developed abdominal viscera infarction, demonstrated by computed tomography.

Treatment of acute migraine attacks in children with analgesics on the World Health Organization Essential Medicines List: A systematic review and GRADE evidence synthesis.

Background The World Health Organization Essential Medicines List (WHO EML) contains two analgesics for treatment of acute migraine attacks in children, ibuprofen and paracetamol. Methods The Embase, CDSR, CENTRAL, DARE and MEDLINE databases were searched up to 18 April 2017. We analyzed randomized controlled trials (RCTs) and systematic reviews (SRs) that investigate the efficacy and safety of ibuprofen or paracetamol for treatment of acute migraine attacks in children. We conducted meta-analysis and assessments of evidence with GRADE, Cochrane risk of bias tool, and AMSTAR. Results Three RCTs (201 children) and 10 SRs on ibuprofen and/or paracetamol for acute migraine attacks in children were included. Meta-analysis indicated that ibuprofen was superior to placebo for pain-free at 2 h or pain relief at 2 h, without difference in adverse events. There were no differences between paracetamol and placebo, or ibuprofen and paracetamol. Ten SRs that analyzed various therapies for migraine in children were published between 2004 and 2016, with discordant conclusions. Conclusion Limited data from poor quality RCTs indicate that ibuprofen and paracetamol might be effective analgesics for treating migraine attacks in children. Inclusion of ibuprofen and paracetamol as antimigraine medicines for children in the WHO EML is supported by indirect evidence from studies in adults.

Acute human herpes virus 7 (HHV-7) encephalitis in an immunocompetent adult patient: a case report and review of literature.

We report a case of an acute HHV-7 encephalitis involving the nucleus of the VI cranial nerve in an immunocompetent host. The patient was an adult male admitted to our Clinic with headache, diplopia, fever, nausea, vertigo, asthenia and general malaise. PCR for viral and bacterial genomes was run on both serum and cerebral spinal fluid (CSF) after performing lumbar puncture, resulting positive only for HHV-7 DNA on CSF. MRI showed hyperintensity in FLAIR signal in the dorsal pons, in the area of the VI cranial nerve nucleus. Empirical therapy with Acyclovir and Dexamethasone was started at the time of admission and was continued after the microbiology results. After three days of therapy diplopia, fever and other previous clinical manifestations improved and the patient recovered normal sight. Our case report contributes to a better understanding of the presentation, diagnosis and treatment of HHV-7 encephalitis in immunocompetent patients due to reactivation in adult age.

Approach to thrombosis at unusual sites: Splanchnic and cerebral vein thrombosis.

Splanchnic vein thrombosis (SVT) and cerebral vein thrombosis (CVT) are two manifestations of unusual site venous thromboembolism (VTE). SVT includes thrombosis in the portal, mesenteric or splenic veins, and the Budd-Chiari syndrome. CVT encompasses thrombosis of the dural venous sinuses and thrombosis of the cerebral veins. Unusual site VTE often represents a diagnostic and therapeutic challenge because of the heterogeneity in clinical presentation, the limited evidence available in the literature on the acute and long-term prognosis of these diseases, and the lack of large randomized controlled trials evaluating different treatment options. This narrative review describes the approach to patients with SVT or CVT by examining the diagnostic process, the assessment of potential risk factors and the appropriate anticoagulant treatment.

Major Bleeding and Case Fatality Rate with the Direct Oral Anticoagulants in Orthopedic Surgery: A Systematic Review and Meta-Analysis.

The novel direct oral anticoagulants (DOACs) have been proposed as alternatives to low-molecular-weight heparins (LMWHs) for the prevention of venous thromboembolism in orthopedic surgery. However, the clinical impact of postsurgical bleeding with the DOACs has not been extensively evaluated. MEDLINE and EMBASE databases, supplemented with conference abstract books and www.clinicaltrial.gov, were searched up to the first week of March 2015. We included phase II and phase III randomized controlled trials comparing the DOACs with LMWHs in patients undergoing major orthopedic surgery. Data regarding major, fatal, and intracranial bleeding were collected, to calculate the pooled relative risk (RR) and the case-fatality rate (CFR), with 95% confidence interval (CI). We retrieved 25 studies (5 evaluating dabigatran, 4 apixaban, 6 edoxaban, and 10 rivaroxaban), enrolling 42,170 patients. There was no significant difference between the DOACs and LMWHs in the risk of major (1.23 vs. 1.16%; RR: 1.07, 95% CI: 0.89-1.29), fatal (0.02 vs. 0.01%; RR: 1.63, 95% CI: 0.39-6.77), and intracranial bleeding (0 vs. 0.01%; RR: 0.33, 95% CI: 0.03-3.18). The weighted mean CFR of major bleeding was 3.3% (95% CI, 1.5-5.7) and 2.3% (95% CI, 0.7-4.6), respectively. Bleeding complications and the associated CFR during prophylactic anticoagulation in orthopedic surgery were very low and not significantly different between the DOACs and LMWHs.

Pros and cons of vitamin K antagonists and non-vitamin K antagonist oral anticoagulants.

Anticoagulant treatment can be currently instituted with two different classes of drugs: the vitamin K antagonists (VKAs) and the newer, "novel" or non-vitamin K antagonist oral anticoagulant drugs (NOACs). The NOACs have several practical advantages over VKAs, such as the rapid onset/offset of action, the lower potential for food and drug interactions, and the predictable anticoagulant response. However, the VKAs currently have a broader spectrum of indications, a standardized monitoring test, and established reversal strategies. The NOACs emerged as alternative options for the prevention and treatment of venous thromboembolism and for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Nevertheless, there remain some populations for whom the VKAs remain the most appropriate anticoagulant drug. This article discusses the advantages and disadvantages of VKAs and NOACs.

Antithrombotic treatment of splanchnic vein thrombosis: results of an international registry.

Treatment of splanchnic vein thrombosis (SVT) is a clinical challenge due to heterogeneity of clinical presentations, increased bleeding risk, and lack of evidences from clinical trials. We performed an international registry to describe current treatment strategies and factors associated with therapeutic decisions in a large prospective cohort of unselected SVT patients. A total of 613 patients were enrolled (mean age 53.1 years, standard deviation ± 14.8); 62.6% males; the majority (468 patients) had portal vein thrombosis. Most common risk factors included cirrhosis (27.8%), solid cancer (22.3%), and intra-abdominal inflammation/infection (11.7%); in 27.4% of patients, SVT was idiopathic. During the acute phase, 470 (76.7%) patients received anticoagulant drugs, 136 patients (22.2%) remained untreated. Incidental diagnosis, single vein thrombosis, gastrointestinal bleeding, thrombocytopenia, cancer, and cirrhosis were significantly associated with no anticoagulant treatment. Decision to start patients on vitamin K antagonists after an initial course of parenteral anticoagulation was significantly associated with younger age, symptomatic onset, multiple veins involvement, and unprovoked thrombosis. Although a nonnegligible proportion of SVT patients did not receive anticoagulant treatment, the majority received the same therapies recommended for patients with usual sites thrombosis, with some differences driven by the site of thrombosis and the pathogenesis of the disease.

Splanchnic Vein Thrombosis: The State-of-the-Art on Anticoagulant Treatment.

Splanchnic vein thrombosis (SVT) is a rare type of venous thromboembolism occurring within the splanchnic venous system. Portal vein thrombosis is the most common presentation, while Budd-Chiari syndrome is the least common. Liver cirrhosis and abdominal solid cancer are the main local risk factors for SVT, whereas myeloproliferative neoplasms are the predominant systemic risk factors. Signs and symptoms of SVT are nonspecific and include abdominal pain, gastrointestinal bleeding, and ascites. Asymptomatic SVT is not uncommon, and the majority would be detected incidentally on routine abdominal imaging performed for the follow-up of liver diseases and tumors. The management of SVT aims to prevent thrombus progression, promote vessel recanalization, and prevent recurrent venous thromboembolism. Anticoagulation should be started early in order to increase the chances of vessel recanalization and reduce the risk of portal hypertension-related complications. Direct oral anticoagulants have been included in recent guidelines, as alternatives to vitamin K antagonists, after clinical stability has been reached; however, caution is required in patients with liver or kidney dysfunction. Treatment duration is based on the presence (or absence) and type (transient vs. permanent) of risk factors. This narrative review aims to summarize the latest evidence on SVT, with a particular focus on the anticoagulant treatment in special categories of patients (e.g., liver cirrhosis, solid cancer, myeloproliferative neoplasms, pancreatitis, incidentally detected SVT, Budd-Chiari syndrome, and chronic SVT).

Allogeneic platelet-rich plasma for knee osteoarthritis in patients with primary immune thrombocytopenia: A randomized clinical trial.

The treatment of painful KOA in adult patients with ITP has not been well studied yet. We conducted a prospective, double-blind, randomized, placebo-controlled trial to evaluate the efficacy of intra-articular allogeneic PRP injections on symptoms and joint structure in patients with KOA and ITP. 80 participants were randomly allocated in a 1:1 ratio to allogeneic PRP group or saline group. The primary outcome was the WOMAC total score at 12 months post-injection. The number of patients in each group who achieved MCID of primary outcome showed a statistically significant difference only at 3-month (27/39 vs. 5/39, p = 0.001) and 6-month (15/39 vs. 3/38, p = 0.032). The difference in WOMAC total score exceeded the MCID only at 3 month (mean difference of -15.1 [95% CI -20.7 to -9.5], p < 0.001). Results suggest that allogeneic PRP was superior to placebo only with respect to symptoms at 3-month of follow-up.

A comparative in vitro study of the anticoagulant effect of branded versus generic rivaroxaban.

BACKGROUND: Several generic formulations of rivaroxaban were recently marketed to be used interchangeably with their branded equivalent. However, there have been no previously published studies that directly compared the in vitro anticoagulant effect of branded vs. generic rivaroxaban. The aim of this in vitro study was to compare the effects of three raw rivaroxaban materials, obtained from the branded (Xarelto®) and two generic (Rivarolto® and Rivaroxaban Sandoz®) rivaroxaban formulations on an array of coagulation assays. METHODS: A pool of normal plasma was spiked with several concentrations of the three rivaroxaban (range 50-750 ng/ml). The concentrations were assessed with a rivaroxaban calibrated anti-Xa assay and confirmed by ultra-high-performance liquid chromatography-mass spectrometry coupled with tandem mass spectrometry (UHPLC-MS/MS). The following assays were performed: Prothrombin time (PT), activated Partial Thromboplastin time (aPTT), Diluted Russell's Viper Venom Test (dRVVT), Thrombin time (TT), Clauss Fibrinogen, Factor VII, VIII and IX assays, and thromboelastography. RESULTS: The results obtained by the three rivaroxaban at similar concentrations were comparable. Increasing concentrations of the three rivaroxaban showed a strong positive correlation with the PT, aPTT and dRVVT assays (r > 0.95, p < 0.01 for all), and a strong negative correlation with the Factors assays (r < -0.95, p < 0.01 for all). TT and Clauss Fibrinogen were not affected by rivaroxaban. No significant difference was identified in the mean assays' results obtained by the three rivaroxaban. CONCLUSION: This study showed that the branded and generic rivaroxaban exert an identical in vitro anticoagulant effect across a wide range of concentrations.

Efficacy and safety of the novel oral anticoagulants in atrial fibrillation: a systematic review and meta-analysis of the literature.

BACKGROUND: Novel oral anticoagulants (NOACs) have been proposed as alternatives to vitamin K antagonists for the prevention of stroke and systemic embolism in patients with atrial fibrillation. Individually, NOACs were at least noninferior to vitamin K antagonists, but a clear superiority in overall and vascular mortality was not consistently proven. METHODS AND RESULTS: We performed a meta-analysis of phase II and phase III randomized, controlled trials comparing NOACs with vitamin K antagonists in patients with atrial fibrillation. The MEDLINE and EMBASE databases, supplemented with conference abstract books and www.clinicaltrials.gov, were searched up to the first week of July 2012 with no language restriction. Two reviewers performed independent article review and study quality assessment. Data on overall and cardiovascular mortality, stroke or systemic embolism, ischemic stroke, major and intracranial bleeding, and myocardial infarction were collected. NOACs were pooled to perform a comparison with vitamin K antagonists, calculating pooled relative risks (RRs) and associated 95% confidence intervals (CIs). We retrieved 12 studies (3 administering dabigatran, 4 administering rivaroxaban, 2 administering apixaban, and 3 administering edoxaban) enrolling a total of 54 875 patients. NOACs significantly reduced total mortality (5.61% versus 6.02%; RR, 0.89; 95% CI, 0.83-0.96), cardiovascular mortality (3.45% versus 3.65%; RR, 0.89; 95% CI, 0.82-0.98), and stroke/systemic embolism (2.40% versus 3.13%; RR, 0.77; 95% CI, 0.70-0.86). There was a trend toward reduced major bleeding (RR, 0.86; 95% CI, 0.72-1.02) with a significant reduction of intracranial hemorrhage (RR, 0.46; 95% CI, 0.39-0.56). No difference in myocardial infarction was observed. CONCLUSIONS: NOACs are associated with an overall clinical benefit compared with vitamin K antagonists. Additional research is required to confirm these findings outside the context of randomized trials.

How to manage splanchnic vein thrombosis in patients with liver disease.

Liver cirrhosis and splanchnic vein thrombosis (SVT) are strictly correlated. Portal vein thrombosis, the most common location of SVT, is frequently diagnosed in liver cirrhosis (pooled incidence 4.6 per 100 patient-years), and liver cirrhosis is a common risk factor for SVT (reported in 24%-28% of SVT patients). In cirrhosis-associated SVT, anticoagulant treatment reduces mortality rates, thrombosis extension, and major bleeding, and increases the rates of recanalization, compared to no treatment. Achieving vessel recanalization improves the prognosis of cirrhotic patients by reducing liver-related complications (such as variceal bleeding, ascites, hepatic encephalopathy). Anticoagulation should be therefore routinely prescribed to cirrhotic patients with acute SVT unless contraindicated by active bleeding associated with hemodynamic impairment or by excessively high bleeding risk. Of note, early treatment is associated with higher probability of achieving vessel recanalization. The standard treatment consists of low-molecular-weight heparin, followed by oral anticoagulants (eg, vitamin K antagonists or direct oral anticoagulants), if not contraindicated by severe liver dysfunction. Cirrhotic patients with SVT should be treated long-term (especially if candidate for liver transplantation) since liver cirrhosis is a persistent risk factor for recurrent thrombosis. In this review, we discuss the management of SVT in patients with liver cirrhosis, with a focus on the anticoagulant treatment in terms of indications, timing, drugs, duration, and particular scenarios, such as gastroesophageal varices and thrombocytopenia.

Anticoagulant therapy for splanchnic vein thrombosis: recent updates for patients with liver cirrhosis.

INTRODUCTION: Liver cirrhosis is accompanied by several hemostatic alterations, which contribute to the current theory of "rebalanced hemostasis." Splanchnic vein thrombosis (SVT) is a frequent complication of liver cirrhosis (17-26% of the cirrhotic patients), and liver cirrhosis is a common risk factor for SVT (24-28% of SVT cases). AREAS COVERED: This narrative review aims to describe the current state of the art on the anticoagulant treatment of cirrhotic SVT, with a particular focus on the possible role of the direct oral anticoagulants (DOACs) and recent guidelines on this topic. EXPERT OPINION: Early anticoagulant therapy is recommended in cirrhotic patients with acute SVT, to obtain vessel recanalization and decrease the rates of portal hypertension-related complications. Gastroesophageal varices do not represent a contraindication to anticoagulation, if adequate prophylaxis of variceal bleeding is established, and varices band ligation can be safely performed without the need to stop the anticoagulant treatment. The conventional treatment of cirrhotic SVT consisted of low molecular weight heparin, as initial treatment of choice, eventually followed by vitamin K antagonists, but the DOACs can be considered as a reasonable alternative in patients with compensated liver cirrhosis.

PROTOCOL: Do hospital leadership styles predict patient safety indicators? A systematic review.

This is the protocol for a Campbell systematic review. The objectives are as follows: The main aim of this systematic review is to identify whether hospital leadership styles predict patient safety as measured through several indicators over time. The second aim is to assess the extent to which the prediction of hospital leadership styles on patient safety indicators varies as a function of the leader's hierarchy level in the organization.