Upper extremity deep vein thrombosis treated with direct oral anticoagulants: a multi-center real world experience.

Upper-extremity deep vein thrombosis (UEDVT) accounts for about 5-10% of all cases of deep vein thrombosis (DVT). It is often associated with cancer and/or presence of a central venous catheter (CVC), but it may also occur in the absence of these favoring conditions. The safety and efficacy of using direct oral anticoagulants (DOACs) in subjects with UEDVT has not been systematically evaluated and the only data available in the literature derive from anecdotal evidence, analysis of registries, and small single-centre studies. In addition, a specific analysis of UEDVT not associated with cancer and/or CVC has never been made. In this study, we specifically focused on patients with no cancer and without a CVC who were diagnosed with a first episode of UEDVT and were treated with a DOAC. We studied 61 patients, treated in six Italian centres between January 2014 and December 2018. Treatment lasted at least 3 months in all patients. In terms of efficacy, no recurrence of thrombosis or pulmonary embolism were recorded, while Doppler ultrasonography, performed after at least three months of treatment, documented in all cases either partial or complete recanalization of obstructed veins. In terms of safety, no cases of major bleedings were recorded. This is the only series available in the literature of patients treated with DOACs for UEDVT not associated with cancer and/or CVC. This small multicenter real world experience supports the concept that DOACs might be safe and effective for treating UEDTV. Further studies are required to better understand the role of DOACs in these patients.

The Hedgehog Signaling Pathway in Ischemic Tissues.

Hedgehog (Hh) proteins are prototypical morphogens known to regulate epithelial/mesenchymal interactions during embryonic development. In addition to its pivotal role in embryogenesis, the Hh signaling pathway may be recapitulated in post-natal life in a number of physiological and pathological conditions, including ischemia. This review highlights the involvement of Hh signaling in ischemic tissue regeneration and angiogenesis, with particular attention to the heart, the brain, and the skeletal muscle. Updated information on the potential role of the Hh pathway as a therapeutic target in the ischemic condition is also presented.

Microparticles Produced by Activated Platelets Carry a Potent and Functionally Active Angiogenic Signal in Subjects with Crohn's Disease.

Microparticles (MPs) are submicron vesicles shed from various cell types upon activation, stimulation, and death. Activated platelets are an important source of circulating MPs in subjects with inflammatory diseases, including Crohn's disease (CD). Angiogenesis is a hallmark of inflammation in CD and plays an active role in sustaining disease progression, while targeting angiogenesis may be an effective approach to block colitis. In this study, we analyzed the angiogenic content of the MPs produced by activated platelets in subjects with CD. We also evaluated whether the angiogenic signal carried by these MPs was functionally active, or able to induce angiogenesis. We found that, in subjects with CD, MPs produced by activated platelets contain significantly higher levels of angiogenic mRNAs, such as epidermal growth factor (EGF), platelet-derived growth factor-α (PDGFα), fibroblast growth factor (FGF-2), and angiopoietin-1 (ANGPT1), compared to MPs isolated from control subjects. They also contain significantly higher levels of prototypical angiogenic proteins, including vascular endothelial growth factor (VEGF), angiopoietin-1, endoglin, endothelin-1, pentraxin 3, platelet factor-4, plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of metalloproteinases-1 (TIMP-1), and thrombospondin 1. The protein content of these MPs is functionally active, since it has the ability to induce a robust angiogenic process in an endothelial cell/interstitial cell co-culture in vitro assay. Our results reveal a potential novel mechanism through which the angiogenic signal is delivered in subjects with CD, with potentially important clinical and therapeutic implications.

Microparticles Carrying Sonic Hedgehog Are Increased in Humans with Peripheral Artery Disease.

Sonic hedgehog (Shh) is a prototypical angiogenic agent with a crucial role in the regulation of angiogenesis. Experimental studies have shown that Shh is upregulated in response to ischemia. Also, Shh may be found on the surface of circulating microparticles (MPs) and MPs bearing Shh (Shh + MPs) have shown the ability to contribute to reparative neovascularization after ischemic injury in mice. The goal of this study was to test the hypothesis that, in humans with peripheral artery disease (PAD), there is increased number of circulating Shh + MPs. This was done by assessing the number of Shh + MPs in plasma of patients with PAD and control subjects without PAD. We found significantly higher number of Shh + MPs in plasma of subjects with PAD, compared to controls, while the global number of MPs-produced either by endothelial cells, platelets, leukocytes, and erythrocytes-was not different between PAD patients and controls. We also found a significant association between the number of Shh + MPs and the number of collateral vessels in the ischemic limbs of PAD patients. Interestingly, the concentration of Shh protein unbound to MPs-which was measured in MP-depleted plasma-was not different between subjects with PAD and the controls, indicating that, in the setting of PAD, the call for Shh recapitulation does not lead to secretion of protein into the blood but to binding of the protein to the membrane of MPs. These findings provide novel information on Shh signaling during ischemia in humans, with potentially important biological and clinical implications.

HepPar1-Positive Circulating Microparticles Are Increased in Subjects with Hepatocellular Carcinoma and Predict Early Recurrence after Liver Resection.

Circulating microparticles (MPs) are novel potential biomarkers in cancer patients. Their role in hepatocellular carcinoma (HCC) is under intensive investigation. In this study, we tested the hypothesis that MPs expressing the antigen HepPar1 are increased in the blood of subjects with HCC and may serve as markers of early recurrence after liver resection (LR). We studied 15 patients affected by HCC undergoing LR, and used flow cytometry to assess the number of circulating HepPar1+ MPs. Ten subjects without HCC (five with liver cirrhosis and five with healthy livers) were used as controls. After LR, HCC patients underwent a follow-up to check for early recurrence, which occurred in seven cases. The number of circulating HepPar1+ MPs was significantly higher in subjects affected by HCC, compared to individuals without cancer (p < 0.01). We also found that, among HCC patients, the number of circulating HepPar1+ MPs, measured before LR, was significantly higher in those who displayed early recurrence compared to those without recurrence (p = 0.02). Of note, other types of circulating MPs, such as those derived from endothelial cells (CD144+) or those produced by the activated endothelium (CD144+/CD62+), were not associated with HCC, nor could they predict HCC recurrence. HepPar1+ MPs deserve further investigation as novel biomarkers of disease and prognosis in HCC patients.

Association between polymorphisms rs1333040 and rs7865618 of chromosome 9p21 and sporadic brain arteriovenous malformations.

BACKGROUND: The chromosomal locus 9p21 is a novel genetic marker for a variety of cardiovascular and cerebrovascular diseases. In a recent study, we have demonstrated an association between the single nucleotide polymorphism (SNP) rs1333040C>T on chromosome 9p21 and sporadic brain arteriovenous malformations (BAVMs). Here, we extended our analysis to an additional SNP on chromosome 9p21 (rs7865618A>G) and increased our sample size including BAVMs from two different Italian neurosurgical centers. METHODS: We studied 206 patients with sporadic BAVMs and 171 unaffected controls. Genomic DNA was isolated from peripheral blood and the rs1333040C>T and rs7865618A>G polymorphisms were assessed by PCR-RFLP using the BsmI and MspI restriction endonucleases, respectively. For each SNP, we performed dominant, recessive, and additive genetic models. RESULTS: The distribution of the three possible genotypes of rs1333040 (TT, TC and CC) was statistically different between cases and controls (p = 0.0008). The TT genotype was significantly associated with BAVMs both in the dominant (p = 0.013) and recessive (p = 0.012) models. The T allele was significantly associated with BAVMs in the additive model (p = 0.002). Also the distribution of the three possible genotypes of rs7865618 (GG, AG and AA) was statistically different between cases and controls (p = 0.005), and the GG genotype and G allele were significantly associated with BAVMs in the dominant (p = 0.032), recessive (p = 0.007), and additive models (p = 0.009). We also detected a significant association between BAVMs with large nidus size and the GG genotype and G allele of rs7865618 and the TT genotype of rs1333040. A deep venous drainage was instead associated with the TT genotype of the rs1333040 and the GG genotype of the rs7865618. The occurrence of bleeding was associated with the TT genotype and T allele of rs1333040, while the presence of seizures appeared associated with the GG genotype of rs7865618. CONCLUSIONS: SNPs of the 9p21 region, in addition to be genetic markers for coronary artery disease, stroke, and intracranial aneurysms, are associated with sporadic BAVMs. These results extend and strengthen the role of the 9p21 chromosomal region as a common risk factor for cerebrovascular diseases.

Angiogenic impairment of the vascular endothelium: a novel mechanism and potential therapeutic target in muscular dystrophy.

OBJECTIVE: Dystrophin, the missing or defective protein in Duchenne muscular dystrophy, is expressed not only in muscle cells but also in vascular endothelial cells (ECs). In this study, we assessed the effects of dystrophin deficiency on the angiogenic capacities of ECs. APPROACH AND RESULTS: We isolated vascular ECs from mdx mice, the murine equivalent of Duchenne muscular dystrophy in humans, and wild-type controls, and we found that mdx-derived ECs have impaired angiogenic properties, in terms of migration, proliferation, and tube formation. They also undergo increased apoptosis in vitro compared with wild-type cells and have increased senescence-associated ß-galactosidase activity. Mdx-derived ECs also display reduced ability to support myoblast proliferation when cocultured with satellite cell-derived primary myoblasts. These endothelial defects are mirrored by systemic impairment of angiogenesis in vivo, both on induction of ischemia, stimulation with growth factors in the corneal model and matrigel plug assays, and tumor growth. We also found that dystrophin forms a complex with endothelial NO synthase and caveolin-1 in ECs, and that NO production and cGMP formation are compromised in ECs isolated from mdx mice. Interestingly, treatment with aspirin enhances production of both cGMP and NO in dystrophic ECs, whereas low-dose aspirin improves the dystrophic phenotype of mdx mice in vivo, in terms of resistance to physical exercise, muscle fiber permeability, and capillary density. CONCLUSIONS: These findings demonstrate that impaired angiogenesis is a novel player and potential therapeutic target in Duchenne muscular dystrophy.

Applicability and feasibility of intraprocedural tip location of femorally inserted central catheters by transhepatic ultrasound visualization of the inferior vena cava in adult patients.

BACKGROUND: The ideal intraprocedural method for tip location during insertion of femorally inserted central catheters (FICCs) is still a matter of debate. When the catheter tip is meant to be in the right atrium or in the supradiaphragmatic inferior vena cava (IVC), tip location by either intracavitary electrocardiography or transthoracic echocardiography may be accurate and easy to perform. When the catheter tip is planned to be placed in the subdiaphragmatic IVC, fluoroscopy-though inaccurate and unsafe-has been regarded as the only option for intraprocedural tip location. METHODS: We have investigated prospectively the applicability and feasibility of transhepatic ultrasound as intraprocedural method for assessing the location of the catheter tip in the subdiaphragmatic tract of IVC, during FICC insertion. RESULTS: We enrolled 169 consecutive patients undergoing FICC insertion by ultrasound guided puncture of the superficial femoral vein. In 165 out of 169 patients, the subdiaphragmatic IVC was visualized by the transhepatic ultrasound view. In all cases of IVC visualization, the catheter tip could be identified by ultrasound, either directly (direct evidence of the tip inside the vein) or indirectly (enhanced visualization of the tip after "bubble test"). There was no immediate or early complication, and very few late complications. CONCLUSION: The intraprocedural method of tip location of FICCs by transhepatic ultrasound was applicable in 97.6% of cases and feasible in 100%. When the position of the catheter tip is planned to be in the subdiaphragmatic IVC, this method of tip location is accurate, safe, and inexpensive, and should be considered as an alternative to fluoroscopy.

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

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

Association between the rs1333040 polymorphism on the chromosomal 9p21 locus and sporadic brain arteriovenous malformations.

BACKGROUND: Single nucleotide polymorphisms (SNPs) on chromosome 9p21 have been recently associated with intracranial aneurysms and stroke. In this study, we tested the association between the rs1333040C>T polymorphism on the 9p21 locus and sporadic brain arteriovenous malformations (BAVMs). METHODS: We studied 78 patients with sporadic BAVMs and 103 unaffected controls. Genomic DNA was isolated from peripheral blood and the rs1333040C>T polymorphism was assessed by PCR-restriction fragment length polymorphism using the BsmI restriction endonuclease. RESULTS: We found that the distribution of the three genotypes (TT/TC/CC) of the rs1333040 polymorphism was significantly different between cases and controls (p=0.02). Using dominant, recessive and additive genetic models, we found that the TT genotype and the T allele were significantly more common in the BAVM group than in controls. We also evaluated whether the rs1333040 polymorphism was associated with prototypical angio-architectural features of BAVMs (such as nidus size, venous drainage pattern and Spetzler-Martin grading) and with the occurrence of seizures and bleeding. We detected a significant association between the homozygous T allele in the recessive model and BAVMs with a nidus >4 cm in diameter. Deep venous drainage was significantly more frequent among subjects carrying at least one T allele in the dominant model. Patients with seizures showed a significant association with the TT genotype and the T allele in all genetic models examined whereas those who experienced intracranial bleeding showed a significant association with the T allele in the trend model. CONCLUSIONS: This is the first study demonstrating an association between an SNP of the 9p21 region and sporadic BAVMs. Our results emphasise the relevance of this chromosomal locus as a common risk factor for various forms of cerebrovascular diseases.

Clinical Implications of Multi-Drug Resistant Organisms' Gastrointestinal Colonization in an Internal Medicine Ward: The Pandora's Box.

Background: Multi-drug resistant organisms (MDRO) are an emerging health problem with an important impact on clinical outcome in Intensive Care Units (ICUs) and immunocompromised patients. Conversely, the role of MDRO colonization in Internal Medicine is less clear. The objective of our study is to evaluate the clinical impact (namely sepsis development, in-hospital and 30-days mortality, and re-hospitalization) of MDRO colonization in Internal Medicine. Methods: Patients admitted to our Internal Medicine Unit between January 2019 and March 2020 were potentially includible. Outcomes in patients with a positive rectal swab for MDRO (RS+) and in patients without a RS+ were compared. Results of the multivariate analyses were expressed as Odds Ratios (ORs) and the corresponding 95% Confidence Interval (CI). Results: In a cohort of 2147 patients, 77 patients with RS+ were consecutively identified; 377 patients with a rectal swab negative for MDRO were randomly selected from the same cohort (five for each patient with RS+). At the multivariate analysis, RS+ was associated with an increased risk of sepsis development during hospitalization (OR 4.18; 95% CI, 1.99-8.78) and with death or re-hospitalization at 30 days (OR 4.79; 95% CI, 2.79-8.23), whereas RS+ did not appear to be associated with death during hospitalization or need for ICU transfer. Conclusions: Our results suggest for the first time a prognostic role for RS+ in Internal Medicine. Thus, assessment of rectal swab at hospital admission appears useful even in this setting. However, larger prospective studies and a cost-benefit analysis are needed to confirm our preliminary findings.

Management of antithrombotic treatment and bleeding disorders in patients requiring venous access devices: A systematic review and a GAVeCeLT consensus statement.

Insertion of venous access devices (VAD) is usually considered a procedure with low risk of bleeding. Nonetheless, insertion of some devices is invasive enough to be associated with bleeding, especially in patients with previous coagulopathy or in treatment with antithrombotic drugs for cardiovascular disease. The current practices of platelet/plasma transfusion in coagulopathic patients and of temporary suspension of the antithrombotic treatment before VAD insertion are based on local policies and are often inadequately supported by evidence, since many of the clinical studies on this topic are not recent and are not of high quality. Furthermore, the protocols of antithrombotic treatment have changed during the last decade, after the introduction of new oral anticoagulant drugs. Though some guidelines address some of these issues in relation with specific procedures (port insertion, etc.), no evidence-based document covering all the aspects of this clinical problem is currently available. Thus, the Italian Group of Venous Access Devices (GAVeCeLT) has decided to develop a consensus on the management of antithrombotic treatment and bleeding disorders in patients requiring VADs. After a systematic review of the available evidence, the panel of the consensus (which included vascular access specialists, surgeons, intensivists, anesthetists, cardiologists, vascular medicine experts, nephrologists, infective disease specialists, and thrombotic disease specialists) has structured the final recommendations as detailed answers to three sets of questions: (1) which is an appropriate classification of VAD-related procedures based on the specific bleeding risk? (2) Which is the appropriate management of the patient with bleeding disorders candidate to VAD insertion/removal? (3) Which is the appropriate management of the patient on antithrombotic treatment candidate to VAD insertion/removal? Only statements reaching a complete agreement were included in the final recommendations, and all recommendations were offered in a clear and synthetic list, so to be easily translated into clinical practice.

A Single Center Retrospective Cohort Study Comparing Different Anticoagulants for the Treatment of Catheter-Related Thrombosis of the Upper Extremities in Women With Gynecologic and Breast Cancer.

Background: Catheter-related thrombosis (CRT) of the upper extremities is a frequent complication among cancer patients that carry a central venous catheter (CVC) and may lead to pulmonary embolism (PE) and loss of CVC function. Despite its clinical impact, no anticoagulant treatment scheme has been rigorously evaluated in these patients. In addition, there is no proven evidence that direct oral anticoagulants (DOACs) are efficacious and safe in this setting because cancer patients with CRT of the upper extremities were not included in the clinical trials that led to the approval of DOACs for the treatment of cancer-associated venous thromboembolism (VTE). Methods: We performed a single center retrospective cohort study on women with gynecologic or breast cancer treated with either low-molecular-weight heparin, fondaparinux, or DOACs for CRT of the upper extremities. Only patients who received anticoagulation at the proper therapeutic dose and for at least 3 months were included in the analysis. Effectiveness was evaluated in terms of preservation of line function, residual thrombosis, and recurrence of VTE (including PE). Safety was evaluated in terms of death, major bleeding (MB), and clinically relevant non-major bleeding (CRNMB). Results: We identified 74 women who fulfilled the criteria to be included in the analysis. Of these, 31 (41.9%) had been treated with fondaparinux, 21 (28.4%) with enoxaparin, and 22 (29.7%) with the DOAC edoxaban. We found no differences between patients treated with the three different therapeutic approaches, in terms of preservation of line function, incidence of residual thrombosis, and VTE recurrence (including PE). Safety was similar as well, with no MBs recorded in any treatment group. Conclusion: These results, although retrospective and based on a relatively small sample size, indicate that, in women with gynecologic or breast cancer, CRT of the upper extremities may be treated with similar effectiveness and safety with fondaparinux, enoxaparin, and edoxaban. Further studies are needed to substantiate these findings.

Upper extremity deep vein thrombosis in COVID-19: Incidence and correlated risk factors in a cohort of non-ICU patients.

BACKGROUND: Venous thromboembolism is a frequent complication of COVID-19 infection. Less than 50% of pulmonary embolism (PE) is associated with the evidence of deep venous thrombosis (DVT) of the lower extremities. DVT may also occur in the venous system of the upper limbs especially if provoking conditions are present such as continuous positive airway pressure (CPAP). The aim of this study was to evaluate the incidence of UEDVT in patients affected by moderate-severe COVID-19 infection and to identify potential associated risk factors for its occurrence. METHODS: We performed a retrospective analysis of all patients affected by moderate-severe COVID-19 infection admitted to our unit. In accordance with the local protocol, all patients had undergone a systematic screening for the diagnosis of UEDVT, by vein compression ultrasonography (CUS). All the patients were receiving pharmacological thromboprophylaxis according to international guidelines recommendations. Univariate and multivariate analyses were used to identify risk factors associated with UEDVT. RESULTS: 257 patients were included in the study, 28 patients were affected by UEDVT with an incidence of 10.9% (95% CI, 7.1-14.7). At univariate analysis UEDVT appeared to be significantly associated (p< 0.05) with pneumonia, ARDS, PaO2/FiO2, D-dimer value higher than the age adjusted cut off value and need for CPAP ventilation. Multivariate analysis showed a significant association between UEDVT and the need for CPAP ventilation (OR 5.95; 95% IC 1.33-26.58). Increased mortality was found in patients affected by UEDVT compared to those who were not (OR 3.71; 95% CI, 1.41-9.78). CONCLUSIONS: UEDVT can occur in COVID-19 patients despite adequate prophylaxis especially in patients undergoing helmet CPAP ventilation. Further studies are needed to identify the correct strategy to prevent DVT in these patients.

Scurvy: A Disease not to be Forgotten.

An 18-year-old man presented to our hospital with muscular pain, diffuse petechiae, spontaneous thigh ecchymosis, edema and pain of the right knee, bilateral pretibial subcutaneous nodules, and gingival hypertrophy and hemorrhage. His history was positive for a mixed anxiety-depressive disorder and a restrictive diet caused by self-diagnosed food allergies. Skin lesions appeared like hyperkeratotic papules with coiled hairs and perifollicular hemorrhages. A diagnosis of scurvy was made upon demonstration of low serum levels of ascorbic acid. An allergy evaluation found cross-reactivity between pollens and food, related to the presence of panallergens. Moreover, we found that our patient was also affected by celiac disease. In conclusion, scurvy should be considered in the differential diagnosis of patients with petechiae and ecchymosis, especially when food restriction, malabsorption, or psychiatric disorders are present.

Sonic hedgehog is expressed in human brain arteriovenous malformations and induces arteriovenous malformations in vivo.

Abnormalities in arterial versus venous endothelial cell identity and dysregulation of angiogenesis are deemed important in the pathophysiology of brain arteriovenous malformations (AVMs). The Sonic hedgehog (Shh) pathway is crucial for both angiogenesis and arterial versus venous differentiation of endothelial cells, through its dual role on the vascular endothelial growth factor/Notch signaling and the nuclear orphan receptor COUP-TFII. In this study, we show that Shh, Gli1 (the main transcription factor of the Shh pathway), and COUP-TFII (a target of the non-canonical Shh pathway) are aberrantly expressed in human brain AVMs. We also show that implantation of pellets containing Shh in the cornea of Efnb2/LacZ mice induces growth of distinct arteries and veins, interconnected by complex sets of arteriovenous shunts, without an interposed capillary bed, as seen in AVMs. We also demonstrate that injection in the rat brain of a plasmid containing the human Shh gene induces the growth of tangles of tortuous and dilated vessels, in part positive and in part negative for the arterial marker αSMA, with direct connections between αSMA-positive and -negative vessels. In summary, we show that the Shh pathway is active in human brain AVMs and that Shh-induced angiogenesis has characteristics reminiscent of those seen in AVMs in humans.

Antithrombotic Therapy in Hereditary Hemorrhagic Telangiectasia: Real-World Data from the Gemelli Hospital HHT Registry.

Although Hereditary Hemorrhagic Telangiectasia (HHT) is characterized by an overwhelming bleeding propensity, patients with this disease may also present medical conditions that require antithrombotic therapy (AT). However, precise information on indications, dosage, duration, effectiveness, and safety of AT in HHT patients is lacking. We performed a retrospective analysis of the HHT Registry of our University Hospital and found 26 patients who received AT for a total of 30 courses (19 courses of anticoagulant therapy and 11 courses of antiplatelet therapy). Indications to treatments included: atrial fibrillation, venous thrombosis and pulmonary embolism, heart valve replacement, retinal artery occlusion, secondary prevention after either stroke or myocardial infarction, and thromboprophylaxis for surgery. The total time of exposure to antiplatelet therapy was 385 months and to anticoagulant therapy 169 months. AT was generally well tolerated, with no fatal bleedings and no significant changes in hemoglobin levels. However, we found three major bleedings, with an incidence rate of 6.5 per 100 patients per year. When only patients treated with anticoagulants were considered, the incidence rate of major bleedings increased to 21.6 per 100 patients per year. Our study indicates that major bleeding may occur in HHT patients receiving AT, with a substantially increased rate in those treated with anticoagulants. Further studies are needed to fully estimate the tolerability of antithrombotic drugs in HHT.

Incidence of deep vein thrombosis among non-ICU patients hospitalized for COVID-19 despite pharmacological thromboprophylaxis.

BACKGROUND: A remarkably high incidence of venous thromboembolism (VTE) has been reported among critically ill patients with COVID-19 assisted in the intensive care unit (ICU). However, VTE burden among non-ICU patients hospitalized for COVID-19 that receive guideline-recommended thromboprophylaxis is unknown. OBJECTIVES: To determine the incidence of VTE among non-ICU patients hospitalized for COVID-19 that receive pharmacological thromboprophylaxis. METHODS: We performed a systematic screening for the diagnosis of deep vein thrombosis (DVT) by lower limb vein compression ultrasonography (CUS) in consecutive non-ICU patients hospitalized for COVID-19, independent of the presence of signs or symptoms of DVT. All patients were receiving pharmacological thromboprophylaxis with either enoxaparin or fondaparinux. RESULTS: The population that we screened consisted of 84 consecutive patients, with a mean age of 67.6 ± 13.5 years and a mean Padua Prediction Score of 5.1 ± 1.6. Seventy-two patients (85.7%) had respiratory insufficiency, required oxygen supplementation, and had reduced mobility or were bedridden. In this cohort, we found 10 cases of DVT, with an incidence of 11.9% (95% confidence interval [CI] 4.98-18.82). Of these, 2 were proximal DVT (incidence rate 2.4%, 95% CI -0.87-5.67) and 8 were distal DVT (incidence rate 9.5%, 95% CI 3.23-5.77). Significant differences between subjects with and without DVT were D-dimer > 3000 µg/L (P < .05), current or previous cancer (P < .05), and need of high flow nasal oxygen therapy and/or non-invasive ventilation (P < .01). CONCLUSIONS: DVT may occur among non-ICU patients hospitalized for COVID-19, despite guideline-recommended thromboprophylaxis.