Low-dose apixaban or rivaroxaban as secondary prophylaxis of upper extremity deep vein thrombosis.

Upper extremity deep vein thrombosis (UEDVT) may occur without inciting factor or may be secondary to malignancy, surgery, trauma, central venous catheter or related to thoracic outlet syndrome (TOS). International guidelines recommend anticoagulant treatment for at least three months, in particular the use of vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). No data on extended anticoagulant therapy and reduced dose of DOACs have been reported in patients affected by UEDVT with persistent thrombotic risk (active cancer, major congenital thrombophilia) or without affected vein recanalization. In our retrospective observational study, including 43 patients, we treated secondary UEDVT with DOACs. In the acute phase of thrombosis (median time of 4 months), we used therapeutic dose of DOACs; the 32 patients with permanent thrombotic risk factors or without recanalization of the UEDVT were shifted to low-dose DOACs (apixaban 2.5 mg twice daily or rivaroxaban 10 mg daily). During therapy with full-dose DOACs, 1 patient presented recurrence of thrombosis; no thromboembolic events were observed during treatment with low-dose DOACs. During full-dose treatment, 3 patients presented minor hemorrhagic complications; no hemorrhagic events were observed during DOACs at low dose. We think our preliminary data could support the indication to extend the anticoagulation with dose reduction of DOACs in patients affected by UEDVT and no-transient thrombotic risk. These data should be confirmed in randomized controlled prospective study.

Prevention of recurrent thrombotic events in children with central venous catheter-associated venous thrombosis.

Central venous catheters (CVC) are the most significant risk factor for pediatric venous thromboembolism (VTE). After an index CVC-associated VTE (CVC-VTE), the role of secondary prophylaxis for subsequent CVC placement is uncertain. Aims of this single-center retrospective study were to evaluate the efficacy of secondary prophylaxis for patients with a prior CVC-VTE and identify risk factors associated with recurrent VTE in patients less than 19 years with an index CVC-VTE between 2003 and 2013. Data collection included clinical and demographic factors, subsequent CVC placement, secondary prophylaxis strategy, recurrent VTE, and bleeding. Risk factors for recurrence and effectiveness of secondary prophylaxis were evaluated using survival and binomial models. Among 373 patients with an index CVC-VTE, 239 (64.1%) had subsequent CVC placement; 17.4% (65/373) of patients had recurrent VTE, of which 90.8% (59/65) were CVC-associated. On multivariable survival analysis, each additional CVC (hazards ratio [HR] 12.00; 95% confidence interval [CI] 2.78-51.91), congenital heart disease (HR 3.70; 95% CI 1.97-6.95), and total parenteral nutrition dependence (HR 4.02; 95% CI 2.23-7.28) were associated with an increased hazard of recurrence. Full dose anticoagulation for secondary prophylaxis was associated with decreased odds of recurrent CVC-VTE (odds ratio [OR] 0.35; 95% CI 0.19-0.65) but not prophylactic dosing (OR 0.61; 95% CI 0.28-1.30). Only 1.3% of CVCs experienced major bleeding with prophylactic or full-dose anticoagulation. In summary, children with CVC-VTE are at increased risk for recurrent VTE. Secondary prophylaxis with full-dose anticoagulation was associated with a 65% reduction in odds of thrombotic events.

Sequential Pneumatic Compression in the Arm in Neurocritical Patients with a Peripherally Inserted Central Venous Catheter: A Randomized Trial.

BACKGROUND: Peripherally inserted central venous catheters (PICCs) are increasingly used for parenteral access in critically ill hospitalized patients, but they increase the incidence of upper extremity deep venous thrombosis (UE DVT). Sequential compression devices (SCDs) applied to the legs effectively reduce lower extremity DVT, but have not been tested in the arms. Our objective was to determine whether SCDs applied to the arm may reduce the risk of PICC-associated UE DVT. METHODS: This was a retrospective study of randomized, single-center, controlled clinical trial on patients hospitalized in the intensive care unit with critical neurological illness who had a PICC and were not receiving anticoagulants. Between January 2014 and October 2016, patients were randomized 1:1 to an intervention group having a custom SCD applied to the arm harboring the PICC or to a control group. The primary endpoint was ultrasound-detected UE DVT. RESULTS: Following randomization of 77 subjects, the study was terminated due to excess DVT in the treatment arm. UE DVT was detected in 18 subjects (29.0%), and it was more frequent among those in the SCD group (13/31 [41.9%] vs. the control group 5/31 [16.1%]; p = 0.049). After accounting for crossovers, the difference was still significant (12/28 [43.0%] vs. 6/34 [17.6%]; p = 0.048). Yet, symptomatic UE DVT (n = 3) and pulmonary embolism without evidence of lower extremity DVT (n = 2) were only observed in patients who were not wearing the SCD on the arm. CONCLUSIONS: Although UE DVT is commonly associated with PICC use, the results of this trial do not support the use of SCD on the arm for DVT prevention. Further research on this strategy may nonetheless be justified. TRIAL REGISTRATION: This trial was registered in ClinicalTrials.gov under the identifier NCT01670188.

The anticoagulants rivaroxaban and low molecular weight heparin prevent PICC-related upper extremity venous thrombosis in cancer patients.

Peripherally inserted central catheter (PICC) is often applied in chemotherapy patients and commonly causes upper extremity venous thrombosis (UEVT), which should be prevented.To assess the preventive effects of the anticoagulants rivaroxaban and low molecular weight heparin (LMWH) on UEVT in patients receiving chemotherapy through PICCs.A total of 423 chemotherapy patients with continuous PICC use between January 2014 and June 2015 at the Oncology Department of Dongying People's Hospital were divided into 3 groups: rivaroxaban (10 mg/day, orally), LMWH (Enoxaparine, 4000 anti-Xa IU/day, subcutaneous injection), and control (no anticoagulant). UEVT incidence and other complications during PICC use were observed and recorded.The rivaroxaban, LMWH, and control groups included 138 (79 males; 54.9 ±â€Š11.0 years), 144 (76 males; 56.0 ±â€Š10.9 years), and 141 (71 males; 53.3 ±â€Š10.9 years) patients, (P = .402 and P = .623 for age and sex respectively). There were no differences in cancer location (P = .628), PICC implantation site (P > .05), body mass index (BMI) (P = .434), blood pressure (all P > .05), blood lipids (5 laboratory parameters included, all P > .5), smoking (P = .138), history of lower limb venous thrombosis (P = .082), and 10 other associated comorbidities (all P > .5). Twenty-nine patients withdrew from the study (5 from the rivaroxaban, 12 from the LMWH, and 12 from the control groups, respectively), and 394 patients were analyzed. There were significant differences in the rivaroxaban group and the LMWH group compared to the control group (P = .010 and P = .009, respectively), but no significant difference was observed between the rivaroxaban group and the LMWH group (P = .743).Anticoagulants such as rivaroxaban and LMWH may reduce the incidence of PICC-related UEVT in patients receiving chemotherapy.

Central venous catheter-related venous thrombosis in children with end-stage renal disease undergoing hemodialysis.

Despite the high rate of central venous catheter (CVC)-related venous thromboembolic (VTE) complications and long-term sequelae, CVCs remain a vital component of patient care in children with complex underlying diseases. In this review, we focus on CVC-related VTE in children with end-stage renal disease (ESRD) undergoing hemodialysis, a population in whom the provision of renal replacement therapy is a lifelong undertaking. Occlusion of the CVC and thrombosis underlie most instances of access malfunction and failure in children on chronic hemodialysis. Frequent CVC replacements are required, resulting in increased risk of central vein thrombosis and stenosis, precluding adequate hemodialysis in years to come. As recurrent CVC malfunction may constitute the sole sign of CVC-related VTE, a high index of suspicion is required for its investigation and the consequent institution of anticoagulation treatment, attempting to salvage the CVC and minimize recurrent line exchanges and venous cannulations and their sequelae. Hemodialysis access planning should take into account potentially modifiable prothrombotic risk factors in order to preserve vascular access. Effective strategies for maintenance of catheter patency and survival are needed for the conservation of future hemodialysis access. Further investigation aiming for identification of predictors of CVC-related VTE in children undergoing hemodialysis will aid in the design and application of much needed multicenter prospective studies examining the benefit and the safety of thromboprophylaxis.

Epidemiology, diagnosis, prevention and treatment of catheter-related thrombosis in children and adults.

In this narrative review, the epidemiology, diagnosis, prevention strategies, and management of catheter-related thrombosis are outlined. Central venous catheters have significantly improved the quality of life of patients requiring chemotherapy, parenteral nutrition, and chronic transfusions. Catheter-related thrombosis (CRT) complicates between 1-5% of inserted catheters, with incidence varying between patient population, catheter type, and vein cannulated. Strategies to prevent CRT, including anticoagulation and locking solutions, have largely been ineffective. Using clinical decision tools and D-dimer testing can limit radiographic testing for patients with suspected CRT. Although most patients with CRT are treated with anticoagulation, the most effective type and duration of treatment have not been established for adults or children. Many unanswered questions remain concerning risk stratification, prevention, and management of CRT. National and international collaborative research networks could be harnessed to perform these much needed studies.

Urokinase-containing locking solution in the prevention of dialysis catheter dysfunction: a double blind randomized controlled trial.

INTRODUCTION: The prophylactic use of recombinant tissue plasminogen activator once weekly reduces the incidence rate of tunneled cuffed catheter (TCC) malfunction and bacteremia as compared to the exclusive use of heparin as locking solution. Restricting the use of prophylactic thrombolytic agents to patients with a history of thrombotic TCC malfunction could be more cost effective. We conduct a multicenter, double-blind, randomized controlled trial and test the hypothesis that weekly use of urokinase lock will reduce the incidence of thrombotic malfunction by 50% in prevalent hemodialysis patients with a history of thrombotic malfunction. METHODS: Patients with a history of at least two separate TCC thrombotic dysfunctions treated with urokinase lock during the 6 months preceding inclusion are recruited in eight Belgian dialysis units. Patients are randomized in two groups: the control group receiving Taurolock™-HEP500 (heparin 500 IU/mL, taurolidine, citrate 4%) after each hemodialysis session and the treatment group receiving Taurolock-U 25,000 (urokinase 25,000, taurolidine, citrate 4%) once a week and the standard Taurolock-HEP500 at the end of the two others sessions. The primary outcome is the incidence rate of TCC thrombotic dysfunction defined by the use of urokinase. The secondary outcomes are the incidence rate of TCC removal and systemic thrombolysis. For the study, both patients and healthcare staff are blinded to treatment allocation. CONCLUSIONS: The present trial is the first to investigate the effect of Taurolock-U 25,000 catheter lock once a week as secondary prevention in hemodialysis patients with the highest risk of TCC-related thrombotic dysfunction. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02036255.

How I treat central venous access device-related upper extremity deep vein thrombosis.

Central venous access device (CVAD)-related thrombosis (CRT) is a common complication among patients requiring central venous access as part of their medical care. Complications of CRT include pulmonary embolism, recurrent deep venous thrombosis, loss of central venous access, and postthrombotic syndrome. Patient-, device-, and treatment-related factors can influence the risk of CRT. Despite numerous randomized controlled trials, the clinical benefit of pharmacologic thromboprophylaxis for the prevention of CRT remains to be established. Therefore, minimizing patient exposure to known risk factors is the best available approach to prevent CRT. Venous duplex is recommended for the diagnosis of CRT. Anticoagulation for at least 3 months or the duration of the indwelling CVAD is recommended for treatment of CRT. Thrombolysis should be considered for patients at low risk for bleeding who have limb-threatening thrombosis or whose symptoms fail to resolve with adequate anticoagulation. CVAD removal should be consider for patients with bacteremia, persistent symptoms despite anticoagulation, and if the CVAD is no longer needed. Superior vena cava filters should be avoided. Prospective studies are needed to define the optimal management of patients with or at risk for CRT.

Thrombosis in the setting of cancer.

Venous thromboembolism (VTE) is a common cause of adverse outcomes in patients with cancer. The risk of VTE varies with cancer type, stage and grade, cancer therapy, and supportive care, as well as patient characteristics including age, ethnicity, and inherited and acquired comorbid conditions. VTE prophylaxis should be provided to all hospitalized cancer patients and high-risk outpatients. Low-molecular-weight heparin (LMWH) remains the first-line therapy for VTE in patients with active cancer. Anticoagulation should be continued as long as there is evidence of active disease or patients are receiving cancer treatment. The efficacy of direct oral anticoagulants in the treatment of cancer-associated thrombosis remains incompletely defined. Central venous catheter (CVC)-associated VTE should be treated with anticoagulation alone, unless the CVC is no longer required. Recent studies indicate that anticoagulation may be appropriate for patients with persistent thrombocytopenia or solid tumor brain metastases. Management of recurrent VTE includes the identification of the cause(s) of the recurrence and solutions targeted at addressing the potential precipitants.

Venous Thromboembolism in Children: Is It Preventable?

The incidence of venous thromboembolism (VTE) in children is increasing. Hospitalized infants and adolescents are at highest risk, and most individuals who have VTE have multiple thrombotic risk factors. The presence of a central venous catheter (CVC) is the most frequent risk factor for childhood thrombosis. Childhood VTE has significant consequences in relation to the thrombotic event and the anticoagulant therapy used for its treatment. Identification of the most prevalent risk factors for VTE, particularly among adolescents, has moved the focus toward prevention of thrombosis. Risk assessment models have been developed to identify individuals who are at higher risk with a view to employing preventative strategies such as mechanical and chemical thromboprophylaxis (TP). There is currently little evidence to support the efficacy of such strategies for preventing either CVC-associated thrombosis or thrombosis at other sites. In addition, there are concerns about adverse consequences of mechanical and chemical TP in a population where the overall incidence of VTE remains low.

Trombosis venosa profunda primaria de miembro superior / Primary lower-limb deep venous thrombosis

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Optimization of dialysis catheter function.

Central venous catheters (CVCs) are essential in the management of hemodialysis patients, but they also carry unintended negative consequences and in particular thrombosis and infection, adversely affecting patient morbidity and mortality. This review will focus on the etiology, prevention, and management of CVC-related dysfunction, which is mainly associated with inadequate blood flow. CVC dysfunction is a major cause of inadequate depuration. Thrombus, intraluminal and extrinsic, as well as fibrous connective tissue sheath (traditionally indicated as fibrin sheath) formation play a central role in establishing CVC dysfunction. Thrombolysis with urokinase or recombinant tissue plasminogen activator (rTPA) can be undertaken in the dialysis unit, restoring adequate blood flow in most patients, preserving the existing catheter, and avoiding an interventional procedure. If thrombolytics fail, mainly because of the presence of fibrous connective tissue sheath, catheter exchange with fibrin sheath disruption may be successful and preserve the venous access site. Prevention of CVC dysfunction is important for containing costly pharmacologic and interventional treatments, which also affect patients' quality of life. Prevention is based on the use of anticoagulant and/or thrombolytic CVC locks, which are only partially effective. Chronic oral anticoagulation with warfarin has also been proposed, but its use for this indication is controversial and its overall risk-benefit profile has not been clearly established.

Vitamin K antagonists in children with central venous catheter on chronic haemodialysis: a pilot study.

BACKGROUND: To date, no study has investigated the use of vitamin K antagonists (VKA) in children undergoing chronic haemodialysis (HD) with a central venous catheter (CVC). METHODS: Consecutive patients aged <18 years with a newly placed tunnelled CVC for chronic HD were enrolled over a 3-year period. Children with active nephrotic syndrome or a history of venous thrombosis received warfarin (VKA group) with therapeutic target international normalised ratios of between 2.0 and 3.0. Patients at standard risk of CVC malfunction were not treated with VKA (standard group). The primary end-point was overall CVC survival. RESULTS: The VKA group consisted of nine patients (median age 10.6 years; range 1.2-15.3 years) with 11 CVC, and the standard group comprised eight patients (11.8 years; 6.1-17.3 years) with ten CVC. The 6- and 12-month CVC survival was significantly longer in the VKA group than in the standard group (100 vs. 60 % and 83.3 vs. 16.7 %, respectively; p < 0.05), with a median survival of 369 and 195 days, respectively (p < 0.05). None of the CVC in the VKA group required removal due to malfunction, as compared to four in the standard group. No major bleeding episodes occurred in either group. CONCLUSIONS: Therapy with VKA would appear to be safe in children on chronic HD and may improve CVC survival in patients at increased risk of CVC thrombosis.

New technology: heparin and antimicrobial-coated catheters.

Although tunneled hemodialysis catheter must be considered the last option for vascular access, it is necessary in some circumstances in the dialysis patient. Thrombosis and infections are the main causes of catheter-related comorbidity. Fibrin sheath, intimately related with the biofilm, is the precipitating factor of this environment, determining catheter patency and patient morbidity. Its association with bacterial overgrowth and thrombosis has led to the search of multiple preventive measures. Among them is the development of catheter coatings to prevent thrombosis and infections. There are two kinds of treatments to cover the catheter surface: antithrombotic and antimicrobial coatings. In nondialysis-related settings, mainly in intensive care units, both have been shown to be efficient in the prevention of catheter-related infection. This includes heparin, silver, chlorhexidine, rifampicine and minocycline. In hemodialysis population, however, few studies on surface-treated catheters have been made and they do not provide evidence that shows complication reduction. The higher effectiveness of coatings in nontunneled catheters may depend on the short average life of these devices. Hemodialysis catheters need to be used over long periods of time and require clinical trials to show effectiveness of coatings over long periods. This also means greater knowledge of biofilm etiopathogeny and fibrin sheath development.

Concentrated citrate locking in order to reduce the long-term complications of central venous catheters: a randomized controlled trial in patients with hematological malignancies.

PURPOSE AND METHODS: Central venous catheter (CVC)-related thrombosis and infections are frequently occurring complications in patients with hematological malignancies. At present, heparin is most often used as a locking solution. Trisodium citrate (TSC) had been shown to be a very effective antimicrobial catheter locking in hemodialysis patients. We performed a prospective randomized phase III multicenter trial to determine the efficacy of TSC as a locking solution compared to heparin in preventing CVC-related thrombosis and infections in patients with hematological malignancies. RESULTS: Thirty-four episodes of CVC-related bloodstream infections (CVC-BSI) occurred in the 108 patients who were randomized to locking with heparin compared with 35 episodes in the 99 patients who were randomized to locking with TSC (P = 0.654). We did find seven times more CVC-BSI with gram-negative rods in CVCs locked with heparin (P = 0.041). The cumulative incidence of symptomatic thrombosis was 10% in the heparin group and 5% in the TSC group (hazard ratio 0.525; 95% confidence interval 0.182-1.512). CONCLUSION: This study shows that locking with TSC in patients with hematological malignancies significantly reduced the incidence of CVC-BSI with gram-negative rods. However, the incidence of CVC-BSI with coagulase-negative staphylococcus or CVC-related thrombosis was not reduced by TSC locking.

Comparison of heparin to citrate as a catheter locking solution for non-tunneled central venous hemodialysis catheters in patients requiring renal replacement therapy for acute renal failure (VERROU-REA study): study protocol for a randomized controlled trial.

BACKGROUND: The incidence of acute kidney injury (AKI) is estimated at 10 to 20% in patients admitted to intensive care units (ICU) and often requires renal replacement therapy (RRT). ICU mortality in AKI patients can exceed 50%. Venous catheters are the preferred vascular access method for AKI patients requiring RRT, but carry a risk of catheter thrombosis or infection. Catheter lock solutions are commonly used to prevent such complications. Heparin and citrate locks are both widely used for tunneled, long-term catheters, but few studies have compared citrate versus heparin for patients with short-term, non-tunneled catheters. We aim to compare citrate 4% catheter lock solution versus heparin in terms of event-free survival of the first non-tunneled hemodialysis catheter inserted in ICU patients with AKI requiring RRT. Secondary objectives are the rate of fibrinolysis, incidence of catheter thrombosis and catheter-related infection per 1,000 catheter days, length of stay in ICU and in-hospital and 28-day mortality. METHODS/DESIGN: The VERROU-REA study is a randomized, prospective, multicenter, double-blind, parallel-group, controlled superiority study carried out in the medical, surgical and nephrological ICUs of two large university hospitals in eastern France. A catheter lock solution composed of trisodium citrate at 4% will be compared to unfractionated heparin at a concentration of 5,000 IU/mL. All consecutive adult patients with AKI requiring extracorporeal RRT, and in whom a first non-tunneled catheter is to be inserted by the jugular or femoral approach, will be eligible. Catheters inserted by the subclavian approach, patients with acute liver failure, thrombopenia or contraindication to systemic anticoagulation will be excluded. Patients will be followed up daily in accordance with standard practices for RRT until death or discharge. DISCUSSION: Data is scarce regarding the use of non-tunneled catheters in the ICU setting in patients with AKI. This study will provide an evidence base for recommendations regarding the use of anticoagulant catheter locks for the prevention of dysfunction in non-tunneled hemodialysis catheters in patients with AKI in critical or intensive care. TRIAL REGISTRATION: Registered with Clinicaltrials.gov (registration number: NCT01962116) on 27 August 2013.

Peripherally inserted central catheter (PICC)-related thrombosis in critically ill patients.

BACKGROUND: Peripherally inserted central catheters (PICC) are being increasingly used in critical care setting. However, PICCs are associated with a number of complications, particularly upper extremity venous thrombosis (UEVT), leading to post-thrombotic syndrome, pulmonary embolism and increased risk of catheter-related infection. OBJECTIVE: To review the literature surrounding PICCs and highlight the epidemiology, pathophysiology, diagnosis and management of PICC-related thrombosis in critically ill patients. DATA SOURCES AND EXTRACTION: We performed an electronic literature search of the databases PubMed, EMBASE and Google scholar using set search terms, from their commencement date to the end of January 2014. SUMMARY OF REVIEW: It has been shown that PICCs may double the risk of deep venous thrombosis compared with centrally inserted venous catheters, in critically ill patients. However, the incidence of PICC-related thrombosis in critically ill patients has not been quantified. Ultrasonography is the preferred diagnostic imaging modality. There are no randomized controlled trials (RCTs) on the best treatment of PICC-related thrombosis in the intensive care unit (ICU) setting and in most cohort studies, anticoagulation strategies with or without PICC removal have been used. CONCLUSIONS: Decision to insert a PICC should be taken after careful risk stratification. There is lack of high-quality evidence assessing prevention strategies and management of PICC-related thrombosis in the ICU. Well-designed RCTs are required to estimate the prevalence of UEVT in ICU patients with PICCs and evaluate the efficacy and magnitude of clinical benefit and cost-effectiveness of therapeutic strategies.