A review of upper extremity deep vein thrombosis.

This review aims to describe the epidemiology, pathophysiology, risk factors, presentation, complications, evaluation/diagnosis, and treatment of upper extremity deep vein thrombosis (UEDVT). Upper extremity deep vein thrombosis (UEDVT) accounts for 6% of cases of deep vein thrombosis (DVT). It can lead to swelling and discomfort in that extremity and can be complicated by pulmonary embolism, post-thrombotic syndrome, and recurrence of DVT. Evaluation can begin with a dichotomized Constans score and fibrin degradation product testing. Diagnosis is typically made with compression ultrasound. Anticoagulation is the mainstay of therapy. Primary UEDVT is known as Paget Schroetter Syndrome (PSS) which occurs due to venous thoracic outlet syndrome (vTOS). Anticoagulation, thrombolysis, and decompression of the venous thoracic outlet are used for treatment but the optimal strategy remains to be elucidated. Secondary UEDVT are most commonly caused by indwelling catheters and malignancy. There is an ongoing realization that UEDVT are more than simply 'leg clots in the arm.' Given the increasing incidence, research needs to be done to further our understanding of this disease state, its evaluation, and its treatment.

Promising biomarkers for the prediction of catheter-related venous thromboembolism in hospitalized children: An exploratory study.

BACKGROUND: Pediatric venous thromboembolism (VTE) has increased over the past 10 years, with central venous catheters (CVC) being the strongest risk factor. Current tools are not sufficient to predict VTE risk. The utility of biomarkers in predicting CVC-related VTE has been minimally explored. Our objective is to determine the utility of microparticles (MPs), factor VIII (FVIII) activity, and thrombin generation (TG) in prospectively predicting VTE occurrence in hospitalized children with CVCs. PROCEDURE: In this nested case-control pilot study, consecutive hospitalized children needing CVC placement (1 month to 21 years) were enrolled. Venous samples were collected prior to or within 24 h of CVC placement. MPs were measured using factor Xa initiated clot-based assay. FVIII was measured using a one-stage clot-based assay. TG was measured using calibrated automated thrombogram. RESULTS: There were three CVC-related VTE events (7%) in our cohort of 42 subjects. Xa clotting time (XaCT) ratio was lower (0.68 ± 0.07 vs 0.95 ± 0.21, P = .4), while FVIII (461 ± 120 vs 267 ± 130, P = .02), peak thrombin (418 ± 89 vs 211 ± 101, P = .001), endogenous thrombin potential (ETP) (1828 ± 485 vs 1282 ± 394, P = .03), and velocity index (VI) (182 ± 28 vs 75 ± 53, P = .001) were higher in subjects with CVC-related VTE compared to those without CVC-related VTE. Sensitivity/specificity analysis revealed optimal cutoff values for XaCT ratio (0.75), FVIII (370), ETP (1680), peak (315), and VI (130), with receiver operating characteristic area under the curve values >0.9. CONCLUSION: MPs, FVIII, and TG can potentially predict pediatric CVC-related VTE in a prospective fashion. Stratification according to VTE risk may aid in guiding preventative efforts in future studies.

Rivaroxaban withdrawal and rebound hypercoagulability leading to upper extremity deep vein thrombosis: a case report.

As the newer oral anticoagulants (NOACs) are increasingly used in older patients, clinical scenarios when they may need to be discontinued temporarily or indefinitely, may be encountered. Similarly with increasing use of permanent pacemakers and other intra-cardiac devices, there is an increased risk of upper limb venous thrombosis even few years after their insertion. We report a case of a patient with a permanent pacemaker, on rivaroxaban (NOAC) for atrial fibrillation, who developed an upper extremity deep vein thrombosis after its temporary withdrawal following a traumatic acute subdural haematoma. Physicians should be aware of the possibility of rebound hypercoagulability and venous thrombosis soon after the withdrawal of NOACs.

Comparison Between Retrograde and Antegrade Peripheral Venous Cannulation in Intensive Care Unit Patients: Assessment of Thrombus Formation.

BACKGROUND: Antegrade cannulation of peripheral veins is the usual practice. Blood stasis between a catheter and the wall of the vein or at its tip in addition to catheter-induced phlebitis may initiate a thrombosis. The use of retrograde ventriculojugular shunts against the direction of the blood flow with resultant decrease in the incidence of venous thrombosis encouraged us to compare retrograde versus conventional antegrade peripheral venous cannulation. METHODS: Monocentric, nonblinded, prospective observational cohort of 40 intensive care unit patients receiving 2 peripheral venous catheters in upper limbs, 1 inserted in the direction of blood flow (antegrade cannula) and the other inserted in an opposite direction to blood flow (retrograde cannula). Daily ultrasound assessment of the angle between the catheter and the vascular wall was done to detect onset and progression of thrombus formation. RESULTS: The study included 40 patients, aged 46.7 ± 10.132 years. The incidence of thrombus formation was 100% in both techniques. The onset time of thrombus formation between the catheter and the wall of a vein was significantly longer with the retrograde catheters than with the antegrade catheters with median time (interquartile range [range]) 6 days (5-6.75 [4-8]) with 95% confidence interval (CI), 5.58-6.42 vs 3 days (3-4 [2-5]) with 95% CI (2.76-3.24), respectively, with a P value <.001. The time needed by the recently detected thrombus to reach the catheter tip determined by ultrasound with or without catheter failure was significantly longer in the retrograde catheters than in the antegrade catheter with median time (interquartile range [range]) 9 days (8-9 [7-10]) with 95% CI, 8.76-9.24 vs 4 days (4-5 [3-6]) with 95% CI, 3.76-4.24, respectively, with a P value <.001. CONCLUSIONS: Retrograde cannulation did not decrease the incidence of thrombus formation, but significantly increased the onset time until thrombus formation and prolonged the time needed by the newly formed thrombus to reach the catheter tip compared with conventional antegrade cannulation.

Improving the diagnostic management of upper extremity deep vein thrombosis.

Essentials The Constans score and D-dimer can rule out upper extremity deep vein thrombosis without imaging. We evaluated the performance of an extended Constans score and an age-adjusted D-dimer threshold. The extended Constans score did not increase the efficiency compared to the original score. Age-adjusted D-dimer testing safely increased the efficiency by 4%, but this needs validation. SUMMARY: Background Among patients with clinically suspected upper extremity deep vein thrombosis (UEDVT), a clinical decision rule based on the Constans score combined with D-dimer testing can safely rule out the diagnosis without imaging in approximately one-fifth of patients. Objectives To evaluate the performance of the original Constans score, an extended Constans score and an age-adjusted D-dimer positivity threshold. Methods Data of 406 patients with suspected UEDVT previously enrolled in a multinational diagnostic management study were used. The discriminatory performance, calibration and diagnostic accuracy of the Constans score were evaluated. The Constans score was extended by selecting clinical variables that may have incremental value in detecting UEDVT, conditional on the original Constans score items. The performance of the Constans rule was evaluated in combination with fixed and age-adjusted D-dimer thresholds. Results The original Constans score showed good discriminatory performance (c-statistic, 0.81; 95% confidence interval [CI], 0.76-0.85). An extended Constans score with five additional clinical items improved discriminatory performance and calibration, but this did not translate into a higher efficiency in avoiding imaging tests. Compared with a fixed threshold, age-adjusted D-dimer testing increased the proportion of patients for whom imaging and anticoagulation could be withheld from 21% to 25% (gain, 3.7%; 95% CI, 2.3-6.0%). Conclusions The Constans score has good discriminatory performance in the diagnosis of UEDVT. Age-adjusted D-dimer testing is likely to safely increase the efficiency of the diagnostic algorithm, but this approach needs prospective validation.

A clinical decision rule and D-dimer testing to rule out upper extremity deep vein thrombosis in high-risk patients.

INTRODUCTION: In a management study, a diagnostic algorithm consisting of a clinical decision rule, D-dimer, and ultrasonography was shown to safely exclude upper extremity deep vein thrombosis (UEDVT). Efficiency may be lower in high-risk subgroups: those with a central venous catheter or pacemaker, inpatients, cancer, and elderly patients. METHODS: Data of 406 patients with suspected UEDVT enrolled in a prospective management study were used for the present analysis. The aim was to evaluate the efficiency of the algorithm in subgroups, defined as the proportion of patients in whom imaging could be safely withheld based on the combination of a decision rule result indicating "UEDVT unlikely" and a normal D-dimer result. RESULTS: The strategy excluded UEDVT in 87 of 406 patients (21%); ultrasonography was withheld in these patients and none developed UEDVT during 3months of follow-up. In contrast, ultrasonography could be withheld in only 4 of 92 patients with a catheter or pacemaker (4.3%; 95% CI: 1.7% to 11%) and in 4 of 83 inpatients (4.8%; 95% CI: 1.9% to 12%). The efficiency was 11% in patients with cancer and 13% in those older than 75years. CONCLUSION: Although the combination of a decision rule and D-dimer testing is safe in excluding UEDVT in the overall population of patients with suspected UEDVT, its efficiency appears limited in some subgroups, in particular those with a central venous catheter or pacemaker, and inpatients.

Developmental Hemostasis and Management of Central Venous Catheter Thrombosis in Neonates.

Neonatal hemostasis differs qualitatively, but in particular quantitatively, from hemostasis in older children and adults. Nevertheless, hemostasis in healthy neonates is functionally stable with no tendency to bleeding or thrombotic complications. In sick neonates, however, risk factors may disrupt this equilibrium and lead to thrombosis. The most important risk factor is the central venous catheter. Management of neonatal central venous catheter thrombosis is challenging, as no controlled trials have been performed. Therapeutic options include (1) observation and supportive treatment; (2) anticoagulant agents, including low-molecular-weight heparin and unfractionated heparin; (3) thrombolytic agents; and (4) thrombectomy. Prevention of thrombosis with anticoagulation is not advised yet. Careful consideration of the necessity of the catheter and optimal hygienic care are important preventative measures.

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.

Upper-Extremity Deep-Vein Thrombosis: A Retrospective Cohort Evaluation of Thrombotic Risk Factors at a University Teaching Hospital Antithrombosis Clinic.

BACKGROUND: Upper-extremity deep-vein thrombosis (UEDVT) causes significant morbidity and mortality and is not well characterized in the existing literature, particularly in underrepresented minorities such as African Americans. OBJECTIVE: To describe the characteristics of a cohort of patients with UEDVT seen at an urban academic medical center. METHODS: This was a retrospective cohort study among patients with a confirmed UEDVT at the University of Illinois Hospital and Health Sciences System between 1996 and 2011. Patients were identified by ICD-9 code for UEDVT. Variables collected include thrombotic risk factors and outcomes, including recurrent thrombosis and bleeding. RESULTS: We identified 229 patients with UEDVT; 71% were African American, and 11% were diagnosed with sickle cell disease. The average number of UEDVT risk factors was 4.40 ± 1.5, the most common being central venous catheter (CVC) use (178, 78%). In the year following UEDVT, 13% experienced recurrent thrombosis, and 6% experienced major bleeding. Of 181 patients receiving warfarin after an UEDVT, 36% of international normalized ratio (INR) values were therapeutic. Patients with sickle cell disease had a lower proportion of INRs within the target range (25% vs 38%, P < 0.01), and were more likely to be lost to follow-up (67% vs 46%, P = 0.05) and experience a recurrent thrombotic event (29% vs 11%, P = 0.02). CONCLUSION: A CVC is the most common risk factor for UEDVT; however, patients with sickle cell disease demonstrate additional unique demographics and risk factors. Patients included in this underrepresented demographic cohort had a low quality of anticoagulation control, particularly those with sickle cell disease.

Hyperhomocysteinemia-induced upper extremity deep vein thrombosis and pulmonary embolism in a patient with methyltetrahydrofolate reductase mutation: a case report and literature review.

The study highlights pulmonary embolism and deep vein thrombosis by methylene tetrahydrofolate reductase (MTHFR) deficiency-related hyperhomocysteinemia occurring in rare locations of left veins superior to the heart extensively. A 59-year-old white man with history of leg pain, smoking, weight loss, benign prostatic hyperplasia, lipoma and panic attack presented with shortness of breath and chest pain for 2 days precipitated by not feeling well for months. The diagnostic workup revealed pulmonary embolism and deep vein thrombosis in the left subclavian vein which extended throughout the left brachiocephalic vein to the superior vena cava and left jugular vein. Further workup showed moderate hyperhomocysteinemia with normal levels of vitamin B6, B12 and folic acid. Methylene tetrahydrofolate reductase genetic study found the patient to be homozygous for G677T variant. He was started on low-molecular-weight heparin and was discharged on oral anticoagulant. No recurrent thrombotic episodes were witnessed after 4 months of follow-up after discharge.

Quantification of fibrin in blood thrombi formed in hemodialysis central venous catheters: a pilot study on 43 CVCs.

PURPOSE: Fibrin deposition and thrombotic occlusion represent a serious cause of access dysfunction in hemodialysis central venous catheters (CVCs). The aim of this work was to define and apply a method for imaging and quantifying fibrin in thrombi formed into the side holes of CVCs. METHODS: Forty-three CVCs removed from a cohort of dialyzed patients were analyzed in this pilot study. Hematoxylin and eosin and a modified Carstair's staining were applied on permanent thrombus sections. Fluorescence microscopy and image analysis were performed to quantify the fibrin amount. RESULTS: Highly fluorescent areas were invariably associated with fibrin by Carstair's method. The deposition of concentric layers of fibrin and erythrocytes was easily identified by fluorescence microscopy, showing growth features of the thrombus. Fibrin amount in diabetic patients was significantly higher than that in nondiabetic patients with median (interquartile range) values of 51% (47-68%) and 44% (30-54%), respectively (p=0.032). No significant difference in fibrin content was found by grouping data according to catheter type, permanence time, insertion site and dialysis vintage. Higher variability in fibrin values was found in thrombi from CVCs removed after 1-15 days compared with 16-60 days. A trend of an increase in fibrin amount in thrombi was noted according to blood platelet count at CVC insertion. CONCLUSIONS: The analytical method presented here proved to be a rapid and effective way for quantifying fibrin content in thrombi formed on CVCs with potential application in future clinical studies.

Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

BACKGROUND: Neonates and children differ from adults in physiology, pharmacologic responses to drugs, epidemiology, and long-term consequences of thrombosis. This guideline addresses optimal strategies for the management of thrombosis in neonates and children. METHODS: The methods of this guideline follow those described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. RESULTS: We suggest that where possible, pediatric hematologists with experience in thromboembolism manage pediatric patients with thromboembolism (Grade 2C). When this is not possible, we suggest a combination of a neonatologist/pediatrician and adult hematologist supported by consultation with an experienced pediatric hematologist (Grade 2C). We suggest that therapeutic unfractionated heparin in children is titrated to achieve a target anti-Xa range of 0.35 to 0.7 units/mL or an activated partial thromboplastin time range that correlates to this anti-Xa range or to a protamine titration range of 0.2 to 0.4 units/mL (Grade 2C). For neonates and children receiving either daily or bid therapeutic low-molecular-weight heparin, we suggest that the drug be monitored to a target range of 0.5 to 1.0 units/mL in a sample taken 4 to 6 h after subcutaneous injection or, alternatively, 0.5 to 0.8 units/mL in a sample taken 2 to 6 h after subcutaneous injection (Grade 2C). CONCLUSIONS: The evidence supporting most recommendations for antithrombotic therapy in neonates and children remains weak. Studies addressing appropriate drug target ranges and monitoring requirements are urgently required in addition to site- and clinical situation-specific thrombosis management strategies.

The effect of heparinized catheter lock solutions on systemic anticoagulation in hemodialysis patients.

BACKGROUND: Hemodialysis catheter thrombosis is associated with loss of catheter patency, catheter-related bacteremia and sepsis. To limit these risks, many renal units use heparin as a catheter-locking solution. In this study we investigate the effect of different concentrations of heparin catheter lock solution on systemic anticoagulation in an investigator-blinded randomized study of patients with non-tunneled (temporary) central venous catheters. METHODS: 28 consecutive patients requiring insertion of a temporary non-tunneled dual lumen central venous hemodialysis catheter were randomly allocated to receive either heparin 5,000 IU/ml or heparin 1,000 IU/ml as catheter lock solutions. The primary outcome measure was the difference in activated partial thromboplastin time (APTT) at 10 minutes following catheter locking with heparin 5,000 IU/ml and heparin 1,000 IU/ml. Secondary outcomes included intradialytic blood flow rates, catheter removal due to insufficient hemodialysis blood flow to maintain hemodialysis and catheter-related bacteremia. RESULTS: 13 patients were randomized to the heparin 1,000 IU/ml group with 15 patients randomized to the heparin 5,000 IU/ml group. There was a statistically significant increase in APTT at 10 minutes between groups with median +22.2% (range 0 - 210) rise in APTT in the heparin 1,000 IU/ml group compared with +373.7% (range 133 - 800) in the heparin 5,000 IU/ml group (p < 0.001). There was no statistically significant difference between groups with the secondary outcomes of intradialytic blood flow, catheter failure rates and catheter-related bacteremia rates. CONCLUSIONS: Heparin 1,000 IU/ml catheter lock solution confers a significantly lower risk of systemic heparinization than heparin 5,000 IU/ml without any overtly detrimental effect on intradialytic blood flow, catheter failure rates and catheter-related bacteremia rates.