Dose escalation of low molecular weight heparin in patients with recurrent cancer-associated thrombosis

Introduction

Patients with cancer-associated thrombosis are at a high risk of developing recurrent events despite anticoagulant therapy. Escalation of the dose of low molecular weight heparin (LMWH) has been suggested as a potential treatment option to manage these patients. We sought to confirm the benefit and risk of this management strategy in patients with recurrent cancer-associated thrombosis.

Material and Methods

A retrospective cohort study of consecutive cancer outpatients seen for management of a symptomatic recurrent cancer-associated thrombosis while on anticoagulation was undertaken. Objectively confirmed episodes of recurrent thrombosis were treated with either dose escalation of LMWH or initiation of therapeutic dose of LMWH in patients already anticoagulated with LMWH or vitamin K antagonist (VKA) respectively. Included patients were followed for a minimum of 3 months after the index recurrent event.

Results

Fifty-five cancer patients with a recurrent venous thromboembolism (VTE) despite anticoagulation were included. At the time of the recurrence, 89% of patients were on LMWH. The median time between the initial cancer-associated thrombosis to the index recurrent event was 2.3 months (range 0.1 to 30.4 months). Four patients (7.3%; 95% CI: 2.0 to 17.6%) had a second recurrent VTE during the 3-month follow-up period. Three patients (5.5%; 95% CI 1.1 to 15.1%) had major bleeding complications after dose escalation of LMWH. There were no recurrent fatal VTE or major bleeding episodes.

Conclusion

Escalating the dose of LMWH seems effective and safe for managing patients with recurrent cancer-associated thrombosis despite anticoagulant therapy.     

Efficacy and Safety of Anticoagulant Therapy for the Treatment of Acute Cancer-Associated Thrombosis: A Systematic Review and Meta-Analysis

Background

Current clinical practice guidelines all recommend the use of therapeutic doses of low molecular weight heparins (LMWH) for the initial and long-term treatment of cancer-related thrombosis. The use of vitamin-K antagonists (VKA) is acceptable if LMWH is not available. Direct oral anticoagulants (DOACs) have been shown to be comparable to conventional therapy for the acute treatment of VTE but their efficacy and safety in cancer patients remains uncertain.

Methods

A systematic literature search strategy was conducted using MEDLINE, EMBASE, and the EBM reviews. Randomized controlled trials (RCTs) reporting rates of recurrent VTE and major bleeding in cancer patients were included. Relative risks (RR) (95% confidence intervals (CI)) for these outcomes were generated.

Results

A total of 9 RCTs (2310 patients) were included in our analysis. In comparison to VKA, LMWH showed a significant reduction in recurrent VTE events (RR: 0.52; 95% CI: 0.36 to 0.74) whereas DOACs did not (RR: 0.66; 95% CI: 0.39 to 1.11). LMWH was associated with a non significant increase in the risk of major bleeding (RR: 1.06; 95% CI: 0.5 to 2.23) whereas DOACs showed a non significant reduction (RR: 0.78; 95% CI: 0.42 to 1.44). Annualized risks of recurrent VTE and major bleeding among patients randomized to VKA were higher in the LMWH studies as compared to the studies assessing DOACs suggesting that a higher risk cancer population were enrolled in the LMWH studies.

Conclusions

LMWH should be used for the treatment of acute cancer-associated thrombosis. The use DOACs cannot be supported until trials comparing them to LMWH are conducted.     

D-dimer,FVIII and thrombotic burden in the acute phase of deep vein thrombosis in relation to the risk of post-thrombotic syndrome

Background

Post-thrombotic syndrome (PTS) is the most common complication of deep vein thrombosis (DVT), but few data are available on the risk factors for PTS.

Aims

To assess whether the time-course of D-dimer, FVIII, and thrombotic burden are related to PTS development.

Methods

Patients (n = 59) with proximal DVT of the lower limbs (age 64; range:20-88 years; male 56%) were enrolled on the day of diagnosis (D0) and all received heparin for 5-7 days, overlapped and followed by vitamin K antagonists (VKA) for 3 months. Whole-leg compression ultrasound examination was conducted on D0 and 7 (D7), 30 (D30), and 90 (D90) days afterwards, when blood samples were also taken for D-dimer (STA Liatest) and FVIII (chromogenic assay) testing. Thrombotic burden was defined at each time point according to a score, which considered thrombosis extent and occlusion degree. Villalta score was evaluated at D30, D90, and D180.

Results

At D90, 12 patients developed PTS (Villalta score ≥ 5) and the median Villalta score was 1 (IQR 0.3-3.0) and was not correlated with either D-dimer or FVIIII time course. At D180, 13 patients had PTS and they had similar thrombotic score at D0, D30 to those without PTS, but higher at D90 (7.6 ± 5.1 vs. 3.2 ± 3.6; p = 0.011). Thrombotic score at D90 was correlated with Villalta score at D90 (rho = 0.374, p = 0.009) and at D180 (rho = 0.436, p = 0.006).

Conclusions

Thrombotic burden after 90 days of VKA is correlated with PTS.     

Unprovoked proximal venous thrombosis is associated with an increased risk of asymptomatic pulmonary embolism

Introduction

Pulmonary embolism (PE) is common in patients with deep venous thrombosis (DVT). The outcome of DVT with concomitant symptomatic PE is worse than the outcome of isolated DVT. The risk factors for DVT and simultaneous asymptomatic PE have not been systematically studied yet.

Aim

To evaluate the frequency and risk factors for asymptomatic PE in patients with DVT.

Patients/methods

In 155 consecutive patients with a first episode of DVT and no PE symptoms, a ventilation-perfusion lung scan was performed. Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated and concentrations of D-dimer, high-sensitivity CRP (hsCRP), tissue plasminogen activator (t-PA) and troponin were measured. Laboratory tests for thrombophilia were performed.

Results

Asymptomatic PE was present in 36% of patients. No differences in gender, age, BMI and WHR were found between the patients with and without PE. PE was more common in patients with proximal DVT than in those with distal DVT (42% vs. 17%, p < 0.01), and in patients with unprovoked DVT compared to patients with provoked DVT (51% vs. 28%, p < 0.01). The risk of silent PE was the highest in patients with unprovoked proximal DVT (OR, 6.9; 95% CI, 2.3–21.0). Patients with asymptomatic PE had significantly higher values of D-dimer, hsCRP, t-PA and troponin than patients with isolated DVT.

Conclusions

Asymptomatic PE affected more than one third of patients with a first DVT. Unprovoked proximal DVT is the most important risk factor for the occurrence of silent PE.     

Treatment patterns of venous thromboembolism in a real-world population: The Q-VTE study cohort

Background

Few studies have assessed treatment patterns of acute venous thromboembolism (VTE) in a real-world population. We aimed to describe anticoagulant treatment patterns for acute VTE using healthcare databases of Québec, Canada.

Methods

We used linked healthcare databases of the province of Québec, Canada to identify all incident cases of deep vein thrombosis (DVT) and pulmonary embolism (PE) between 2000 and 2009. We formed two patient cohorts, one with definite cases (definite VTE cohort, N = 40,776) and the other including cases with definite or probable VTE (any VTE cohort, N = 54,803) that were followed until death, end of health coverage, or end of study (December 31, 2009).

Results

In the definite cohort, 73.6% of subjects were dispensed an anticoagulant following the diagnosis of VTE. Of those who were dispensed a vitamin K antagonist (VKA), median duration of use was 61 days (interquartile range 89). VKA initiation was more likely in patients with pulmonary embolism than deep vein thrombosis alone (HR 1.62, 95% CI (1.58-1.66)). Among outpatients, those managed initially in the outpatient setting were less likely to initiate VKA therapy (HR 0.75, 95% CI (0.68-0.77)), while those requiring admission to hospital for VTE management were more likely to initiate (HR 1.81, 95% CI (1.76-1.87)). Findings were similar in the any VTE cohort.

Conclusion

Our study describes VTE treatment patterns in a real-world setting and suggests that there may be important gaps. These may include significant numbers of patients who did not initiate oral anticoagulant therapy, particularly in the outpatient setting, and shorter duration of oral anticoagulant use than recommended.     

Screening high-risk cancer patients for VTE: A prospective observational study

Background

The utility of screening for venous thromboembolism (VTE) in cancer patients is unknown. We evaluated this in a prospective cohort study of cancer patients initiating a new chemotherapy regimen and deemed high-risk (score ≥ 3) based on a validated Risk Score.

Methods

Patients were evaluated with baseline and Q4 (± 1) week serial ultrasonography for up to 16 weeks; additionally, computed tomography scans for restaging were also evaluated for VTE.

Results

The study population comprised 35 patients. Pancreatic and gastro-esophageal cancers were the most common diagnoses. Of these, 8 (23%) developed a VTE. This included 5 patients with DVT alone (14%), 1 patient with PE alone (3%) and 2 (6%) with both. Ultrasound examinations identified asymptomatic DVT in 9.3% of patients at baseline; 0% at weeks 4 and 8 and 5.6% at week 12. Restaging CT scans identified asymptomatic PE in one patient at week 6 and in one patient at week 9 with subsequent DVT at week 10.

Conclusions

Screening for asymptomatic VTE has not been previously used as a clinical strategy in ambulatory cancer patients. We report that one-tenth of patients at baseline had occult DVT and in this high-risk population, screening at baseline may be of value.     

Outpatient management of acute deep vein thrombosis: results from the OTIS-DVT registry

Objectives

We aimed to investigate clinical practice patterns for the outpatient management of acute deep vein thrombosis (DVT).

Methods

In the prospective Outpatient Treatment of Deep Vein Thrombosis in Switzerland (OTIS-DVT) registry, 534 consecutive outpatients with acute DVT (49% proximal, 24% recurrent, and 12% cancer-associated) were enrolled: 41% patients were managed in private angiology practice, 34% in an outpatient hospital department, and 25% in private general or internal medicine practice.

Results

For diagnosis, ultrasound was used in 95% and D-dimer testing in 53%. Low-molecular-weight heparin (LMWH) was prescribed for a median (IQR) duration of 7 (5-12) days in 83% of patients, and vitamin K-antagonists for 163 (92-183) days in 81%. Mechanical measures to prevent post-thrombotic syndrome were prescribed in 83%; compression stockings or bandages for a median (IQR) duration of 364 (101-730) days from hospital physicians, and 92 (45-183) days from private practice physicians (p < 0.001). Among patients with symptomatic proximal DVT, mechanical measures were prescribed for at least 2 years in 24% patients; 55% in hospital, and 6% in private practice (p < 0.001). Among patients with cancer-associated DVT, the median (IQR) duration of LMWH therapy was 16 (8-45) days, and 35% received LMWH for less than 90 days.

Conclusions

The OTIS-DVT registry provides representative information on clinical practice patterns for outpatients with acute DVT managed by hospital or private practice physicians. The use of mechanical measures in patients with symptomatic proximal DVT and the administration of LMWH for a long-term therapy of cancer-associated DVT require improvement to comply with current guidelines.     

Anti-thrombosis effect of LRRFIP1 shRNA lentivirus in a mouse model of deep vein thrombosis

Introduction

Deep vein thrombosis (DVT) is one of the common complications of orthopedic surgery. Low molecular weight heparin (LMWH) is a usually used agent for DVT, but it would increase the risk of bleeding. LRRFIP1 has been shown to play an important role in the formation of thrombosis. Therefore, we investigated the effect of LRRFIP1 shRNA lentivirus on DVT in mice.

Materials and Methods

Lentiviral Vectors carrying LRRFIP1 shRNA were constructed and transfected into cultured mouse bone marrow cells (BMCs). Male ICR mice were irradiated with a single dose of 9.5 Gy and then were injected with different agents through the tail vein. Stasis venous thrombosis was induced by inferior vena cava (IVC) ligation. Mice were sacrificed on the 1st, 3rd and 7th day post operation and the thrombi were removed, blotted the excess blood on it with filter paper and immediately weighed. P-selectin and d-Dimer were determined by enzyme-linked immunosorbent assay (ELISA).

Results

LRRFIP1 shRNA significantly suppressed the expression of LRRFIP1 in the thrombi. In contrast, low molecular weight heparin (LMWH) and negative shRNA exhibited little effect on the expression of LRRFIP1. LRRFIP1 shRNA, LMWH and negative shRNA inhibited the thrombus formation in vivo significantly. The plasma P-selectin and d-Dimer levels were significantly increased after IVC ligation. LRRFIP1 shRNA significantly decreased the plasma P-selectin and d-Dimer levels. However, LMWH and negative shRNA showed little effects on the levels of plasma P-selectin and d-Dimer.

Conclusion

LRRFIP1 shRNA might represent a promising prevention strategy for DVT.     

Microparticle-associated tissue factor activity in patients with acute unprovoked deep vein thrombosis and during the course of one year

Background

Tissue factor (TF) is the main in-vivo initiator of blood coagulation. Microparticles (MPs) are small procoagulant membrane vesicles. Elevated TF-bearing MPs have been found in different prothrombotic conditions and MP-associated TF activity may contribute to the pathogenesis of unprovoked deep vein thrombosis (DVT).

Objective

To determine MP-TF activity levels at diagnosis of DVT and at four additional time points during the course of one year in a well-defined group of patients with unprovoked DVT of the lower limb.

Patients/Methods

In this study, 41 patients with acute unilateral symptomatic and unprovoked DVT of the lower limb were included and followed for 1 year. Venous blood samples for determination of MP-TF activity were drawn at diagnosis of acute DVT, and 1-, 3-, 6-, and 12 months later. In addition, 10 young and healthy control subjects were included.

Results

The median MP-TF activity was 0.06 pg/mL (25th-75th percentile: 0.0-0.53) in patients with acute DVT and 0.18 pg/mL (0.07-0.33) in healthy controls, and did not differ significantly (p = 0.35). No significant changes in MP-TF activity were found in the follow-up measurements. MP-TF activity did also not differ significantly between patients with proximal- or distal DVT and between those with- or without residual DVT after 6 months.

Conclusions

MP-TF activity is low at the acute event in patients with unprovoked DVT of the lower limb and remains unchanged during the course of the disease. Our data do not support the hypothesis that TF-bearing MPs play a determining role in the pathogenesis of unprovoked DVT.     

Association between obstructive sleep apnea and deep vein thrombosis / pulmonary embolism: A population-based retrospective cohort study

Background

Obstructive sleep apnea (OSA) is a major contributor to cardiovascular disease, and may cause severe morbidity and mortality. Recent studies have indicated that OSA patients exhibited elevated platelet activity, fibrinogen levels, and platelet aggregation.

Objectives

We investigated the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients diagnosed with OSA compared with age- and sex-matched unaffected people.

Patients/Methods

This longitudinal, nationwide, population-based cohort study was conducted using data from Taiwan National Health Insurance Research Database (NHIRD) recorded between January 2000 and December 2011. The study consisted of 3511 patients with OSA and 35110 matched comparison individuals. A Cox proportional hazard regression was used to compute the risk of DVT and PE in patients with OSA compared with those without OSA.

Results

The DVT and PE risks were 3.50- and 3.97-fold higher (95% CI = 1.83–6.69 and 1.85–8.51) respectively, in the OSA cohort than in the reference cohort after we adjusted for age, sex, and comorbidities.

Conclusion

This nationwide population-based cohort study indicates that patients with OSA exhibit a higher risk of subsequent DVT and PE.     

Incidence and predictive factors of symptomatic thrombosis related to peripherally inserted central catheters in chemotherapy patients

Introduction

The incidence of symptomatic catheter-related deep vein thrombosis (DVT) in cancer patients remains unclear and there is a lack of reliable data on the risk factors of PICC-related DVT.

Materials and Methods

We performed a retrospective cohort study of consecutive cancer patients who received an ultrasound guided PICC line for the administration of chemotherapy. Univariable and multivariable logistic regression analyses were performed to identify risk factors for symptomatic PICC-related DVT.

Results

In total, 340 cancer patients obtained PICC lines for the administration of chemotherapy. Of these patients, 19 (5.6%; 95% CI: 3.6-8.6) developed symptomatic PICC-related DVT. Factors previously associated with catheter-related DVT, including side of catheter placement, lumen size, tip location, need for repositioning, and number of insertion attempts, were not significant determinants in our analysis. Patients with diabetes were three times more likely to develop PICC-related DVT (OR 3.0, p = 0.039), while the presence of COPD and metastatic cancer also increased the odds (OR 3.3, p = 0.078 and OR 2.3, p = 0.083 respectively). Diabetes remained a significant risk factor after adjustment for effect of metastases and COPD (OR 3.175, p = 0.039). Further, the presence of metastases was a significant predictor (OR 3.34, p = 0.024) in our multivariable model.

Conclusions

Symptomatic PICC-related DVT are frequent in cancer patients receiving chemotherapy. Previously described factors associated with catheter-related thrombosis were not predictive of PICC-related DVT in our study. Diabetes, advanced disease and COPD appear to increase the risk of developing PICC-related DVT in chemotherapy patients.     

Accuracy of a portable international normalized ratio monitor for patients receiving a low molecular weight heparin as a bridge pending full oral anticoagulant efficacy

Background

Point of care (POC) devices measuring the international normalized ratio (INR) are accurate for patients with stable disease, but their efficiency has not been prospectively assessed during the “bridging period” when patients are receiving a low molecular weight heparin (LMWH) on top of a vitamin K antagonist (VKA) until the target INR is reached.

Methods

188 dual INR measurement using the POC (INR_POC) and the laboratory (INR_lab) at the same time were consecutively determined : 69 in patients receiving LMWH + VKA (bridging group) and 119 in patients receiving only a VKA (control group). INRpoc was compared to INR_lab.

Results

Test strip failure rate was higher in the bridging group than in the control group (29% vs 4% ; p < 0,001).In successful tests, POC accuracy was not modified by LMWH administration: the correlation coefficients between POC and lab INR values for the bridging group and the control group were 0,81 and 0,87 respectively, and the relative measure of divergence (RMD = INR_lab - INR_poc / INR_lab) was lower in the bridging group than in the control group (4 ± 7% vs 10 ± 14%; p = 0,02). Finally, clinically relevant agreement between POC and laboratory was of 90% in the bridging group and 92.1% in the control group (p = 0.6).

Conclusion

With the POC used (INRatio), in patients receiving LMWH when the POC gives a result, it is as accurate as in patients not receiving a LMWH.     

Rivaroxaban for the treatment of venous thromboembolism. A “real-life” perspective in 103 patients

Introduction

Randomized clinical trials have demonstrated non-inferiority of rivaroxaban compared with vitamin K antagonists (VKAs) in the treatment of venous thromboembolism (VTE). Our objective was to analyze in real life, tolerance, recurrence, bleeding and adverse events of rivaroxaban in patients with acute symptomatic VTE.

Material and Methods

Open follow-up study of a cohort of patients aged 18 and over diagnosed with deep vein thrombosis (DVT) and/or pulmonary embolism (PE) treated with rivaroxaban from December 2011 to January 2014.

Results

The total number of patients treated with rivaroxaban was 103. The mean age was 58 +/-17 years. The most frequent co-morbidities were: hypertension (30.0%), dyslipidemia (23.3%) and respiratory disease (25.2%). The type of thromboembolic event treated was: DVT (64.1%), PE (18.4%), DVT + PE (17.5%). Of the rivaroxaban-treated patients, 30% did so from the initial anticoagulant therapy and the other 70% in long-term or extended anticoagulant therapy. The median time of treatment with rivaroxaban was 5 months. There was one recurrence and no deaths occurred. Six patients had bleeding, one of which was severe.

Conclusions

Rivaroxaban provides a therapeutic alternative in a group of patients with VTE with advantages over VKAs, because of the convenience in dosing, lack of requirements for periodic monitoring and limited interaction with other drugs.     

Increased Risk of Deep Vein Thrombosis and Pulmonary Thromboembolism in Patients with Spinal Cord Injury: A Nationwide Cohort Prospective Study

Background

We investigated the effect of spinal cord injury (SCI) on the development of deep vein thrombosis (DVT) and pulmonary thromboembolism (PE) by conducting a nationwide longitudinal cohort study.

Methods

We studied the entire hospitalized population in Taiwan for the 1998–2008 period, with a follow-up period extending to the end of 2010. We identified SCI patients using the Taiwan National Health Insurance Research Database (NHIRD), and selected a cohort that was 1:4 frequency-matched by age (5-y span), sex, and index year from the general population. We analyzed the risks of DVT and PE using Cox proportional-hazards regression models, which included the demographic variables of sex, age, and comorbidities.

Results

A total of 47,916 SCI patients (62.7% men, mean age of 50.0 y) and 191,664 controls were followed for 308,266 and 1,341,169 person-years, respectively. The adjusted hazard ratio (HR) of DVT and PE development was 2.46-fold and 1.57-fold among the SCI patients, respectively. The highest risk of DVT and PE developed within 3 months after an SCI occurred (HR: 16.9 and 3.64, respectively). The adjusted HR of DVT and PE rose markedly with increasing age. The adjusted HR of DVT was highest among C-spine SCI patients, and the adjusted HR of PE was highest among T-spine SCI patients.

Conclusion

This nationwide prospective cohort study demonstrated that the risk of DVT and PE increased significantly in SCI patients compared with that of the general population. The highest risk of DVT and PE developed within 3 months after an SCI occurred.     

Association of F11 polymorphism rs2289252 with deep vein thrombosis and related phenotypes in population of Latvia

Introduction

Deep vein thrombosis (DVT) has a strong inherited predisposition that is partly explained by the strong genetic risk factors such as mutations in factor V, prothrombin, antithrombin III, protein C and S genes. Only recently the first GWAS have been performed on DVT resulting in discovery of novel genetic variants, however, the information on the common polymorphisms predisposing to the risk of DVT is still scarce.

Materials and Methods

Here we selected six SNPs (rs5361 in SELE, rs2066865 in FGG, rs2227589 in SERPINC1, rs1613662 in GP6, rs13146272 in CYP4V2, rs2289252 in F11) reported to be associated with venous thrombosis conditions and studied the association of these common variants in selected case (n = 177) and control (n = 235) groups from population of Latvia. Genotyping was performed using TaqMan hybridization probe SNP genotyping assay.

Results

Patients with DVT had a significantly higher frequency of F11 rs2289252 polymorphism (p = 0.001; OR [95%CI] = 1.61 [1.20-2.14]). When stratified by recurrence of DVT the tendency was observed that the same SNP had higher OR value in group of DVT patients with repeated episodes of DVT compared to patients with single DVT episode (p = 0.009; OR [95%CI] = 2.27[1.22-4.21] and p = 0.009; OR [95%CI] = 1.52[1.11-2.08] respectively), but due to limited group of cases this finding should be replicated.

Conclusion

We conclude that F11 gene variant rs2289252 contribute to inherited forms of DVT incidence and correlation of other analysed SNPs should be explored in populations with greater sample size and associated with various thrombosis related traits.     

A case series of LMWH use in pregnancy: Should trough anti-Xa levels guide dosing?

Introduction

Pregnancy is a thrombogenic state, increasing the risk for venous thromboembolism (VTE), and the risk of valve thrombosis amongst women with mechanical heart valves (MHV). While low molecular weight heparins (LMWH) are generally dosed based on weight (i.e., enoxaparin 1 mg/kg every 12 hours), data in pregnant women have shown that weight-based dosing does not consistently achieve target anti-Xa levels. In women with MHV, our practice includes titrating LMWH doses to target both trough and peak anti-Xa levels, while for those with VTE peak anti-Xa levels guide dosing.

Materials/Methods

This retrospective case series included pregnant women requiring LMWH treatment doses with at least 3 peak (+/− trough) anti-Xa levels. Our primary objective was to describe the actual LMWH dose required to achieve targeted anti-Xa levels relative to weight-based dosing in patients with MHV. Secondarily, we compared the same for VTE patients; compared actual dosing between those with MHV and VTE; and examined maternal and fetal outcomes.

Results/Conclusion

Women with MHV (N = 4) required greater than weight-based dosing of enoxaparin (1.35 mg/kg Q12H) to achieve targeted anti-Xa levels. Importantly, achieving target peak anti-Xa levels did not always ensure maintenance of minimum trough levels. VTE patients (N = 12) did not require more enoxaparin (0.96 mg/kg Q12H) than weight based dosing. MHV patients received more enoxaparin compared to VTE patients (P < 0.001). No bleeding or clotting complications were associated with LMWH administration. In pregnant women with MHV at high risk of thromboembolism, LMWH dosing guided by trough and peak anti-Xa levels should be considered.     

The role of soluble P selectin in the diagnosis of venous thromboembolism

Introduction

Soluble P selectin (sPsel), a member of the selectin family of cell adhesion receptors, has been proposed as a key molecule in hemostasis and thrombosis mediating platelet rolling, generating procoagulant microparticles and enhancing fibrin deposition. The aim of this study was to examine the role of sPsel in the diagnosis of venous thromboembolism (VTE).

Materials and Methods

We performed a systematic review and we used meta-analysis to synthesize data from published studies reporting sPsel levels in patients with i) VTE (deep venous thrombosis; DVT or DVT and pulmonary embolism; PE) and ii) DVT only. Pooled Odds Ratios (ORs) with 95% Confidence Intervals (CIs) were appropriately calculated among patients and controls. Diagnostic performance of sPsel was tested with pooled sensitivity, specificity, Diagnostic Odds Ratio (DOR) and summary receiver operator characteristic (SROC) curve.

Results

Eleven studies, comprising of 586 VTE patients and 1,843 controls were deemed eligible. The sPsel was significantly increased after VTE (OR = 2.89, 95%CI = 2.31-3.61, p < 0.001), or DVT only (OR = 2.64, 95%CI = 1.95-3.56, p < 0.001). Subgroup analysis evidenced that sPsel was also increased after VTE when evaluating only studies with patients that had no prior medical history (OR = 2.88, 95%CI = 1.98-4.19, p < 0.001). Exclusion of studies including patients with solid organ tumor, HIV or lupus anticoagulants positive patients did not alter findings. Pooled sensitivity and specificity of sPsel was 0.57 (95%CI = 0.30-082, p < 0.001) and 0.73 (95%CI = 0.51-0.90, p < 0.001), respectively and DOR was 4.31 (95%CI = 2.22-8.37, p < 0.01). SROC curve yielded in significant accuracy of sPsel performance (AUC = 0.74, p = 0.05).

Conclusions

The sPsel was significantly elevated in patients with DVT, both uncomplicated and complicated with PE and presented with high levels of diagnostic performance. sPsel is a plasma biomarker that may help in the diagnosis of VTE.     

Mid-term results of self-testing of the international normalized ratio in adults with a mechanical heart valve

Background

Commonly the frequency of international normalized ratio (INR) monitoring with a conventional laboratory test in stable patients is once a month. When using a dedicated personal device for INR assessment, the frequency may be increased to two or more times a month.

Objective

To show that INR assessed by self-measurement at home is reliable and feasible in the mid-term and improves medical care.

Patients and methods

All patients in the study on INR self-measurement (clinical trial.gov: NCT00925197), conducted between 2004 and 2007, were re-contacted for mid-term follow-up. One hundred and seventy eight out of 192 patients who participated in the study answered a questionnaire. The average follow-up time was 4.2 years (± 1) for the self-measurement group and 4.9 years (± 1) for the laboratory-analyzed control group.

Results

Only 26 patients (group A) continued to use INR self-measurement to monitor treatment with vitamin K antagonists (VKA). The main reasons to stop INR self-measurement were its high cost and difficulty in obtaining strips. There were significantly fewer bleeding complications (p = 0.04) and complications related to VKA (p = 0.01) in self-measured patients compared to the control group. Feelings of security and quality of life were also significantly better (p = 0.002) for self-measured patients.

Conclusion

Many patients with a mechanical heart valve, who self-measured INR, continue to use this method for their follow-up because of its positive effects on their health and quality of life.     

Circulating microparticle tissue factor,thromboembolism and survival in pancreaticobiliary cancers

Background

Tissue factor (TF), the physiologic initiator of coagulation, is over-expressed in pancreatic cancer, and is associated with a pro-coagulant and pro-angiogenic state. We hypothesized that in patients with pancreaticobiliary cancers (PBC), elevated circulating microparticle-associated TF (MP-TF) activity would be associated with thrombosis and worsened survival.

Patients and Methods

Clinical data and plasma were obtained for consecutive patients with PBC seen at Roswell Park Cancer Institute from 2005-08. MP-TF activity levels were measured using a TF-dependent FXa generation assay.

Results

The study population comprised 117 patients, including pancreatic (n = 80), biliary (n = 34) or unknown primary histologically consistent with PBC (n = 3). Of these, 52 patients (44.5%) experienced thromboembolism, including pulmonary embolism (n = 15), deep venous thrombosis (n = 21) and other arterial or venous events (n = 32). Mean TF was 2.15 (range 0.17- 31.01) pg/mL. Median survival was 98.5 days for MP-TF activity ≥ 2.5 pg/mL versus 231 days for MP-TF activity < 2.5 pg/mL (p < 0.0001). In multivariate analysis, elevated MP-TF activity was associated with both VTE (OR 1.4, 95% CI 1.1-1.6) and mortality (HR 2.5, 95% CI 1.4-4.5).

Conclusions

Elevated circulating MP-TF activity is associated with thrombosis and worsened survival in patients with PBC. MP-TF activity as a prognostic biomarker warrants further prospective evaluation.