Lower dosage of recombinant tissue-type plasminogen activator (rt-PA) in the treatment of acute pulmonary embolism: A systematic review and meta-analysis

Background and Objective

According to US Food and Drugs Administration (FDA), 2 hour recombinant tissue plasminogen activator (rt-PA) 100 mg infusion is recommended for eligible patients with acute pulmonary embolism (PE). However,there exists evidence implying that a lower dosage of rt-PA can be equally effective but potentially safer compared with rt-PA 100 mg regimen. The aim of this systematic review and meta-analysis is to assess the efficacy and safety of low dose rt-PA in the treatment of acute PE.

Material and Method

We searched Pubmed, EMBASE, the Cochrane library and CBM Literature Database for randomized controlled trials (RCT) focusing on low dose rt-PA for acute PE. Outcomes were described in terms of changes of image tests and echocardiography, major bleeding events, all-cause death, and recurrence of PE.

Results

Five studies (440 patients) were included, three of which compared low dose rt-PA (0.6 mg/kg, maximum 50 mg or 50 mg infusion 2 h) with standard dose (100 mg infusion 2 h). There were more major bleeding events in standard dose rt-PA group than in low dose group (OR 0.33, 95%CI 0.12-0.91;P = 0.94,I² = 0%), while there were no statistical differences in recurrent PE or all cause mortality between these two groups. Two studies compared low dose (0.6 mg/kg, maximum 50 mg/2 min bolus or 10 mg bolus, ≤ 40 mg/2 h) with heparin. There was no significant difference in major bleeding events (OR 0.73, 95% CI 0.14-3.98;P = 0.72), recurrent PE or all cause mortality. No dose-related heterogeneity was found for all the included studies.

Conclusions

The results of this meta-analysis were hypothesis-generating. Based on the limited data, our systematic review suggested that low dose rt-PA had similar efficacy but was safer than standard dose of rt-PA. In addition, compared with heparin, low dose rt-PA didn’t increase the risk of major bleeding for eligible PE patients.     

Treatment of patients with acute deep vein thrombosis and/or pulmonary embolism: Efficacy and safety of non-VKA oral anticoagulants in selected populations

Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), presents a large clinical burden. Prompt, effective and sustained anticoagulation is vital because of the risk of recurrent events, including life-threatening PE, and complications such as post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension. Dual-drug standard therapy is effective; however, parenteral low molecular weight heparin, coupled with routine coagulation monitoring and dose adjustment of vitamin K antagonists (VKAs), presents challenges for patients and healthcare providers. Non-VKA oral anticoagulants provide a simplified option for VTE treatment. Phase III studies have investigated rivaroxaban and apixaban as single-drug approaches, and edoxaban and dabigatran in conjunction with initial heparin therapy. These agents demonstrated non-inferiority to standard therapy, and most showed significant reductions in major bleeding. However, clinical information is limited in patient subgroups, e.g. fragile patients or patients with renal impairment or cancer, who may be at higher risk of bleeding and/or VTE. A prespecified pooled analysis of the EINSTEIN DVT and EINSTEIN PE studies (8281 patients), undertaken to evaluate clinical outcomes with rivaroxaban versus standard therapy, confirmed the non-inferiority of rivaroxaban, with significant reductions in major bleeding and fewer intracranial and retroperitoneal bleeding events. Consistent efficacy and safety were observed with rivaroxaban, irrespective of fragility, cancer or clot severity. The introduction of the non-VKA oral anticoagulants and approval of rivaroxaban in the EU, US and Canada for the treatment and secondary prevention of DVT and PE offer the potential for improvements in effective care across a broad spectrum of patients with VTE.     

Outpatient treatment of symptomatic pulmonary embolism: A systematic review and meta-analysis

Background

Patients with acute deep vein thrombus (DVT) can safely be treated as outpatients. However the role of outpatient treatment in patients diagnosed with a pulmonary embolism (PE) is controversial. We sought to determine the safety of outpatient management of patients with acute symptomatic PE.

Materials and Methods

A systematic literature search strategy was conducted using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and all EBM Reviews. Pooled proportions for the different outcomes were calculated.

Results

A total of 1258 patients were included in the systematic review. The rate of recurrent venous thromboembolism (VTE) in patients with PE managed as outpatients was 1.47% (95% CI: 0.47 to 3.0%; I²: 65.4%) during the 3 month follow-up period. The rate of fatal PE was 0.47% (95% CI: 0.16 to 1.0%; I²: 0%). The rates of major bleeding and fatal intracranial hemorrhage were 0.81% (95% CI: 0.37 to 1.42%; I²: 0%) and 0.29% (95% CI: 0.06 to 0.68%; I²: 0%), respectively. The overall 3 month mortality rate was 1.58% (95% CI: 0.71 to 2.80%; I²: 45%). The event rates were similar if employing risk stratification models versus using clinical gestalt to select appropriate patients for outpatient management.

Conclusions

Independent of the risk stratification methods used, the rate of adverse events associated with outpatient PE treatment seems low. Based on our systematic review and pooled meta-analysis, low-risk patients with acute PE can safely be treated as outpatients if home circumstances are adequate.     

Combined risk stratification with computerized tomography /echocardiography and biomarkers in patients with normotensive pulmonary embolism

Background

Right ventricular dysfunction (RVD) detected by computerized tomography (CT)/echocardiography or elevated biomarkers is associated with a poor prognosis for pulmonary embolism (PE). However, these prognostic factors have not previously been concomitantly elucidated in the same patient group.

Methods

This prospective study included 108 consecutive patients with normotensive PE confirmed by CT pulmonary angiography (CTPA). On admission, patient serum NT-proBNP and troponin T (Tn-T) levels were measured, and echocardiography was performed within 24 hours after diagnosis of PE. Receiver operating characteristic (ROC) analysis was performed to determine the optimal echocardiographic end-diastolic diameters of the right ventricle, the ratio of the right ventricle to left ventricle (RV/LV ratio) on CTPA, and NT-proBNP and Tn-T cut-off levels with regard to prognosis.

Results

All-cause 30-day mortality was 13% and PE-related mortality was 5.6%. RVD was defined as a right/left ventricular dimension ratio ≥ 1.1 on CTPA and RV > 30 mm on echocardiography by ROC analysis. A cut-off level of NT-proBNP ≤ 90 pmol/ml had a high positive predictive value of 98% for survival, whereas NT-proBNP > 300 and Tn-T ≥ 0.027 had a negative predictive value, for all-cause deaths, of 95% and 96%, respectively. PE mortality in patients with NT-proBNP > 300 and Tn-T ≥ 0.027 reached 64%. In univariable analysis, the combination of Tn-T ≥ 0.027 ng/ml with a echocardiographic RVD were the most significant predictors of overall mortality and PE-related death [HR: 14 (95% CI: 4.6–42,) and HR: 37.6 (95% CI: 4.4–324)], respectively. In multivariable Cox's regression analysis, NT-proBNP > 300 and Tn-T ≥ 0.027 HR: 26.5 (95% CI: 4.1-169.9, p < 0.001) were the best combination to predict all-cause of mortality.

Conclusions

The combination of NT-proBNP and Tn-T clearly appears to be a better risk stratification predictor than biomarkers plus RVD on CT/ echocardiography in patients with normotensive PE.     

Use of anticoagulants in elderly patients

Thromboembolic disorders are a major cause of morbidity and mortality, and the risk of thromboembolism increases with age. Anticoagulants are recommended for indications including the prevention of venous thromboembolism in surgical and medical patients, treatment of venous thromboembolism and stroke prevention in patients with atrial fibrillation. Traditional anticoagulants that have been used include unfractionated heparin, low molecular weight heparin, fondaparinux and vitamin K antagonists. However, these agents are all associated with drawbacks (i.e. parenteral administration or frequent coagulation monitoring/dose titration), and it has been particularly challenging to treat elderly patients with anticoagulants. Some specific characteristics of elderly patients may influence the safety of anticoagulant therapy, such as decreased renal function, co-morbidities and the use of multiple medications. The complexity of anticoagulation therapy and the increased risk of bleeding complications in elderly patients may prevent some physicians from prescribing anticoagulants to these patients, which leaves them at risk of thromboembolic events. Thus, safer and more convenient anticoagulants are needed, particularly for elderly patients. New oral anticoagulants have been developed in recent years and have shown promise in clinical studies that included elderly patients. These agents could simplify the management of thromboembolic disorders and improve the safety of anticoagulation.     

Catheter-directed ultrasound-accelerated thrombolysis for the treatment of acute pulmonary embolism

Background

Systemic thrombolysis rapidly improves right ventricular (RV) dysfunction in patients with acute pulmonary embolism (PE) but is associated with major bleeding complications in up to 20%. The efficacy of low-dose, catheter-directed ultrasound-accelerated thrombolysis (USAT) on the reversal of RV dysfunction is unknown.

Materials and methods

We performed a retrospective analysis of 24 PE patients (60 ± 16 years) at intermediate (n = 19) or high risk (n = 5) from the East Jefferson General Hospital who were treated with USAT (mean rt-PA dose 33.5 ± 15.5 mg over 19.7 hours) and received multiplanar contrast-enhanced chest computed tomography (CT) scans at baseline and after USAT at 38 ± 14 hours. All CT measurements were performed by an independent core laboratory.

Results

The right-to-left ventricular dimension ratio (RV/LV ratio) from reconstructed CT four-chamber views at baseline of 1.33 ± 0.24 was significantly reduced to 1.00 ± 0.13 at follow-up by repeated-measures analysis of variance (p < 0.001). The CT-angiographic pulmonary clot burden as assessed by the modified Miller score was significantly reduced from 17.8 ± 5.3 to 8.7 ± 5.1 (p < 0.001). All patients were discharged alive, and there were no systemic bleeding complications but four major access site bleeding complications requiring transfusion and one suspected recurrent massive PE event.

Conclusions

In patients with intermediate and high risk PE, low-dose USAT rapidly reverses right ventricular dilatation and pulmonary clot burden.     

Hospital mortality due to pulmonary embolism and an evaluation of the usefulness of preventative interventions

Background

Mortality rates due to pulmonary embolism (PE) are difficult to estimate often due to the presence of comorbid disease.

Objectives

To determine the accuracy of hospital records in identifying PE cases, PE-related mortality, and the number of PE-related deaths which are potentially preventable.

Methods

Retrospective chart review of PE cases hospitalized at The Ottawa Hospital over an 8 year period. Cases were reviewed to determine accuracy of coding, as well as the certainty with which PE was the cause of death. In PE-related deaths, a determination was made as to whether any interventions may have been life-saving.

Results

498 cases of 612 (81%) cases coded as PE were correctly coded. 111 (22%) died during hospitalization, 63% of deaths were attributed to PE. The presence of a cardiorespiratory comorbidity or cancer was independently associated with an increased rate of death due to PE. 54% of PE-related deaths were determined to be potentially preventable, most commonly by appropriate DVT prophylaxis. A significantly higher number of cancer patients as compared to non-cancer patients may have potentially had their death due to PE prevented by an inferior vena cava filter (IVCF). Systemic thrombolysis was deemed to be potentially life-saving in 1/38 PE-related deaths.

Conclusion

Hospital mortality due to clinically recognized PE can be determined by chart review of PE cases identified using the ICD coding system. Death due to PE is often potentially preventable; in the subgroup with cancer and DVT/PE, an IVCF may be a potentially useful intervention to prevent death due to PE. Prospective studies are needed to confirm these results.     

Pregnancy-related venous thromboembolism: risk and the effect of thromboprophylaxis

Venous thromboembolism (VTE) is a leading cause of maternal mortality and morbidity during pregnancy in developed countries. The incidence of VTE per pregnancy-year increases about 4-fold during pregnancy and at least 14-fold during the puerperium. Risk factors include a personal history of VTE, presence of inherited or acquired thrombophilia, a family history of VTE and general medical conditions, such as immobilisation, overweight, varicose veins, some haematological diseases and inflammatory disorders. VTE is considered potentially preventable with the prophylactic administration of anticoagulants, but there are no high quality randomized clinical trials that compared different strategies of thromboprophylaxis in pregnant women. Balancing the absolute risk of VTE against the risks of exposure to anticoagulants, this review provides advice regarding which women may benefit from thromboprophylaxis during and after pregnancy.     

Evaluation of a rapid qualitative immuno-chromatography D-dimer assay (Simplify D-dimer) for the exclusion of pulmonary embolism in symptomatic outpatients with a low and intermediate pretest probability. Comparison with two automated quantitative assays

The performance of a rapid qualitative solid-phase immuno-chromatography-based D-dimer assay (Simplify D-dimer) for diagnosing pulmonary embolism (PE) was evaluated in 469 outpatients with a low or intermediate pretest probability. They were referred to the emergency department of a university hospital during a 4-month period. Test results were compared to those of two automated quantitative assays. Simplify D-dimer assay result was positive in all 47 patients in whom the diagnosis of PE was retained and in 219 of the 422 patients without PE (51.2%), leading to a sensitivity of 100% (95%CI, 92.5 to 100%), a specificity of 48.8% (95%CI, 44.0 to 53.6%) and a negative predictive value (NPV) of 100% (95%CI, 98.2 to 100%). These results compared favorably with those of the Vidas D-dimer New assay [sensitivity = 100% (95%CI, 92.5 to 100), specificity = 49.8% (95%CI, 45.0 to 54.6%) and NPV = 100% (95%CI, 98.3 to 100%)] and the STA^®-Liatest^® D-DI assay [sensitivity = 100% (95%CI, 92.5 to 100%), specificity = 48.1% (95%CI, 43.3 to 52.9%) and NPV = 100% (95%CI, 98.2 to 100%)]. The inter-observer (n = 2) variability was very good with 1.7% discordant readings and a kappa coefficient (K) value = 0.97 (95%CI, 0.93 to 1.00). In conclusion, the Simplify D-dimer assay could be a valuable tool for ruling out PE in out-patients but a specific learning course of those having to work with is required in order to minimize the number of ambiguous reading and to overcome the inter-observer variability.     

Use of the Delphi method to facilitate antithrombotics prescription during pregnancy

Introduction

Management of pregnant women at risk for venous thromboembolism (VTE) remains complex. Guidelines do not definitively fix optimal strategies due to limited trial data. Our objective was to build an easy-to-use tool allowing individualised, risk-adapted prophylaxis.

Materials and Methods

A Delphi exercise was conducted to collect 19 French experts’ opinions on pregnancy-related VTE.

Results

Experts with an active interest in clinical research and care of VTE and placental vascular complications were selected. The risk score was classified by an anonymous computer vote. A scoring system for VTE risk in pregnant women was developed, each score being associated with a specific treatment: graduated elastic compression stockings, aspirin, prophylactic Low Molecular Weight Heparin (LMWH: variable durations), or adjusted-dose of LMWH through pregnancy and postpartum.

Conclusions

Our simple consensual scoring system offers an individual estimation of thrombosis risk during pregnancy together with its related therapeutic strategy, in accordance with most of the new international recommendations. The accuracy of our individual risk score-based therapeutic guidance is currently being prospectively evaluated in a multicenter trial (Clinicaltrials.gov registry no: NCT00745212).     

Prospective diagnostic accuracy assessment of the HemosIL HS D-dimer to exclude pulmonary embolism in emergency department patients

Introduction

Chest pain and shortness of breath are among the most common symptoms requiring immediate evaluation. Testing for pulmonary embolism (PE) has become easier and widespread due to D-dimer blood tests. Safe use of these tests is only possible if sensitivity is high and they are used in non-high probability patients. We evaluated diagnostic performance of the HemosIL HS D-dimer, which despite FDA approval in 2005, has been minimally reported in prospective standard clinical care.

Materials and methods

We used a prospective observational study design to follow patients in a single center with the HemosIL HS ordered for symptoms of possible PE with positive test result if > 243 ng/ml. The outcome was PE or deep venous thrombosis (DVT) at the time of presentation or subsequent 45 days determined by structured evaluation of imaging tests, phone, or medical record follow-up in all patients.

Results

529 patients received a D-dimer and 4.7% were ultimately diagnosed with PE or DVT. The sensitivity of the HemosIL HS was 96.0% (95% CI; 79.6 to 99.9%) specificity was 65.7% (95% CI; 61.4 to 69.8%) and likelihood ratio negative was 0.06 (95% CI; 0.01 to 0.42). The probability of PE in patients with a negative D-dimer was 1/332 or 0.3% (95% CI; 0.01% to 1.67%). The receiver operator curve had an area under the curve of 0.87 and supported the current cut-point as optimal.

Conclusions

The HemosIL HS D-dimer had high sensitivity, very low negative post-test probability and is useful in excluding PE in the acute care setting.     

Venous thromboembolism risk assessment and thromboprophylaxis among hospitalized acute medical patients in China - the RAMP study

Background

In developed countries, hospitalized patients with acute medical conditions are at significant risk for venous thromboembolism (VTE). Little is known about VTE risk and prophylaxis practices in China.

Objective

To determine the VTE risk and the frequency of recommended VTE prophylaxis in hospitalized Chinese patients with acute medical conditions.

Methods

Multi-center, cross-sectional, observational study. Eligibility criteria: ≥ 30 years, admitted to an intensive care unit (ICU)/coronary care unit (CCU) for acute medical illness, had ≥ 1 VTE risk factor/1 disease that predisposes to VTE, and provided informed consent. We used 2004 American College of Chest Physicians (ACCP) evidence-based consensus guidelines to assess VTE risk and the frequency of recommended VTE prophylaxis.

Results

1247 patients from 19 hospitals in 11 cities across 11 provinces of China were enrolled from July 2007 to June 2008. 57.3% patients had > 2 VTE risk factors. Only 20.2% received ACCP-recommended VTE prophylaxis (CCU patients: 22.7%, ICU patients: 16.9%, p = 0.0117).

Limitations

Excluding some patients with VTE risk factors did not allow assessment of the prevalence of VTE risk in the acute hospital-care setting. We could not determine whether the duration of prophylaxis complied with the ACCP recommendations. Our results may not be representative of hospitals in small cities/rural areas in China.

Conclusions

The prevalence of VTE risk factors in Chinese patients was similar to that in developed countries; however, only a small proportion of eligible patients received the recommended VTE prophylaxis. Our findings highlight the need for dissemination and implementation of appropriate VTE prophylaxis guidelines in China.     

Reversal of rivaroxaban-induced anticoagulation with prothrombin complex concentrate,activated prothrombin complex concentrate and recombinant activated factor VII in vitro

Introduction

Anticoagulation therapies carry a risk of bleeding; reversal agents may be beneficial in cases of severe bleeding even for anticoagulants with a relatively short half-life, such as the oral factor Xa inhibitor rivaroxaban.

Materials and Methods

We investigated the in vitro reversal effect of prothrombin complex concentrate (PCC; 0.2-1.0 U/mL), activated PCC (aPCC; 0.2–1.0 U/mL) and recombinant activated factor VII (rFVIIa; 5–50 μg/mL) on rivaroxaban-induced (200–1000 ng/mL) changes in prothrombin time (PT) and thrombin generation (TG) in plasma, and in thromboelastometry (clotting time [CT]) in whole blood from healthy subjects.

Results

All three agents were partially effective in reversing rivaroxaban-induced anticoagulation but showed different profiles. rFVIIa and aPCC were more effective than PCC in reversing prolongations of PT, CT and TG lag time; rFVIIa was more effective than aPCC. However, the reversal effect reached a plateau with a maximal effect of approximately 50%. Inhibition of maximum thrombin concentration was slightly reversed by these agents; aPCC was the most effective. In contrast, inhibition of endogenous thrombin potential (ETP) was strongly reversed by aPCC, with significant increases over baseline at low rivaroxaban concentrations. Compared with aPCC, PCC showed a similar but less effective reversal profile. rFVIIa reversed ETP inhibition by approximately 50%.

Conclusions

The extent of reversal by aPCC, PCC and rFVIIa was dependent on the parameter measured in rivaroxaban-anticoagulated plasma or blood. ETP measurements may have predictive power for assessing the reversal potential of PCC or aPCC and may be used to indicate an increased prothrombotic risk.     

Benefits and risks of oral anticoagulation for stroke prevention in nonvalvular atrial fibrillation

Nonvalvular atrial fibrillation is the most common clinically significant cardiac arrhythmia in the United States. It increases both the risk for and the severity of strokes and is associated with substantial morbidity, mortality, decreased quality of life, and related health care costs. Guidelines recommend anticoagulation therapy for the majority of patients with atrial fibrillation. Clinical trials have established that vitamin K antagonists are effective for stroke prevention for patients with atrial fibrillation for whom anticoagulation is recommended. However, vitamin K antagonists remain underutilized for a variety of reasons, including drug, physician, and patient factors. While vitamin K antagonists considerably reduce the risk of stroke, the absolute risk reduction varies according to individual patient risk factors. Accurately assessing each patient's true risk of stroke and bleeding is essential when determining which (if any) antithrombotic strategy should be used. Several stroke risk stratification schemes exist; of these, CHADS₂ is widely employed and simple. New, more sophisticated schemes may generate more precise risk estimates and better identify those patients for whom anticoagulant therapy offers a net clinical benefit. More studies are needed to determine the utility of bleeding risk stratification systems, as well as the role of surgical and interventional alternatives to anticoagulation treatment. Several novel oral anticoagulants are in (or have completed) phase 3 clinical trials. Dabigatran etexilate, approved in the United States in October 2010 for reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, now offers the first oral alternative to warfarin for patients with atrial fibrillation.     

Impact of thromboprophylaxis guidelines on clinical outcomes following total hip and total knee replacement

Background

The American College of Chest Physicians (ACCP) guidelines recommends thromboprophylaxis for total hip replacement (THR) and total knee replacement (TKR) patients. We examined alignment with ACCP thromboprophylaxis guidelines among THR/TKR patients, and compared symptomatic venous thromboembolism (VTE), bleeding event rates and risk factors for VTE between patients receiving ACCP-recommended thromboprophylaxis (‘ACCP’) and those who did not (‘non-ACCP’).

Methods

This retrospective observational study used a large US health plan claims database that was linked to an inpatient database containing detailed inpatient medication use and a database containing date-of-death information. Patients who had THR/TKR surgery between April 01, 2004 and December 31, 2006 were included. Comparisons of VTE and bleeding events between ACCP and non-ACCP patients were analyzed using chi-squared tests and multivariate logistic regression.

Results

Of 3,497 linked patients, 1,395 (40%) received ACCP recommended thromboprophylaxis. Of the patients who received non-ACCP recommended prophylaxis the majority (81%) received shorter than the recommended minimum 10 day prophylaxis and 118 (5.6%) of patients received no prophylaxis. Overall, non-ACCP patients were almost twice as likely to experience an incident DVT (3.76% versus 2.01%, p = 0.003) and more than eight times as likely to experience an incident PE (1.19% versus 0.14%, p = 0.001) relative to ACCP patients; there were no statistically significant difference in bleeding rates. Multivariate logistic regression indicated that the odds of a VTE event were significantly lower for ACCP patients (DVT: OR = 0.54; p = 0.006; PE: OR = 0.12; p = 0.004).

Conclusions

This study offers a unique perspective on ‘real-world’ thromboprophylaxis patterns and associated outcomes in THR and TKR patients in the US. It suggests that only 40% of THR/TKR patients receive ACCP-recommended thromboprophylaxis and that not receiving ACCP thromboprophylaxis is an independent risk factor for both DVT and PE.     

Out of hospital anticoagulant therapy in patients with acute pulmonary embolism is frequently practised but not perfect

Introduction

Traditionally, patients with pulmonary embolism (PE) are treated in-hospital until they reach an adequate international normalized ratio (INR). Analogous to patients with a deep venous thrombosis, therapy with low-molecular-weight heparin facilitates out of hospital treatment of PE. We retrospectively analysed the current practice of early anticoagulant therapy in 86 acute PE patients with emphasis on the occurrence and safety of outpatient treatment.

Methods

Data were collected from two large regional teaching hospitals and from a specialized anticoagulation clinical, where patients were followed in the period after hospital discharge. The course of hospitalization and LMWH transitioning therapy and the quality of treatment in the first three months after diagnosis were compared between patients discharged before and patients discharged after reaching adequate INR.

Results

Forty-four patients (51.2%) were discharged early, before reaching an adequate INR, and 42 patients (48.8%) were discharged after reaching adequate INR. Early discharged patients needed more time to reach adequate INR compared to other patients (13 versus 6 days). In 28 patients (32.6%), the LMWH transitioning therapy was stopped prematurely; 21 patients were from the early discharged group. During the first 3 months, the mean individual times below, in and above the INR range were equal between the two groups.

Conclusion

Enhanced compliance to existing guidelines and tools, and further development of guidelines, with focus on intensification of monitoring of INR values in an outpatient setting and preventing premature discontinuation of transitioning therapy, are warranted for a safe and early discharge of stable patients with PE.     

Anticoagulation in children

Neonates and children are receiving anticoagulation therapy much more frequently now than at any time in the past. There are a multitude of factors which contribute to this trend and they are well described elsewhere. The majority of recent reviews of anticoagulation therapy in children have focussed, not inappropriately, on the specific anticoagulant agents used, and our lack of knowledge about their basic pharmacokinetics, pharmacodynamics, and impact on commonly used monitoring tests. This review will address some of the difficulties of anticoagulation in children from the other perspective, considering specific patient populations such as neonates and adolescents, and also specific clinical situations which increase the complexity of anticoagulation such as in children with cancer, or children who need invasive procedures. There remains just as much research required into how best to manage these populations and circumstances as is required to understand the basic mechanisms of anticoagulant interactions with paediatric plasma.     

Performance of the Wells score in patients with suspected pulmonary embolism during hospitalization: A delayed-type cross sectional study in a community hospital

Introduction

The role of the Wells score for patients who develop signs and symptoms of pulmonary embolism (PE) during hospitalization has not been sufficiently validated. The aim of this study is to evaluate the performance of the Wells score for inpatients with suspected PE and to evaluate the prevalence of pulmonary embolism.

Materials and Methods

We conducted a cross sectional study nested in the prospective Institutional Registry of Thromboembolic Disease at Hospital Italiano de Buenos Aires from June 2006 to March 2011. We included patients who developed symptoms of pulmonary embolism during hospitalization. Patients were stratified based on the Wells score as PE likely (> 4 points) or PE unlikely (≤ 4 points). The presence of pulmonary embolism was defined by pre-specified criteria.

Results

Six hundred and thirteen patients met the inclusion criteria, with an overall prevalence of PE of 36%. Two hundred and nineteen (34%) were classified as PE likely and 394 (66%) as PE unlikely with a prevalence of PE of 66% and 20%, respectively. The Wells score showed a sensitivity of 65 (95% CI 59-72), specificity 81 (95% CI 77-85), positive predictive value 66 (95% CI 60-72) and negative predictive value 80 (95% CI 77-84).

Conclusions

The Wells Score is accurate to predict the probability of PE in hospitalized patients and this population had a higher prevalence of PE than other cohorts. However, the score is not sufficiently predictive to rule out a potentially fatal disorder.     

Underestimation of unfractionated heparin therapy assessment due to platelet activation when using partial-draw (pediatric) citrate collection tubes

The “so-called” pediatric tubes are often used when collecting smaller blood volume is necessary, particularly in pediatric patients or in case of difficult/recurrent sampling. The aim of this multicenter study was to compare coagulation test results evaluated in evacuated polymer tubes containing 0.109 M citrate (1 vol./9 vol.) specifically designed to allow either a partial (2.0 mL,“pediatric”) or a total (3.5 mL) filling. No significantly relevant discrepancy was found between routine coagulation test results in both tubes collected from untreated patients and from patients on vitamin K antagonist or low molecular weight heparin. In contrast, aPTT was significantly shorter and anti-FXa activity was significantly lower in partial-draw than in full-draw tubes collected from 46 patients receiving unfractionated heparin (UFH). This discrepancy was likely related to increased platelet activation in partial-draw tubes, as suggested by higher platelet factor 4 plasma concentrations and platelet P-Selectin expression in partial-draw than in full-draw citrate tubes. To confirm this hypothesis, we then evaluated partial-draw tubes containing CTAD, a mixture of anticoagulant and antiplatelet agents. In 25 patients on UFH, aPTT and anti-FXa activity were not significantly different in partial-draw CTAD tubes and in full-draw citrate tubes. In conclusion, despite increased platelet activation, samples collected into partial-draw citrate tubes allow accurate routine coagulation testing in all patients but those requiring UFH assessment, in which their use could lead to significant underestimation of anticoagulation. In such cases, partial-draw tubes containing CTAD could be validly used to monitor heparin therapy as well as to perform routine coagulation testing.