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.     

Thromboprophylaxis use and concordance with guidelines among medical and surgical patients in Morocco

Introduction

No data are available on thromboprophylaxis use in Morocco. Our aim was to characterize patients at risk of venous thromboembolism and assess the rate of appropriate thromboprophylaxis.

Materials and Methods

This was a national, observational, multicentre survey of venous thromboembolism risk and thromboprophylaxis use in hospitalized patients. Data were collected on a predefined date in three university hospitals in Morocco using a standardized pre-printed form. Thromboembolic risk was assessed according to the American College of Chest Physicians (ACCP) 2008 guidelines. Patients were classified as “thromboprophylaxis indicated” or “thromboprophylaxis not indicated”.

Results

784 patients were analysed: 307 (39.2%) medical and 477 (60.8%) surgical. 421 (53.7%) were female. Medical patients were older than surgical patients (57.6 ± 11.5 vs. 46.2 ± 16.9 years, p < 0.0001) and were more likely to have risk factors for thromboembolism (50.5% vs. 45.7% of patients, p = NS). 57% of patients without contraindications or bleeding risk were at risk of thromboembolism according to ACCP guidelines and thromboprophylaxis was prescribed to 42.8% of these patients. In contrast, 7.4% of patients with no thromboembolic risk also received thromboprophylaxis (proportion agreement: 61.0%; Kappa = 0.296). Over half (54.5%) of medical patients at risk of thromboembolism did not receive thromboprophylaxis whereas 6.3% of those with no risk did receive it (proportion agreement: 76.4%; Kappa = 0.433). These figures were 57.9% and 9.2%, respectively, for surgical patients (proportion agreement: 52.7%; Kappa = 0.191). Thromboprophylaxis was given to 19.2% of patients with contraindications or a bleeding risk.

Conclusions

Educational initiatives are imperative to inform doctors about appropriate thromboprophylaxis.     

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.     

The interval between prothrombin time tests and the quality of oral anticoagulants treatment in patients with chronic atrial fibrillation

BACKGROUND: The incidence of stroke in patients with atrial fibrillation (AF) can be significantly reduced with warfarin therapy especially if optimally controlled. OBJECTIVES: To evaluate the effect of the interval between consecutive prothrombin time measurements on the time in therapeutic range (INR 2-3) in a cohort of patients with AF on chronic warfarin treatment in the community. METHODS: All INR measurements available from a relatively large cohort of patients with chronic AF were reviewed and the mean interval between consecutive INR tests of each patient was correlated with the time in therapeutic range (TTR). RESULTS: Altogether 251,916 INR measurements performed in 4408 patients over a period of seven years were reviewed. Sixty percent of patients had their INR measured on average every 2 to 3 weeks and most others were followed at intervals of 4 weeks or longer. A small proportion (3.6%) had their INR measured on average every week. A significant decline in the time in therapeutic range was observed as the intervals between tests increased. At one to three weeks interval the TTR was 48%, at 4 weeks interval 45% and at 5 weeks 41% (P<0.0005). A five percent increment in TTR was observed if more tests were performed at multiplications of exactly 7 days (43% vs 48% P<0.0001). CONCLUSIONS: A better control with an increase in the TTR was observed in patients with atrial fibrillation if prothrombin time tests are performed at regular intervals of no longer than 3 weeks.     

Predictive blood coagulation markers for early diagnosis of venous thromboembolism after total knee joint replacement

Pulmonary embolism development may be prevented if asymptomatic venous thromboembolism (VTE) can be predicted and treated preoperatively or soon after total knee arthroplasty (TKA). The purpose of this study was to evaluate whether asymptomatic VTE can be predicted by blood coagulation markers preoperatively or early after TKA. This prospective single-centre study enrolled 68 patients (6 men, 62 women; mean age: 71 years) who underwent TKA between September 2004 and August 2009. Sixteen-row multidetector computed tomography was performed 4 days before and after surgery for diagnosis of asymptomatic VTE. Blood samples were taken to measure the plasma levels of soluble fibrin monomer complex (SFMC), D-dimer and cross-linked fibrin degradation products by leukocyte elastase (e-XDP) at 4 days preoperatively, and at 1 hour, 1 day and 4 days postoperatively. The preoperative SFMC, D-dimer and e-XDP levels did not differ significantly between the thrombus (n = 36) and no-thrombus (n = 32) groups. D-dimer and e-XDP levels showed the most significant increases at days 4 and 1, respectively, after surgery in the thrombus group. With cut-off points of 7.5 μg/ml for D-dimer and 8.2 U/ml for e-XDP, the sensitivities were 75% and 75%, and the specificities were 63% and 59%, respectively. By multiple logistic regression analysis, D-dimer at day 4 and e-XDP at day 1 postoperatively were independent markers for early diagnosis of VTE (odds ratio = 1.61 and 1.19, P = 0.01 and 0.04, respectively). The postoperative occurrence of new asymptomatic VTE may be predicted by D-dimer at day 4 and e-XDP at day 1 after TKA.     

舒筋活络丸联合硫酸羟氯喹治疗类风湿性关节炎的临床研究

目的 探讨舒筋活络丸联合硫酸羟氯喹片治疗类风湿性关节炎的临床疗效。方法 选取2020年3月—2022年3月在聊城市第二人民医院诊治的90例类风湿性关节炎患者,依据用药区别分为对照组和治疗组,每组各45例。对照组口服硫酸羟氯喹片,0.1 g/次,4次/d;治疗组在对照组的基础上口服舒筋活络丸,2丸/次,2次/d。两组患者治疗4周。观察两组患者临床疗效,比较治疗前后两组患者症状改善时间,DAS-28评分、HAQ指数、VAS评分和HSS评分,及血清肽聚糖识别蛋白-1（PGLYRP-1）、抗环瓜氨酸多肽抗体（ACCP）、胰岛素样生长因子结合蛋白-6（IGFBP-6）、中粒细胞集落刺激因子（GM-CSF）、白细胞介素-17（IL-17）和金属蛋白酶-3（MMP-3）水平。结果 经治疗,治疗组有效率为97.78%,明显高于对照组（82.22%,P＜0.05）。经治疗,治疗组症状改善时间均早于对照组（P＜0.05）。经治疗,两组患者DAS-28评分、HAQ指数、VAS评分均明显降低,而HSS评分明显升高（P＜0.05）,且治疗组评分较对照组改善更明显（P＜0.05）。经治疗,两组患者血清PGLYRP-1、ACCP、IGFBP-6、GM-CSF、IL-17、MMP-3水平均明显下降（P＜0.05）,且治疗组患者比对照组降低更明显（P＜0.05）。结论 舒筋活络丸联合硫酸羟氯喹片治疗类风湿性关节炎可有效改善患者症状,减轻患者疼痛,促进细胞因子水平改善。     

血清ACCP在HCV感染并发冷球蛋白血症的诊断价值

目的探讨血清抗环瓜氨酸肽抗体(ACCP)在丙型肝炎病毒(HCV)感染并发冷球蛋白血症中的诊断价值。方法收集HCV感染患者20例、HCV感染伴冷球蛋白血症患者5例、混合型冷球蛋白血症(MC)患者5例和健康献血者20例,分别用酶联免疫吸附试验(ELISA)和比浊法测定其血清ACCP和类风湿因子(RF)水平。结果20例HCV感染患者,血清ACCP试验均为阴性,最大值为10U。其中9例(45%)RF>15U/ml,3例(15%)RF>50 U/ml,最高者RF为526 U/ml。HCV感染伴冷球蛋白血症患者5例中,3例(60%)血清ACCP试验为阳性,均值为47U;混合型冷球蛋白血症患者5例中,4例(80%)RF试验阳性,其中3例(60%)RF>50 U/ml,最大值为540 U/ml;1例(20%)冷球蛋白血症患者ACCP试验呈临界值阳性结果(25U)。20例健康献血者血清ACCP和RF试验均为阴性。结论ACCP检测有助于慢性HCV感染并发冷球蛋白血症患者的早期诊断。     

Incidence and time course of asymptomatic deep vein thrombosis with fondaparinux in patients undergoing total joint arthroplasty

Introduction

There are many reports concerning fondaparinux prophylaxis of asymptomatic deep vein thrombosis (DVT) after total hip arthroplasty (THA) or total knee arthroplasty (TKA), but little is known about the time course of aymptomatic DVT development during the administration of fondaparinux. The aim of the present study was to define the incidence and time course of aymptomatic DVT development during administration of fondaparinux, and to assess the efficacy of fondaparinux in resolving DVT.

Materials and Methods

We studied consecutive71 patients who underwent THA surgery, and 30 patients who underwent TKA surgery with fondaparinux prophylaxis. Patients received once-daily subcutaneous injections of 2.5 mg of fondaparinux for 14 days after surgery. DVT was diagnosed by ultrasonography, and it was scheduled on the day of surgery on day 1, day 4, and day 14 after surgery.

Results

In patients who received fondaparinux for 14 days after THA surgery, the incidence of DVT was 0% on the day of the surgery, 13.6% at day 1, 27.1% at day 4, and 11.9% at day 14. In patients who received fondaparinux for 14 days after TKA surgery, the incidence of DVT was 4.2% on the day after surgery, 50.0% at day 1, 58.3% at day 4, and 20.8% at day 14. The incidence of DVT after THA or TKA surgery at day 14 was significantly reduced compared to that at day 4.

Conclusion

The incidence of asymptomatic DVT up to day 4 was high, but with 14 days continued treatment of fondaparinux, the incidence of asymptomatic DVT occurring at postoperative day 4 was significantly reduced at day 14.