神经重症患者静脉血栓栓塞的发生率、危险因素及住院结局分析

目的 探讨神经重症患者静脉血栓栓塞(venous thromboembolism,VTE)的发生率,并分析VTE相关的危险因素及其对住院结局的影响.方法 基于电子病历系统数据回顾性分析2019年10月-2020年9月首都医科大学附属北京天坛医院的神经重症患者,根据患者住ICU期间是否发生VTE分为VTE组和无VTE组,...     

Incidence and risk factors associated with in-hospital venous thromboembolism after aneurysmal subarachnoid hemorrhage

Our purpose was to determine the incidence and risk factors associated with in-hospital venous thromboembolism (VTE) in patients with aneurysmal subarachnoid hemorrhage (aSAH). The Nationwide Inpatient Sample database was queried from 2002 to 2010 for hospital admissions for subarachnoid hemorrhage or intracerebral hemorrhage and either aneurysm clipping or coiling. Exclusion criteria were age <18, arteriovenous malformation/fistula diagnosis or repair, or radiosurgery. Primary outcome was VTE (deep vein thrombosis [DVT] or pulmonary embolus [PE]). Multivariate logistic regression was used to assess association between risk factors and VTE. Secondary outcomes were in-hospital mortality, discharge disposition, length of stay and hospital charges. A total of 15,968 hospital admissions were included. Overall rates of VTE (DVT or PE), DVT, and PE were 4.4%, 3.5%, and 1.2%, respectively. On multivariate analysis, the following factors were associated with increased VTE risk: increasing age, black race, male sex, teaching hospital, congestive heart failure, coagulopathy, neurologic disorders, paralysis, fluid and electrolyte disorders, obesity, and weight loss. Patients that underwent clipping versus coiling had similar VTE rates. VTE was associated with pulmonary/cardiac complication (odds ratio [OR] 2.8), infectious complication (OR 2.8), ventriculostomy (OR 1.8), and vasospasm (OR 1.3). Patients with VTE experienced increased non-routine discharge (OR 3.3), and had nearly double the mean length of stay (p < 0.001) and total inflation-adjusted hospital charges (p < 0.001). To our knowledge, this is the largest study evaluating the incidence and risk factors associated with the development of VTE after aSAH. The presence of one or more of these factors may necessitate more aggressive VTE prophylaxis.     

Population-based epidemiology of postoperative venous thromboembolism in Taiwanese patients receiving hip or knee arthroplasty without pharmacological thromboprophylaxis

Introduction

Population-based evaluation on the incidence of postoperative venous thromboembolism (VTE) has not yet been reported for Asians receiving arthroplasty. In Taiwan, thromboprophylaxis was not commonly applied for patients. The population-based cohort study aimed to investigate the epidemiology, and to determine the risk factors VTE for patients receiving hip or knee replacement without pharmacological thromboprophylaxis in Taiwan.

Materials and Methods

We retrospectively acquired patients’ data from National Health Insurance databases representing more than 99% of about 23 million Taiwanese citizens. The primary outcome was the incidence of composite symptomatic VTE within 28 days after receiving hip or knee replacement surgery.

Results

During 2002 to 2006, there were 114,026 patients undergoing hip (n = 61,460) or knee (n = 52,566) replacement surgery. The occurrence rate of overall postoperative VTE was 0.44%. The incidence of pulmonary embolism was four in 10,000 patients receiving hip replacement or seven in 10,000 individuals undergoing knee replacement. The weekly cumulative incidence of VTE was persistently rising up to 28 days after surgery. Dramatic increase in risk of post-surgical VTE was associated with prior disease history of PE (p < 0.001 for hip replacement, p = 0.01 for knee replacement) or DVT (p = 0.004 for hip replacement, p < 0.001 for knee replacement). Prior claim of congestive heart failure was an independent risk factor associated with patients receiving knee arthroplasty (p = 0.01).

Conclusion

Life-threatening PE occurred and increased cumulatively up to 28 days after hip or knee arthroplasty in Asians. Proper prophylaxis for patients with the exposure of high risks needs to be scrutinized.     

Efficacy and Safety of Prolonged Thromboprophylaxis with a Low Molecular Weight Heparin (Dalteparin) after Total Hip Arthroplasty- The Danish Prolonged Prophylaxis (DaPP) Study

The aim of this study was to compare the efficacy and safety of prolonged (35 days) thromboprophylaxis with a standard length (7 days) regimen of a low molecular weight heparin in patients undergoing total hip arthroplasty. The study was multicentre, randomised, double-blind, and prospective with two groups. Following seven days on a standard length regimen of dalteparin (5000 antifactor Xa units subcutaneously once daily starting 12 h before surgery), patients were randomized to continue the prophylaxis with either subcutaneous injections of dalteparin or placebo injections for a further 28 days. Efficacy was evaluated at the end of the study (day 35) in all patients with bilateral ascending phlebography to detect deep vein thrombosis. Bleeding complications and other adverse events were registered throughout the study period. Three hundred consecutive patients agreed to participate before the operation: 281 were finally randomised and 215 completed the study; two patients died before randomisation; 17 developed deep vein thrombosis; none developed pulmonary embolism; and five of 113 patients (4.4%, 95% CI 1–10%) developed deep vein thrombosis in the dalteparin group, compared with 12 of 102 (11.8%; 95% CI 6–20%) in the placebo group . Deep vein thrombosis in the proximal veins was diagnosed in one patient (0.9%; 95% CI 0–5%) in the dalteparin group, and in five (5.0%; 95% CI 2-11%) in the placebo group . Major bleeding was observed in one patient in the placebo group; minor bleeding complications and adverse events were equally distributed between the groups. We concluded that prolonged (35 days) thromboprophylaxis with dalteparin is more effective than a standard length (7 days) regimen without increased risk of bleeding complications or other adverse events.     

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.     

Is progestin an independent risk factor for incident venous thromboembolism? A population-based case-control study

Introduction

Because the risk of venous thromboembolism (VTE) associated with progestin is uncertain, we tested oral contraceptives, estrogen and progestin as independent VTE risk factors.

Materials and Methods

Using longitudinal, population-based Rochester Epidemiology Project resources, we identified all Olmsted County, MN women with objectively-diagnosed incident VTE over the 13-year period, 1988-2000 (n = 726) and one to two Olmsted County women per case matched on age, event year and duration of prior medical history (n = 830), and reviewed their complete medical history in the community for previously-identified VTE risk factors (i.e., hospitalization with or without surgery, nursing home confinement, trauma/fracture, leg paresis, active cancer, varicose veins and pregnancy/postpartum), and oral contraceptive, oral estrogen, and oral or injectable progestin exposure. Using conditional logistic regression we tested these hormone exposures as VTE risk factors, both unadjusted and after adjusting for previously-identified VTE risk factors.

Results

In unadjusted models, oral contraceptives, progestin alone, and estrogen plus progestin were significantly associated with VTE. Individually adjusting for body mass index (BMI) and previously-identified VTE risk factors, these effects remained essentially unchanged except that progestin alone was not associated with VTE after adjusting for active cancer. Considering only case-control pairs without active cancer, progestin alone was positively but non-significantly associated with VTE (OR = 2.49; p = 0.16). Adjusting for BMI and previously-identified VTE risk factors including active cancer, oral contraceptives, estrogen alone, and progestin with or without estrogen were significantly associated with VTE.

Conclusions

Oral contraceptives, estrogen alone, estrogen plus progestin, and progestin with or without estrogen are independent VTE risk factors.     

Venous thromboembolism in patients with pancreatic adenocarcinoma: lower incidence in Asian ethnicity

BACKGROUND: Pancreatic adenocarcinoma is one of the cancers most frequently associated with venous thromboembolism (VTE), with the varying incidences of 10%-20% reported in Western countries. Asians are known to have a lower risk for VTE than Caucasians, but few studies have been conducted regarding the incidence of VTE in Asian cancer patients. MATERIALS AND METHODS: Incidence of radiologically confirmed VTE was assessed by review of medical records of all patients histologically diagnosed with advanced pancreatic adenocarcinoma, with follow-up conducted at a regional teaching hospital from Jun 2003 to Dec 2005. RESULTS: Seventy five patients with advanced pancreatic adenocarcinoma were identified for evaluation (M:F=44:31, locally advanced:metastatic=25:50, median age:67 years). Four patients (5.3%) developed VTE during median follow-up period of 124 days. Three of four patients had metastatic disease and were receiving chemotherapy when VTE developed. The mean time from cancer diagnosis to the detection of VTE was 160 days. No episodes of peripheral arterial thrombosis were detected, but three multiple cerebral infarctions occurred, which proved fatal in all three. Median survival time was shorter in patients with VTE than those without, but the difference was not statistically significant (4.3 vs 6.6 months). CONCLUSION: The incidence of VTE complications in Korean patients with advanced pancreatic cancer was 5.3%, which is lower than that observed in other ethnic groups. Our study warrants further prospective investigations on the incidence and mechanism of VTE and cerebral infarctions in cancer patients of different ethnic groups.     

低分子肝素预防脑出血后深静脉血栓有效性和安全性研究

目的 评估自发性脑出血（spontaneous intracerebral hemorrhage,sICH）患者早期皮下注射低分子肝素 （low molecular weight heparin,LMWH）预防深静脉血栓形成（deep vein thrombosis,DVT）的有效性。 方法 共104例急性sICH患者纳入研究,其中LMWH组51例,对照组53例。LMWH组在入院后第4天开始, 连续7 d皮下注射低分子肝素0.4 ml/d;对照组相对应给予下肢间断充气加压（intermittent pneumatic compression,IPC）措施。两组患者均于入院当天及LMWH治疗第7天检测溶血磷脂酸（lysophosphatidic acid,LPA）水平及抗凝血因子Ⅹa活性,并观察患者有无出血征象。 结果 治疗期间所有患者均未出现颅内血肿扩大及再出血事件,与对照组比较,治疗后LMWH组LPA 水平（11.74±5.30）ng/ml明显低于对照组（26.81±5.12）ng/ml,比较差异具有统计学意义（P＜0.05）。 治疗后LMWH组抗凝血因子Xa活性（25.96±7.97）ng/ml明显较对照组（8.06±1.32）ng/ml增高,比较 差异具有统计学意义（P＜0.05）。 结论 急性sICH住院患者为DVT的高发人群,sICH患者在急性期皮下注射低剂量LMWH预防DVT是有效 和安全的。     

Efficacy of low- molecular- weight- heparin versus vitamin K antagonists for long term treatment of cancer-associated venous thromboembolism in adults: a systematic review of randomized controlled trials

Background

Patients with malignancy have a 4-fold increase in the risk of developing a venous thrombosis and a 3-fold increase in risk of bleeding. Both low-molecular-weight-heparin (LMWH) and vitamin K antagonists (VKA) have been used for treatment of cancer-associated thrombosis. However, the best anticoagulation approach remains a matter of debate.

Objective

In adult patients with cancer and an acute venous thromboembolic event we sought to determine the rates of recurrent venous thromboembolism (VTE) and major hemorrhage when treated with prolonged LMWH therapy compared to vitamin-K antagonists.

Patients/Methods

A systematic literature search strategy was used to identify potential trials on MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and Medline in-process using an OVID interface. Risk assessment of bias of randomized controlled trials (RCTs) was performed according to the Cochrane Collaboration-Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome measure was symptomatic VTE recurrence rate during the anticoagulation period. Relative risk (RR) was used as the primary measurement with 95% confidence intervals (CIs). Pooled measurements were calculated using random –effects and fixed-effects model.

Results

Five articles met our inclusion criteria. All compared LMWH and VKA for secondary prevention of VTE. The pooled RR of VTE recurrence was 0.53 (95% CI: 0.36-0.76; p = 0.007). The pooled RR of major bleeding was 0.98 (95% CI: 0.49-1.93, p = 0.95). Minor bleeding events and all cause mortality were similar between the 2 intervention arms.

Conclusions

The results of our review suggest that the long term use of LMWH after the acute first week of treatment is superior to VKAs for secondary prevention of venous thromboembolism in adult patients with cancer.     

Factors associated with the timing of diagnosis of venous thromboembolism: results from the MASTER registry

INTRODUCTION: Signs and symptoms of venous thromboembolism (VTE) are non-specific and thus can make diagnosis difficult, even for an experienced clinician. We aimed to evaluate the timing of diagnosis of deep vein thrombosis (DVT) and pulmonary embolism (PE) in Italian hospitals and to identify individual and clinical predictors of timely or delayed diagnosis. MATERIAL AND METHODS: MASTER is a multicenter prospective registry of patients with acute DVT and PE. Information on clinical presentation and diagnostic methods, temporary and permanent risk factors, were captured by an electronic data network at the time of the index event. RESULTS: Data on 2047 patients (1024 males), 1505 with DVT and 542 with PE, were analysed. Delayed diagnosis (i.e. more than 10 days from onset of symptoms) was observed in 340 (22.6%) patients with DVT and in 88 (16.2%) with PE, respectively. In DVT patients, factors associated with earlier diagnosis were the presence of multiple signs or symptoms (p=0.014), the presence of pain (p=0.049), and previous venous thrombosis (p=0.016). Neither the presence of other known risk factors nor ongoing prophylaxis influenced the timing of diagnosis. In PE patients, only multiple signs or symptoms at presentation (p=0.014) and the presence of transient risk factors (p=0.001) were significantly associated with earlier diagnosis. CONCLUSIONS: Substantial delays occur when diagnosing both DVT and PE. The severity of presentation, but not patient risk profile are associated with earlier diagnosis, even in patients with signs or symptoms of PE.     

Unsolved issues in the treatment of pulmonary embolism

The three most controversial and unsolved issues in the treatment of pulmonary embolism (PE) are: (1) the role of thrombolysis, (2) the role of low molecular weight heparin and length of hospital stay, and (3) the optimal duration of anticoagulation. The trend is to use thrombolysis more frequently, to administer low molecular weight heparin and shorten the hospitalization duration in low-risk patients, and to give prolonged courses of anticoagulation with warfarin. PE thrombolysis appears most beneficial in patients at high risk of adverse clinical outcomes in whom the potential hazards of bleeding can be justified by the danger of conservative management with anticoagulation alone. With respect to utilizing low molecular weight heparin as a way of shortening the duration of hospitalization, there are no data to warrant this approach. The current FDA mandate for symptomatic PE patients is to administer intravenous unfractionated heparin administered as a bridge to therapeutic warfarin. Finally, the optimal duration of anticoagulation following acute PE remains mired in controversy. Despite the high rate of recurrent venous thrombosis after discontinuation of anticoagulation, there are currently insufficient data to recommend indefinite warfarin therapy.     

利伐沙班治疗脑卒中后急性肺栓塞的疗效观察

目的观察利伐沙班治疗脑卒中后高出血风险急性肺栓塞的疗效。方法选取脑卒中后高出血风险急性肺栓塞患者62例,随机分成2组。对照组31例给予低分子量肝素钠皮下注射和口服华法林序贯治疗,根据INR调整剂量;治疗组31例给予低分子量肝素钠皮下注射,口服利伐沙班10mg,1次/d。比较2组治疗前和治疗1、3、6个月后的血气分析、血氧饱和度(SaO_2)、呼吸困难VAS评分、圣乔治呼吸问卷评分和超声心动图检查,比较2组不良事件发生率。结果与治疗前比较,2组治疗后PaO_2、PaCO_2、SaO_2、RVEF水平均有所升高,呼吸困难VAS评分、圣乔治呼吸问卷评分、PASP、MPAP、RAP和PVR水平均有所降低,差异均有统计学意义(P0.05)。与对照组比较,治疗组治疗后3、6个月PaO_2、PaCO_2、SaO_2、RVEF水平较高,呼吸困难VAS评分、圣乔治呼吸问卷评分、PASP、MPAP、RAP、PVR水平较低,差异均有统计学意义(P0.05);2组不良事件发生率比较,差异无统计学意义(P0.05)。结论采用利伐沙班治疗脑卒中后高出血风险急性肺栓塞疗效满意,出血风险与常规抗凝相当。     

Venous thromboembolism during treatment with antipsychotics: Results of a drug surveillance programme

Objectives: Venous thromboembolism (VTE) can be a life-threatening medical condition that may lead to leg swelling, respiratory distress and death.

Methods: The AMSP (Arzneimittelsicherheit in der Psychiatrie) is a continuous multicentre drug surveillance programme that assesses severe adverse drug reactions during treatment of psychiatric inpatients. We report on a total of 264,422 inpatients who were treated with antipsychotics (APs) and monitored from 1993 to 2011 in 99 psychiatric hospitals.

Results: During this period VTE events were reported for 89 inpatients, corresponding to an occurrence rate of 34 cases per 100,000 inpatient admissions treated with APs or 43 cases per 10,000 person-years. The occurrence of VTE was greatest in patients over the age of 65 years of age with mood disorders. The chemical class of butyrophenones (48/100,000) followed by atypical APs (36/100,000) showed the highest occurrence rate for VTE compared to thioxanthenes (23/100,000), which were less associated with VTE. If imputed alone, pipamperone (61/100,000) and risperidone (55/100,000) were most frequently associated with VTE. In general, there was no difference in occurrence rate of VTE between high- and low-potency APs.

Conclusions: These results suggest that clinicians should consider AP drug exposure as a potential risk factor for VTE for patients older than 65 years. Additionally, the diagnosis of an affective disorder seems to increase the risk for VTE.     

Risk of Deep vein thrombosis in neurosurgery: State of the art on prophylaxis protocols and best clinical practices

ObjectiveTo analytically discuss some protocols in Deep vein thrombosis (DVT)/pulmonary Embolism (PE) prophylaxis currently use in Neurosurgical Departments around the world.Data sourcesAnalysis of the prophylaxis protocols in the English literature: An analytical and narrative review of literature concerning DVT prophylaxis protocols in Neurosurgery have been conducted by a PubMed search (back to 1978).Data extraction80 abstracts were reviewed, and 74 articles were extracted.Data analysisThe majority of DVT seems to develop within the first week after a neurosurgical procedure, and a linear correlation between the duration of surgery and DVT occurrence has been highlighted. The incidence of DVT seems greater for cranial (7.7%) than spinal procedures (1.5%). Although intermittent pneumatic compression (IPC) devices provided adequate reduction of DVT/PE in some cranial and combined cranial/spinal series, low-dose subcutaneous unfractionated heparin (UFH) or low molecular-weight heparin (LMWH) further reduced the incidence, not always of DVT, but of PE. Nevertheless, low-dose heparin-based prophylaxis in cranial and spinal series risks minor and major postoperative haemorrhages: 2–4% in cranial series, 3.4% minor and 3.4% major haemorrhages in combined cranial/spinal series, and a 0.7% incidence of major/minor haemorrhages in spinal series.ConclusionThis analysis showed that currently most of the articles are represented by case series and case reports. As long as clear guidelines will not be defined and universally applied to this diverse group of patients, any prophylaxis for DVT and PE should be tailored to the individual patient with cautious assessment of benefits versus risks.     

Adjuvant therapy with bemiparin in patients with limited-stage small cell lung cancer: Results from the ABEL study

Introduction

The haemostatic system plays an important role in the process of cancer development and spread. Anticoagulants, mainly low molecular weight heparins, could prolong survival in cancer patients, particularly in patients with lung cancer, beyond prevention of thromboembolic events.

Methods

In a multicenter, investigator-initiated, open-label, randomized, sequential study, 38 patients with newly-diagnosed, limited-stage small-cell lung cancer were randomized to receive standard chemoradiotherapy or the same therapy plus 3,500 IU daily of bemiparin for a maximum of 26 weeks. The primary outcome was progression-free survival.

Results

The study was terminated early due to slow recruitment. Median progression-free survival was 272 days with chemoradiotherapy alone and 410 days in the bemiparin group; hazard ratio, 2.58 (95% confidence interval [CI], 1.15-5.80); p = 0.022. Median overall survival was 345 days with chemoradiotherapy alone and 1133 days in the bemiparin group; hazard ratio, 2.96 (95% CI, 1.22-7.21); p = 0.017. The rate of tumor response was similar in both study arms. There was no significant between-group difference in the rates of major bleeding. Toxicity related with the experimental treatment was minimal.

Conclusion

The addition of bemiparin to first line therapy with chemoradiotherapy significantly increases survival in patients with newly-diagnosed, limited-stage small-cell lung cancer. (Funded by the Instituto Científico y Tecnológico, University of Navarra. ClinicalTrials.gov identifier: NCT00324558).     

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.     

Safety assessment of new antithrombotic agents: lessons from the EXTEND study on ximelagatran

BACKGROUND: Ximelagatran, the first oral direct thrombin inhibitor, was shown to be an effective antithrombotic agent but was associated with potential liver toxicity after prolonged administration. OBJECTIVES AND METHODS: The aim of the EXTEND study was to assess safety and efficacy of extended administration (35 days) of ximelagatran or enoxaparin for the prevention of venous thromboembolism after elective hip replacement and hip fracture surgery. A follow-up period, including assessment of liver enzymes (in particular alanine aminotransferase; ALAT), until post-operative day 180 was planned, with visits at days 56 and 180. RESULTS: Randomization and administration of study drugs were stopped following a report of serious liver injury occurring 3 weeks after completion of ximelagatran treatment. At the time of study termination, 1158 patients had been randomized and 641 had completed the 35-day treatment; with 303 ximelagatran and 265 enoxaparin patients remaining in the study through to the day 56 follow-up visit. Overall, 58 patients showed an ALAT increase to >2x upper limit of normal: 31 treated with enoxaparin, 27 with ximelagatran. Three ximelagatran patients also showed symptoms potentially related to liver toxicity. Eleven ximelagatran patients showed an ALAT increase after study treatment ended. The clinical development of ximelagatran was terminated and the drug withdrawn from the market. Evaluation of the relative efficacy of the two treatments as specified in the protocol was impossible due to the premature termination of the study. CONCLUSIONS: Prolonged administration of ximelagatran was associated with an increased risk of liver toxicity. In a substantial proportion of patients, ALAT increase occurred after treatment withdrawal. The findings seen with ximelagatran should be considered when designing studies with new antithrombotic agents.     

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.     

Changes in D-dimer levels after cesarean section in women with singleton and twin pregnancies

Objective

To determine how the D-dimer level changes after cesarean section, a topic that has not been studied extensively.

Methods

The D-dimer level (μg/mL) was measured in 792 and 119 women with singleton and twin pregnancies, respectively, on the day or one day before cesarean section and on postpartum days 1, 3, and 7. None of the women developed venous thromboembolism with clinical symptoms. The data for other two women who underwent a cesarean section and developed pulmonary thromboembolism on postpartum days 0 to 1 were also presented.

Results

The preoperative D-dimer level (median, μg/mL) of 2.4 increased on postpartum day 1 to 6.0, then decreased to 2.8 on postpartum day 3, and again increased to 4.5 on postpartum day 7 in the singleton pregnancies. A similar pattern, but with slightly higher values, was seen in the twin pregnancies. The 95 percentile value of D-dimer for singleton and twin pregnancies was 6.9 and 10.5 on days – 1/0, 19.7 and 25.7 on day 1, 9.7 and 13.5 on day 3, and 15.7 and 17.7 on day 7, respectively. The D-dimer level after pulmonary thromboembolism was greater than the 99 percentile value and the 98 percentile value in the two women, respectively.

Conclusion

Our data regarding the D-dimer level may be helpful when considering the normal range of D-dimer for postpartum women with cesarean delivery.