关节置换并发深静脉血栓形成因素分析及干预

通过对下肢深静脉血栓形成(DVT)因素环境、饮食、患肢情况、心理、病情观察、用药及静脉输液等方面进行观察,对患者提供有效的护理干预及康复指导,取得良好的效果,提高了患者的生活质量,为人工关节置换术后并发下肢深静脉血栓的护理提供了有效的方法。     

The potential biomarkers for thromboembolism detected by SELDI-TOF-MS

Introduction

Few studies were concerned about searching for specific biomarkers for thromboembolic (arterial and venous) diseases by the use of Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS).

Materials and Methods

We screened for potential biomarkers in 69 plasma samples, including samples from 20 patients with idiopathetic deep vein thrombosis (DVT), 20 patients with acute myocardial infarction (AMI), and 29 healthy controls without a history of thromboembolism. Pretreated plasma samples were analyzed on the Protein Biology System IIc plus SELDI-TOF-MS (Ciphergen Biosystems, Fremont, CA). Proteomic spectra of mass to charge ratio (m/z) were generated by the application of plasma to immobilized metal affinity capture (IMAC-3) ProteinChip arrays activated with copper.

Results

A pattern of three biomarkers (m/z: 2 667, 5 914, and 6 890 Da, respectively) with a total accuracy of 100% was selected based on their collective contribution to the optimal separation between patients with AMI and healthy controls. Another spattern consisting of only one biomarker (m/z: 5 914 Da) could totally discriminate patients with DVT and control subjects. For further analysis between patients with AMI and those with DVT, a pattern of four biomarkers (m/z: 3 418, 5 271, 33 378, and 68 125 Da, respectively) was selected with a total accuracy of 82.5%.

Conclusions

Plasma proteomic profiling with SELDI-TOF-MS and ProteinChip technologies provides high sensitivity and specificity in discriminating patients with thrombosis and healthy subjects. The discovered biomarkers might show great potential for early diagnosis of thromboembolic diseases.     

左旋咪唑对骨折创伤后红细胞生物学行为的影响

目的 通过探讨左旋咪唑(LMS)对骨折创伤后机体红细胞生物学行为的影响,为预防和治疗创伤后深静脉血栓的形成提供新的思路. 方法 选取30只成年健康雄性家兔随机分为两组(n=15):创伤对照组(A组)与创伤用药组(B组).麻醉后,两组家兔均于小转子下方3 cm截骨并用钢板螺钉固定,其中A组不予处理,B组于术前30 min按照24 mg/kg肌肉注射LMS.所有家兔均于术前30 min,术后30 min、1 d、4 d、7 d抽取血样,分别测定红细胞丙二醛含量;检测不同时间点红细胞Ⅰ型补体受体花环率(RC3bRR)、红细胞免疫复合物花环率(RICR)、自然肿瘤红细胞花环率(NTERR),以及血流变性、红细胞刚性指数、聚集指数、变形指数等. 结果 红细胞免疫在术后30 min、1 d、4 dRC3bRR、NTERR B组比A组同时相高,而RICR B组比A组同时相低,差异均有统计学意义(P<0.05);以上三项指标A组术后较术前差异有统计学意义(P<0.05),B组术后较术前差异无统计学意义(P>0.05).红细胞脂质过氧化在术后30 min、1 d、4 d红细胞中丙二醛均比术前高,同时B组比A组同时相低,差异均有统计学意义(P<0.05);A组术后较术前差异有统计学意义(P<0.05),B组术后较术前差异无统计学意义(P>0.05). 结论 创伤能引起机体红细胞免疫功能降低,脂质过氧化增强,流变性变差;LMS可以明显改善创伤后红细胞生物学行为,即可能对于降低骨折创伤后深静脉血栓的形成提供新的思路.     

Evidence of Thromboembolism Prophylaxis in Bariatric Surgery—Results of a Quality Assurance Trial in Bariatric Surgery in Germany from 2005 to 2007 and Review of the Literature

Background  Since January 1st, 2005, the current situation for bariatric surgery has been examined by means of a voluntary quality assurance study in Germany with a multicenter design in which 38 hospitals and surgical departments participated. The data are registered in cooperation with the Institute of Quality Assurance in Surgery at the Otto-von-Guericke University of Magdeburg (Germany). Methods  Data describing peri-interventional characteristics were prospectively documented in an internet online data registry. All primary bariatric procedures performed since January 1st, 2005, were registered. In addition, reoperations in patients who had previously undergone primary surgical intervention were included. As a representative excerpt from the overall prospective multicenter observational study on obesity surgery, data on the type, regimen, and time course of deep venous thrombosis (DVT) prophylaxis were documented. From the number and spectrum of complications, the incidences of clinically manifest DVT or pulmonary embolism (PE) were derived during the in-hospital course and follow-up in conjunction with the type of surgical procedure and body mass index (BMI). Results  Overall, 3,122 bariatric procedures were performed at 38 German hospitals between January 2005 and December 2007. These procedures were subdivided into 2,869 primary operations and 253 revisions (sex ratio, male to female = 25.6:74.4%). The average BMI of all patients was 48.5 kg/m2 in 2005, 48.4 kg/m2 in 2006, and 48.0 kg/m2 in 2007. In 2005 and 2006, gastric banding (GB) was the most commonly performed operation, followed by Roux-en-Y gastric bypass (RYGBP). In 2007, RYGBP was carried out in 42.1% of all bariatric procedures. Interestingly, the incidence of deep venous thrombosis (DVT) was only 0.06%, whereas PE occurred in 0.06% of patients only after hospital discharge. The DVT prophylaxis protocol used has been changed for the last 2 years: the majority of patients with a BMI above 50 kg/m2 received low-molecular-weight heparin twice a day. Conclusion  In Germany, a trend from GB to sleeve gastrectomy (SG) and malabsorptive approach has been evaluated. This trend is associated with differences of the DVT prophylaxis regimen in the profile of bariatric surgical patients depending on BMI and the type of bariatric procedure. Despite the low incidence of DVT and pulmonary embolism (PE) detected, there is a lack of evidence on a reasonable regimen for sufficient DVT prophylaxis in bariatric surgery; instead, there are only recommendations from the guidelines and statements of a specific medical society. Therefore, prospective studies are necessary to determine the optimal DVT prophylaxis for bariatric surgical patients as well as obese patients undergoing surgery.     

The treatment of venous thromboembolism in special populations

Anticoagulant therapy for the typical venous thromboembolism patient is straightforward with predictably favorable outcomes. However, for certain patients with venous thromboembolism, there remains uncertainty and controversy about optimal treatment. These controversial areas include venous thromboembolism patients with: heparin resistance, renal insufficiency, morbid obesity, cancer, antiphospholipid antibody syndrome, recurrent thrombosis despite appropriate anticoagulation, and patients with unprovoked VTE who may or may not benefit from thrombophilia testing. This review summarizes the current data for these special patient populations with venous thromboembolism and provides our recommendations for management.     

Monocytes and plasma tissue factor levels in normal individuals and patients with deep venous thrombosis of the lower limbs: potential diagnostic tools?

INTRODUCTION: Tissue factor (TF) is the main physiological initiator of blood coagulation; it is membrane-bound on monocytes (mTF) and free in plasma (pTF). Abnormal expression of TF by monocytes has been implicated in various diseases. We therefore quantified monocytes expressing TF and pTF levels in patients with lower-limb deep venous thrombosis (DVT). MATERIALS AND METHODS: DVT was confirmed by Duplex Scan. Blood mTF levels under resting condition (baseline), after incubation without (unstimulated) and with (stimulated) lipopolysaccharide (LPS), and total mTF levels were determined by flow cytometry using two analytical methods (Histogram and Quadrant-Statistics). Plasma TF levels were measured using an enzyme-linked immunoabsorbent assay (ELISA). Results were compared with age-matched controls. RESULTS: Histogram analysis in patients with DVT showed significantly elevated mTF levels for baseline, unstimulated and total mTF over controls. For Quadrant-Statistics, DVT patients also showed significantly raised baseline, unstimulated, stimulated and total mTF. Similarly, pTF levels were significantly raised in subjects with DVT compared to controls. Baseline mTF levels correlated with pTF levels by Histogram and Quadrant-Statistics analysis. Using the relative operating characteristic (ROC) curve, baseline mTF and pTF assays displayed sensitivity and specificity in detecting DVT. Quadrant-Statistics baseline mTF and pTF gave the best discrimination. CONCLUSIONS: The TF assays used in this study showed acceptable sensitivity and specificity and are cost-effective and practical. Therefore, they should be considered in patients with, or at risk of, DVT.     

Haplotype of thrombomodulin gene associated with plasma thrombomodulin level and deep vein thrombosis in the Japanese population

INTRODUCTION: Thrombomodulin (TM) is an essential cofactor in protein C activation by thrombin. Here, we evaluated the contribution of genetic variations in the TM gene to soluble TM (sTM) level and deep vein thrombosis (DVT) in Japanese. PATIENTS AND METHODS: We sequenced the TM putative promoter, exon, and 3'-untranslated region in DVT patients (n=118). Among 17 genetic variations we identified, two missense mutations (R385K, D468Y) and three common single nucleotide polymorphisms (-202G>A, 2487A>T, 2729A>C) were genotyped in a general population of 2247 subjects (1032 men and 1215 women) whose sTM levels were measured. We then compared the frequency of these mutations in DVT patients with that in the age, body mass index-adjusted population-based controls. RESULTS: We identified one neutral mutation (H381) and three missense mutations (R385K; n=2, A455V; n=53 heterozygous, n=14 homozygous, D468Y; n=2) of TM in the DVT patients. Age-adjusted mean values of sTM were lower in C-allele carriers of 2729A>C than in noncarriers in the Japanese general population (women: 16.7+/-0.3 U/ml vs. 17.9+/-0.2 U/ml, p<0.01, men: 19.4+/-0.3 U/ml vs. 20.4+/-0.3 U/ml, p=0.03). Additionally, the CC genotype of this mutation was more common in the male DVT patients than in the male individuals of the general population (odds ratio=2.76, 95% confidence interval=1.14-6.67; p=0.02). This mutation was in linkage disequilibrium (r-square>0.9) with A455V mutation. CONCLUSIONS: TM mutations, especially those with a haplotype consisting of 2729A>C and A455V missense mutation, affect sTM levels, and may be associated with DVT in Japanese.     

Sialic acid is an inflammation marker associated with a history of deep vein thrombosis

INTRODUCTION: Deep vein thrombosis (DVT) induces a systemic chronic inflammation and it has been associated with atherosclerosis. Increased levels of total sialic acid (TSA) have been shown to correlate with inflammation and atherosclerotic processes. The aim of this study was to investigate whether or not increased levels of TSA are associated with a history of DVT and with inflammation and coagulation markers, as well as with the lipid profile. MATERIALS AND METHODS: TSA, fibrinogen, C-reactive protein (CRP), fibrin D-dimer (D-dimer), prothrombin fragment 1+2 (F1+2), endogenous thrombin generation, cholesterol and triglycerides were measured in 68 patients who had suffered, in the previous 6-12 months, a first episode of idiopathic DVT, and in 68 age- and sex-matched healthy subjects. RESULTS: Levels of TSA, fibrinogen, CRP and D-dimer observed in patients were significantly higher than those detected in healthy subjects. TSA positively correlated with fibrinogen (R=0.47, p<0.01), cholesterol (R=0.46, p<0.01), triglycerides (R=0.38, p<0.01) and CRP (R=0.28, p<0.05). The logistic regression analysis confirmed that both high fibrinogen (> or =340 mg/dl) and cholesterol (> or =267 mg/dl) levels significantly and independently influence the TSA concentration. TSA levels above the 95th percentile of controls (>72 mg/dl) were detected in 33% of patients (OR=8.9; p<0.0001; 95% CI 2.4 to 31.7). CONCLUSIONS: Patients with a history of DVT had associated high levels of TSA. In these patients, TSA correlated to markers of inflammation activity and lipid profile. Thus, TSA appears to be a useful vascular inflammatory marker in idiopathic DVT.     

A prospective long-term study of 220 patients with a retrievable vena cava filter for secondary prevention of venous thromboembolism

BACKGROUND: The immediate and long-term clinical events associated with the placement and removal of a retrievable filter (ALN filter; ALN Implants Chirurgicaux; Ghisonaccia, France) remain largely unknown. METHODS: This was a prospective cohort study with an 18-month follow-up. All consecutive patients scheduled for placement of an ALN filter between April 1999 and June 2005 in the Radiology Department of our hospital were included. RESULTS: During the study period, placement of an ALN filter was indicated in 220 patients (mean age, 70.8 years), who were followed up for a median duration of 338.5 days (range, 1 to 561 days); 148 patients (67.3%) completed the 18-month follow-up. No patients were unavailable for follow-up. All patients had an acute or past venous thromboembolism. Main indications were recurrent venous thromboembolism despite adequate anticoagulation therapy (10.9%), transient bleeding event (21.8%), definitive contraindication for anticoagulant therapy (26.8%), or obligation to stop anticoagulant therapy due to major surgery, major trauma, or invasive procedure (37.7%). Filter insertion was successful in 98.6% of patients and resulted in an immediate complication in 11.8%. The median duration of filter implantation was 166 days (first to third quartiles, 34 to 478 days). Meanwhile, 17.0% (37 of 217 patients) had at least one venous thromboembolic event. Filter retrieval was attempted in 25.3% of patients after a median of 51 days (range, 6 to 352 days); removal was successful at the first attempt in 92.7% of patients. CONCLUSIONS: The filter could be easily inserted and successfully removed up to 1 year after insertion. Its safety and efficacy in preventing pulmonary embolism should be properly assessed in a randomized study.     

Thalidomide in the treatment of multiple myeloma

Thalidomide--either alone or in combination with dexamethasone or chemotherapy--has shown significant activity in relapsed/refractory disease. When used in the induction regimens in untreated patients, it significantly increases the response rates as well progression-free survival. Moreover, thalidomide as a maintenance therapy has become a very attractive option. However, the toxicity profile of the drug, mainly neurotoxicity and thrombotic events, mandate careful monitoring of patients treated with thalidomide, whether as the first line, in the relapsed setting, or as maintenance. In this chapter we will review the pharmacology, mechanisms of action, and toxicity of the drug, and will focus on available data from clinical experience and randomized trials of thalidomide in the different settings of multiple myeloma: refractory/relapsed disease, upfront treatment in patients who are eligible for high-dose therapy as well as those who are not, and finally the use of thalidomide as a maintenance treatment.