Long-Term Survival in a Large Cohort of Patients with Venous Thrombosis: Incidence and Predictors

Background

Venous thrombosis is a common disease with a high mortality rate shortly after the event. However, details on long-term mortality in these patients are lacking. The aim of this study was to determine long-term mortality in a large cohort of patients with venous thrombosis.

Methods and Findings

4,947 patients from the Multiple Environmental and Genetic Assessment study of risk factors for venous thrombosis (MEGA study) with a first nonfatal venous thrombosis or pulmonary embolism and 6,154 control individuals without venous thrombosis, aged 18 to 70 years, were followed up for 8 years. Death and causes of death were retrieved from the Dutch death registration. Standardized mortality ratios (SMRs) were calculated for patients compared with control individuals. Several subgroups were studied as well.736 participants (601 patients and 135 controls) died over a follow-up of 54,948 person-years. The overall mortality rate was 22.7 per 1,000 person-years (95% CI 21.0–24.6) for patients and 4.7 per 1,000 person-years (95% CI 4.0–5.6) for controls. Patients with venous thrombosis had a 4.0-fold (95% CI 3.7–4.3) increased risk of death compared with controls. The risk remained increased up to 8 years after the thrombotic event, even when no additional comorbidities were present. The highest risk of death was found for patients with additional malignancies (SMR 5.5, 95% CI 5.0–6.1). Main causes of death were diseases of the circulatory system, venous thrombosis, and malignancies. Main limitation was a maximum age of 70 at time of inclusion for the first event. Therefore results can not be generalized to those in the highest age categories.

Conclusions

Patients who experienced a first venous thrombosis had an increased risk of death which lasted up to 8 years after the event, even when no comorbidities were present at time of thrombosis. Future long-term clinical follow-up could be beneficial in these patients. Please see later in the article for the Editors'' Summary     

Factor V Leiden in patients with venous thrombosis in Slovak population

Resistance to activated protein C determined by factor V Leiden (FVL) is the most frequent inherited risk factor of venous thrombosis. The purpose of our work was to reveal the frequency of FVL in Slovak patients with venous thromboses, to characterise the nature of venous thromboses in this inherited thrombophilia, and to consider the screening approach to investigation of FVL in patients with venous thromboses. 350 patients with a diagnosis of venous thromboembolic disease from various regions of Slovakia were investigated. FVL, detected by polymerase chain reaction, was found in 128/350 (37%) patients with venous thromboses. 118/128 (92%) patients were heterozygous and 10/128 (8%) were homozygous carriers. In 108/128 (84%) patients with FVL the thromboembolic disease occurred spontaneously. Phlebothrombosis occurred predominantly in the lower limbs--117/128 (91%) patients, atypical localisations were rare. The first thromboembolic event was manifested before 40 years of age in 69% of patients. The family history was positive in 60/128 (47%) FVL carriers with thromboembolic disease. Recurrent thrombosis occurred in 30% of patients with FVL. In agreement with findings in other European countries, the prevalence of FVL was high in Slovak patients with thromboembolic disease. The investigation of FVL seems to be justified in patients before 40 years of age with venous thrombosis of lower limbs, in the absence of triggering factors and with a family history of venous thromboembolic disease.     

Duplex-Doppler ultrasonography in the detection of lower extremities deep venous thrombosis and in the detection of alternative findings

The diagnoses observed in patients referred for the Doppler ultrasonographic examination of peripheral and iliac veins for suspected deep venous thrombosis (DVT) are presented in this study. During 48 months 2,610 patients were examined by duplex Doppler ultrasonography (US). Among these, 1,879 were women (72%) and 731 men (28%), with the age-range 16-91 (mean 56, 2) years. Ultrasonic scanners Acuson 128 XP 10, ATL HDI 5000, GE Logiq 7, and GE Logiq 9 were used, with transducers in the frequency range from 2.5-14 MHz. Findings were categorized into four main categories: (1) deep venous thrombosis (DVT); (2) pathology predominantly related to superficial veins without DVT, (3) pathology of adjacent structures; (4) normal findings. 562 patients had DVT (21.5%). 1,108 patients (42.5%) had predominant pathology of superficial veins: postthrombotic syndrome, superficial thrombophlebitis and varicose veins. 390 patients (14.9%) had pathology of surrounding structures, unrelated to veins, the most common pathology being popliteal cysts and muscular hematomas. These lesions must be properly diagnosed by US to avoid erroneous anticoagulant treatment.     

Effect of acute and chronic hypernatremia on myoinositol and sorbitol concentration in rat brain and kidney

In animal models of hypernatremia, increases in brain electrolyte content account for the entire increase in osmolality in acute but not chronic hypernatremia, suggesting that there is generation of additional intracellular solutes ("idiogenic osmoles") in chronic hypernatremic states. In the present study, the concentration of the polyols myoinositol and sorbitol and water content were determined in the brain and kidneys of rats made acutely (2 hours) and chronically (72 hours) hypernatremic by intraperitoneal injection of NaCl and water restriction. Both the brain and the kidney responded to chronic hypernatremia with increased levels of myoinositol. Sorbitol levels increased in the kidney in response to both acute and chronic hypernatremia. Water content dropped in acute hypernatremia, but remained unchanged during chronic hyperosmolar challenge. We conclude that the polyols, myoinositol and sorbitol, may play a significant role in cellular osmoregulation in brain and kidney during chronic hypernatremia in the rat.     

Results of ultra-high streptokinase (Awelysin) doses in patients with thrombophlebitis

The results of 6-hour fibrinolysis with ultra-high streptokinase doses in 30 patients with peripheral venous thrombosis were presented. In 33.3% of the patients complete, and in 40% partial repatency was attained, while no repatency occurred in 20%. Deterioration was observed in two patients. The most beneficial effects were seen in postoperative and posttraumatic thrombosis. Bleeding complications did not occur. In one female patient treatment was discontinued due to bronchospasm.     

Deep venous thrombosis and occult malignancy: an epidemiological study.

OBJECTIVE--To determine the risk of subsequent cancer in patients with deep venous thrombosis confirmed by venography. DESIGN--Follow up of all patients who had venography for suspected deep venous thrombosis during 1984-88. Patients were traced through a cancer registry up to 1 January 1991. SUBJECTS--4399 patients who had phlebography in one hospital. SETTING--General hospital in Malmö, Sweden, serving a population of 230,000. MAIN OUTCOME MEASURE--Number of cancers recorded. RESULTS--4399 patients had venography for suspected deep venous thrombosis; 604 were known to have a malignancy at the time of venography and were excluded from further analysis. 1383 had deep venous thrombosis, 150 of whom subsequently developed cancer. 182 of the 2412 patients without thrombosis developed cancer. During the first six months after venography 66 patients with thrombosis developed malignancy compared with 37 patients without thrombosis (P < 0.0001). 38 of the cancers in the deep venous thrombosis group were detected by history, physical examination, and laboratory tests. Three patients had postoperative or post-traumatic deep venous thromboses. Only two of the remaining patients would have benefited from early detection by extensive screening. After six months the incidence of cancer was identical in patients with and without thrombosis. CONCLUSION--Deep venous thrombosis is associated with a significantly higher frequency of malignancy during the first six months after diagnosis. Malignancies can be found with simple clinical and diagnostic methods and extensive screening is not required.     

Diagnostic Accuracy in Venous Thrombosis

A group of 111 surgical patients at high risk of venous thrombosis were studied after operation by independent clinical assessment and with ¹²⁵I-fibrinogen to detect venous thrombosis. Almost half of the patients developed venous thrombosis. Of these, two-thirds were not suspected clinically despite careful scrutiny. In the patients in whom a clinical diagnosis of venous thrombosis was made this diagnosis was falsely positive in a quarter. More than half of all thrombotic episodes were detectable on the day after operation.The prevalence of venous thrombosis, together with the difficulty in diagnosing it, strongly supports the argument that a reduction in the incidence of pulmonary embolism must depend on widespread adoption of effective prophylaxis, especially in the large number of patients at high risk of venous thrombosis. Prophylactic trials must be objectively assessed, and it is in this field that the ¹²⁵I-fibrinogen technique probably has the most to offer.     

MiR-296-5p ameliorates deep venous thrombosis by inactivating S100A4

Deep venous thrombosis is one of the most common venous thromboembolic diseases and has a low cure rate and a high postoperative recurrence rate. Furthermore, emerging evidence indicates that microRNAs are involved in deep venous thrombosis. miR-296-5p is an important microRNA that plays a critical role in various cellular functions, and S100A4 is closely related to vascular function. miR-296-5p is downregulated in deep venous thrombosis patients, and its predicted target S100A4 is upregulated in deep venous thrombosis patients. Therefore, it was hypothesized that miR-296-5p may play a vital role in the development of deep venous thrombosis by targeting S100A4. An Ox-LDL-stimulated HUVEC and deep venous thrombosis mouse model was employed to detect the biological functions of miR-296-5p and S100A4. Dual luciferase reporter assays and pull-down assays were used to authenticate the interaction between miR-296-5p and S100A4. ELISA and Western blotting were employed to detect the protein levels of thrombosis-related factors and the endothelial-to-mesenchymal transition (EndMT)-related factors. The miR-296-5p levels were reduced, while the S100A4 levels were enhanced in deep venous thrombosis patients, and the miR-296-5p levels were negatively correlated with the S100A4 levels in deep venous thrombosis patients. miR-296-5p suppressed S100A4 expression by targeting the 3ʹ UTR of S100A4. MiR-296-5p knockdown accelerated ox-LDL-induced HUVEC apoptosis, oxidative stress, thrombosis-related factor expression, and EndMT, while S100A4 knockdown antagonized these effects in ox-LDL-induced HUVECs. S100A4 knockdown reversed the effect induced by miR-296-5p knockdown. Moreover, the in vivo studies revealed that miR-296-5p knockdown in deep venous thrombosis mice exacerbated deep venous thrombosis formation, whereas S100A4 knockdown had the opposite effect. These results indicate that elevated miR-296-5p inhibits deep venous thrombosis formation by inhibiting S100A4 expression. Both miR-296-5p and S100A4 may be potential diagnostic markers and therapeutic targets for deep venous thrombosis.     

Detection of non-ST-elevation myocardial infarction and unstable angina in the acute setting: meta-analysis of diagnostic performance of multi-detector computed tomographic angiography

Background

Post thrombotic syndrome (PTS) is a burdensome and costly complication of deep venous thrombosis (DVT) that develops in 20–40% of patients within 1–2 years after symptomatic DVT. Affected patients have chronic leg pain and swelling and may develop ulcers. Venous valve disruption from the thrombus itself or thrombus-associated mediators of inflammation is considered to be a key initiating event for the development of venous hypertension that often underlies PTS. As existing treatments for PTS are extremely limited, strategies that focus on preventing the development of PTS in patients with DVT are more likely to be effective and cost-effective in reducing its burden. Elastic compression stockings (ECS) could be helpful in preventing PTS; however, data on their effectiveness are scarce and conflicting.

Methods/Design

The SOX Trial is a randomized, allocation concealed, double-blind multicenter clinical trial. The objective of the study is to evaluate ECS to prevent PTS. A total of 800 patients with proximal DVT will be randomized to one of 2 treatment groups: ECS or placebo (inactive) stockings worn on the DVT-affected leg daily for 2 years. The primary outcome is the incidence of PTS during follow-up. Secondary outcomes are severity of PTS, venous thromboembolism (VTE) recurrence, death from VTE, quality of life and cost-effectiveness. Outcomes will be evaluated during 6 clinic visits and 2 telephone follow ups. At baseline, 1 and 6 months, blood samples will be obtained to evaluate the role of inflammatory mediators and genetic markers of thrombophilia in the development of PTS (Bio-SOX substudy).

Discussion

The SOX Trial will be the largest study and the first with a placebo control to evaluate the effectiveness of ECS to prevent PTS. It is designed to provide definitive data on the effects of ECS on the occurrence and severity of PTS, as well as DVT recurrence, cost-effectiveness and quality of life. This study will also prospectively evaluate the predictive role of biomarkers that are reflective of putative underlying pathophysiological mechanisms in the development of clinical PTS. As such, our results will impact directly on the care of patients with DVT.

Trial Registration

NCT00143598 and ISRCTN71334751     

急性右下肢深静脉血栓的临床治疗分析

目的:探讨右下肢深静脉血栓的临床治疗方法。方法:对我院2015年6月-2017年6月收治的63例右下肢深静脉血栓形成患者进行回顾性分析,从小腿周径差、彩超检查及造影3方面对疗效进行评价,并统计导管接触溶栓后患者复查肺部增强CT情况。结果:63例患者中,57例进行导管接触溶栓+下腔静脉滤器,6例进行导管接触溶栓+下腔静脉滤器+肺动脉碎栓、溶栓。治疗后,患者小腿周径差较治疗前明显降低,差异具有统计学意义(P0.05)。患者显效26例,有效28例,好转8例,无效1例,临床治愈率为85.7%。63例下腔静脉滤器,取出60例,3例留置为永久性滤器。新增肺栓塞12例,无致死性肺栓塞发生。结论:导管接触溶栓对右下肢深静脉血栓的治疗效果较好,但导管接溶栓时有较高肺栓塞发生率,应积极放置下腔静脉滤器。     

Genetic analysis of factor V Leiden in a family with history of thrombosis and venous leg ulcers

Inherited resistance to activated protein C has been recognized as a major risk factor for thrombosis. The factor V Leiden mutation, which is detectable by molecular DNA techniques, is responsible for 95% of cases of activated protein C resistance. In our study one patient with venous leg ulcers from a family with a history of thrombosis showed factor V Leiden mutation. Genotypic analysis demonstrated that the patient was homozygous for factor V Leiden. All family members of the index subject showed the same abnormalities. Two were homozygous and 3 were heterozygous for factor V Leiden mutation. The polymerase chain reaction was used to amplify exon 10 of the factor V gene, followed by enzymatic digestion with MnlI for mutation detection. Patients with a family history of thrombosis and factor V Leiden have an increased risk of venous leg ulcers. Screening for factor V Leiden may be indicated in patients with venous leg ulcers and their family members.     

Venous volume displacement plethysmography: Its diagnostic value in deep venous thrombosis as determined by receiver operator characteristic curves

The pitfall of several reviews of noninvasive venous assessment has been the expression of the test data solely in terms of diagnostic accuracy (the number of correct tests in ratio to all tests performed), where results of a test will vary according to disease prevalence. The advantages of receiver operator characteristic curve analysis are twofold: (1) it describes the dynamic relationship between sensitivity (the ratio of the number of true positive tests to the patients with deep venous thrombosis) and specificity (the ratio of true negative tests to the number of patients with no deep venous thrombosis) independent of disease prevalence; and (2) the threshold criteria that defines a positive test can be set by the best balance between sensitivity and specificity and then applied to a given patient population for its diagnostic accuracy. Venous volume plethysmography is a widely used, simple and rapid method. It was compared to the "gold standard" of phlebography in a prospective blind study of 70 limbs that were clinically suspect of having deep venous thrombosis (DVT). Venous volume displacement plethysmography was defined objectively by three quantitative parameters: (1) maximum venous outflow, (2) integer ratio, and (3) segmental venous capacitance ratio. The DVT (22 to 70 positive phlebograms) was divided by anatomic location into either calf vein DVT or proximal DVT (popliteal vein or above). By combining these three parameters, a balance between sensitivity and specificity was obtained to provide a rapid, objective method for screening patients with suspected DVT.     

Hypofibrinolysis and thrombophilia

The fibrinolytic capacity was assessed in 18 healthy subjects and in 8 patients each with non-idiopathic venous thrombosis, idiopathic venous thrombosis and myocardial infarction after intravenous administration of 1-deamino-8-D-arginine vasopressin (DDAVP) (0.4 microgram/kg) in comparison to venous occlusion. In healthy subjects the results obtained by either stimulus were approximately in agreement. Compared to the control group, in patients with non-idiopathic venous thrombosis the fibrinolytic capacity was not changed either after venous occlusion or after administration of DDAVP. In 5 out of 8 patients with idiopathic venous thrombosis the capacity was significantly reduced both after venous occlusion and after administration of DDAVP. In 4 out of 8 patients with myocardial infarction the capacity was significantly below the limit after administration of DDAVP while it was not after venous occlusion. In determining the fibrinolytic capacity DDAVP proved to be superior to venous occlusion.     

Risk Factors for Vascular Occlusive Events and Death Due to Bleeding in Trauma Patients; an Analysis of the CRASH-2 Cohort

Background

Vascular occlusive events can complicate recovery following trauma. We examined risk factors for venous and arterial vascular occlusive events in trauma patients and the extent to which the risk of vascular occlusive events varies with the severity of bleeding.

Methods and Findings

We conducted a cohort analysis using data from a large international, double-blind, randomised, placebo-controlled trial (The CRASH-2 trial) [1]. We studied the association between patient demographic and physiological parameters at hospital admission and the risk of vascular occlusive events. To assess the extent to which risk of vascular occlusive events varies with severity of bleeding, we constructed a prognostic model for the risk of death due to bleeding and assessed the relationship between risk of death due to bleeding and risk of vascular occlusive events. There were 20,127 trauma patients with outcome data including 204 (1.01%) patients with a venous event (pulmonary embolism or deep vein thrombosis) and 200 (0.99%) with an arterial event (myocardial infarction or stroke). There were 81 deaths due to vascular occlusive events. Increasing age, decreasing systolic blood pressure, increased respiratory rates, longer central capillary refill times, higher heart rates and lower Glasgow Coma Scores (all p<0.02) were strong risk factors for venous and arterial vascular occlusive events. Patients with more severe bleeding as assessed by predicted risk of haemorrhage death had a greatly increased risk for all types of vascular occlusive event (all p<0.001).

Conclusions

Patients with severe traumatic bleeding are at greatly increased risk of venous and arterial vascular occlusive events. Older age and blunt trauma are also risk factors for vascular occlusive events. Effective treatment of bleeding may reduce venous and arterial vascular occlusive complications in trauma patients.     

Deep venous thrombosis and pulmonary embolus after face lift: a study of incidence and prophylaxis

Deep venous thrombosis and pulmonary embolus are known risks of surgery. However, the incidence of these conditions in face lift is unknown. In this study, the incidence of deep venous thrombosis/pulmonary embolus after face lift is studied and factors associated with thromboembolic complications are evaluated. One-third of the active members of the American Society for Aesthetic Plastic Surgery were randomly selected. Participating surgeons completed a one-page survey providing information on face-lift procedures during a 12-month study period. A response rate of 80 percent was achieved, with 273 of the 342 surgeons responding to the survey. A total of 9937 face-lift procedures were reported in the 1-year study period. There were 35 patients with deep venous thrombosis (0.35 percent), 14 patients with pulmonary embolus (0.14 percent), and 1 patient death in the series. Although 43.5 percent of patients underwent face lift under general anesthesia, 83.7 percent of deep venous thrombosis/pulmonary embolus events occurred with general anesthesia. For prophylaxis for deep venous thrombosis/pulmonary embolus, 19.7 percent of the surgeons used intermittent compression devices, 19.6 percent used thromboembolic disease hose or Ace wraps, and 60.7 percent used no prophylaxis. Of patients developing deep venous thrombosis/pulmonary embolus, 4.1 percent were treated prophylactically with intermittent compression devices, 36.7 percent with thromboembolic disease hose/Ace wraps, and 59.2 percent with no prophylaxis. It was found that deep venous thrombosis/pulmonary embolus after face lift is a measurable complication experienced by one of nine surgeons surveyed. Deep venous thrombosis/pulmonary embolus is more likely to occur when the procedure is performed under general anesthesia. The majority of plastic surgeons surveyed used no prophylaxis for deep venous thrombosis when performing face-lift procedures. Intermittent compression devices were associated with significantly fewer thromboembolic complications, whereas Ace wrap/thromboembolic disease hose afforded no protection against deep venous thrombosis/pulmonary embolus when used alone. In conclusion, aesthetic surgeons should consider adopting intermittent compression devices when performing face lift under general anesthesia.     

Certain biological function of leukocytes in venous thrombosis and influence of factors released during clot lysis

In patients with venous thrombosis the behaviour of leukocyte random locomotion, migration, phagocytosis, blast transformation and NBT reduction properties were investigated. During the course of venous thrombosis the leukocyte adherence activity and their NBT reduction properties increased whereas their random locomotion decreased. The lymphocytes evaluated by the migration and blast transformation tests showed no signs of stimulation nor was their immunologic response changed. The thermolabile factor present in the clot lysis products affected only the adherence activity and the NBT reduction properties.     

The first case of septicemia due to nontoxigenic Corynebacterium diphtheriae in Poland: case report

Background

CMV-induced vasculopathy and thrombosis have been reported, but they are rare conditions usually encountered in immunocompromised patients. However more and more complications of CMV infections are recognized in immunocompetent patients.

Case presentation

We present a case report of a previously healthy adult with cytomegalovirus infection that was complicated by tibiopopliteal deep venous thrombosis and in whom Factor V Leiden heterozygous mutation was found.

Conclusion

This new case report emphasizes the involvement of cytomegalovirus in induction of vascular thrombosis in patients with predisposing risk factors for thrombosis. It is necessary to screen for CMV infection in patients with spontaneous thrombosis and an history of fever.     

门静脉高压症脾切断流术后血栓形成的临床研究

目的:探讨门静脉高压症脾切断流术后门静脉系统血栓形成的相关原因。方法:回顾性分析2010年4月-2011年12月我科450例因肝硬化门静脉高压症行脾切断流术患者的临床资料,应用超声多普勒检测手术前后门静脉血流速度、门静脉直径及脾静脉、肠系膜上静脉、门静脉血栓情况,用Logistic回归分析术前肝功能Child-Pugh分级、门静脉直径、门静脉血流速度、脾脏的质量及术后血小板数量与门静脉系统血栓形成的关系。结果:术前门静脉系统有血栓患者75例,占16.7%。术后门静脉血栓再形成率52.9%。Logistic单因素分析提示门静脉系统血栓形成与门静脉内径、门静脉血流速度、脾脏质量、血清总胆红素、术后血小板数量有关。多因素分析发现门静脉系统血栓形成与门静脉内径、门静脉血流速度、脾脏质量有关,而与血清总胆红素、术后血小板数量无关。结论:肝硬化门静脉高压症脾切除术后门静脉系统血栓形成与门静脉内径、门静脉血流速度、脾脏质量有关。     

Indium-111 labelled platelets in diagnosis of leg-vein thrombosis: preliminary findings.

Platelets from eight patients thought clinically to have deep venous thrombosis were labbelled with indium-111 and reinjected. Subsequent scanning of the patients with a wholebody scanner and imaging with a gammacamera showed focal accumulation of the label at five sites in four legs, which correlated precisely with the sites of venous thrombi identified by ascending venography. This technique is a useful addition to methods for diagnosis venous thrombosis.