Venous thromboembolism after severe injury in children

BACKGROUND: Deep vein thrombosis and pulmonary embolism are considered common complications after major trauma. Their incidence and the associated risk factors have rarely been identified in injured children. METHODS: Severely injured children (age <18 years; admitted in a pediatric intensive care unit or length of stay > or = 72 h) with a discharge diagnosis of venous thromboembolism (VTE; deep venous thrombosis and/or pulmonary embolism) were identified from the institutional trauma registry between January 1, 1999 and April 31, 2002. The study centers included a dedicated pediatric trauma center and an adult trauma center with pediatric patients. Risk factors for VTE were identified using multivariate analysis. RESULTS: VTE was found in 11 of the 3,291 admissions, for a rate of 3.3/1,000 admissions. Children with VTE were older and had higher Injury Severity Scores. Independent risk factors for VTE included thoracic injuries [odds ratio (OR): 6.9; 95% confidence interval (CI): 1.4-35.1] and spinal injuries (OR: 37.4; 95% CI: 3.5-396.7). The greatest risk of VTE was in children with central venous catheters (OR: 64.0; 95% CI: 16.8-243.9). CONCLUSION: Older children with high Injury Severity Scores, thoracic injuries, spinal injuries or venous catheters are at risk for VTE. Because VTE prophylaxis, screening and treatment are associated with complications and costs, it is essential to identify subgroups of pediatric patients in whom these strategies might be studied.     

Venous thromboembolism in malignancy and malignancy in venous thromboembolism

The activation of coagulation in patients with cancer contributes significantly to morbidity and mortality rates and may play a fundamental role in the host response to growing tumours. Patients with cancer are clearly at high risk for the development of venous thromboembolism (VTE), particularly during chemotherapy and surgery. This situation is aggravated by the use of venous access catheters and possibly growth factors. Data derived from large, randomized, controlled trials have been used to determine the true incidence of this complication of cancer and its treatment. The incidence based on the analyses of these randomized controlled trials varies from 1% for limited stage patients with breast cancer treated with tamoxifen to 60% for patients with any type of cancer who are subjected to orthopaedic surgery and do not receive prophylactic therapy. In view of the morbidity and mortality attributable to VTE in cancer, widespread utilization of prophylactic anticoagulation therapy, which has proven safe and effective in a variety of situations, should be considered. While migratory thrombophlebitis is a clear indicator of an underlying neoplasm, the risk of cancer in patients with the more typical form of VTE has been the subject of intense debate over recent years. Some investigators have suggested that the relative risk of being diagnosed with an occult cancer within 6 months of an episode of VTE (particularly recurrent VTE) could be up to 10-fold. However, the cost-effectiveness of aggressive screening for cancer in patients with VTE has not yet been defined adequately.     

Venous thromboembolism and ethnicity

Venous thromboembolism (VTE) has long been considered a disease that affects predominantly white populations, a misconception resulting from a paucity of epidemiological data from non-Western countries, and the low incidence of hereditary thrombophilia in those of non-Caucasian background. Over the last decade, interest has grown in this area with the emergence of evidence that VTE is as prevalent, if not more so, in the black population and is also common in Asian groups. Much is still to be learned, as our current knowledge of hereditary thrombophilia and acquired risk factors do not fully explain the risk of VTE in non-Caucasian groups. This review summarises the current understanding of ethnic variation in VTE and highlights the need for further research in this area.     

Venous thromboembolism in pediatrics

Venous thromboembolism (VTE) in pediatrics is quickly becoming a well-recognized cause of significant morbidity and mortality in children. Most children diagnosed with VTE have a serious underlying primary illness such as cancer, chronic total parenteral nutrition (TPN) dependency, or congenital heart disease. Infants and adolescents are most at risk of developing VTE, and the most significant risk factor is the presence of a central venous line (CVL). The incidence of VTE varies widely with study design and the diagnostic test used to detect thrombosis. Venography remains the gold standard diagnostic test, although ultrasound is increasingly used due to its noninvasive nature, despite concern regarding the sensitivity in upper system VTE. The treatment of uncomplicated VTE in children consists primarily of unfractionated heparin (UFH) initially, followed by oral anticoagulation or low molecular weight heparin (LMWH) for 3 months. LMWH offers many advantages over UFH due to the longer half-life, increased bioavailability, and ease of administration and monitoring in children. Acute complications of VTE in children are numerous and include pulmonary embolism (PE), chylothorax, and superior vena cava syndrome. Long-term morbidity includes recurrent VTE, postthrombotic syndrome, repeat general anesthetics for CVL placement, and eventual destruction of the upper venous system in children with repeat CVL-related VTE. Death from VTE is rare and is primarily due to PE.     

Venous thromboembolism in women

AbstractThe risk of venous thromboembolism (VTE) varies throughout a woman's life and is associated primarily with underlying hormonal exposure. Alteration in hemostatic mechanisms, including resistance to activated protein C, may explain this altered risk. Initially, development of VTE with the use of contraception in young adulthood may reveal inherited thrombophilia. Pregnancy, and particularly the post-partum period, likely confer the greatest risk of VTE, but the absolute risk is small. Guidelines for prevention of VTE during pregnancy are based on personal or family history of VTE, and known inherited thrombophilia. Use of hormone replacement therapy later in life is associated with increased risk of VTE, and may be safest if given as an estrogen-only preparation to young postmenopausal women for less than 5 years. Universal screening for thrombophilia prior to pregnancy or initiating hormonal therapy is not recommended; however, selected testing in high-risk groups may be warranted. The lack of firm recommendations for the prevention of VTE in women highlights the need for future investigation aimed at identifying high-risk groups and evaluating the efficacy of prophylactic measures.     

我国静脉血栓栓塞症的研究现状

由于肺血栓栓塞 (PTE)的栓子主要来自深静脉血栓 (DVT),另一方面,DVT常引起PTE,两者密不可分,故人们将两者合称为静脉血栓栓塞症(VTE)。多年来,国内外不少学者均认为我国VTE的发病率明显低于西方国家,病因和临床特征也有所不同,但是否的确如此一直存在异议。让我们先看一下     

P-选择素与静脉血栓栓塞症

血小板激活是静脉血栓形成的重要组成步骤,P-选择素是血小板的活性受体,也能被上皮细胞所识别.作为血小板/内皮细胞活化标志和细胞黏附受体.其可通过介导血小板、内皮细胞黏附及与白细胞的相互作用,启动参与包括炎症和血栓形成等多种病理生理起始过程,是血栓形成的重要介质和靶分子.检验P.选择素可以通过流式细胞仪检测血小板表面的P一选择素或通过酶联免疫吸附试验检测血液中可溶性P-选择素,方法简便,这些数据可作为血小板激活的判断.从而为血栓形成提供依据.抑制P一选择素及其配体的结合,可使病理状态下血栓局部白细胞聚集减少,细胞因子及组织因子表达降低,纤维蛋白生成减少,从而有助于抑制血栓的形成.     

Venous thromboembolism and cancer

INTRODUCTION: Thromboembolic venous disease, which includes both peripheral venous thrombosis and pulmonary embolism, is a frequent disorder in patients with cancer. Although thromboembolic manifestations may precede the diagnosis of cancer, the value of extensive clinical search for potential underlying cancer when faced with venous thromboembolic manifestations has not been demonstrated. CURRENT KNOWLEDGE AND KEY POINTS: Clinical and biological studies have demonstrated that acquired abnormalities in blood hemostasis, especially procoagulant factors, account for the onset of thromboembolic manifestations in patients with cancer. Classical anticoagulant therapy is associated with low efficacy and tolerance in patience with cancer who are at high risk for hemorrhagic complications and recurrence of thromboembolic disease. FUTURE PROSPECTS AND PROJECTS: Recent data suggest the value of anticoagulant therapy using either low molecular weight heparin or warfarin at low doses (INR < 2) according to the specific surgical or medical context.     

Venous thromboembolism in pregnancy

Opinion statement  Low molecular weight heparins (LMWHs) appear to be as safe and effective as unfractionated heparin (UFH) for venous thromboembolic disease (VTED) treatment or prophylaxis during pregnancy. Experience with other parenteral anticoagulant drugs is very limited, and no alternative oral anticoagulants are available to date. In addition to cost, challenges of long-term LMWH use during pregnancy that have not been addressed by controlled clinical trials include a) ideal dosing as pregnancy advances, b) the need for LMWH monitoring by anti-Xa activity levels, and c) ideal therapeutic management as the delivery date nears. Because therapeutic-intensity anticoagulation during pregnancy is challenging, many practitioners favor a more “aggressive” approach toward VTED prophylaxis in women perceived to be at very high risk of thrombosis during pregnancy. Best evidence to date suggests that most women with thrombophilias or with a previous “situational” VTED event probably do not require VTED prophylaxis antepartum, but postpartum anticoagulation prophylaxis is recommended for a few weeks. For those with a history of previous idiopathic VTED or VTED associated with “hormonal challenge” (such as with contraceptive use or previous pregnancy), prophylaxis beginning antepartum may be considered and discussed with the patient. Selected cases of “severe” thrombophilia are probably best managed by initiation of pharmacologic VTED prophylaxis antepartum. However, it must be emphasized that data from prospective controlled clinical trials are lacking.     

Venous thromboembolism in pregnancy

In Western nations, venous thromboembolism (VTE) is an important cause of morbidity and the most common cause of maternal death during pregnancy and the puerperium. Pregnancy is a hypercoagulable state in which coagulation is activated and thrombolysis inhibited. This prothrombotic risk is compounded when hereditary and acquired thrombophilias and other prothrombotic risk factors are present. The risk of venous thrombotic events is increased fivefold during pregnancy and 60-fold in the first 3 months after delivery (postpartum period) compared with nonpregnant women. Many of the signs and symptoms of VTE overlap those of a normal pregnancy, which complicates the diagnosis. Patients with history of previous VTE should use graduated compression stockings throughout pregnancy and the puerperium, and should receive postpartum anticoagulant prophylaxis. The indications for antepartum anticoagulant prophylaxis are somewhat controversial. This article reviews the management of VTE during pregnancy and in the postpartum period.     

Venous thromboembolism and neoplasms

Venous thromboembolism, including deep vein thrombosis and pulmonary embolism, is a major cause of morbidity and mortality. In most cases, one or more risk factors for removable or persistent venous thromboembolism can be identified. Persistent risk factors include inherited or acquired abnormalities of the hemostatic system and cancer. As Armand Trousseau first suggested, venous thromboembolism may be the first clinical manifestation of an occult cancer. This relationship has recently been confirmed by methodologically well designed studies. Furthermore, venous thromboembolism is the second cause of death in patients with clinically overt cancer. This review summarizes the state of the art of this association. The clinical trials described focus on the need to perform screening for occult cancer in patients with idiopathic venous thromboembolism. How extensive this screening should be is still matter of debate. On the other hand, patients with clinically overt cancer should be considered at high risk for developing venous thromboembolism, and adequate prophylaxis should be used.     

Venous thromboembolism and cancer

OBJECTIVES: The risk of venous thrombosis during cancer is largely increased especially in case of chemotherapy, surgery, advanced stage disease, coagulation abnormalities. Survival of patients with cancer experiencing venous thrombosis seems to be worse. Although thrombosis may be a presenting feature of occult malignancy, there are insufficient data to support a more extensive screening than comprehensive medical history, physical examination, routine laboratory tests and chest radiography. CURRENT KNOWLEDGE AND KEY POINTS: Pathophysiology of venous thrombosis during cancer is unspecific: venous stasis, vessel wall damage, hypercoagulability). Other factors like platelet abnormalities or the direct responsibility of chemotherapy or hormonotherapy have recently been though to play a causative role. Treatment of cancer-associated thrombosis usually requires at least 6 months of low-molecular-weight heparin therapy rather than oral anticoagulant. Inferior vena cava filters are not indicated. Primary prophylaxis of thrombosis during cancer could safely been achieved with low-molecular-weight heparin. Central venous catheters can be associated with thrombotic complications. Many risks factors have been identified: catheter's type, modalities of catheter's implantation, type of perfusion, bulky mediastinal mass... Prophylactic anticoagulation is not routinely recommended. FUTURE PROSPECTS AND PROJECTS: Knew oral anticoagulants could facilitate the treatment of venous thrombosis occurring during cancer in the next years.     

Venous thromboembolism and melanoma

The association between venous thromboembolism and cancer has been known for many years. The clotting system may be activated because of enhanced platelet aggregation and adhesion or by stimulation from the endothelial cells or the tumour cells themselves. Furthermore, thrombosis may develop as a result of prolonged immobilization, surgery, chemotherapy or hormone therapy. We present a case of a patient who underwent surgery for excision of a Clark level II melanoma on the back who developed pulmonary metastasis four years after the operation. The metastasis manifested with very severe venous thromboembolism which, despite anticoagulant therapy and the placement of a vena caval filter, led to the patient's death from pulmonary embolism. The case is uncommon, in terms of both the rarity with which venous thromboembolism is associated to melanoma, and the severity with which it manifested.