BACKGROUND: Deep venous thrombosis (DVT) arises with an incidence of about 1 per 1000 persons per year; 4-10% of all DVTs are located in an upper extremity (DVT-UE). DVT-UE can lead to complications such as post-thrombotic syndrome and pulmonary embolism and carries a high mortality.
METHODS: This review is based on pertinent literature, published from January 1980 to May 2016, that was retrieved by a systematic search, employing the PRISMA criteria, carried out in four databases: PubMed (n = 749), EMBASE (n = 789), SciSearch (n = 0), and the Cochrane Library (n = 12). Guidelines were included in the search.
RESULTS: DVT-UE arises mainly in patients with severe underlying diseases, especially cancer (odds ratio [OR] 18.1; 95% confidence interval [9.4; 35.1]). The insertion of venous catheters-particularly central venous catheters-also elevates the risk of DVT-UE. Its clinical manifestations are nonspecific. Diagnostic algorithms are of little use, but ultrasonography is very helpful in diagnosis. DVT-UE is treated by anticoagulation, with heparin at first and then with oral anticoagulants. Direct oral anticoagulants are now being increasingly used. The thrombus is often not totally eradicated. Anticoagulation is generally continued as maintenance treatment for 3-6 months. Interventional techniques can be used for special indications. Patients with DVT-UE have a high mortality, though they often die of their underlying diseases rather than of the DVT-UE or its complications.
CONCLUSION: DVT of the upper extremity is becoming increasingly common, though still much less common than DVT of the lower extremity. The treatment of choice is anticoagulation, which is given analogously to that given for DVT of the lower extremity.
BACKGROUND: We update recommendations on 12 topics that were in the 9th edition of these guidelines, and address 3 new topics.
METHODS: We generate strong (Grade 1) and weak (Grade 2) recommendations based on high- (Grade A), moderate- (Grade B), and low- (Grade C) quality evidence.
RESULTS: For VTE and no cancer, as long-term anticoagulant therapy, we suggest dabigatran (Grade 2B), rivaroxaban (Grade 2B), apixaban (Grade 2B), or edoxaban (Grade 2B) over vitamin K antagonist (VKA) therapy, and suggest VKA therapy over low-molecular-weight heparin (LMWH; Grade 2C). For VTE and cancer, we suggest LMWH over VKA (Grade 2B), dabigatran (Grade 2C), rivaroxaban (Grade 2C), apixaban (Grade 2C), or edoxaban (Grade 2C). We have not changed recommendations for who should stop anticoagulation at 3 months or receive extended therapy. For VTE treated with anticoagulants, we recommend against an inferior vena cava filter (Grade 1B). For DVT, we suggest not using compression stockings routinely to prevent PTS (Grade 2B). For subsegmental pulmonary embolism and no proximal DVT, we suggest clinical surveillance over anticoagulation with a low risk of recurrent VTE (Grade 2C), and anticoagulation over clinical surveillance with a high risk (Grade 2C). We suggest thrombolytic therapy for pulmonary embolism with hypotension (Grade 2B), and systemic therapy over catheter-directed thrombolysis (Grade 2C). For recurrent VTE on a non-LMWH anticoagulant, we suggest LMWH (Grade 2C); for recurrent VTE on LMWH, we suggest increasing the LMWH dose (Grade 2C).
CONCLUSIONS: Of 54 recommendations included in the 30 statements, 20 were strong and none was based on high-quality evidence, highlighting the need for further research.
The preferred dosification for low molecular weight heparins is in two doses for most patients with venous thromboembolic disease. A daily dose would make treatment simpler, less expensive and more comfortable while retaining a similar benefit and safety. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified two systematic reviews including five randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded it is not clear whether the risk of recurrence differs between the two alternatives because the certainty of the evidence is very low, and that administering low molecular weight heparin in two doses might be associated to little or no difference in the risk of major bleeding and mortality.
This article describes the pharmacology of approved parenteral anticoagulants. These include the indirect anticoagulants, unfractionated heparin (UFH), low-molecular-weight heparins (LMWHs), fondaparinux, and danaparoid, as well as the direct thrombin inhibitors hirudin, bivalirudin, and argatroban. UFH is a heterogeneous mixture of glycosaminoglycans that bind to antithrombin via a unique pentasaccharide sequence and catalyze the inactivation of thrombin, factor Xa, and other clotting enzymes. Heparin also binds to cells and plasma proteins other than antithrombin causing unpredictable pharmacokinetic and pharmacodynamic properties and triggering nonhemorrhagic side effects, such as heparin-induced thrombocytopenia (HIT) and osteoporosis. LMWHs have greater inhibitory activity against factor Xa than thrombin and exhibit less binding to cells and plasma proteins than heparin. Consequently, LMWH preparations have more predictable pharmacokinetic and pharmacodynamic properties, have a longer half-life than heparin, and are associated with a lower risk of nonhemorrhagic side effects. LMWHs can be administered once daily or bid by subcutaneous injection, without coagulation monitoring. Based on their greater convenience, LMWHs have replaced UFH for many clinical indications. Fondaparinux, a synthetic pentasaccharide, catalyzes the inhibition of factor Xa, but not thrombin, in an antithrombin-dependent fashion. Fondaparinux binds only to antithrombin. Therefore, fondaparinux-associated HIT or osteoporosis is unlikely to occur. Fondaparinux exhibits complete bioavailability when administered subcutaneously, has a longer half-life than LMWHs, and is given once daily by subcutaneous injection in fixed doses, without coagulation monitoring. Three additional parenteral direct thrombin inhibitors and danaparoid are approved as alternatives to heparin in patients with HIT.
Venous thromboembolism (VTE) is a condition in which a blood clot (a thrombus) forms in a vein and then dislodges to travel in the blood (an embolus). A venous thrombus most commonly occurs in the deep veins of the legs or pelvis; this is then called a deep vein thrombosis (DVT). Blood flow through the affected vein can be limited by the clot, and it can cause swelling and pain in the leg. If it dislodges and travels to the lungs, to the pulmonary arteries, it is called a pulmonary embolism (PE), which in some cases may be fatal. VTE as a term includes both DVT and PE. Major risk factors for VTE include a prior history of DVT, age over 60 years, surgery, obesity, prolonged travel, acute medical illness, cancer, immobility, thrombophilia (an abnormal tendency for the blood to clot) and pregnancy. The diagnosis of VTE is not always straightforward as other conditions may have similar symptoms, thus highlighting the need for guidance on the diagnostic pathways used for the assessment of possible DVT and PE. Failure to diagnose a case of VTE correctly may result in a patient not receiving the correct treatment and potentially suffering a fatal PE as a result. This guideline includes advice on the Wells score, D-dimer measurement, ultrasound and radiological imaging. We have looked at the diagnostic pathways for PE and DVT separately but this guideline did not consider PE risk stratification or the outpatient management of PE as these were beyond our scope. We have focussed on proximal DVT rather than isolated calf vein DVT as the latter is less likely to cause PTS than proximal DVT and also less likely to embolise to the lungs. The current standard practice for the treatment of VTE is anticoagulation. These drugs “thin” the blood and prevent further clotting. There is a wide variation in practice, but patients are usually given a brief course of heparin treatment initially while they start on a 3–6 month course of warfarin. Patients who have had recurrent VTE or who are at high risk of recurrence may be given indefinite treatment with anticoagulants to prevent further VTE episodes. However, anticoagulation treatment is not without risk, for example, the risk of bleeding, and requires the patient to have regular monitoring blood tests. There is a need for guidance about which patients should have such prolonged treatment and how the monitoring should be performed. In addition, there is a wide variation in practice regarding when to test for thrombophilia after VTE and controversy as to how thrombophilia should be managed if it is found on testing. There is also the potential to dissolve the clots using drugs termed thrombolytics which can be achieved both for DVT and PE. Dissolving the clots in the pulmonary arteries may reduce the risk of fatal PE and longer term problems with CTEPH. In the case of DVT, thrombolysis may reduce the risk of fatal PE and PTS. However, the use of thrombolytics may cause side-effects such as bleeding and guidance is needed as to which patients may benefit from their use. This guideline considers the aforementioned in adults (18 years and older) with a suspected or confirmed DVT or PE in primary, secondary and tertiary health-care settings. Within this guideline the following will be considered as special risk groups; people with cancer, people who misuse intravenous drugs, residents of nursing homes, people with physical disabilities who have restricted movement following a VTE and those with learning disabilities who require long-term medication to be taken at home. In particular, people with cancer are at higher risk of developing VTE and may need special advice on how it should be managed, as they may not respond as well when treated with warfarin. Children, people younger than 18 years and pregnant women will not be considered. Prophylaxis against VTE is not addressed as it is already the subject of a NICE clinical guideline (CG92).
CONTEXTE: Cet article porte sur le traitement de la maladie de TEV.
MÉTHODES: Nous avons généré une forte (Grade 1) et la faiblesse des recommandations (Grade 2) Sur la base (Grade A), (Grade B), et les preuves de haute qualité de qualité moyenne à faible qualité (grade C).
RÉSULTATS: Pour thrombose veineuse profonde aiguë ou d'embolie pulmonaire (EP), nous recommandons un traitement initial de l'anticoagulant par voie parentérale (Grade 1B) ou anticoagulation par rivaroxaban. Nous suggérons héparine de bas poids moléculaire (HBPM) ou le fondaparinux sur IV héparine non fractionnée (Grade 2C) ou sous-cutanée d'héparine non fractionnée (Grade 2B). Nous suggérons un traitement thrombolytique pour PE avec hypotension (Grade 2C). Pour TVP proximale ou une EP, nous recommandons un traitement de 3 mois sur des périodes plus courtes (Grade 1B). Pour une première thrombose veineuse profonde proximale ou EP qui est provoquée par une chirurgie ou par un facteur de risque transitoire non chirurgicale, nous recommandons 3 mois de traitement (1b année; Grade 2B si provoquée par un facteur de risque non chirurgicale et le risque faible ou modéré saignements), qui est sans provocation , nous vous proposons un traitement prolongé si le risque de saignement est faible ou modérée (Grade 2B) et nous recommandons 3 mois de traitement si le risque de saignement est élevé (Grade 1B), et qui est associée à un cancer actif, nous recommandons un traitement prolongé (Grade 1B, 2B grade en cas de risque élevé de saignement) et de proposer des HBPM sur les antagonistes de la vitamine K (Grade 2B). Nous suggérons des antagonistes de la vitamine K ou HBPM sur dabigatran ou rivaroxaban (Grade 2B.) Nous suggérons des bas de contention pour éviter le syndrome post-thrombotique (Grade 2B). Pour une thrombose veineuse superficielle, nous vous suggérons fondaparinux prophylactique à dose unique ou HBPM plus aucune anticoagulation (Grade 2B), et suggérons fondaparinux sur HBPM (Niveau 2C).
CONCLUSION: Des recommandations fortes s'appliquent à la plupart des patients, alors que les recommandations faibles sont sensibles aux différences entre les patients, y compris leurs préférences.
INTRODUCTION: Deep venous thrombosis (DVT) or pulmonary embolism may occur in almost 2 in 1000 people each year, with up to 25% of those having a recurrence. Around 5% to 15% of people with untreated DVT may die from pulmonary embolism. Risk factors for DVT include immobility, surgery (particularly orthopaedic), malignancy, pregnancy, older age, and inherited or acquired prothrombotic clotting disorders.
METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for proximal DVT? What are the effects of treatments for isolated calf DVT? What are the effects of treatments for pulmonary embolism? What are the effects of interventions on oral anticoagulation management in people with thromboembolism? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS: We found 45 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: anticoagulation; compression stockings; low molecular weight heparin (short and long term, once or twice daily, and home treatment); oral anticoagulants (short and long term, high intensity, abrupt discontinuation, and computerised decision support); prolonged duration of anticoagulation; thrombolysis; vena cava filters; and warfarin.
BACKGROUND: New treatments are available for treatment of venous thromboembolism. PURPOSE: To review the evidence on the efficacy of interventions for treatment of deep venous thrombosis (DVT) and pulmonary embolism. DATA SOURCES: MEDLINE, MICROMEDEX, the Cochrane Controlled Trials Register, and Cochrane Database of Systematic Reviews from the 1950s through June 2006. STUDY SELECTION: Randomized, controlled trials; systematic reviews of trials; and observational studies; all restricted to English-language articles. DATA EXTRACTION: Paired reviewers assessed study quality and abstracted data. The authors pooled results about optimal duration of anticoagulation. DATA SYNTHESIS: This review includes 101 articles. Low-molecular-weight heparin (LMWH) is modestly superior to unfractionated heparin at preventing recurrent DVT and is at least as effective as unfractionated heparin for treatment of pulmonary embolism. Outpatient treatment of venous thromboembolism is likely to be effective and safe in carefully chosen patients, with appropriate services available. Inpatient or outpatient use of LMWH is cost-saving or cost-effective compared with unfractionated heparin. In observational studies, catheter-directed thrombolysis safely restored vein patency in select patients. Moderately strong evidence supports early use of compression stockings to reduce postthrombotic syndrome. Limited evidence suggests that vena cava filters are only modestly efficacious for prevention of pulmonary embolism. Conventional-intensity oral anticoagulation beyond 12 months may be optimal for patients with unprovoked venous thromboembolism, although patients with transient risk factors benefit little from more than 3 months of therapy. High-quality trials support use of LMWH in place of oral anticoagulation, particularly in patients with cancer. Little evidence is available to guide treatment of venous thromboembolism during pregnancy. LIMITATIONS: The authors could not address all management questions, and excluded non-English-language literature. CONCLUSIONS: The strength of evidence varies across the study questions but generally is strong.
Deep venous thrombosis (DVT) arises with an incidence of about 1 per 1000 persons per year; 4-10% of all DVTs are located in an upper extremity (DVT-UE). DVT-UE can lead to complications such as post-thrombotic syndrome and pulmonary embolism and carries a high mortality.
METHODS:
This review is based on pertinent literature, published from January 1980 to May 2016, that was retrieved by a systematic search, employing the PRISMA criteria, carried out in four databases: PubMed (n = 749), EMBASE (n = 789), SciSearch (n = 0), and the Cochrane Library (n = 12). Guidelines were included in the search.
RESULTS:
DVT-UE arises mainly in patients with severe underlying diseases, especially cancer (odds ratio [OR] 18.1; 95% confidence interval [9.4; 35.1]). The insertion of venous catheters-particularly central venous catheters-also elevates the risk of DVT-UE. Its clinical manifestations are nonspecific. Diagnostic algorithms are of little use, but ultrasonography is very helpful in diagnosis. DVT-UE is treated by anticoagulation, with heparin at first and then with oral anticoagulants. Direct oral anticoagulants are now being increasingly used. The thrombus is often not totally eradicated. Anticoagulation is generally continued as maintenance treatment for 3-6 months. Interventional techniques can be used for special indications. Patients with DVT-UE have a high mortality, though they often die of their underlying diseases rather than of the DVT-UE or its complications.
CONCLUSION:
DVT of the upper extremity is becoming increasingly common, though still much less common than DVT of the lower extremity. The treatment of choice is anticoagulation, which is given analogously to that given for DVT of the lower extremity.
