Search

Item does not contain fulltext

Contains fulltext : 291124.pdf (Publisher’s version ) (Open Access) BACKGROUND: In upper extremity thrombosis research, the occurrence of upper extremity postthrombotic syndrome (UE-PTS) is commonly used as the main outcome parameter. However, there is currently no reporting standard or a validated method to assess UE-PTS presence and severity. In a recent Delphi study, consensus was reached on a preliminary UE-PTS score, combining 5 symptoms, 3 signs, and the inclusion of a functional disability score. However, no consensus was reached on which functional disability score to be included. OBJECTIVES: The aim of the current Delphi consensus study was to determine the specific type of functional disability score to finalize UE-PTS score. METHODS: This Delphi project was designed as a three-round study using open text questions, statements with 7-point Likert scales, and multiple-choice questions. The CREDES recommendations for Delphi studies were applied. In this context, a systematic review was conducted before the start of the Delphi rounds to identify the available functional disability scores as available in the literature and present these to the expert panel. RESULTS: Thirty-five of 47 initially invited international experts from multiple disciplines completed all the Delphi rounds. In the second round, consensus was reached on the incorporation of the quick disabilities of the arm, shoulder, and hand (QuickDASH) in the UE-PTS score, rendering the third round obsolete. CONCLUSION: Consensus was reached that the QuickDASH should be incorporated in the UE-PTS score. The UE-PTS score will need to be validated in a large cohort of patients with upper extremity thrombosis before it can be used in clinical practice and future research. 01 januari 2023

Contains fulltext : 286867.pdf (Publisher’s version ) (Closed access) Gender dysphoria refers to psychological distress that results from an incongruence between gender identity and sex assigned at birth. Administration of sex hormones is most often used as a first step to develop and maintain physical characteristics consistent with gender identity. Gender-affirming hormone treatment is considered beneficial for the quality of life and reduction of depression. However, estrogen and androgen-lowering hormone therapies used in transwomen are in particular associated with increased risk of venous thromboembolism. In this review, introduced by a clinical case, we provide an overview of the currently available medical therapies in transgender medicine, and put the associated increased risk of venous thromboembolism into perspective.

Patients with subarachnoid hemorrhage (SAH) who are using antiplatelet drugs prior to their hemorrhage, often receive platelet transfusions to reverse antiplatelet effects prior to life-saving surgical interventions. However, little is known about the effect of platelet transfusion on patient outcome in these patients. The aim of this study is to investigate the effect of platelet transfusion on clinical outcome in patients with aneurysmal SAH (aSAH) who use antiplatelet agents. Consecutive adult patients with an aSAH admitted between 2011 and 2015 to the Academic Medical Center (Amsterdam, the Netherlands) were included. Demographic characteristics and in-hospital complications were compared and clinical outcome was assessed after six months. Multivariable logistic regression analysis was performed to correct for confounding variables. A total of 364 patients with an aSAH were included. Thirty-eight (10%) patients underwent platelet transfusion during admission. Patients receiving platelet transfusion had worse clinical outcome (modified Rankin Scale score 4–6) at six months compared to patients without platelet transfusion (65% versus 32%, odds ratio 4.0, 95% confidence interval:1.9–8.1). Multivariable logistic regression analysis showed that platelet transfusion during admission was associated with unfavorable clinical outcome after six months; adjusted for age, treatment modality, modified Fisher and WFNS on admission (adjusted odds ratio 3.3, 95% confidence interval: 1.3–8.4). In this observational study, platelet transfusion was associated with poor clinical outcome at six months after correcting for confounding influences. In aSAH patients who need surgical treatment at low risk of bleeding, the indication for platelet transfusion needs careful weighing of the risk-benefit-balance.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is diagnosed if there is venous or arterial thrombosis with thrombocytopenia caused by antibodies against platelet factor 4 (PF4) that activate thrombocytes and is confirmed by a heparin-induced platelet activation (HIPA) test, occurring 4 to 28 days after vaccination against COVID19. This extremely rare syndrome has been recognized after Astra Zeneca (reporting incidence 0.91 per 100.000) and Janssen vaccins (0.22 per 100.000). Causality with the vaccine is difficult to ascertain if the HIPA test is negative, or if there is severe thrombosis (such as cerebral sinus or splanchnic thrombosis) without thrombocytopenia. Symptoms compatible with thrombosis or bleeding occurring in a specific time window after vaccination should prompt urgent assessment of the thrombocyte count and appropriate diagnostic tests. Heparin-like anticoagulants should be avoided and central laboratory assessment is essential. Early recognition likely improves prognosis of this extremely rare but severe complication of vaccination against COVID-19.

In the middle of the worldwide COVID-19 crisis, the whole of Europe was alarmed about a possible side effect of the AstraZeneca vaccine against COVID-19. Consequently, the use of this AstraZeneca vaccine was temporarily suspended in many European nations including the Netherlands. In this article, we chronologically describe the decisions that were made about the use of this vaccine in the Netherlands and we discuss the risk-benefit ratios of these actions as well as possible non-medical reasons that may explain why these actions were taken.

The optimal management of oral contraception and menstrual bleeding during treatment of venous thromboembolism (VTE) is largely unknown. We aimed to elicit expert opinion and compare that to current practice as assessed by a world-wide international web-based survey among physicians.10 international thrombosis experts and 10 abnormal uterine bleeding experts independently completed a questionnaire containing three hypothetical patient cases each with four different scenarios, and additional queries covering different severities of VTE, patient circumstances, hormonal contraceptives and both thrombotic and bleeding complications. The consensus percentage was set a priori at ≥70%. The same questionnaire with randomized case scenarios was presented to international physicians via newsletters of the ISTH and national scientific communities. Differences between the expert groups and daily clinical care were assessed.Expert recommendations were divergent and differed in several important points from clinical practice. In contrast to common practice in which contraceptives are discontinued at the moment of a VTE diagnosis, the thrombosis experts agreed to continue oral contraception (OC) during the anticoagulation treatment period. Also, experts reached consensus on treating patients with anticoagulation-associated abnormal uterine bleeding with tranexamic acid, although this is not supported by strong evidence from the literature. No consensus was reached on the optimal anticoagulant drug class.International experts' opinions on handling of contraceptives and management of anticoagulant-associated abnormal uterine bleeding in female VTE patients are divergent and management in clinical practice is heterogeneous. There is a great need of further studies on these topics.

Several aspects of the diagnostic and therapeutic management of women with venous thrombosis are uncertain. In this overview, I will discuss three major areas. First, the contribution of hormone use to venous thromboembolism (VTE) will be discussed as prudent prescribing of safe preparations can further reduce the risk of hormone-related VTE. Uncertainties remain regarding certain low-dose progestagens and transdermal routing of hormones and their associated risk of VTE. Second, I will review the diagnosis, treatment, and prevention of pregnancy-related VTE. As direct evidence is largely absent for these individuals, these areas are subject to extrapolation from the non-pregnant population. There is therefore an urgent need for the evaluation of diagnostic strategies that safely exclude the diagnosis of acute pulmonary embolism in pregnant women without the need for diagnostic imaging, which is currently the gold standard, as no studies have confidently demonstrated the safety of ruling out VTE by clinical probability assessment combined with the use of D-dimer levels. Although identification of women at increased risk of pregnancy-related VTE is relatively well established, controversy remains for asymptomatic women from thrombophilic families. The optimal duration and intensity of anticoagulant treatment for, and prophylaxis of, pregnancy-related VTE with low molecular weight heparin is unknown. Third, anticoagulant therapy to prevent recurrence in women with unexplained recurrent miscarriage has shown to have no benefit and should not be prescribed. However, whether antithrombotic therapy prevents recurrent miscarriage in thrombophilic women, or in women with severe pregnancy complications, remains unknown and urgently requires future research.

Essentials The priority of ISTH was to establish a global core curriculum in thrombosis and hemostasis. International survey to determine competencies required for clinical specialists was carried out in the field. Competency framework provides a reference point for mapping and developing regional curricula. Core curriculum informs and links to a variety of ISTH educational materials. Background The International Society on Thrombosis and Haemostasis (ISTH) identified the need for an international core curriculum on thrombosis and hemostasis for its society members and the larger thrombosis and hemostasis community. Aims The current research sought consensus on the core competencies required by medical doctors who are ready to practise as independent clinical specialists in thrombosis and hemostasis with the aim of developing a core clinical curriculum for specialists in the field. Method A draft list of competencies was developed by the Working Group and formed the basis of an online survey. ISTH members and the larger thrombosis and hemostasis community were asked to rate the importance of each competency, on a Likert scale, for clinical specialists in thrombosis and hemostasis. Results There were a total of 644 responses to the online survey with broad geographical representation. There was general agreement on what level of competency would be required for clinical specialists in thrombosis and hemostasis at the specified level of training. Conclusions Using the survey to gain consensus on the level of competency required by clinical specialists in the field of thrombosis and hemostasis enabled the development of a core clinical curriculum that has been endorsed by the ISTH Council. The curriculum will offer a framework and international reference that will be used by the society, by national and regional organizations, and for further research

Oral contraceptive (OC) use increases venous thrombosis (VTE) risk and causes activated protein C (APC) resistance. Plasma glucosylceramide (GlcCer) deficiency is associated with VTE and GlcCer functions as an APC anticoagulant cofactor. Because estradiol decreases GlcCer in cultured cells, we hypothesized OC use would decrease plasma GlcCer and contribute to APC resistance. In a pilot study, seven female adults alternatively took second and third generation OCs and plasma samples were analyzed for GlcCer using high performance liquid chromatography and for APC sensitivity using modified prothrombin time assays. Second and third generation OC usage decreased the APC sensitivity ratio by 8.1% +/- 4.7% (P = 0.004) and 11.7% +/- 8.2% (P = 0.013) and plasma GlcCer levels by 10.1% +/- 6.8% (P = 0.008) and 11.0% +/- 5.1% (P = 0.002), respectively. The plasma GlcCer level correlated with the sensitivity of plasma to APC (P = 0.017, r = 0.51, n = 21 plasma samples). Thus, both second and third generation OC usage decreased plasma GlcCer which could cause a reduction in the plasma sensitivity to APC/protein S, thereby potentially increasing VTE risk.

Summary. This review on the treatment of patients with venous thromboembolic disease consists of three sections. The first section describes the epidemiology, natural history and reasons for treatment of venous thromboembolism (VTE), as well as a short overview on the evaluation of the use of antithrombotic agents and the spectrum of treatment options. In the second section, the evidence from clinical studies available to us in 2005 with the various treatment modalities is summarized. This section describes the current recommendations about how to treat patients with VTE initially and long term. Finally, in the third section the challenges for the treatment of patients beyond 2005 are discussed.

Recent wetenschappelijk onderzoek heeft veel duidelijk gemaakt over erfelijke en verworven risicofactoren voor trombose; veel is echter ook nog niet duidelijk. Met name de praktische consequenties voor de patient met trombose of voor de patient met trombofilie vragen aandacht. In dit artikel worden de risico's op trombotische complicaties voor deze patienten besproken en er worden aanbevelingen voor het praktisch handelen bij deze patienten verstrekt.

Travellers to tropical destinations who seek medical attention after returning to their home country often present with fever, frequently as a result of an imported infectious disease. For this reason, clinicians initially focus on an infectious cause when a clear relationship in time exists between travel and disease onset. We present a case of a patient, who developed fever 2 weeks after his return from Ghana and who was finally diagnosed with an auto-immune disease: arteritis of the large arteries. This case illustrates that broad differential diagnostic thinking is paramount in the assessment of returned travellers.

The anticoagulant effect of unfractionated heparin (UFH) is usually monitored by means of the activated partial thromboplastin time (aPTT). In critically ill patients, however, increased levels of acute phase proteins may decrease the accuracy of the aPTT, leading to inadequate UFH dosing. In these circumstances, the anti-Xa assay is recommended for monitoring.We aimed to analyse the accuracy of the aPTT for the monitoring of UFH dosing in critically ill patients.In critically ill patients treated with therapeutic doses of UFH, we compared aPTT levels with simultaneously measured anti-Xa levels as the gold standard. Sensitivity and specificity of the aPTT were determined for different cut-off points, receiver operating characteristic (ROC) curves were constructed and their areas under the curve (AUCs) were calculated.A total of 171 paired blood samples from 58 patients were analysed. Concordant aPTT and anti-Xa values were observed in 108 (63.2%) data pairs. In 33 data pairs (19.3%) the aPTT was discordantly high and in 30 data pairs (17.5%) discordantly low. The sensitivity of the aPTT in detecting UFH underdosing and overdosing was 0.63 and 0.37, respectively. When considering alternative thresholds, ROC curves for underdosing and overdosing had AUCs of 0.71 and 0.81, respectively.In this small cohort of critically ill patients, the aPTT was accurate in 63.2% of the blood samples. Its sensitivity to detect UFH underdosing and overdosing was low (0.63 and 0.37, respectively). We conclude that in critically ill patients, the aPTT is not accurate enough to detect UFH underdosing and overdosing.

In critically ill patients, dosing of unfractionated heparin (UFH) is difficult due to unpredictable pharmacokinetics, which has an impact on the time to reach therapeutic anticoagulation. We evaluated the quality of UFH therapy in critically ill patients in terms of activated partial thromboplastin time (APTT) test values and time to therapeutic range.Patients admitted to the Intensive Care Unit (ICU) and Medium Care Unit (MCU) were screened for intravenous UFH administration. Time to therapeutic range was categorised into 0-12, 13-24 and24 hours. APTT results were classified into categories of subtherapeutic, supratherapeutic and therapeutic tests. We identified to what extent the sub- and upratherapeutic values were aberrant of the limit of the therapeutic range (15%).In 101 patients admitted to the ICU and MCU, time to therapeutic range was 24 hours in 56% of the population, whereas in 10% of the patients no therapeutic APTT was achieved during UFH treatment. Among the APTT levels, 29% of all test results measured in 24 hours were within the therapeutic range. Subtherapeutic values were found in 53% of the test results, of which 160/203 were more than 15% under the lower limit, whereas 18% of the test results were supratherapeutic, of which 40/69 more than 15% above the upper limit.In this cohort of critically ill patients, therapeutic APTT values were reached within 24 hours in 56% of the patients. We conclude that intravenous UFH therapy can be improved in critically ill patients.

The effect of cardiovascular risk factors (CVRs) and thrombophilic defects on the risk of arterial cardiovascular complications in patients with prior venous thromboembolism (VTE) is unclear.We investigated whether the risk of arterial cardiovascular complications is increased after VTE and whether CVRs and thrombophilic defects influence this risk.Subjects were selected from three family cohorts of probands with VTE or arterial cardiovascular complication before the age of 50 and thrombophilic defects (i.e. hyperhomocysteinaemia, prothrombin G20210A or elevated FVIII). For this analysis, probands with arterial cardiovascular complications before inclusion and their relatives as well as relatives without the studied thrombophilic defects were excluded. We calculated the incidence of arterial cardiovascular complications (e.g. myocardial infarction, ischaemic stroke, transient ischaemic attack or peripheral arterial disease) in subjects with and without VTE and adjusted the relative risk for at least one CVR, two or more thrombophilic defects and quintiles of a propensity score (considering risk factors conditional to VTE history).861 subjects were included, of whom 399 had experienced VTE before inclusion. Twelve arterial cardiovascular complications occurred in subjects with and nine in subjects without VTE history. Hence the annual incidence was 1.0 (95% CI 0.5 to 1.7) and 0.7 (0.3 to 1.2) in subjects with and without VTE (RR 1.5, 0.6 to 3.6). Adjusting for possible confounders did not change this relative risk.The mildly elevated risk of arterial cardiovascular complications in patients with prior VTE appears to be independent of cardiovascular risk factors and thrombophilic defects.

The absolute risk of deep venous thrombosis (DVT) and pulmonary embolism (PE) as well as extension and/or recurrence in superficial vein thrombosis (SVT) of the leg is considerable and underestimated. We retrospectively evaluated therapeutic management, thrombophilic risk factors and clinical outcome of SVT.A database search was performed for consecutive patients with a suspected SVT of the lower extremities referred to our institution between 1 January 1999 and 31 December 2004. The primary outcome measure was pain reduction at follow-up. Secondary outcome measures were progression or recurrence of SVT in the leg and the occurrence of (a)symptomatic DVT or symptomatic PE at follow-up.In 73 patients follow-up information was present (3/76 non-evaluable patients). In 9/32 (28%) of the patients treated with carbasalate calcium, there was progression of SVT as assessed by ultrasonographic evaluation, compared with 3/11 (27%) in the low-molecular-weight heparin (LMWH) group and 3/6 (50%) in the no treatment group. DVT was diagnosed in 5/36 (14%) of the patients treated with carbasalate calcium compared with 1/13 (1%) in the LMWH and 1/3 (33%) in the other treatment groups at follow-up. Furthermore, 34 were tested for thrombophilic defects, 27 of whom had one or more thrombophilic defect.The results of our study show that SVT may be prone to venous thromboembolism and therefore needs to be treated or carefully followed up.

In de definitie van evidence-based medicine (het zorgvuldig, expliciet en oordeelkundig gebruik van het huidige beste bewijsmateriaal om beslissingen te nemen voor individuele patienten) wordt gesproken over individuele patienten.

In the past decade, numerous publications on the association between venous thrombosis (VT) and travel have been published. Relative and absolute risks of VT after travel, and particularly after travel by air, have been studied in case-control and observational follow-up studies, whereas the effect of prophylaxis has been studied through intervention trials of asymptomatic clots. The mechanism responsible for the association between travel and VT was addressed in pathophysiologic studies. Here, we systematically reviewed the epidemiologic and pathophysiologic studies about the association between travel and VT. We conclude that long-distance travel increases the risk of VT approximately two to fourfold. The absolute risk of a symptomatic event within 4 weeks of flights longer than 4 h is 1/4600 flights. The risk of severe pulmonary embolism (PE) occurring immediately after air travel increases with duration of travel, up to 4.8 per million in flights longer than 12 h. The mechanism responsible for the increased risk of VT after (air) travel has insufficiently been studied to draw solid conclusions, but one controlled-study showed evidence for an additional mechanism to immobilization that could lead to coagulation activation after air travel.

Erectile dysfunction is a common multifactorial complication of diabetes mellitus. In recent years, phosphodiesterase type 5 (PDE-5) inhibitors have been introduced in the management of erectile dysfunction. A recent Cochrane systematic review assessed the effects ofPDE-5 inhibitors in patients with diabetes mellitus and erectile dysfunction from 8 randomized placebo-controlled trials (a total of 1759 participants). The duration of therapy was mainly 12 weeks. The weighted mean difference (WMD) for the International Index of Erectile Function (erectile dysfunction domain) at the end of the study period was 6.6 in favour of the PDE-5 inhibitors arm. The relative risk for answering 'yes' to a global efficacy question ('did the treatment improve your erections?') was 3.8 in the PDE-5 inhibitors arm compared with the control arm. Headache and flushing were the most common adverse events, followed by flu-like symptoms, dyspepsia, myalgia, vision disorders and lower back pain. The overall risk ratio for developing any adverse reaction was 4.8 in the PDE-5 inhibitors arm as compared to the control arm. It was concluded that sufficient evidence exists that treatment with PDE-5 inhibitors can improve erectile dysfunction in diabetic men.

Basic research and clinical studies have generated the hypothesis that anticoagulation may improve survival in patients with cancer through an antitumour effect in addition to the antithrombotic effect.To evaluate the efficacy and safety of heparin (including unfractionated heparin (UFH) and low molecular weight heparin (LMWH)) and fondaparinux to improve survival of patients with cancer.A comprehensive search for studies of anticoagulation in cancer patients including (1) A January 2007 electronic search of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ISI the Web of Science; (2) Hand search of the American Society of Clinical Oncology and of the American Society of Hematology; (3) Checking of references of included studies; and (4) Use of "related article" feature in PubMed.We included randomized controlled trials (RCTs) in cancer patients without clinical evidence of venous thromboembolism comparing UFH, LMWH or fondaparinux to no intervention or placebo and RCTs comparing two of the three agents of interest.Using a standardized form we extracted in duplicate data on methodological quality, participants, interventions and outcomes of interest including all cause mortality, venous thrombosis, symptomatic pulmonary embolism, major bleeding and minor bleeding.Of 3986 identified citations five RCTs fulfilled the inclusion criteria. In all included RCTs the intervention consisted of heparin ( either UFH or LMWH). The overall methodological quality of the included studies was acceptable. Overall, heparin therapy was associated with a statistically and clinically significant survival benefit (hazard ratio (HR) = 0.77; 95% CI: 0.65 to 0.91). In subgroup analyses, patients with limited small cell lung cancer experienced a clear survival benefit (HR = 0.56; 95% CI: 0.38 to 0.83). The survival benefit was not statistically significant for either patients with extensive small cell lung cancer (HR = 0.80; 95% CI: 0.60 to 1.06) or patients with advanced cancer (HR = 0.84; 95%: 0.68 to 1.03). The increased risk of bleeding with heparin was not statistically significant (RR = 1.78; 95% CI: 0.73 to 4.38).Heparin has a survival benefit in cancer patients in general, and in patients with limited small cell lung cancer in particular. Heparin might be particularly beneficial in cancer patients with limited cancer or a longer life expectancy. Future research should investigate the survival benefit of different types of anticoagulants (in different dosing, schedules and duration of therapy) in patients with different types and stages of cancers.

Aspirin is the prophylactic antiplatelet drug of choice for people with cardiovascular disease. However, protection with antiplatelet therapy in people with a high risk of cardiovascular disease is unsatisfactory in absolute terms. Adding a second antiplatelet drug to aspirin may produce additional benefit for those at high risk and those with established cardiovascular disease.To quantify the effects (both benefit and harm) of adding clopidogrel to standard long-term aspirin therapy for preventing cardiovascular events in people at high risk of cardiovascular disease and those with established cardiovascular disease.CENTRAL (Issue 2 2006), MEDLINE (2002 to May 2006) and EMBASE (2002 to May 2006) were searched. Online registers of ongoing trials and reference lists from original articles and reviews were checked.All randomized controlled trials comparing long term (30 days) use of aspirin plus clopidogrel with aspirin plus placebo or aspirin alone in patients with coronary disease, ischemic cerebrovascular disease, peripheral arterial disease, or at high risk of atherothrombotic disease (with data for at least one of the outcomes) were included.Data were collected on the following outcomes and analysed where appropriate: mortality (from myocardial infarction, stroke, cardiovascular causes, all-causes), non-fatal myocardial infarction, non-fatal stroke, unstable angina, heart failure, revascularizations, major and minor bleeding, and all adverse events. Quantitative analysis of outcome was based on an intention-to-treat principle. The overall treatment effect was estimated by the pooled odds ratio (OR) with 95% confidence interval (CI) using a fixed-effect model (Mantel-Haenszel).Two RCTs were found. Patients enrolled in the CHARISMA study were at high risk for cardiovascular events, either with or without an established cardiovascular disease. Patients enrolled in the CURE study had a recent non-ST segment elevation acute coronary syndrome. The use of clopidogrel plus aspirin, compared with placebo plus aspirin, was associated with a lower risk of cardiovascular events (OR: 0.87, 95% CI 0.81 to 0.94; P0.01) and a higher risk of major bleeding (OR 1.34, 95% CI 1.14 to 1.57; P0.01). Overall, we would expect 13 cardiovascular events to be prevented for every 1000 patients treated with the combination, but 6 major bleeds would be caused. Treatment effects differed in the two trials: the CURE trial, confined to people with acute non-ST segment coronary syndromes, showed definite evidence of benefit from treatment. For every 1000 people treated for an average of 9 months, 23 events would be avoided and 10 major bleeds would be caused. In the CHARISMA trial that randomized people at high cardiovascular risk defined either in terms of pre-existing cardiovascular diseases or risk factors, the effects of treatment were less marked and were consistent with the play of chance. For every 1000 people treated for an average of 28 months, 5 cardiovascular events would be avoided and 3 major bleeds would be caused.The available evidence demonstrates that the use of clopidogrel plus aspirin is associated with a reduction in the risk of cardiovascular events compared with aspirin alone in patients with acute non-ST coronary syndrome. In patients at high risk of cardiovascular disease but not presenting acutely, there is only weak evidence of benefit and hazards of treatment almost match any benefit obtained.

Background The optimal treatment of superficial thrombophlebitis (ST) of the legs remains poorly defined. While improving or relieving the local painful symptoms, treatment should aim at preventing venous thromboembolism (VTE), which might complicate the natural history of ST. This is an update of a review first published in 2007. Objectives To assess the efficacy and safety of topical, medical, and surgical treatments in patients presenting with ST of the legs. Search methods For this update the Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched 29 November 2011) and CENTRAL (2011, Issue 4). We handsearched reference lists of relevant papers and conference proceedings. Selection criteria Randomised controlled trials (RCTs) evaluating topical, medical, and surgical treatments for ST of the leg that included participants with a clinical diagnosis of ST of the legs or objective diagnosis of a thrombus in the superficial vein. Data collection and analysis Two authors assessed the trials for inclusion in the review, extracted the data, and assessed the quality of the studies. Data were independently extracted from the included studies and any disagreements resolved by consensus. Main results Twenty-six studies involving 5521 participants with ST of the legs were included in this review. The methodological quality of most of the trials was poor. Treatment ranged from fondaparinux, low molecular weight heparin (LMWH), unfractionated heparin (UFH), nonsteroidal anti-inflammatory agents (NSAIDs), topical treatment, oral treatment, intramuscular treatment, and intravenous treatment to surgery. In a placebo-controlled RCT of about 3000 patients, fondaparinux was associated with a significant reduction in symptomatic VTE (RR 0.15; 95% CI 0.04 to 0.50), extension (RR 0.08; 95% CI 0.03 to 0.22), and recurrence of ST (RR 0.21; 95% CI 0.08 to 0.54) with comparable rates of major bleeding (RR 0.99; 95% CI 0.06 to 15.86) relative to placebo. Both prophylactic and therapeutic doses of LMWH (RR 0.40; 95% CI 0.22 to 0.72 and RR 0.42; 95% CI 0.23 to 0.75, respectively) and NSAIDs ( RR 0.41; 95% CI 0.23 to 0.75) reduced the extension and recurrence of ST in comparison to placebo, with no significant effects on symptomatic VTE nor major bleeding. Overall, topical treatments improved local symptoms. However, no data were provided on the effects of these treatments on VTE and ST extension. Surgical treatment combined with elastic stockings in ST was associated with a lower VTE rate and ST progression compared with elastic stockings alone. Authors' conclusions Prophylactic dose fondaparinux given for six weeks appears to be a valid therapeutic option for ST of the legs. Further research is needed to assess the role of new oral direct thrombin and activated factor-X inhibitors, LMWH, NSAIDs; the optimal doses and duration of treatment; and whether a combination therapy may be more effective than single treatment. Adequately designed and conducted studies are required to clarify the role of topical and surgical treatments

A recent Cochrane systematic review assessed the effects of wearing compression stockings during long-distance flights on the risk of deep-vein thrombosis (DVT). Ten randomised trials were included, 9 of which compared wearing compression stockings on both legs during the whole flight (at least 7 hours) with not wearing compression stockings. In these 9 trials, 50 of 2637 participants with 1 week of follow-up had asymptomatic DVT; 3 had worn stockings, 47 had not (odds ratio: 0.10; 95% CI: 0.04-0.25). No deaths, pulmonary emboli or symptomatic DVTs were reported. Wearing stockings had a significant impact in reducing oedema of the lower legs. No significant adverse effects of wearing stockings were reported.

Approximately 30% of people over 65 years of age and living in the community fall each year; the percentage is higher in institutions. A fifth of the incidents require medical attention. A Cochrane systematic review of 62 studies, encompassing 21,668 elderly people, showed that several interventions are effective in preventing falls, especially in people who have already fallen once, including multidisciplinary interventions targeting multiple risk factors, individually prescribed muscle strengthening combined with balance training at home, cardiac pacing for hypersensitivity of the sinus node, and withdrawal of psychotropic medication. Individually tailored interventions delivered by a health professional were more effective than standard or group-delivered programmes. Some potential interventions were of unknown effectiveness or unlikely to be beneficial. Examples of these are physical exercises, the use of dietary supplements and the correction of impaired vision.

A Cochrane systematic review of 30 randomised clinical trials assessed the effects of current treatments for adults with mild-to-severe changes in facial and forearm skin that occurred as a result of prolonged exposure to the sun ('photodamage'). Topical tretinoinor = 0.02% improved the appearance of mild-to-severe photodamage. Tazarotene 0.01-0.1% and isotretinoin 0.1% provided benefit to patients with moderate photodamage. The treatment duration was 4-11 months. Adverse effects were pain and redness. Both the efficacy and adverse effects were dose-dependent. Other treatments, such as polysaccharides, hydroxy acids, surgical procedures and laser, cannot be recommended.

Antitrombine(voorheen antitrombine-III)-deficientie is een zeldzame risicofactor voor het krijgen van veneuze trombo-embolie met een prevalentie van 1 a 2% bij opeenvolgende patienten met veneuze trombose (1).

Risicofactoren voor veneuze trombo-embolie en arteriele hart- en vaatziekten verschillen van elkaar. Roken, hypertensie en hypercholesteremie zijn duidelijke risicofactoren voor arterieel vaatlijden, terwijl zij geen invloed hebben op de kans op veneuze trombose of longembolieen. Erfelijke afwijkingen die gepaard gaan met een verhoogd risico op veneuze trombo-embolie zijn daarentegen meestal niet geassocieerd met een grotere kans op arteriele aandoeningen. Naar aanleiding van bovenstaande vraag bespreek ik de factor-V-Leiden-mutatie en zijn associatie met veneuze en arteriele hart- en vaatziekten en het risico en eventuele nut van aspirine bij deze aandoening.

De Mirena®-spiraal is een intra-uterien anticonceptiemiddel (‘spiraaltje’) dat gedurende 5 jaar ongeveer 20 mcg levonorgestrel per dag afgeeft. Door de hormonaal geinduceerde endometriumatrofie is innesteling van een bevruchte eicel niet mogelijk. De effectiviteit als anticonceptivum is even goed als die van orale anticonceptiva (1).

Removing dental plaque plays a key role in maintaining oral health and reducing gingivitis and parodontitis. A systematic Cochrane review ofrandomised controlled trials encompassing participants from the general public with uncompromised manual dexterity showed that when compared to the use of manual toothbrushes, the use of powered toothbrushes with a rotating oscillation action for a period of three months reduced gingivitis and (although not statistically significantly) plaque. The long-term clinical relevance of the differences is unclear. Electric toothbrushes that did not have an oscillating rotating movement were not consistently better than manual toothbrushes.

Sweeping ('stripping') of the membranes has the potential to initiate labour by increasing local production of prostaglandins and, thus, to reduce pregnancy duration or to pre-empt formal induction of labour with either oxytocin, prostaglandins or amniotomy. A Cochrane systematic review of 22 trials (2797 women) comparing membrane sweeping with no treatment, with prostaglandins and with oxytocin revealed that stripping of the membranes was associated with reduced frequency of pregnancy continuing beyond 41 and 42 weeks. To avoid formal induction of labour in one instance, membrane sweeping must be performed in 8 women. Discomfort during vaginal examination and other adverse effects (bleeding, irregular contractions) were reported more frequently by women allocated to sweeping. When used as a means of inducing labour, the reduction in the use of more formal methods of induction must be balanced against the resulting discomfort and other adverse effects.

The routine use of nasogastric tubes after abdominal operations is intended primarily to hasten the return of bowel function. A Cochrane systematic review of 28 studies, encompassing 4195 patients (2108 randomised to routine tube use and 2087 randomised to temporary or no tube use), showed that routine prophylactic nasogastric decompression was not effective in achieving its primary goal. It also appeared not to be statistically significantly effective in achieving secondary goals, such as the prevention of pulmonary complications, wound infection, and ventral hernia, nor in increasing patient comfort and shortening hospital stay. Routine nasogastric decompression should be abandoned in favour of temporary use of the nasogastric tube.

Since hypercoagulability might result in recurrent pregnancy loss, anticoagulant agents could potentially increase the live-birth rate in subsequent pregnancies in women with either inherited thrombophilia or unexplained pregnancy loss.To evaluate the efficacy and safety of anticoagulant agents, such as aspirin and heparin, in women with a history of at least two spontaneous miscarriages or one later intrauterine fetal death without apparent causes other than inherited thrombophilias.We searched the Cochrane Pregnancy and Childbirth Group trials register (March 2004), the Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2004), MEDLINE (January 1966 to March 2004), and EMBASE (1980 to March 2004). We scanned bibliographies of all located articles for any unidentified articles.Randomised and quasi-randomised controlled trials that assessed the effect of anticoagulant treatment on the live-birth rate in women with a history of at least two spontaneous miscarriages or one later intrauterine fetal death without apparent causes other than inherited thrombophilias were eligible. Interventions included aspirin, unfractionated heparin, and low molecular weight heparin for the prevention of birth loss. One treatment could be compared with another or with placebo.Two authors assessed the trials for inclusion in the review and extracted the data. Data were entered into the Review Manager software and double checked.Two studies (242 participants) were included in the review and for both of them data were extracted for the subgroups of women fulfilling the inclusion criteria of the review. In one study, 54 pregnant women with recurrent spontaneous abortion without detectable anticardiolipin antibodies were randomised to low-dose aspirin or placebo. Similar live-birth rates were observed with aspirin and placebo (relative risk (RR) 1.00, 95% confidence interval (CI) 0.78 to 1.29). In another study, a subgroup of 20 women who had had a previous fetal loss after the 20th week and had a thrombophilic defect were randomised to enoxaparin or aspirin. Enoxaparin treatment resulted in an increased live-birth rate, as compared to low-dose aspirin, RR 10.00, 95% CI 1.56 to 64.20).The evidence on the efficacy and safety of thromboprophylaxis with aspirin and heparin in women with a history of at least two spontaneous miscarriages or one later intrauterine fetal death without apparent causes other than inherited thrombophilias is too limited to recommend the use of anticoagulants in this setting. Large, randomised, placebo-controlled trials are urgently needed.

INTRODUCTION: Heparin-induced allergic reactions may cause problems if heparin administration is needed for thrombo-embolic disease in pregnancy. CASE REPORTS: We report two cases of hypersensitivity to low molecular weight heparin (LMWH) in pregnancy. DISCUSSION: Alternative methods and new antithrombotic agents are discussed

In 70% to 80% of patients with venous thromboembolism, a thrombophilic defect can be identified. The most important defects are: antibodies to phospholipids or lupus anticoagulants, mutation of factor V Leiden, prothrombin mutation, mild hyperhomocysteinaemia, and increased factor VIII levels. Deficiencies of antithrombin, protein C or protein S are rare. Whether or not screening for thrombophilia in patients with idiopathic venous thromboembolism is justified, depends on the potential benefits for the patients, or their relatives. At present, patients with a thrombophilic defect do not appear to have a much higher risk for recurrent venous thromboembolism, than patients with thrombosis but without a defect. The absolute risks of venous thromboembolism in asymptomatic relatives with a thrombophilic defect are too low to justify initiating a general policy of family screening. In conclusion, a conservative approach towards thrombophilia screening in idiopathic venous thromboembolism is warranted.

The risk of venous thromboembolism (VTE) is increased in pregnancy and during the post-partum period. The absolute risk for pregnancy-related VTE in heterozygous women with the factor V Leiden mutation is approximately 2%, but studies on this risk for homozygous women show conflicting results. In a retrospective family study, we found that the risk of pregnancy-related VTE in women with a symptomatic first-degree relative was 17% per pregnancy (95%CI 4.7-37.4). Anticoagulant prophylaxis during the post-partum period appears to be indicated in asymptomatic homozygous women from symptomatic kindred, whereas this could be decided on an individual basis during pregnancy.

Use of oral contraceptives induce changes in haemostatic parameters: changes occur in the procoagulant, anticoagulant, and fibrinolytic systems. The increased risk of venous thromboembolism with use of third, as compared with second generation oral contraceptives, found in epidemiological studies, has stimulated new research in haemostatic changes induced by both generations of oral contraceptives. A randomized crossover study showed that use of the third generation pill caused a greater increase of factor VII and prothrombin and a more pronounced decrease of factor V than the second generation pill. Acquired resistance to activated protein C (APC) was induced more strongly by preparations of the third than by those of the second generation. The concentration of protein S decreased markedly exclusively during use of the third generation pill, while it did not change during use of the second generation pill. The oral contraception-related effects on the anticoagulant system strongly resemble those of some forms of hereditary thrombophilia. If a woman with hereditary APC resistance (caused by factor V Leiden) uses oral contraceptives as well, and especially when she uses those of the third generation, she is subject to a considerable increase of the risk of venous thrombosis and becomes even more resistant to the anticoagulant action of protein C. In view of the epidemiological backgrounds of the difference in risk of thrombosis between second and third generation contraceptives, the second generation pill is recommended as the first choice for oral contraception.

Combined oral contraceptives (OC) are known to increase the risk of venous thromboembolism. The aim of this randomized, cycle-controlled, cross-over study in 28 healthy volunteers was to assess potential differences between the effects of an OC containing 150 microg levonorgestrel (as representative of the so-called second generation OC) and an OC containing 150 microg desogestrel (as representative of the third generation OC) in combination with 30 microg ethinylestradiol on several coagulation factors and markers of thrombin formation. All participants used each OC for two cycles, and were switched to the other OC after a washout period of two menstrual cycles. The plasma concentrations of factors II, VII, X, and fibrinogen significantly increased during use of both the levonorgestrel- and desogestrel-containing OC's. The plasma concentrations of factor VIII increased, and of factor V decreased, changes which only reached statistical significance during the use of the desogestrel-containing OC. During exposure to the desogestrel-containing OC, as compared with the levonorgestrel-containing OC, both factor VII and factor II showed a greater increase (FVII: 32% and 12% respectively; p0.0001; FII: 16% and 12% respectively; p = 0.048), whereas factor V showed a greater decrease (-11% and -3% respectively; p = 0.010). Only one of the markers for ongoing coagulation (prothrombin fragment 1+2) showed a significant increase during OC use, whereas concentrations of thrombin-antithrombin complexes and soluble fibrin remained unchanged. For these markers, there was no difference between the tested OC's. We conclude that there are differences between the effects of levonorgestrel and desogestrel-containing OC's on some coagulation factors. Whether these changes provide a biological explanation for the reported differences in venous thromboembolic risk is as yet unclear. The real challenge now becomes to define a pattern of changes in the various systems which, if affected simultaneously, may tip the hemostatic balance towards a prethrombotic state and may lead to overt clinical venous thromboembolism.

Lupus anticoagulant (antiphospholipid antibodies) is associated with venous and arterial thrombosis in patients with and without autoimmune disorders. Vitamin K antagonists are the treatment of choice in patients with thrombosis, of which the dose is titrated by INR monitoring. Several recent reports suggest that the presence of the lupus anticoagulant disturbs the INR test and may lead to unreliable results with a large variation in INR values, dependent on the reagents used.We studied 11 lupus anticoagulant positive patients and 11 lupus anticoagulant negative patients, all using vitamin K antagonists. The INR value was determined using seven different tests and the variation in INR values was compared between the two groups. The amidolytic Factor X levels were used as an phospholipid independent measure for intensity of warfarin therapy. Factor VII and X activity were measured to assess the stability of warfarin therapy.The variation of the results with different INR tests within one patient was minimal and comparable in the two groups for INR's in the therapeutic range. The coefficient of variation for the cases and control group was 10.43 and 9.35, respectively. Variation in both groups increased at supratherapeutic levels of anticoagulation and when the anticoagulation was unstable (measured with Factor X/Factor VII ratio). The relationship between INR values and Factor X analysis revealed no influence of the lupus anticoagulant.In this study, lupus anticoagulant antibodies do not disturb INR laboratory tests. Differences in INR measurements are seen in patients with a high intensity of anticoagulation and in patients who either just started or in whom no stable anticoagulation has been achieved. Abbreviated Abstract. This study investigates the influence of lupus anticoagulant on INR determination tests in patients treated with warfarin. Eleven cases and eleven lupus anticoagulant negative control patients, also on warfarin therapy, were included. Seven INR results per patient were obtained using different laboratory tests. A factor X assay was performed to obtain an independent measure for the intensity of warfarin therapy. The variation of INR results between the cases and controls revealed no difference in these groups. In addition, the relationship between INR values and Factor X analysis indicated no influence of the lupus anticoagulant. What was observed was an increased difference in INR values in patients with a high intensity of anticoagulation and in patients who either just started or in whom no stable anticoagulation has been achieved